This study presents a detailed comparative analysis of Molecular Docking data, focusing on the binding interactions of conventional ligands and natural compounds, Apigenin and Luteolin, with TP-53, pRb, and APOBEC. Utilizing advanced bioinformatics techniques, coupled with Ar-tificial Intelligence software and High-Performance Computing (HPC), we measured and con-trasted the binding energies of these interactions. Additionally, we investigated protein-protein interactions between HPV-16 oncoprotein E6 and tumor suppressors TP-53 and pRb. Our findings demonstrate that the natural compounds Apigenin and Luteolin exhibit significantly higher binding affinities to TP-53, pRb, and APOBEC compared to conventional pharmacological ligands. The binding energies for Apigenin and Luteolin were approximately -6.9 kcal/mol and -6.6 kcal/mol, respectively, indicating their strong potential as therapeutic agents in inhibiting the oncogenic functions of HPV-16. In contrast, conventional ligands showed lower binding affinities, with energies around -4.5 to -5.5 kcal/mol. The study further revealed that the protein-protein interactions between E6 and TP-53, and E6 and pRb, exhibited considerably higher binding en-ergies, approximately -976.7 kcal/mol, due to the multiple interaction sites and the complex nature of protein interfaces. A conversion formula was developed to translate these high-energy inter-actions to a comparable scale for non-protein-protein interactions, highlighting the superior binding potential of natural compounds, which, through the same conversion formula, was shown to be higher than that of interaction between E6 with TP-53 and E6 with pRb. These results underscore the therapeutic promise of Apigenin and Luteolin in preventing HPV-16-related on-cogenesis. By demonstrating their higher binding affinities to crucial tumor suppressors, this study supports the development of natural compound-based therapies. The findings also em-phasize the necessity for further experimental validation to explore these compounds' efficacy in clinical settings. This comprehensive analysis provides a robust framework for understanding the comparative binding interactions and lays the groundwork for innovative therapeutic strategies against HPV-16.

This manuscript explores significant advancements and emerging challenges in CAR T cell therapies, focusing on the production methodologies and regulatory complexities. The discussion highlights ongoing challenges like the lack of in vivo persistence, lengthy production times, and elevated costs associated with current CAR T cell therapies. It analyzes innovative solutions such as genetic engineering techniques aimed at enhancing cellular efficacy and endurance, alongside cutting-edge manufacturing processes, including closed systems and development of allogeneic products. These advancements hold promise for reducing costs and improving production efficiency, potentially increasing patient access to these transformative therapies globally. Furthermore, the manuscript underscores the necessity for expanding ongoing research and enhancing regulatory frameworks to fully realize and implement these innovations in CAR T cell manufacturing and bring these innovations to fruition.

Parkinson's disease (PD) is a prevalent neurodegenerative disorder marked by progressive motor and non-motor symptoms. Traditional treatments primarily manage symptoms rather than address the disease's root causes, highlighting the need for novel therapeutic approaches. Natural phytochemicals, particularly phenolic compounds, have shown potential due to their neuroprotective effects. Antiaris africana is commonly used in traditional African medicines to treat several illnesses including neurodegenerative disorders. However, its neuroprotective mechanism remains elusive. This study aimed to employ network pharmacology-based prediction to identify key targets and pathways through which A. africana exerts its effects on PD. Targets associated with Parkinsonism were identified and analyzed for interaction with compounds from A. africana. Protein-protein interaction (PPI) networks were constructed, and key hub genes were identified using Cytoscape. Functional enrichment analysis highlighted significant pathways involved in PD. Molecular docking was performed to evaluate the binding affinities of the compounds to PD-related targets. Our results reveal that compounds such as caffeic acid, chlorogenic acid, catechin, ellagic acid, epigallocatechin, gallic acid, isoquercitrin, kaempferol, quercetin, quercitrin, and rutin interact with key proteins implicated in PD, including APP, EGFR, CASP3, ESR1, AKT1, and MAPK8. Notably, rutin exhibited strong binding affinity for EGFR, and chlorogenic acid showed potential in modulating the APP pathway. These findings suggest that phenolic compounds in A. africana may exert neuroprotective effects through multiple molecular mechanisms, offering potential therapeutic strategies for PD. This study underscores the importance of integrating molecular docking and network pharmacology to elucidate the therapeutic potential of natural compounds in complex diseases like Parkinson's disease

The blood-brain barrier (BBB) acts as a structural and functional barrier for brain homeostasis. This review highlights the pathological contribution of BBB dysfunction to neuroimmunological diseases, including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), autoimmune encephalitis (AE) and paraneoplastic neurological syndrome (PNS). The transmigration of massive lymphocytes across the BBB caused by the activation of cell adhesion molecules is involved in the early phase of MS, and dysfunction of the cortical BBB is associated with the atrophy of gray matter in the late phase of MS. In the onset of NMOSD, increased permeability of the BBB causes the entry of circulating AQP4 autoantibodies into the central nervous system (CNS). Recent reports have shown the importance of glucose-regulated protein (GRP) autoantibodies as BBB-reactive autoantibodies in NMOSD, inducing antibody-mediated BBB dysfunction. BBB breakdown has also been observed in MOGAD, NPSLE, and AE with anti-NMDAR antibodies. Our recent report demonstrated the presence of GRP78 autoantibodies in patients with MOGAD and the molecular mechanism responsible for GRP78 autoantibody-mediated BBB impairment. Disruption of the BBB may explain the symptoms in the brain and cerebellum in the development of PNS, as it induces the entry of pathogenic autoantibodies or lymphocytes into the CNS by autoimmunity against tumors in the periphery. GRP78 autoantibodies were detected in paraneoplastic cerebellar degeneration and Lambert-Eaton myasthenic syndrome and were associated with cerebellar ataxia with anti-P/Q type voltage-gated calcium channel antibodies. This review reports that therapies affecting the BBB that are currently available for disease-modifying therapies for neuroimmunological diseases have the potential to prevent BBB damage.

Traditional Chinese medicine requires decoction and consumption, which is time-consuming and labor-intensive. Scientific Chinese medicine (SCM), on the other hand, uses concentrated granules that can be taken with hot water, making it widely welcomed. With the widespread adoption of SCM, the packaging technology has started to receive attention. Whether it is manpower allocation, operation time, or the uniformity and residue of the medicine powder, these factors can become bottlenecks in the process. A traditional SCM pharmacy machine is purely mechanically hardwired. This paper proposes SCMtalk, an Internet of Things (IoT)-based SCM mechanism designed to enhance the efficiency and accuracy of SCM medicine packets generation. We show how SCMtalk develops IoT hardware and software modules for medicine selection, mixing, dispensing, packaging, and cleaning. We also explain how the mechanical IoT hardware is integrated with the corresponding software module to become an individual IoT device. These IoT devices can be transparently replaced, allowing us to easily upgrade the individual components of the SCM packet generation through the IoT concept. Finally, we address quality control issues by leveraging IoT. One contribution of this paper is to introduce an interesting SCM application to IoT experts and to demonstrate how we collaborated with pharmacists and mechanical experts to use a powerful IoT platform to create a smart pharmacy.

Astragalus plants belong to the legume family and have obvious rhizosphere effect. The northwestern area of Yunnan China is the main distribution region of Astragalus plants with high application value, but low recognition and resource reserves. The aim of this research is to explore the species diversity of cultivable rhizosphere fungi derived from A. acaulis, A. forrestii, and A. ernestii growing in special high-cold environment of northwest Yunnan, and discover anti-infective components from these fungi. A total of 93 fungal strains belonging to 38 species in 18 genera were isolated and identified. Antibacterial and antimalarial screening yielded 10 target strains. Among them, the ethyl acetate crude extract of the fungus Aspergillus calidoustus AA12 from A. acaulis fermentation substance showed a broad antibacterial spectrum and the best antimalarial activity. Further chemical investigation led to the first discovery of seven compounds from the species of A. calidoustus, including a sesterterpine 6-epi-ophiobolin G (1), two sesquiterpenes penicisochroman A (2), pergillin (3) and 7-methyl-2-(1-methylethylethlidene)-furo[3,2-H]isoquinoline-3-one (4), and three polyketides trypacidin (5), 1,2-seco-trypacidin (6) and questin (7). Compound 1 exhibited moderate to strong antibacterial activity against six Gram-positive pathogens with the minimum inhibitory concentration (MIC) ranging from 25 to 6.25 μg/mL, and prominent inhibitory effect on the biofilm of Streptococcus agalactiae at MIC value of 3.125 μg/mL. This compound also displayed potent antimalarial activity against Plasmodium falciparum strains 3D7 and chloroquine-resistant Dd2 at the half maximal inhibitory concentration (IC50) values of 3.319 and 4.340 µmol/L at 72 h, respectively. This study contributed to our understanding of the cultivable rhizosphere fungi Astragalus-derived in special high-cold environment and further increased the library of fungi available for natural anti-infectious products screening.

Renal replacement therapy (RRT), widely used in the treatment of renal injury in the course of sepsis, aims to eliminate the toxins and proinflammatory cytokines, involved in the pathomechanism underlying septic shock. Dialysis filters characterised by a high adsorption potential for cytokines in RRT when septic renal injury is the case. It is of key importance in the antibiotics treatment of sepsis to achieve desired values of PK/PD indices. Continuous renal replacement therapy (CRRT) may affect antimicrobial clearance, increasing their elimination in some cases. The aim of this study was to determine the degree of adsorption for linezolid, on three different types of filters used in CRRT. In our in vitro study a continuous veno-venous hemofiltration (CVVH) was conducted using 3 types of filters: polysulfone (PS), polyethyleneimine-treated polyacrylonitrile (PAN PEI) and non-PEI-treated polyacrylonitrile (PAN) filters. Each type of filter was used in 3 CVVH cycles, involving the use of 600 mg of linezolid dissolved in 700 ml of bovine blood or in 700 ml of 0.9% NaCl. In each case the total volume of the obtained solution was 1000 ml. Blood samples, at particular time points, were collected in order to measure drug concentration. The differences in mean drug/NaCl adsorption and drug/ blood adsorption were determined using one-way ANOVA with multiple comparisons by Tukey post-hoc test. A p-value of < 0.05 was considered to be significant. A significant adsorption of linezolid was found for PAN PEI filter, both in samples obtained from bovine blood and 0.9% NaCl solutions, at the endpoint. No significant adsorption was demonstrated on PAN or PS filters. There is a need for in vivo research to confirm the effect of filter type on linezolid concentration in patients undergoing CRRT.

Brain metastasis is the most common intracranial malignancy in adults. The prognosis is extremely poor, partly because most patients have more than one brain lesion, and the currently available therapies are nonspecific or inaccessible to those occult metastases due to an impermeable brain-tumor-barrier (BTB). Phosphatidylserine (PS) is externalized on the surface of viable endothelial cells (ECs) in tumor blood vessels. In this study, we have applied a PS-targeting antibody to assess brain metastases in mouse models. Fluorescence microscopic imaging revealed that extensive PS exposure was found exclusively on vascular ECs of brain metastases. The highly sensitive and specific binding of the PS antibody enables individual metastases, even micrometastases containing an intact BTB, to be clearly delineated. Furthermore, conjugation of the PS antibody with a fluorescence dye, IRDye 800CW, or a radioisotope, ¹²⁵I, allowed clear visualization of individual brain metastases by optical imaging and autoradiography, respectively. In conclusion, we demonstrated a novel strategy of targeting brain metastases based on our finding that abundant PS exposure occurs on blood vessels of brain metastases but not normal brain, which may be useful for the development of imaging and targeted therapeutics for brain metastases

Background/Objectives: Boscia senegalensis (BS) Pers.) Lam. Ex Poir (Capparaceae), is an important local famine food plant in Africa and widely exploited by healers for its seeds in Sahelian region to reduce hyperglycaemia. Purpose: We studied the efficacy of commercial dosage form of BS namely Boscisucrophage (BSP) on type 2 diabetes (T2DM) patients with Oral antihyperglycemic drugs resistant. Study Design: Clinical benefits of BSP, were evaluated in multicentre cohort observational study on naïve patients (43) or diabetic patients resistant of oral antidiabetic drugs (289). All patients received capsules of the fixed dose containing 350 mg of BSP twice daily for 12 weeks and overactive control on vein blood sugar, glycosylated haemoglobin (HbA1c), urine glucose excretion (UGE), aspartate aminotransferase, alanine aminotransferase, creatinine, and clinical examination of functional symptoms. Results: In clinical study, BSP induced the reduction of glycaemia, HbA1c, and increase UGE, with removal of side effects functional symptoms of T2DM. Conclusions: In clinical studies, our findings lend support to use of BSP to reduce glycaemia, and HbA1c in T2DM patients with Oral antihyperglycemic drugs resistant without over adverse effects. BSP supressed clinical examination of functional symptoms.

Histomorphological studies were conducted to evaluate the effects of NS-Oil (NS) on ovarian toxicity induced by cyclophosphamide in female rats. The research aimed to assess the histological changes in ovarian tissue and correlate these findings with alterations in serum gonadotropin levels. The experimental design involved three (3) experimental groups treated with cyclophosphamide, NS-Oil oil, or a combination, with control group for comparison. Histological assessments of ovarian sections were performed to analyze structural integrity, follicular development, and toxicity signs, while serum samples were analyzed for estradiol, progestin levels.Cyclophosphamide administration significantly disrupted ovarian architecture, reducing follicle count and causing follicular degeneration. Conversely, NS-Oil oil treatment exhibited protective effects, restoring normal histological features and improving gonadotropin levels. Image J software, calibrated with a table micrometer, was used to measure diameters of follicles, follicular cells, and oocytes. Primary, secondary, and tertiary follicles were classified according to Oktay et al. (2017). Body weight showed no significant difference across groups, but ovarian weight decreased in cyclophosphamide-treated groups compared to controls (p < 0.05). However, ovarian weight increased dose-dependently in NS-Oil-treated groups (p < 0.05).Cyclophosphamide reduced ovarian cortex and medulla volumes (p < 0.05), while NS-Oil treatment increased these volumes (p < 0.05). Pre-antral and antral follicle counts decreased with cyclophosphamide but increased following NS-Oil treatment (p < 0.05). Atretic follicle counts decreased in both cyclophosphamide and NS-Oil-treated groups (p < 0.05). The diameters of pre-antral and antral follicles, as well as follicular cells, decreased with cyclophosphamide but increased post NS-Oil treatment (p < 0.05).These results suggest that NS-Oil may offer a therapeutic strategy to mitigate ovarian damage associated with cyclophosphamide treatment, highlighting its potential role in preserving reproductive health in patients undergoing chemotherapy. Further investigations are warranted to elucidate the underlying mechanisms of action and the efficacy of NS-Oil in clinical settings.

This study investigates the use of artificial intelligence (AI) and ethnobotanical knowledge to identify natural compounds with potent antiviral activity against HPV-16. Through molecular docking simulations, we evaluated the binding affinities of various essential oil components, in-cluding Apigenin, against the key antigenic determinants of HPV-16 (E6, E7 oncoproteins, and L1 major capsid protein). Apigenin exhibited strong binding affinities, particularly to E6 Oncopro-tein. To further enhance these findings, we employed an AI-driven reverse engineering approach to predict a natural compound with superior efficacy. The AI identified Luteolin, a flavonoid with additional hydroxyl groups, as a promising candidate. Comparative docking studies demon-strated that Luteolin possesses significantly stronger binding affinities to all three HPV-16 targets, surpassing the efficacy of Apigenin. This work highlights the potential of AI in accelerating the discovery and optimization of natural antiviral agents, providing a powerful tool for pharmaco-logical and ethnopharmacological screenings. Our findings suggest that AI-guided identification of natural compounds can lead to the development of more effective antiviral therapies, warranting further experimental validation and potential synthesis in laboratory settings.

Background and objectives: Chronic Kidney Disease and Mineral Bone Disorders (CKD-MBD) are frequently associated with an increased risk of both Vascular Calcifications (VCs) and bone fractures (BFs). The complex pathogenesis of VCs and BFs involves various factors such as calcium overload, phosphate imbalance, and secondary hyperparathyroidism. Key players, such as the vitamin K-dependent proteins (VKDPs) matrix Gla protein (MGP) and osteocalcin (BGP), have pivotal roles both for VCs and BFs. The Vitamin K Italian (VIKI) dialysis study, highlighted that hemodialysis patients treated with calcimimetics had higher levels of total BGP and MGP as compared to those untreated, suggesting a potential protective effect of these drugs on BFs and VCs, beyond the beneficial effect to reduce PTH levels. Methods: ETERNITY-ITA is a multi-center, comparative effectiveness, observational, longitudinal study that will enroll 160 hemodialysis patients (80 patients treated with Etelcalcetide and 80 age and sex-matched patients treated with Calcitriol or vitamin D analogs). Nephrologists will tailor the target dose of Etelcalcetide on individual level to achieve the KDIGO PTH target. In the Etelcalcetide-treated group, the addition of calcitriol will be allowed when required by clinical practice (for correction of hypocalcemia). Conclusion: The study will evaluate the real-world effect of Etelcalcetide on VKDP levels, such as BGP and MGP, at 3, 9, and 18 months from baseline. The resulting preservation of vascular and bone health will be assessed for the first time by examining aortic and iliac artery calcifications and vertebral fractures, respectively. Keywords: bone fractures; etecalcetide; hemodialysis; vascular calcification; vitamin K

Background: Previous studies have found variable impact of the coronavirus disease 2019 (COVID-19) pandem-ic on the consumption of antimicrobial drugs in human medicine, with trends in several European countries differing between community and inpatient prescribing. Aim: This study analysed changes in the volumes and use density of antibacterial and antifungal drugs dis-pensed in acute care hospitals in Germany between 2019 and 2022. Methods: Surveillance data for the four years available from 279 hospitals, among them 272 for antifungals, were expressed as the total volumes of daily doses or as use density (daily doses per 100 patient/occupied bed days) per year and analysed descriptively, using recommended hospital-adapted daily dose definitions (RDD) and (as sensitivity analysis) WHO/ATC-defined daily dose definitions (DDD). Hospitals were stratified according to size (number of beds) and university affiliation, and location (East, West, South). Results: There were significant decreases both in the total number of patient days and antibacterial drug vol-umes in 2020 through 2022 compared with 2019. The relative changes between 2019 and 2020, 2021 and 2022 were -12.8%, -13.5%, and -13.3% for patient days, and -9.7%, -11.0%, and -10.1% for antibacterial RDD, respec-tively. Broad-spectrum betalactams, notably piperacillin-tazobactam and carbapenems, increased in volume unlike most other drug classes. The resulting antibacterial drug use density was slightly but significantly increas-ing with pooled means (and medians) of 43.3 (40.0) RDD/100 in 2019 compared to 44.8 (41.7), 44.5 (40.80), and 44.9 (41.7) RDD/100 in the years 2020 through 2022, respectively. Antifungal drug volumes and use density increased after 2019 and peaked 2021 (differences between 2019 and 2021 for total volumes +6.4%, and for pooled mean use density values +22.9%, respectively). These trends were similar in the different hospital strata and comparable when DDD instead of RDD were used. Conclusions: Similar to what has been observed in a majority of European countries the total volume of antibac-terial drug use in German acute care hospitals decreased with the pandemic without a rebound phenomenon in 2022. In association with restricted hospital capacities and presumably more immunocompromised general medi-cine patients, however, inpatient prescribing of (primarily broad-spectrum) antibacterials and of antifungal drugs increased.

Balanites aegyptiaca del. (Zygophyllaceae) is widely used in traditional medicine, both human and veterinary, throughout Africa for its many properties, including antiparasitic properties. This experimental study aims to optimise the extraction conditions of the seeds of Balanites aegyptiaca del. Aqueous maceration was carried out with mass to volume ratios of 40%, 30%, 20%, 10% and 5% and extraction times of 6, 12, 24, 36 and 48 hours. Extraction yields, phytochemical screening, saponins assay, antioxidant activities (ABTS and FRAP) and antiparasitic tests on Heligmosomoides bakeri were used to compare the different extracts. The pharmaco-chemical study generally showed that aqueous maceration gave the best results, with a mass/volume ratio of 10% after 12 hours of maceration. The yield obtained was 28.03% with a saponins content of 13.81 mg/g. The antioxidant activities were 4.25 ± 0.17µg/mL by the ABTS method and 0.739µg/mL by the FRAP method. The larvicidal activity also showed that the 10%12h extract produced 100% larval mortality from 25ug/mL. These data provide a basis for guiding the choice of extraction process parameters in producing this antiparasitic phytomedicine.

The COVID-19 pandemic has underscored the intricate interplay between viral infections and opportunistic bacterial pathogens such as Klebsiella pneumoniae. K. pneumoniae harbors various antibiotic resistance determinants like extended-spectrum and plasmid-mediated AmpC β-lactamases and carbapenemases. In the two years following the pandemic, carbapenemase producing K. pneumoniae isolates obtained routinely in outpatient and inpatient setting demonstrated similar resistance patterns which prompted research. The aim was to compare and subsequently analyze carbapenem-resistant hospital and outpatient’s K. pneumoniae isolates’ resistance mechanisms, traits and molecular epidemiology, following the COVID-19 pandemic. Disk diffusion and broth dilution method were the methods of choice to determine antibiotic susceptibility. β-lactamases were screened by phenotypic methods and confirmed with PCR. In total 113 isolates were analysed. Resistance to amoxicillin-clavulanate and ertapenem was confirmed in all strains. High resistance rates (over 90%) were observed for extended-spectrum cephalosporins, and ciprofloxacin. OKNV testing and PCR detected OXA-48 in 106, NDM in 7 and KPC in only one isolate. ESBLs accompanied carbapenemases in 103 isolates. Carbapenem resistance in K. pneumoniae is becoming a global problem, hence careful monitoring of its resistance traits is of utmost importance in order to combat the arising threat. OXA-48 seems to continue predominating in the turbulent period after pandemic.

Underreporting is the main limitation of the spontaneous reporting systems. This study aims to reduce underreporting enhancing public participation in vaccinovigilance through an SMS-based reporting system integrated with electronic immunization registries (IRs). Using the VigiVax software, parents of vaccinated children aged 2 years or younger received a single SMS inquiry about adverse events following immunization (AEFI). Responses were collected, validated by health operators and integrated with the information on IRs. AEFI reports were automatically submitted to the Italian Pharmacovigilance system. Among 254,160 SMS messages sent, corre-sponding to 451,656 administered doses (AD), 71,643 responses were collected (28.2% response rate), 21,231of them (8.3%) reporting an AEFI. After seriousness assessment based on clinical criteria, 50 reports (0,24%) were classified as serious. Among these, causality assessment identi-fied 31 reports at least potentially related to the vaccination (RR: 6.86/100,000 AD). Febrile seizures following MMRV vaccination accounted for 11 of these 31 cases, with an incidence of 32 per 100,000 AD. No fatal outcomes were reported. Our findings support the highly favorable risk profile of pediatric vaccinations and the possibility to improve spontaneous reporting through the integration of digital technologies.

Introduction: Acute rhinosinusitis (ASR) is a common condition in children, which can be burdened by orbital complication (OC) or intracranial complications (IC) that are rare but have potential for serious sequelae; therefore, it needs prompt diagnosis and treatment. The first line of treatment is intravenous antibiotic therapy. In case of failure of clinical improvement after 48 hours, hypovisus or negative prognostic factors (intracranial abscess, large orbital abscess or in intraconic or lateral localization, cavernous sinus thrombosis), surgical treatment is indicated. Objective: the purpose of this work is to describe the clinical profile, treatments and outcome of a series of patients undergoing surgical treatment for complications of ARS at a tertiary referral center. Material and methods: a retrospective analysis of clinical databases was conducted to identify all patients under 16 years of age who underwent surgical treatment for complications of ARS during the 20-year period 2000-2023. Demographic characteristics, clinical data, radiological investigations, surgical treatment, and follow-up performed were reported for each case. Results: 29 patients (20 males and 9 females), mean age 13 years, were included, 69% of whom had OC, 21% had IC, and 7% had both OC and IC. The main symptoms of OC were orbital edema, hypovisus and diplopia; while the main symptoms of IC were headache, fever, comitial seizures and focal neurological symptoms. Mean hospitalization time was 11.75 (± 9.2) days. The mean length of hospital stay (LOS) was 9.1 days for OC, 21 days for IC and 14 days for OC + IC. A single patient manifested a Potts Puffy Tumor, with a LOS of 10 days. Basal CT and gadolinium-enhanced MRI were performed in all cases. Intravenous antibiotic therapy and surgical clearance was undertaken. The majority of patients (76%) underwent endoscopic endonasal approach, 24% external transorbital approach, 1,16% orbital decompression and 0,58% superior eyelid approach. Any complications related to the surgical procedures were found. All patients with hypovisus and diplopia had complete recovery. During follow-up 7 patients (24%) had sinus recurrences, at a time range of 1 to 4 years after surgery. Conclusion: our experience, in agreement with the data reported in the literature, confirmed the importance of appropriate diagnostic-therapeutic management to avoid potentially serious sequelae of complicated ARS.

In vitro circular RNA (circRNA) preparation methods have been gaining a lot of attention recently as several reports suggest that circRNAs are more stable with better performances in cells and in vivo than linear RNAs in various biomedical applications. Self-splicing ribozymes are considered a major in vitro circRNA generation method for biomedical applications due to their simplicity and efficiency in circularization of gene of interest. This review summarizes updates and discusses recently developed self-circularization methods based on the self-splicing ribozyme such as group I and II intron ribozymes and pros and cons of each method to prepare circRNA in vitro.

Background and Aim: Patients with Type 2-diabetes condition tend to have multiple medications in various dosage which leads to complex medication regimens. Complexity of regimen results in poor adherence, uncontrolled glycemic value and treatment failure. The research aimed to investigate medication regimen complexity index, medication adherence, and impact of medication regimen complexity on glycemic control and medication adherence.Materials and Methods: A Crossectional Study methods was conducted at Bheri Hospital Nepalgunj, among 145 Diabetes patients. Medication adherence was assessed by using a General Medication Adherence Scale (GMAS Nep-Tool). Medication regimen complexity was assessed by using a Medication Regimen Complexity Index (MRCI) tool. Chi-square test, One-way ANOVA, Paired t-test, and binary logistic regression were used for inferential statistics. Results: This study shows that most of the participants were female and aged group 50-59 years. Hypertension was the most common comorbidity, followed by hypothyroidism. The majority of participants exhibited partial adherence 90 (62.1%) to their medication regimen. It was seen that medications prescribed for diabetes were more complex than non-diabetes medications (Mean±SD MRCI: 8.28±3.155 vs. 4.57±2.107). The negative correlation was seen with diabetes MRCI and medication adherence (r=-0.090). There was statistically significant association between diabetes MRCI and glycemic control, (p<0.05). Binary logistic regression revealed that females had lower odds of high MRCI compared to males ( multivariate p-value: 0.014, AOR: 0.403, 95% CI: 0.195-0.832), while sedentary lifestyle showed high Diabetes MRCI (COR: 4.709, 95% CI: 0.962-23.05) and abnormal BMI were associated with higher MRCI (binary p-value: 0.067, COR: 2.30, 95% CI: 0.942-5.65; multivariate p-value: 0.092, AOR: 2.323, 95% CI: 0.878-5.67). Conclusion: Diabetes medications are more complex, reducing adherence and worsening A1C outcomes. Simplifying regimens improves results, with MRCI being valuable for healthcare providers. The medication adherence and therapeutic outcomes can be improved by the improved by the involvement of clinical pharmacist using MRCI.

Long COVID is a persistent symptom that appears in many COVID-19 patients, regardless of whether they are asymptomatic, mild, or severe. At least 10% worldwide are suffering from long COVID. The anti-inflammatory effect was evaluated in LPS-treated RAW264.7 cells using six Korean national insurance-covered herbal prescriptions with therapeutic potential for mitigating inflammation in the respiratory tract, and additional network pharmacology analysis was performed. Soshihotang (SST) significantly downregulated iNOS and COX2 expression, reduced the production of NO (nitric oxide) and inflammatory cytokines, such as TNFα, IL-1β, and IL-6, and inhibited IκBα phosphorylation and reduced the nuclear translocation of NF-κB in LPS-treated RAW264.7 cells. Network pharmacological analysis showed that SST was closely related to the NF-κB signaling pathway. Further study on the potential of herbal prescriptions will be needed before they can be used clinically by long COVID patients.

The medical research field has been tremendously galvanized to improve the prediction of therapy efficacy by the revolution in artificial intelligence (AI). An earnest desire to find better ways to predict the effectiveness of therapy with the use of AI has propelled the evolution of new models in which it can become more applicable in clinical settings such as breast cancer detection. However, in some instances, the U.S. Food and Drug Administration was obliged to back some previously approved inaccurate models for AI-based prognostic models because they eventually produce inaccurate prognoses for specific patients who might be at risk of heart failure. In light of instances in which the medical research community has often evolved some unrealistic expectations regarding the advances in AI and its potential use for medical purposes, implementing standard procedures for AI-based cancer models is critical. Specifically, models would have to meet some general parameters for standardization, transparency of their logistic modules, and avoidance of algorithm biases. In this review, we summarize the current knowledge about AI-based prognostic methods and describe how they may be used in the future for predicting antibody-drug conjugate efficacy in cancer patients. We also summarize findings of recent late-phase clinical trials using these conjugates for cancer therapy.

Insulin resistance is a condition characterized by a reduced biological response to insulin. It is one of the most common metabolic diseases of modern civilization. Numerous naturally occurring substances have shown to have a positive effect in restoring the proper sensitivity to insulin. Mature 3T3-L1 adipocytes with artificially induced insulin resistance by palmitic acid (16:0) were used for the study. Cinnamic acid and 1,2-dicinnamoyl-sn-glycero-3-phosphocholin (1,2-diCA-PC) were tested at three concentrations: 25 μM, 50 μM, and 125 μM. The number of mitochondria and the expression of genes encoded by mtDNA were elucidated in control and experimental cells. In experimental cells treated with 1,2-diCA-PC, we displayed increased insulin-stimulated glucose uptake in a dose-dependent manner, accompanied by an increase in mtDNA copy number. Moreover, in experimental cells treated with 1,2-diCA-PC at the concentration of 125 μM, we observed a significant increase in the expression level of all analyzed genes encoded by mtDNA compared to control cells. Our study showed a relationship between improved cellular sensitivity to insulin by 1,2-diCA-PC and an increase in the number of mitochondria and expression levels of genes encoded by mtDNA. Summarizing, the results suggest a therapeutic potential of cinnamic acid derivative 1,2-diCA-PC in enhancing the insulin sensitivity of adipocytes.

One of the bottlenecks to bringing new therapies to the clinic has been a lack of vectors for delivering novel therapeutics in a targeted manner. Cell penetrating peptides (CPPs) have received a lot of attention and have been the subject of numerous developments since their identification nearly 3 decades ago. Known for their transduction abilities, they have generally been considered inert vectors. In this review we present a schema for their classification, highlight what is known about their mechanism of transduction, and outline the existing literature, as well as our own experience, vis a vis the intrinsic anti-inflammatory properties that certain CPPs exhibit. Given the inflammatory responses associated with viral vectors, CPPs represent a viable alternative to these vectors; further, the anti-inflammatory properties of CPPs, mostly through inhibition of the NF-κB pathway, are encouraging. Much work in relevant animal models, toxicity studies in large animal models, and ultimately human trials are needed before their potential is fully realized.

The research article provides an in-depth analysis of the European Medicines Agency (EMA) and the Directorate General of Drug Administration (DGDA), focusing on their historical development, organizational structures, and functional roles in ensuring the quality and safety of pharmaceuticals. The study highlights the origins of drug regulation, tracing back to the early 19th century in the United States with the establishment of the Food and Drug Administration (FDA), and discusses the evolution and significance of drug regulatory bodies worldwide. The EMA and DGDA are scrutinized for their efforts in maintaining high standards for drug approval, monitoring clinical trials, and managing post-marketing surveillance to prevent adverse drug reactions (ADRs). The EMA’s role in coordinating with EU member states on pharmacovigilance and the DGDA’s initiatives in Bangladesh, including the implementation of a nationwide drug database and pharmacovigilance system, are explored in detail. The article concludes by emphasizing the essential role of these regulatory bodies in safeguarding public health through stringent regulation and continuous monitoring of pharmaceuticals, thereby ensuring that only safe and effective medicines are available to consumers . It also provides an in-depth analysis of the roles, structures, and historical contexts of the European Medicines Agency (EMA) and the Directorate General of Drug Administration (DGDA). It outlines how these regulatory bodies ensure the safety, efficacy, and quality of medicinal products. The EMA, serving the European Union, and the DGDA, operating in Bangladesh, play critical roles in drug approval processes, pharmacovigilance, and maintaining public health standards. By setting rigorous guidelines and monitoring compliance, these agencies help safeguard the health of millions, ensuring that only safe and effective medications are available in the market. The paper underscores the importance of these regulatory bodies in promoting public health and supporting the pharmaceutical industry's development and innovation.

Pomegranate extract has potential benefits for women's reproductive health, including fertility enhancement, menstrual cycle regulation, pregnancy support, and polycystic ovary syndrome (PCOS) treatment. It possesses antioxidant properties, reducing oxidative stress and improving fertility. Phytoestrogens in pomegranate extract may help regulate hormonal imbalances and promote regular menstrual cycles. The extract's rich nutrient profile supports placental development and fetal growth and may reduce the risk of preterm birth. Additionally, pomegranate extract shows promise in improving insulin sensitivity and reducing inflammation and oxidative damage in PCOS. Some studies suggest its potential anticancer properties, particularly against breast cancer. However, further research, including human clinical trials, is necessary to establish its effectiveness and safety. The current evidence is limited and primarily based on in vitro studies, animal studies, and clinical trials. This review provides a comprehensive summary of the benefits of pomegranate extract for women's reproductive health and breast cancer, serving as a reference for future research.

The growing global threat of multidrug-resistant (MDR) bacteria has been exacerbated by inadequate antibiotic consumption and the difficulty in developing new therapeutic strategies. Selective Digestive Decontamination (SDD) is presented as an encouraging measure to prevent the appearance and colonization of MDR bacteria. We compared the pattern of antibiotic consumption in the Intensive Care Unit (ICU) of our hospital before and after the implementation of the SDD protocol. This quasi-experimental study was conducted in an ICU from June-2021 to June-2023. The incidence of nosocomial infections, colonizations, and the number of isolated MDR bacteria, as well as the defined-daily-dose (DDD), were monitored. A total of 3266 patients were included, with 1532 in the pre-intervention group and 1734 in the post-intervention group. The median age was 62 years, 66% were male, and the average APACHE II and SOFA scores were 15 and 6.5, respectively. There was a significant reduction in overall antibiotic consumption in the post-SDD group (p= 0.028), highlighting a decrease in Carbapenemase-Producing Enterobacteriaceae (CPE) (p= 0.0099). There was also a reduction in colonization incidence density and nosocomial infections. Implementing the SDD protocol significantly reduced antibiotic consumption in the ICU, suggesting important implications for infection control and antimicrobial resistance management.

Alzheimer's Disease (AD) and Parkinson's Disease (PD) are two neurodegenerative diseases posing a significant disease burden due to their increasing prevalence and socio-economic cost. Traditional therapeutic approaches for these diseases exist but provide limited symptomatic relief without addressing the underlying pathologies. This review examines the potential of immunotherapy, specifically monoclonal antibodies (mAbs), as disease-modifying treatments for AD and PD. We analyze the pathological mechanisms of AD and PD, focusing on the roles of amyloid-beta (Aβ), tau (τ), and alpha-synuclein (α-syn) proteins. We discuss the latest advancements in mAbs therapies targeting these proteins, evaluating their efficacy in clinical trials and preclinical studies. We also explore the challenges faced in translating these therapies from bench to bedside, including issues related to safety, specificity, and clinical trial design. Additionally, we highlight future directions for research, emphasizing the need for combination therapies, improved biomarkers, and personalized treatment strategies. This review aims to provide insights into the current state and future potential of antibody-based immunotherapy in modifying the course of AD and PD, ultimately improving patient outcomes and quality of life.

The global need for rapid diagnostic methods for pathogen identification and antimicrobial susceptibility testing (AST) is underscored by the increasing bacterial resistance and limited therapeutic options, especially critical in sepsis management. The evolution from traditional phenotype-based methods to rapid molecular and mass spectrometry techniques has significantly decreased result turnaround times, improving patient outcomes. Despite advancements, the complex decision-making in antimicrobial therapy often exceeds the capacity of many clinicians, highlighting the importance of antimicrobial stewardship programs (ASP). These programs, integrating mHealth and eHealth, leverage technology to enhance healthcare services and patient outcomes, particularly in remote or resource-limited settings. However, the application of such technologies in antimicrobial management remains underexplored in hospitals. The development of platforms combining antimicrobial prescription data with pharmacotherapeutic algorithms and laboratory integration can significantly reduce costs and improve hospitalization times and mortality rates. Yet, the effectiveness of empirical antibiotic therapy, influenced by rapid diagnostic tests, becomes cost-effective when error rates exceed 20%, emphasizing the need for technological integration in ASPs to combat the rising challenge of antimicrobial resistance (AMR) and healthcare sustainability.

Background: The utilization of nutrient supplementation as a tool to address issues such as iron and vitamin A deficiencies among children in Sub–Saharan Africa (SSA) has been beneficial. Nevertheless, there is a dearth of evidence on the effect of vitamin A and iron supplementation on infectious diseases in pre–school children in SSA. We aimed to assess the association of vitamin A and iron supplementation on the incidence of major clinical features of infectious diseases (diarrhea, cough, and fever) in children aged 6–59 months in Ghana. Methods: A cross–sectional study that utilized data from the Ghana Demographic and Health Survey, involving a sample size of 2,408 children. The collected data was analyzed using binomial logistic regression. Results: Dual supplementation with vitamin A and iron was associated with an increased risk of fever (OR: 1.68 95% CI: 1.22–2.32) and cough (OR: 1.43, 95% CI: 1.02–1.99) in children 6–59 months. Iron supplementation alone was associated with an increased risk of fever (OR: 1.32, 95% CI: 1.01–1.72) while Vitamin A alone significantly increased the risk of diarrhea (OR: 1.73, 95% CI: 1.03–2.92). Conclusions: Dual supplementation of vitamin A and iron is associated with an increase in childhood morbidity, endorsement of combined supplementation should be done with caution.

Chronic obstructive pulmonary disease (COPD) is a condition that significantly impacts both patients and healthcare systems. The management of COPD involves various pharmacological intervention strategies, and addressing the issue of low adherence to these strategies has become a subject of significant interest. In response to this concern, there has been a shift towards utilizing telemedicine and mobile applications. The primary objective of this scoping review is to delineate the usage of mobile applications to enhance pharmacological therapeutic adherence in adult patients with COPD. The study involved a search of databases such as Medline, Google Scholar, Cochrane, and ClinicalTrial.gov, focusing on literature published in English and Spanish over the last decade. The selected studies assessed interventions involving mobile applications (mobile apps) designed to improve pharmacological adherence. Four digital aids were identified, available on online platforms, mobile apps, or both: m-PAC, myCOPD, Wellinks mHealth, and Propeller Health. Pro-peller Health, in particular, is an app that directly measures pharmacological adherence through electronic medication monitors attached to participants' inhalers. Opening the app was associated with higher odds of using control medications compared to participants who did not open the app. The findings suggest that these digital interventions serve as valuable tools to enhance patient adherence to treatment. Future research should focus on evaluating the effectiveness of different digital devices, such as digital inhalers and mobile applications, that directly measure pharmacological adherence.

Objectives: To analyze the clinical characteristics and factors associated with adverse drug reactions (ADR) in liver cancer patients receiving oxaliplatin‐based hepatic arterial infusion chemotherapy (HAIC). Methods: A retrospective analysis was performed on the clinical data of 137 patients with liver cancer who received oxaliplatin‐based HAIC. Changes in baseline characteristics, inflammatory factors, and other laboratory indicators in the no‐ADR and ADR groups were analyzed. Results: The incidence of serious ADR (CTCAE ≥ 3) was 21.9% (30/137). There was no significant difference in the cumulative dose of oxaliplatin between the two groups [157.3 (80.3, 322.4) vs. 206.6 (139.1, 324.2), P=0.161]. The increase in NEUT and IL‐6 was greater in the group treated with ADR than in the group not treated with ADR. Changes in NEUT [4.1 (1.5, 6.2) vs. 2.5 (0.5, 4.9), P=0.045] and changes in NEUTIL‐6 [4.2 (‐0.2, 22.9) vs. 0.8 (‐3.9, 7.7), P=0.026]. TBIL, ALT, AST, ALP, WBC, NEUT, PCT, CRP, TNF, IL‐2R, IL‐6, and IL‐10 were significantly higher after treatment than before in the ADR group (P < 0.05). In contrast, ALB and AFP were decreased. Conclusions: The severe ADR (CTCAE ≥ 3) associated with oxaliplatin‐based HAIC may be closely related to increased inflammatory factors such as NEUT and IL‐6. We should be vigilant for allergic reactions to oxaliplatin and increase monitoring during treatment

Genetic factors influence medication response (pharmacogenetics), affecting the pharmacody-namics and pharmacokinetics of many medicaments used in clinical care. The ability of medica-tions to cross the blood-brain barrier (BBB) represents a critical putative factor in the effectiveness and tolerability of various central nervous system (CNS) medications at a pharmacokinetic (dosing) level. Pharmacogenetics has the potential to personalise medicine to a greater extent than has been possible, with the potential to help reduce heuristic delays to effective tolerable pharmacotherapy. Here, we critically examine and summarise the evidence, particularly for ABCB1 polymorphisms associated with various CNS medications. These transporters appear to have a role in BBB pharmacogenetics. We identify some of the most promising variants for clinical translation while spotlighting the complexities of the involved systems and limitations of the current empirical literature.

Modular nanotransporters (MNTs) are drug delivery systems for targeted cancer treatment. Being composed of several modules, they offer the advantage of high specificity and biocompatibility in delivering drugs to the target compartment of cancer cells. The large carrier module brings together functioning MNT modules and serves as a platform for drug attachment. The development of smaller-sized MNTs via truncation of the carrier module looks advantageous in facilitating tissue penetration. In this study, two new MNTs with a truncated carrier module containing either an N-terminal (MNTN) or a C-terminal (MNTC) part were developed by genetic engineering. Both new MNTs demonstrated high affinity for target receptors, as revealed by fluorescently labeled ligand-competitive binding. The liposome leakage assay proved the endosomolytic activity of MNTs. Binding to the importin heterodimer of each truncated MNT was revealed by a thermophoresis assay, while only MNTN possessed binding to Keap1. Finally, the photodynamic efficacy of the photosensitizer attached to MNTN was significantly higher than when attached to either MNTC or the original MNT. Thus, this work reveals that MNT’s carrier module can be truncated without losing MNT functionality, favoring the N-terminal part of the carrier module due to its ability to bind Keap1.

Bone injury is a common side effect of radiotherapy to tumors, which is a long-term response after damage to osteoblasts, especially reducing osteoblasts proliferation and differentiation. Currently, there are few studies on radiation-induced bone injury, the molecules involved in the ionizing radiation (IR) induced osteoblasts damage remain need to be excavated. In this study, the optimal IR damage conditions (8Gy, 2.22Gy/min) were firstly determined by measuring cell proliferation, cell cycle, cell apoptosis and further cell differentiation and mineralization abilities and the related genes (p-AKT, p-ERK1/2, cyclinB, BAX, BCL2, ALP, OPN, RUNX2, Collagen1) expression level changes in radiation-induced osteoblast injury model. Then, we screened 26 differentially expressed genes after the RNA-sequencing of the 8 Gy-irradiated MC3T3-E1 cells, and they were mainly involved in DNA damage and repair, cell apoptotic progress and cell cycle regulation, meanwhile, participated in several main pathway including PI3K-AKT signaling pathway, p53 signaling pathway and signaling pathway involved in cell cycle and cell senescence. We focused on verifying the differential expression genes and confirmed the MDM2, NOTCH1, CDKN1A and GCLC were upregulated after IR treatment, suggesting the key roles in the response of the IR. In addition, regarding on our sequencing results, the DNA damage and repair were also verified and the results suggested that IR induced DNA damage and repair in MC3T3-E1 cells. In summary, IR damaged MC3T3-E1 cells by inhibiting cell proliferation, impacting cell cycle process, inducing cell apoptosis and affecting the osteoblasts differentiation, which maybe due to the DNA damage and the differential expression of the key genes (MDM2, NOTCH1, CDKN1A and GCLC ).

Knee osteoarthritis (KO) is an important health condition, affecting one third of the people aged 65 years or more. Pain is the main cause of disability. Pain management in KO includes pharmacological and non-pharmacological modalities. Patient education, lifestyle changes, physical exercise and physical agents are prescribed as a first approach for pain control. Laser therapy is part of many therapeutical protocols, with two forms, low-level laser therapy (LLLT) and high-intensity laser therapy (HILT). The paper aimed at stressing the advantages of HILT, based on a greater wavelength, higher energy delivery and deeper tissue penetration. Research on 23 published trials revealed that analgesic effect is rapid, cumulative and long lasting. Compared to sham, to LLLT or to other associations of therapeutical modalities, HILT provided significantly better results on pain reduction and functional improvement. Ultrasound examination showed reduction of intraarticular inflammation.

Mortality in children accounts for 15% of all AIDS-related deaths globally, with a higher burden among Cameroonian children (25%), likely due to poor virological response. We sought to evaluate viral suppression (VS) and its determinants in a nationally representative paediatric and young adult population receiving antiretroviral therapy (ART). A cross-sectional and multicentric study was conducted among Cameroonian children (

This paper investigates the safety profile of the Shingrix vaccine, focusing particularly on persistent adverse events post-vaccination. Shingrix, crucial for preventing shingles caused by the varicella-zoster virus, has shown efficacy in clinical trials but is associated with varying degrees of adverse reactions. This retrospective, cross-sectional survey-based study, spanning two years and involving 77 respondents who experienced severe adverse events after vaccination, reveals a spectrum of symptoms ranging from mild to severe, including reports of Guillain-Barré syndrome and neuropathy. These findings underscore the need for ongoing vigilance in vaccine safety monitoring and highlight the importance of personalized care approaches for managing post-vaccination adverse effects. The study aims to contribute to informed decision-making regarding shingles vaccination strategies and calls for continued research into the long-term safety and efficacy of Shingrix.

Obesity has increasingly become a worldwide epidemic, as demonstrated by epidemiological and clinical studies. Obesity may lead to development of a broad spectrum of cardiovascular diseases (CVDs), such as coronary heart disease (CHD), hypertension, heart failure (HF), cerebrovascular disease, atrial fibrillation (AF), ventricular arrhythmias, and sudden cardiac death (SCD). In addition to hypertension, there are other cardiometabolic risk factors (CRFs) such as visceral adiposity, dyslipidemia, insulin resistance, diabetes, elevated levels of fibrinogen, and C-reactive protein and others, all of which increase the risk of CVD events. Mechanisms involved between obesity and CVD mainly include insulin resistance, oxidative stress, inflammation, and adipokines dysregulation, which cause maladaptive structural and functional alterations of the heart, particularly left ventricular (LV) remodeling and diastolic dysfunction. Natural products of plants, provide a diversity of nutrients and different bioactive compounds, including phenolics, flavonoids, terpenoids, carotenoids, anthocyanins, vitamins, minerals, fibers, and others, which possess a wide range of biological activities including antihypertensive, antilipidemic, antidiabetic, and other activities, thus conferring cardiometabolic benefits. In this review, we discussed the main therapeutic interventions using extracts from herbs and plants in preclinical and clinical trials with protective properties targeting CRFs. Molecular mechanisms and therapeutic targets of herbs and plants extracts for the prevention and treatment of CRFs are also reviewed.

Bacillus Calmette-Guérin (BCG) immunotherapy has been a cornerstone treatment for non-muscle invasive bladder cancer for decades and still faces challenges, such as severe immune adverse reactions, which reduce its use as a first-line treatment. This review examines BCG therapy’s history, mechanisms, and current status, highlighting how nanotechnology and bioengineering are revitalizing its application. We discuss novel nanocarrier systems aimed at enhancing BCG's efficacy while mitigating specific side effects. These approaches promise improved tumor targeting, better drug loading, and enhanced stimulation of anti-tumor immune responses. Key strategies involve using functional BCG cell wall components and co-delivering BCG with chemotherapeutics to achieve synergistic effects. While most studies remain experimental, this research direction offers hope for overcoming BCG's limitations and advancing bladder cancer immunotherapy. Further elucidation of BCG's mechanisms and rigorous safety evaluations of new delivery systems will be crucial for translating these innovations into clinical practice.

This study uses machine learning to identify key factors influencing the cost-effectiveness of over-the-counter (OTC) medications. By developing a novel cost-effectiveness rating (CER) from user ratings and prices, we analyzed data from Amazon. The findings indicate that FSA/HSA eligibility, symptom treatment range, safety warnings, special effects, active ingredients, and packaging size significantly impact cost-effectiveness across cold, allergy, digestion, and pain relief medications. Medications eligible for FSA or HSA funds, treating a broader range of symptoms, and having smaller packaging are perceived as more cost-effective. Cold medicines with safety warnings were found to be cost-effective due to their lower average price and effective ingredients like phenylephrine and acetaminophen. Allergy medications with kid-friendly features showed higher cost-effectiveness, and ingredients like calcium, famotidine, and magnesium boosted the cost-effectiveness of digestion medicines. These insights help consumers make informed purchasing decisions and assist manufacturers and retailers in enhancing product competitiveness. Overall, this research supports better decision-making in the pharmaceutical industry by highlighting factors that drive cost-effective medication purchases.

In recent years, bioengineered and biotechnological products have gained tremendous attention to identify unique biologic features associated with oncology. To overwhelm the complexity of tumor personalized medicines (PM) or vaccines could be a promising way-out to be considered. Cancer is a heterogeneous disease. This characteristic variability of cancer provides itself to the emergent era of PM i.e., precision oncology. The prime objective of PM is merely to deliver the right treatment to the right patient at the right time. For instance, imatinib was effectively targeted chronic myeloid leukemia. To date, attainment in using PM approaches to cancer treatment have been mixed. The next-generation sequencing (NGS), and the use of several biomarkers (e.g., HER2, BRAF, ALK, etc.), to drive precise cancer treatment through a timely and cost-effective manner. In current review, author summarizes the advancement in the field of PM such as CRISPR-Cas9, NGS, pharmacogenomics, and the benefits of machine learning techniques. The precise communication between healthcare professionals, regulatory bodies, and patients is essential to translate advances in PM into immense benefits for patients with cancer globally.

The intranasal route of drug administration is characterized by high bioavailability and is considered promising for rapid delivery of drugs with systemic action to the central nervous system, bypassing the blood-brain barrier. This is particularly important for the use of neuroprotective drugs in the treatment of brain tissue damage in infants caused by the effects of intrauterine hypoxia. Creation of new dosage forms for neonatology with the use of software and mathematical technologies in pharmaceutical development allows to create cerebroprotective drugs with controlled pharmaco-technological properties, thus reducing time and resources for necessary research. We developed a formulation of a new nasal gel formulation with Angiolin using Box-Benken experiment design for the therapy of prenatal CNS damage. It was found that the consistency properties of the nasal gel were significantly influenced by the gelling agent and mucoadhesive component - sodium salt of carboxymethylcellulose. We have optimized the composition of nasal gel formulation with Angiolin using the formed models and relationships between the factors. The optimized composition of the obtained nasal gel has satisfactory parameters of thixotropic properties. The developed 1% gel for neuroprotection with Angiolin meets all the requirements for harmlessness and safety to drug forms of this group - low toxicity, absence of local irritant and allergic effect.

Interferon-gamma (IFN-γ) is an important cytokine in host defense against tuberculosis infection. In some cases, administration of IFN-γ during tuberculosis infection can promote faster cure. In the present work, we have shown that in a mouse model, human interferon-gamma, exhibits some anti-tuberculosis activity, especially in combination with isoniazid.

The purpose of the study is to analyse and to identify specific structural characteristics of melanocytic nevi. Using the optical microscope, could be possible a proper describtion related melanocytic nevi, reffering to youth pacients. In this study direction play a significant role, different factors, such as genetic, epigenetic, microbiomic, and proteomic factors. Future directions refers to preventive and prophylactic methods. Disease diagnostic and management directions are also important.

According to many research groups, high glucose induces over production of superoxide anions, and reactive oxygen species (ROS) in general is the link between high glucose levels and the toxicities seen at cellular levels. Respiratory complex anomalies could lead to the production of ROS. Calcium [Ca2+], at physiological levels serves as a second messenger in many physiological functions. Accordingly, mitochondrial calcium [Ca2+]m overload leads to ROS production which could be lethal to the mitochondria through various mechanisms. The F1F0-ATPase (ATP syn-thase or complex V) is the enzyme that is responsible for catalyzing the final step of oxidative phosphorylation. It does so by coupling the translocation of protons in the mitochondrial in-termembrane space and shuttling them to the mitochondrial matrix for ATP synthesis to take place. Mitochondrial complex V T8993G mutation specifically blocks the translocation of protons across the intermembrane space thereby blocking ATP synthesis leading to Neuropathy, Ataxia and Retinitis Pigmentosa Syndromes (NARP). This study seeks to explore the possibility of [Ca2+]m overload mediating the pathological roles of high glucose in defective respiratory chain mediated mitochondrial stress. The NARP cybrids are the in vitro experimental models for the cells with F1FO-ATPase defects, these cells harbor 98% of mtDNA T8993G mutation. Their coun-terparts 143B osteosarcoma cell lines are the parental cell lines used for comparisons. We uncov-ered that, NARP cells mediated and enhanced the death of the cells (apoptosis) when incubated with hydrogen peroxide (H2O2) and high glucose respectively as depicted by the MTT assay of cell viability. Furthermore, using the fluorescence probe-coupled laser scanning confocal imag-ing microscopy, NARP cells significantly enabled mitochondrial reactive oxygen species (mROS) formation and enhanced the depolarization of the mitochondrial membrane potential (ΔΨm). Elucidating the mechanisms of sugar enhanced toxicity on mitochondria would help in the fu-ture to alleviate the symptoms of patients associated with (NARP) syndromes.

Ulcerative colitis (UC) is a chronic inflammatory disease, the incidence of which is increasing worldwide. However, the etiology and pathogenesis of UC remains unclear. The n-butanol extract of pulsatilla decoction (BEPD) of the traditional Chinese medicine herbal formula has been shown to be effective in treating UC. We aimed to explore the molecular mechanism underlying the effects of BEPD on UC, in particular its effects on neutrophil extracellular trap (NET) formation by neutrophils. High-performance liquid chromatography was used to determine the principal compounds of BEPD. UC was induced in mice using dextran sodium sulfate, and mice were treated with 20, 40, or 80 mg/kg BEPD daily for seven days. Colonic inflammation was determined by assessing the disease activity index, histopathology, colonic mucosal damage index, colonic mucosal permeability, and pro- and anti-inflammatory cytokine levels. The infiltration and activation status of neutrophils in the colon were determined by analyzing the levels of chemokine (C-X-C motif) ligand (CXCL)1 and CXCL2, reactive oxygen species, Ly6G, and numerous NET proteins. Our results showed that BEPD improved the disease activity index, histopathology, and colonic mucosal damage index scores of mice with UC, and restored colonic mucosal permeability compared with untreated mice. The expression levels of the pro-inflammatory cytokines interleukin-1β, interleukin-6, and tumor necrosis factor-α in colon tissues were significantly decreased, while the expression levels of anti-inflammatory cytokines in colon tissues were significantly increased, exceeding those of control mice. In addition, BEPD reduce the expression of the neutrophil chemokines CXCL1 and CXCL2 in the colon tissue of mice with UC, reduced neutrophil infiltration, reduced reactive oxygen species levels, and significantly reduced the expression of NET proteins. BEPD also significantly reduced NET formation. The results of this study suggest that BEPD exerts therapeutic effects in a murine model of UC by inhibiting neutrophil infiltration and activation in the colon, as well as by inhibiting the expression of key proteins involved in NET formation and reducing NET formation, thereby alleviating local tissue damage and disease manifestations.

Non-Vitamin K Oral Anticoagulants (NOACs) have revolutionized anticoagulant therapy, offering improved safety and efficacy over traditional agents like warfarin. This review comprehensively examines the dual roles of NOACs—Apixaban, Rivaroxaban, Edoxaban, and Dabigatran—not only as anticoagulants but also as modulators of inflammation via Protease-Activated Receptor (PAR) signaling. We highlight the unique pharmacotherapeutic properties of each NOAC, supported by key clinical trials demonstrating their effectiveness in preventing thromboembolic events. Beyond their established anticoagulant roles, emerging research suggests that NOACs influence inflammation through PAR signaling pathways, implicating factors such as FXa and Thrombin in the modulation of inflammatory responses. This review synthesizes current evidence on the anti-inflammatory potential of NOACs, exploring their impact on inflammatory markers and conditions like atherosclerosis and diabetes. By delineating the mechanisms by which NOACs mediate anti-inflammatory effects, this work aims to expand their therapeutic utility, offering new perspectives for managing inflammatory diseases. Our findings underscore the broader clinical implications of NOACs, advocating for their consideration in therapeutic strategies aimed at addressing inflammation-related pathologies. This comprehensive synthesis not only enhances understanding of NOACs' multifaceted roles but also paves the way for future research and clinical applications in inflammation and cardiovascular health

Medicinal mushrooms, especially Ganoderma species hold immense promise for production of a wide range of bioactive compounds with various effects. The biochemical potential of indigenous fungal strains, specific to a region, could play a critical role in the continuous search for novel strains with superior activities on a global scale. This research focused on the ethanolic (EtOH) and hot-water (H2O) extracts of fruiting bodies of two wild-growing Ganoderma species: G. pfeifferi and G. resinaceum with an aim to assess its nutritional (total carbohydrate content-TCC), and mineral composition in relation to bioactive properties: antioxidant, antiproliferative and lipid-lowering. Atomic absorption spectrophotometry (AAS) revealed that G. pfeifferi is a promising source of minerals that are essential for numerous physiological functions in the human body like bone health and muscle and nerve function, with calcium (Ca 4.55 ± 0.41 mg/g d.w.) and magnesium (Mg 1.33 ± 0.09 mg/g d.w.), being the most abundant macro element present. Zinc (Zn), manganese (Mn), and chromium (Cr) were particularly notable, with concentrations ranging from 21.49 to 41.70 mg/kg d.w. The EtOH extract of G. pfeifferi demonstrated significantly elevated levels of TCC, essential macromolecules for energy and structural functions in the body, with higher quantities of all three standard carbohydrates detected in this type of extract. Similar to revealed composition the same species, G. pfeifferi stood out as the most prominent antioxidant agent, with H2O extract being stronger than EtOH in ABTS assay (86.85 ± 0.67 mg TE/g d.w.), while EtOH extract displayed the highest anti OH• radical scavenging ability (IC50 = 0.18 ± 0.05 μg/mL) as well as the most notable reducing potential among all. The highest antiproliferative effect against the breast cancer cell line (MCF-7), demonstrated the H2O extracts from G. resinaceum with the most pronounced activity after 24 hours (IC50 = 4.88 ± 0.50 μg/mL) which surpasses that of the standard compound, ellagic acid (IC50 = 33.94 ± 3.69 μg/mL). Administration of both Ganoderma extracts mitigated diabetic lipid disturbances and exhibited potential renal and hepatic protection in vivo on white Wistar rats by preservation of kidney function parameters in G. resinaceum H2O pre-treatment (urea: 6.27 ± 0.64 mmol/L, creatinine: 50.00 ± 6.45 mmol/L) and the reduction of ALT levels (17.83 ± 3.25 U/L) com-pared to diabetic control groups treated with saline (urea: 46.98 ± 6.01 mmol/L, creatinine: 289.25 ± 73.87 mmol/L, and ALT: 60.17 ± 9.64 U/L). These results suggest that pre-treatment with G. resinaceum H2O extracts may have potential antidiabetic properties. In summary, detected microelements are vital for maintaining overall health, supporting metabolic processes, and protecting against various chronic diseases. Further research and dietary assessments could help determine the full potential and applications of two underexplored Ganoderma species native to Serbia in nutrition and health supplements.

Microneedle technology is a novel platform technology that revolutionizes ocular drug delivery and addresses critical challenges in the treatment of ocular diseases. Routine treatment methods, such as eye drops and intravitreal injections, suffer from low bioavailability and poor patient compliance. So, novel advanced platform technologies are required to overcome these challenges. Microneedle is a minimally invasive and promising alternative technique that helps precisely control drug delivery to targeted tissues and organs. This review investigates the potential impact of microneedle technology for eye care, underscoring recent advancements, underlying mechanisms, and emerging preclinical and clinical uses. Different types of microneedles, including solid, coated, dissolvable, and hollow, have demonstrated their potential and capability to bypass several barriers in the cornea and sclera. This ensures effective drug penetration and delivery. The current innovations in material science and fabrication methods have enhanced the safety and efficacy of microneedles, reducing discomfort and the chances of infections. These microneedle technologies offer sustained and controlled drug delivery, which could improve therapeutic outcomes for various disease conditions like age-related macular degeneration, glaucoma, diabetic neuropathy, etc. In the current review, recent preclinical and clinical studies emphasize microneedle-based ocular drug delivery's feasibility and potential benefits. These include improved pharmacokinetics, reduced dosing frequency, enhanced patient adherence, and, most importantly, microneedles offer versatile platforms for delivering a wide range of small and large molecules and gene therapies. Despite the exciting progress, obstacles such as regulatory barriers, scalability, and long-term biocompatibility persist. It will be essential to tackle these challenges through interdisciplinary research and partnerships to integrate microneedle technology into standard clinical use effectively. Ultimately, microneedle drug delivery offers a revolutionary method that has the potential to significantly enhance the treatment and results of ocular diseases, marking the dawn of a new era in eye care.

Extensive polymorphism screening of elacestrant dihydrochloride, an Active Pharmaceutical Ingredient (API), was conducted using various methods and solvents. The solubility assessment and polymorph screening of elacestrant dihydrochloride (referred to as elacestrant throughout the paper) utilized both crystalline and amorphous forms of the API as input material with 40 non-conventional solvents, employing slow cooling, maturation, and/or evaporation. Crystalline material underwent further screening via anti-solvent addition, polymer templating, and solvent-drop grinding. A total of 7 new polymorphs were identified. No solvated forms were identified, but some samples contained notable water content, tentatively classified as hydrated forms. Comprehensive solid-state characterization data for representative crystalline samples of each polymorph is presented. Polymorph A exhibited the highest melt (225-226 °C, onset). Thermal analysis of polymorphs B, C, D, E, F and G showed an endothermic-exothermic event (with an onset temperature between 136 and 184 °C), indicating a form conversion, followed by a melt at 205-222 °C (onset), consistent with the previously identified and most stable form of elacestrant. This suggests that these materials convert to the most stable form prior to melting. Pattern G does not show an endothermic-exothermic event, but after desolvation, the material melts at 222 °C (onset temperature).

The emergence of drug-resistant mycobacteria has rendered many clinical drugs and regimens ineffective, imposing significant economic and healthcare burden on individuals and society. Repurposing drugs intended for treating other diseases is a time-saving, cost-effective, and efficient approach for identifying excellent anti-mycobacterial candidates or lead compounds. This study is the first to demonstrate that rupatadine (RTD), a drug used to treat allergic rhinitis, possesses excellent activity against mycobacteria without detectable resistance, particularly Mycobacterium tuberculosis and Mycobacterium marinum, with a minimal inhibitory concentration as low as 3.13 µg/mL. Furthermore, RTD exhibited moderate activity against nonreplicating M. tuberculosis with the minimal inhibitory concentrations lower than drugs targeting the cell wall, suggesting that RTD has the great potential to be modified and used for the treatment of nonreplicating M. tuberculosis. Additionally, RTD exhibits partial synergistic effects when combined with clofazimine, pretomanid, and TB47 against M. tuberculosis, providing the theoretical foundation for the development of treatment regimens. Transcriptomic profiling leads us to speculate that eight essential genes may be the targets of RTD or may be closely associated with the mycobacterial resistance to RTD. In summary, RTD may be a promising hit for further anti-mycobacterial drug or regimen optimization, especially in case of nonreplicating mycobacteria.

Background: Potential calcium-related adverse events of vitamin D supplement use have not been addressed in large-scale, real-world data so far. Methods: Leveraging data from the UK Biobank, encompassing 445,493 individuals aged 40-69, we examined associations of high 25-hydroxyvitamin (25[OH]D) levels ≥100 nmol/L and vitamin D supplementation with hypercalcemia (plasma calcium >2.6 mmol/L), kidney stones, and atherosclerosis assessments (pulse wave arterial stiffness index and carotid intima-medial thickness). Regression models were comprehensively adjusted for 49 covariates. Results: Approximately 1.5% of the participants had high 25(OH)D levels, 4.3% regularly used vitamin D supplements, and 20.4% reported regular multivitamin use. At baseline, the hypercalcemia prevalence was 1.6%, and 1.1% were diagnosed with kidney stones during follow-up. High 25(OH)D levels were neither associated with calcium-related adverse events nor atherosclerosis assessments. Vitamin D and multivitamin supplementation were associated with an increased prevalence of hypercalcemia (odds ratios and 95% confidence intervals: 1.46[1.32-1.62] and 1.11[1.04-1.18], respectively) but were neither associated with atherosclerosis nor future kidney stones. Conclusion: High 25(OH)D levels observable in routine care were not associated with any adverse outcome. Vitamin D users have a slightly higher prevalence of hypercalcemia, possibly due to co-supplementation with calcium, but without higher atherosclerosis prevalence or risk of kidney stones.

Keywords: Antibacterial activity, Antioxidant activity, Bioactive compounds, Elementary analysis, Nutritional and phytochemical composition, Seaweed.

Liver fibrosis, a consequence of chronic liver damage or inflammation, is characterized by the excessive buildup of extracellular matrix components. This progressive condition significantly raises the risk of severe liver diseases like cirrhosis and hepatocellular carcinoma. The lack of approved therapeutics underscores the urgent need for novel anti-fibrotic drugs. Hepatic stellate cells (HSCs), key players in fibrogenesis, are promising targets for drug discovery. This study investigated the anti-fibrotic potential of Citrus hystrix DC. (KL) and its bioactive compound, β-citronellol (β-CIT), in a human HSC cell line (LX-2). Cells exposed to TGF-β1 to induce fibrogenesis were co-treated with crude KL extract and β-CIT. Gene expression was analyzed by Real-Time qRT-PCR to assess fibrosis-associated genes (ACTA2, COL1A1, TIMP1, SMAD2). The releasing of matrix metalloproteinase 9 (MMP-9) was measured by ELISA. Proteomic analysis and molecular docking identified potential signaling proteins and modeled protein-ligand interactions. Results showed that both crude KL extract and β-CIT suppressed HSC activation genes and MMP-9 levels. The MAPK signaling pathway emerged as a potential target of β-CIT. This study demonstrates the ability of KL extract and β-CIT to inhibit HSC activation during TGF-β1-induced fibrogenesis, suggesting a promising role of β-CIT in anti-hepatic fibrosis therapies.

For the first time to optimize the creation of new neuroprotective agents based on bioflavonoids, we applied information technologies - docking analysis to calculate the binding of candidate molecules to the pharmacological target protein transthyretin, as well as the program of virtual screening of NO scavengers. As a result of this approach, the substance catechin was isolated from candidate molecules - quercetin, catechin, Epicatechin gallate, Epicatechin, Procyanidin B1, Procyanidin B2, Procyanidin B3, Catechin-3-gallate according to docking analysis. As a result of virtual screening, catechin was identified as a potential NO scavenger (55.15% prediction). The results of the prediction were confirmed by in vitro experiments. Course administration of catechin to animals with experimental multiple sclerosis (MS) against the background of methylprednisolone administration completely eliminated lethal cases, reduced the number of diseased animals by 20%, as well as prevented the development of severe neurological symptoms by 20% (compared to the methylprednisolone group) and by 60% compared to the control group. Course administration of catechin with methylprednisolone leads to decrease of neurodegradation markers in the cytosol of rats with EAE: NSE by 37%, and S-100 - by 54.8%. The combined administration of methylprednisolone significantly exceeds the combination of methylprednisolone with the reference drug mexidol by the degree of NSE reduction. The obtained results indicate a significant neuroprotective effect of ocular combinations of methylprednisolone and catechin. The above-mentioned confirms the correctness of bioflavonoid selection with the help of virtual screening program.

المستخلص تصنيع لقاح مكون من الحمض النووي الريبوزي الرسول الخاص بالبروتينات المسئولة عن انتاج البروتينات نيورامنيديز والهيم اجليوتونين لفيروسي الانفلونزا الخنازير والطيورمحاط بجزيئات دهنية بحجم النانوميتر عدوى انفلونزا الخنازير وانفلونزا الطيور مشكلة خطيرة تؤرق العالم كله هذه الايام خصوصا انها مميتة لكثير من اطفال العالم . بعد فترة التعافي من الاصابة تتكون المناعة المكتسبة ضدها لمدة عام تقريبا. هذه الانفلونزا تسبب تسمم فيروسي في الدم بالاضافة للالتهاب الرئوي وهذامن بين اكبرالاسباب للوفاة بين الاطفال قبل سن عامين عالميا بشكل مباشر. الهدف من الدراسة هو انتاج لقاح الحمض النووي الريبوزي الرسول من نوع الام بالنانوتكنولوجي لبروتينات الهيم اجليوتونين والنيورامنيديز الموجودة على سطح هذه الفيروسات التي تساعدتها في الاتصاق بالعائل الذي ستتكاثر داخل خلاياه بالجهاز التنفسي. هذه الدراسة دراسة استكشافية ومن خلالها استطاعنا تصميم هذا اللقاح باستعمال نظام توصيل للقاح بالنانوتكنولوجي حجم جزيئاته 70نانوميمتر. اللقاح الجديد اظهر فاعلية بنسبة 60% واظهر فاعلية حيوية مقاربة واثار جانبية اقل بالمقارنة باللقاحات المتوفرة حاليا بالسوق الدوائي ضد هذا النوع من الفيروسات الوبائية. ABSTRACT Background: Worldwide, Swine and Avian influenza, or the H1N1 and H5N1 serotypes of the Influenza A virus, is a highly contagious illness. In recent years, the global incidence of mortality rate has surpassed 284,000 fatalities. Aim of the study: The production of mRNA vaccine lipid nanoparticles (LNP) to combat the deadly strains of Avian and Swine influenza (H1N1 and H5N1 of the influenza A serotype). Methodology: Polymerase chain reaction (PCR) was used to clone genes of interest encoding Haemagglutinin (HA) and Neuraminidase (NA) of Influenza A virus strains (H5N1 and H1N1) known as Avian flu and Swine flu, respectively. The genes were then inserted using the EcoR1, BAM Hind II restriction endonuclease type II, and Ligase enzyme into the pET-21(+) transcription vector plasmid. On the other hand, the hybrid transcription vectors were mixed with T7 RNA polymerase and ribonucleotides within a test tube after being linearized using EcoR II. Following their purification via reversed-phase high-performance liquid chromatography (RP-HPLC), the mRNAs of the HA and NA were encased in 70 nm LNPs and subjected to reverse-phase high-performance liquid chromatography (RP-HPLC). Lastly, immunogenicity studies were performed in stages 1/2 of randomized human and preclinical clinical trials. Results: The bivalent vaccination had around 63% efficacy in preclinical studies and approximately 60% efficacy in randomized human clinical trials. As shown by the ELISA test, strong neutralizing antibodies against HA were prevalent. Conclusion: The current study is a promising effort because of the development of the novel LNP-mRNA vaccine, which could lower the incidence of Avian and Swine flu infectious disorders.

Supplementation with 200% of the recommended daily dietary quantity of copper modified vascular contraction and relaxation through increased reactive oxygen species (ROS) and prostaglandin formation, which modified the antioxidant status of middle–aged rats. In this study, young (1 month old) male Wistar rats (n/group = 10) received a diet supplemented with 6.45 mg copper/kg (100%—Group A) for 8 weeks. The experimental group received 12.9 mg copper/kg of diet (200%—Group B). Experimental supplementation with 200% copper increased the copper concentration in the blood, liver, and kidneys; increased the ROS concentration in the aortic rings; and enhanced the sensitivity of the aortic rings to acetylcholine. We observed increased participation of nitric oxide (NO) derived from inducible NO synthase (iNOS) in vascular contraction and a decreased net effect of vasodilator prostanoids derived from cyclooxygenase–2 (COX–2) in vascular relaxation. Supplementation with 200% copper was less significant than expected after previous studies conducted with middle–aged rats.

Objective: Meningococcal meningitis (MM) is an acute, severe respiratory infectious disease caused by Neisseria meningitidis and remains an important cause of morbidity/mortality in children. Immunization with meningococcal vaccine (MV) is the most effective measure to control and prevent the transmission of MM. In this study, in order to support the appropriate use of various MVs in the prevention of MM, the effects of MVs, especially single-dose and inter-booster administered, on inflammatory parameters in

Diagnosing congenital heart disease (CHD) remains challenging because of its complex morphology. Representing the intricate structures of CHD on conventional two-dimensional flat screens is difficult owing to wide variations in the pathologies. Technological advancements, such as three-dimensional printed heart models (3DPHM) and virtual reality (VR), could potentially address the limitations of viewing complex structures using conventional methods. This study aimed to investigate the usefulness and clinical value of four visualization modalities across three different cases of CHD, including ventricular septal defect, double outlet right ventricle, and tetralogy of fallot. Seventeen cardiac specialists were invited to participate in this study, which was aimed at assessing the usefulness and clinical value of four visualization modalities, namely, DICOM images, 3DPHM, VR, and 3D PDF. Of these modalities, 76.4% of the specialists ranked VR as the best for understanding the spatial associations among cardiac structures and for presurgical planning. Meanwhile, 94.1% ranked 3DPHM as the best modality for communicating with patients and their families. Of the various visualization modalities, VR was the best tool for assessing anatomical locations and vessels, comprehending the spatial relationships among cardiac structures, and for presurgical planning. The 3DPHM models were the best tool for medical education as well as communication. In summary, both 3DPHM and VR have their own advantages and outperform the other two modalities, i.e., DICOM images and 3D PDF, in terms of visualizing and managing CHD.

Despite the effectiveness of insulin injections in managing hyperglycemia in Type 1 Diabetes, they fall short in addressing autoimmunity and regenerating damaged islets. This review aims to explore the potential of various treatment modalities for T1DM, including mesenchymal stem cells (MSCs), MSC-derived exosomes, gene therapy, islet allotransplantation, and pancreatic islet cell transplantation. Results: MSCs demonstrate efficacy in T1DM treatment through immunomodulation and tissue regeneration, although further research is warranted to optimize their therapeutic potential. Gene therapy presents a promising approach despite challenges such as donor shortage and immune rejection. Pancreatic islet cell transplantation emerges as a viable option, albeit with associated risks including graft rejection and the need for immunosuppression. Teplizumab, an FDA-approved humanized monoclonal antibody, revolutionizes the treatment landscape of Type 1 Diabetes by significantly delaying its onset, offering a paradigm shift since the discovery of insulin Conclusion: Ongoing studies and technological advancements in T1DM management offer a promising outlook for improved treatments and possibly even eradication on a global scale. MSCs, MSC-derived exosomes, gene therapy, and pancreatic islet transplantation hold considerable potential.

Respiratory Syncytial Virus (RSV) continues to pose a significant challenge, contributing to elevated hospitalization rates among children up to 5 years old, with a disproportionate burden on newborn and infants under 6 months old. The unique characteristics of the young immune system make it prone to altered responses to infections and vaccinations, requiring a tailored approach to disease prevention. The recent approval of the maternal RSV vaccine, (brand name ABRYSVO), represents a pivotal advancement in preventive strategies among newborns and infants, marking a milestone in RSV research as the first market-approved maternal vaccine. The present review examines clinical trial data on both recent and previous vaccine candidates, as well as the licensed vaccine, focusing on the prevention of RSV disease in newborns and young infants through the passive acquisition of antibodies following maternal immunization. Additionally, it evaluates the safety profile of these vaccines.

Abstract: Physicians, physical therapists, and occupational therapists have traditionally assessed hand motor function in hemiplegic patients but often struggle to evaluate complex hand move-ments. To address this issue, in 2019, we developed Fahrenheit, a device and algorithm that uses infrared camera image processing to estimate hand paralysis. However, due to Fahrenheit's de-pendency on specialized equipment, we conceived a simpler solution: developing a smartphone app that integrates MediaPipe. The objective of this study was to measure hand movements in stroke patients using both MediaPipe and Fahrenheit and to assess their criterion-related validity. The analysis revealed moderate-to-high correlations between the two methods. Consistent results were also observed in the peak angle and velocity comparisons across severity stages. Because Fahrenheit determines finger recovery status based on these measures, it has the potential to transfer this function to MediaPipe. This study highlighted the potential use of MediaPipe in pa-ralysis estimation applications.

With around one billion of the world's population affected, the era of Metabolic-associated fatty liver disease (MAFLD) pandemic has entered the global stage. MAFLD is a chronic progressive liver disease with accompanying metabolic disorders such as type 2 diabetes mellitus and obesity which can progress asymptomatically to liver cirrhosis and subsequently to hepatocellular carcinoma (HCC), and for which, to date there is almost no approved pharmacologic options. Because MAFLD has a very complex etiology and it affects also extrahepatic organs, a multidisciplinary approach is required when it comes to finding an effective and safe active substance for MAFLD treatment. The optimal drug for MAFLD should diminish steatosis, fibrosis and inflammation in the liver, and the winner for MAFLD drug authorisation seems to be the one that significantly improves liver histology. Saroglitazar (Lipaglyn®) was approved for Metabolic dysfunction associated steatohepatitis (MASH) in India in 2020; however, the drug is still being investigated in other countries. Despite that a pharmaceutical industry is still lagging behind to develop an ap-proved pharmacologic therapy for MAFLD, research has been recently intensified and many molecules which are underway in the final stages of clinical trials are expected to be approved in the coming few years. Already this year, the first drug (Rezdiffra™) in the United States was ap-proved via accelerated procedure for treatment of MAFLD, i.e. of MASH in adults. This review underscores the most recent information related to the development of drugs for MAFLD treatment, focusing on the molecules that have come furthest towards approval.

Copper (Cu) is a critical element for cancer cell proliferation and considerably accumulates in the nucleus. 64Cu2+ is an anticancer radiopharmaceuticals targeting the copper requirement of cancer cells. However, intravenously injected 64Cu2+ ions primarily accumulate in the liver. Ligand complexation of 64Cu2+ would be a promising method for increasing tumor delivery by reducing liver uptake. Herein, we used three tripodal amine ligands [tris(2-aminoethyl)amine (Tren), diethylenetriamine (Dien), and tris(2-pyridylmethyl)amine (TPMA)] to enclose 64Cu2+ ions and compared their in vivo tumor and liver uptake using a tumor-bearing xenograft mouse model of the extrahepatic bile duct carcinoma cell line TFK-1. We examined intracellular Cu distribution using microparticle-induced X-ray emission (micro-PIXE) analysis for these compounds. 64Cu2+-Tren and 64Cu2+-Dien showed higher tumor uptake than 64Cu2+-TPMA and 64Cu2+ ions in TFK-1 tumors. Among the three 64Cu2+ complexes and 64Cu2+ ions, liver uptake was inversely correlated with tumor uptake. Micro-PIXE analysis showed that in vitro cellular uptake was similar to in vivo tumor uptake and nuclear delivery was the highest for 64Cu2+-Tren. Conclusively, an inverse correlation between tumor and liver uptake was observed using three 64Cu2+ complexes of tripodal amine ligands and 64Cu2+ ions. These results provide useful information for the future development of anticancer 64Cu radiopharmaceuticals.

Multiple myeloma (MM) is a common type of cancer that unfortunately leads to a significant number of deaths each year. The majority of the reported MM cases are detected in the advanced stages, posing significant challenges for treatment. Additionally, all MM patients eventually develop resistance or experience relapse, therefore advances in treatment are needed. However, developing new anti-cancer drugs, especially for MM, requires significant financial investment and a lengthy development process. The study of drug repurposing involves exploring the potential of existing drugs for new therapeutic uses. This can significantly reduce both time and costs, which is typically a major concern for MM patients. The utilization of pre-existing non-cancer drugs for various myeloma treatments presents a highly efficient and cost-effective strategy, considering their prior preclinical and clinical development. The drugs have shown promising potential in targeting key pathways associated with MM progression and resistance. Thalidomide exemplifies the success that can be achieved through this strategy. This review delves into the current trends, the challenges faced by conventional therapies for MM, and the importance of repurposing drugs for MM. This review highlights a noncomprehensive list of conventional therapies that have potentially significant anti-myeloma properties and anti-neoplastic effects. Additionally, we offer valuable insights into the resources that can help streamline and accelerate drug repurposing efforts in the field of MM.

The process of developing therapies to treat rare diseases is fraught with financial, regulatory, and logistical challenges that have limited our ability to build effective treatments. Recently, a novel type of therapy called antisense therapy has shown immense potential for the treatment of rare diseases, particularly through single-patient N-of-1 trials. Several N-of-1 antisense therapies have been developed recently for rare diseases, including the landmark study of milasen. In response to the success of N-of-1 antisense therapy, the Food and Drug Administration (FDA) has developed unique guidelines specifically for the development of antisense therapy to treat N-of-1 rare diseases. This policy change establishes a strong foundation for future therapy development, and addresses some of the major limitations that previously hindered the development of therapies for rare diseases.

Background and Aim: It is generally accepted that oxidative stress mediators play an important role in ischemia-reperfusion injury(I/R), although the exact mechanism is not fully elucidated. While the impact of silymarin on I/R injury in several tissues, including the myocardial, cerebral, gastric and liver tissue, has been examined, the present state of research on this topic remains insufficient to provide a widely accepted understanding. For this purpose, our objective was to examine the effect of silymarin on muscle tissue in rats subjected to lower extremity I/R injury. Method: After ethics committee approval, 18 male Wistar albino rats weighing between 225-275 g were used. The rats were divided into three groups containing six mice each, Control,Ischemia-Reperfusion and Silymarin-Ischemia/Reperfusion groups. Silymarin was administered intraperitoneally 30 minutes before the procedure.( 100 mg/kg-1 ) In the I/R groups, an atraumatic microvascular clamp was placed in the infrarenal abdominal aorta. After 120 minutes, the clamp was removed and reperfusion was achieved for 120 minutes. In muscle tissue samples taken at the end of the reperfusion period; Malondialdehyde (MDA) levels, catalase (CAT) enzyme activity levels and histopathological parameters were compared. Results: In the histopathological examination, no degeneration was observed in the muscle fibers in the control group, while findings of striated muscle damage such as muscle atrophy hypertrophy, muscle degeneration-congestion, internal of the muscle nucleus-oval-central nucleus, fragmentation-hyalinization and leukocyte cell infiltration were observed in the I/R group. In the S-I/R group, muscle atrophy hypertrophy, internal of the muscle nucleus-oval-central nucleus, fragmentation-hyalinization and leukocyte cell infiltration were observed to improve these damaged areas compared to the I/R group. MDA levels in the I/R group were found to be significantly higher than in the control and S-I/R groups. CAT enzyme activity was found to be significantly higher in the I/R group than in the control group. Conclusion:Our study revealed that the administration of silymarin at a dosage of 100 mg/kg-1 by intraperitoneal injection 30 minutes before ischemia in rats effectively decreased lipid peroxidation and oxidative stress. Additionally, it successfully reduced the injury caused by ischemia/reperfusion in muscle histology.

Stroke causes disability and significantly affects patient quality of life. Post-stroke rehabilitation of upper limb function is crucial, as it affects daily activities and individual autonomy. Traditional rehabilitation methods often require frequent visits to specialized centers, which can be costly and challenging. This study investigated the effectiveness of a home-based self-training device, "Kenko Yusuri," in improving upper limb function in patients with chronic stroke. This multicenter prospective intervention study used a quasi-randomized controlled trial design. Ninety-three outpatients from five hospitals in Japan were enrolled and assigned to either the intervention group who used the "Kenko Yusuri" device or the control group who underwent conventional rehabilitation. All patients received botulinum toxin type A (BoNT-A) injections to treat upper limb spasticity. The primary outcome measure was the Fugl-Meyer Assessment (FMA) of upper-extremity motor function. Secondary outcomes included the modified Ashworth scale (MAS) score, range of motion (ROM), and chronic pain assessments. The intervention group demonstrated significantly greater improvements in FMA total scores than the control group. Patients with moderate paralysis experienced the greatest benefits from the intervention. There were no significant between-group differences in MAS scores or ROM measurements. Pain and wrist ROM showed improvement in the intervention group. Home-based training with a shaking device significantly improved upper limb function in patients with moderate chronic post-stroke paralysis. This approach aligns with the principles of use-dependent plasticity and offers a feasible and cost-effective alternative to traditional rehabilitation methods.

Abstract: Steamed ginseng water (SGW), the by-product generated from the heated processing of red ginseng, with high content of active substances, better skincare activities, and large amount output ineffective utilization, resulted in environmental pollution and resource waste. In current study, UHPLC-Q-Exactive-MS/MS liquid chromatography-mass spectrometry and multivariate statistical analysis were conducted to characterize the compositional features of the repeated thermal-treated SGW. The total sugar content, total sugar content, total reducing sugar content, total non-reducing sugar content, DPPH, ABTS+, Fe3+ reducing capacity, and the hydroxyl radical scavenging abilities were employed to evaluate the gross contents variation connect with anti-oxidant activities during heat processes. The result revealed the SGW content and antioxidant activity were highly correlated, the 7th SGW sample showed the highest content and the strongest ability on anti-aging capacities. 38 significant common differential markers were screened, by the four compared SGW groups (1- and 3-, 1- and 5-, 1- and 7-, and 1- and 9) through OPLS-DA analysis. The current study showed that the thermal proceeding times could be a vital index value during the recycling operation quality control of SGW, which has a huge potential in anti-aging cosmetic raw materials, In the meanwhile, our results provided a green, sustainable, low-cost thinking of rational application on ginseng resource.

Antimicrobial peptides (AMPs) are promising tools for combating microbial resistance. However, their therapeutic potential is hindered by two intrinsic drawbacks – low target affinity and poor in vivo stability. Macrocyclization, a process that improves the pharmacological properties and bioactivity of peptides, can address these limitations. As a result, macrocyclic peptides represent attractive drug candidates. Moreover, many drugs are macrocycles that originated from natural product scaffolds, suggesting that nature offers solutions to the challenges faced by AMPs. In this review, we explore natural cyclic peptides from the DBAASP database. DBAASP is a comprehensive repository of data on antimicrobial/cytotoxic activities and structures of peptides. We analyze the data on small (≤25 AA) ribosomal and non-ribosomal cyclic peptides from DBAASP according to their amino acid composition, bonds used for cyclization, targets they act on, and mechanisms of action. This analysis will enhance our understanding of the small cyclic peptides that nature has provided to defend living organisms.

Despite a large amount of research on synchronous and mutually induced kidney and heart damage, the basis of the disease is still not fully clarified. Healthy mitochondria are essential for normal kidney and heart function. Mitochondrial dysfunction occurs when the clearance or process of generation and fragmentation of mitochondria is disturbed. The kidney is the second organ after the heart in the number of mitochondria. Kidney tubules are rich in mitochondria due to the high energy requirements for absorption processes of large amounts of ultrafiltrate and dissolved substances. The place of action of oxidative stress is the influence on the balance in the production and breakdown of mitochondrial reactive oxygen species . A more precise determination of the place and role of key factors that play a role in the onset of the disease is necessary for understanding the nature of the onset of the disease and the creation of therapy in the future. The narrative review integrates results found in previously performed studies which have evaluated oxidative stress participation in renocardial syndrome type 3.

The prevalence of diabetes mellitus (DM) continues to rise globally, posing significant health challenges and burdens. This metabolic disorder, characterized by elevated blood glucose levels, contributes to various complications including cardiovascular diseases, kidney failure, and stroke. While conventional diabetic drugs exist, they often come with adverse side effects, necessitating the exploration of safer and more cost-effective alternatives, particularly from natural sources like medicinal plants. This study investigates the potential of Neocarya macrophylla (Nm) Ethyl acetate leaf fraction in managing DM. Utilizing a high-fat diet/streptozotocin-induced diabetic rat model, the study explores several key aspects including effective dose determination, biological activity, impact on body mass index (BMI), and complete blood count. Statistical analysis was conducted using GraphPad Prism version 9.1. The determination of the minimum effective dose reveals that 120mg/kg of Ethyl acetate fraction of Nm reduced the blood glucose by 28.9% after 4 hours. In addition, ethyl acetate fraction (120 mg/kg) possessed the most hypoglycemic activity compared to the other fractions of Nm. The Ethyl acetate fraction of Nm at 120mg/kg significantly reduced fasting blood glucose levels compared to the diabetic control(p=0.001) and slightly decreased BMI. Furthermore, the fraction demonstrated significant improvement in the parameters of some of the blood count indices such as red blood cells (p<0.001), total white cells (p<0.01) and platelet (p<0.001) compared to the diabetic control. These findings underscore the potential of Nm as a holistic therapeutic option for managing DM and its haematological complications. In conclusion, this study sheds light on the hypoglycemic potential of Nm Ethyl acetate leaf fraction, offering valuable insights into its effectiveness, safety, and broader physiological impacts. Further research into the mechanisms underlying its therapeutic effects is warranted to fully harness its therapeutic potential in diabetes management.

Due to the host immunological disease brought on by infection is sepsis, multiple organ dysfunction syndrome (MODS), which has a high morbidity and mortality rate, could be the result. With advances in pathogen detection technologies, breakthroughs in anti-infection drugs, and the creation of organ function support, the clinical diagnosis and treatment of sepsis have advanced significantly. Pathogen-induced abnormal immunological responses, which can range from excessive inflammation to immunosuppression, are recognized to play a significant role in the high death rate. Unfortunately, no medications that are specifically intended to treat sepsis have been licensed. In order to offer a theoretical foundation for the management of sepsis, we will now discuss current advancements in research on immunological responses in sepsis. The prognosis of sepsis patients may be improved by developing and optimizing a dynamic immune system treatment plan based on anti-infection therapy, fluid replacement, support for organ function, and timely application of immunomodulatory therapies

Background: Breast cancer and other neoplasms like acute lymphocytic leukemia pose a serious threat to public health worldwide. Treatment for malignancies including acute lymphocytic leukemia and breast cancer requires enzymes that break down L-glutamine. An amidohydrolase called L-glutaminase can be an effective chemotherapeutic tool for treating various cancers. Methods: On mineral L-glutamine agar selective medium (MGA), a few bacterial isolates were examined in the current investigation to see if they produced L-glutaminase. However, the most effective positive bacterial isolates generating L-glutaminase were identified using morphological and biochemical testing. Molecular detection using the direct Southern blotting approach was also used to determine the main positive isolate that produces L-glutaminase. L-glutaminase synthesis by bacteria was evaluated for its characteristics. Using an MTT test, the anticancer activity was evaluated. Results: exclusive bacterial isolates that used L-glutamine as their sole source of metabolic nitrogen exhibited favorable growth on MGA. PH 7.4 and a temperature of 37 0C were the ideal environmental and physiological conditions for developing positive bacterial isolates. From the soil samples taken from various soil conditions in Egypt, the morphological and biochemical analyses showed that Bacillus cereus 14579 was the main positive bacterial generating L-glutaminase isolate. At a pH of 7.4 and a temperature of 37 °C, the following activators—KCL, ZnSO4, FeSO4, K2HPO4, and MgSO4—provided the high-grade circumstances for characterizing L-glutaminase synthesis. Bacillus cereus-produced L-glutaminase has shown excellent bioavailability and effectiveness as an anticancer therapy. The yield [productivity] was 5.2 U/ml during the original manufacture from MGA, but it increased to 42.96 U/ ml by bacterial recombinant DNA manufacturing. The molecular mass of L-glutaminase was roughly 37 KDa. L-glutaminase was purified, yielding final enzyme recovery of 55 1.23%, total activity 12,990± 19.76 ( U), specific activity 384.66± 8.92( U/ mg of protein), and purification fold 2± 2.99. Furthermore, the L-glutaminase activity was raised by 19%, 23%, 15%, and 9%, respectively, by the enzymatic activators Mn2+, K+, Na+, and Fe3+. It demonstrated strong DPPH scavenging activity (IC50 = 61 μg/ mL) and anticancer activity( IC50 = 40.72, 9.7, 7.39, 20.61, 51.28, and 11.55 μg/ mL, respectively) against human liver (HepG-2), colon ( HCT-116), breast ( MCF-7), lung( A-549), lymphocytic( CCL-120), and cervical( Hela) cancer cell lines. A stronger affinity for its substrate was shown by the kinetic parameters of Km and Vmax, which were 13.2 10-5 M and 119.86 μmol/ ml/ min, respectively. Conclusion: Acute lymphocytic leukemia and breast cancer are examples of auxotrophic malignancies for which L-glutamine serves as the only metabolic source, and L-glutaminase generated by Bacillus cereus was an appropriate enzyme in the therapy of these diseases.

Cigarette smoke (CS) is a major driver of many respiratory diseases including chronic obstructive pulmonary disease (COPD) and non-small cell lung cancer (NSCLC). Tobacco causes oxidative stress, impaired phagocytosis of alveolar macrophages (AMs), and alterations in gene expression in the lungs of smokers. MicroRNAs (miRNAs) are small non-coding RNAs that influence several bi-ological processes and interfere with several regulatory pathways. The purpose of this study was to assess the effect of active CS on miRNAs expression in AMs obtained from bronchoalveolar lavage (BAL) of ever- or never-smoker subjects and patients with COPD or NSCLC. BAL specimens were collected from 43 sex-matched subjects to determine the expression of has-miR-34a-5p, 17-5p, 16-5p, 106a-5p, 223-5p, and 20a-5p before and after in vitro CS exposure by RT-PCR. In addition, bioin-formatic analysis of miRNAs target genes linked to inflammation was performed. Distinct and common miRNA expression profiles were identified in response to CS, suggesting their possible role in smoking-related diseases. It is noteworthy that, following exposure to CS, the expression levels of hsa-miR-34a-5p and 17-5p in both ever- or never-smokers, 106a-5p in never-smokers and 20a-5p in ever-smokers, shifted towards those found in individuals with COPD, suggesting them like a risk factor in developing this lung condition. Moreover, we identified miRNA targets involved in the immune system or AMs property regulation using in silico analysis. In conclusion, our study iden-tified miRNA signatures in AMs exposed to CS, indicating that CS is an important driver of epige-netic changes that contribute to the onset of various lung diseases.

Myocardial fibrosis is a pivotal pathophysiological step of various cardiovascular diseases, which eventually leads to heart failure and death. Cardiac fibroblasts activation and subsequently differentiate into myofibroblasts are pivotal pathophysiological step in myocardial fibrosis. Phosphoglycerate mutase 1 (PGAM1) directly interacts with α-smooth muscle actin (ACTA2) and participate in fibrosis regulation. Allosteric inhibitor of PGAM1 could attenuates fibrosis through break the interaction of PGAM1 and ACTA2. In this study, we aimed to screen and identify novel ligand of PGAM1 in natural product library. Firstly, various natural products were screened via DARTS assay and Carthamus tinctorius L. was identified as a target pool for molecular docking. Then, in silico screening assay identified baicalein as a novel ligand. In addition, baicalein could directly bind to the PGAM1 protein with a KD value of 34.6 μM. Molecular dynamics simulation revealed that baicalin and PGAM1 interactions were stable. These findings indicate that PGAM1 is a direct pharmacological target of baicalein. Immunoblot analysis further demonstrated that baicalin inhibits the activation of fibroblasts in vitro. Finally, the anti-myocardial fibrosis effect of baicalein was verified in vivo. Taken together, our findings suggest that baicalein is a novel PGAM1 templates for developing new therapeutics against myocardial fibrosis.

Plant-derived compounds have been historically used for the treatment of various diseases and an important source of several clinically useful anti-cancer agents. The Artemisia annua is known as a medicinal herb that is effective against cancer. Thus, the purpose of this study was to investigate whether ethanol extracts of Artemisia annua could increase an anti-cancer effect against LS174T cells. Our results show that Artemisia annua extracts (AAE) induces apoptosis through the regulation of mitochondria outer membrane potential. We demonstrate that apoptosis is induced by p53-dependent manner when cells were treated with Nutlin-3 (MDM2 inhibitor) and LY294002 (Akt inhibitor). In addition, the apoptotic effect was also observed in the p53-independent manner through pifithrin-α (p53 inhibitor) and celecoxib (COX-2 inhibitor) treatment. As in in vitro, AAE induced apoptotic effects and regulated apoptosis-related proteins in LS174T xenograft model. Taken together, these results suggest that Artemisia annua extracts exerts an anti-cancer effect through p53-independent manner, as well as p53-dependent manner by p53´ translocation in LS174T colon cancer cells.

Background: Antibiotic resistance is an overwhelming serious difficulty globally. This necessitates the exploration of novel sources of antibiotics to overcome this challenge. Aim of the study: Bacterial Myxopyronin A production from various soil environments Egypt; as well as testing its antimicrobial activity in preclinical animal testing and randomized human clinical trials phases 1/2. Type of the study: Screening experimental study. Methodology: Different soil environments in Egypt were screened for the growth of bacterial isolates producing Myxopyronin A as an antimicrobial agent. Purification of Myxopyronin A was performed via reversed-phase HPLC. Paper disc diffusion assay, as well as broth dilution technique, were exploited to assess the invitro antimicrobial and minimum inhibitory concentration( MIC) of the test antibiotic. Furthermore, in vivo antimicrobial spectrum, adverse drug reactions, and pharmacokinetics were detected during animal model testing stages and human randomized clinical trials phases 1/2. Results: From the culture supernatant of the Myxobacterium Myxococcus fulvus 124B02 which was the predominant soil bacterial isolate grown on the Casein yeast peptone plate, Myxopyronin A was produced. The test antibiotic blocked the growth of many Gram +ve bacteria with MICs less than 100 mcg/ ml; whereas it inhibited the growth of a few Gram -ve bacteria such as Escherichia coli at MICs greater than 100 mcg/ ml. On the other hand, Eukaryotic cells such as fungal and human cells were not affected. Prokaryotic DNA-dependant-RNA polymerase( RNLP) was noticed to be inhibited via the test antibiotic suggesting its bactericidal action. Cmax was 7-8 mcg/ ml at Tmax 2 hours when 600 mg dose was orally administered in randomized human clinical trials phases 1/2; as well as T1/2 reached 2.5 hours following first-order kinetics of elimination. The duration of its action was nearly 12 hours after oral administration. Rare toxicity was detected during preclinical and randomized human clinical trials phases 1/2 in the form of mild diarrhea and cholestatic jaundice in less than 5 % of experimental candidates. Conclusion: The present study was promising due to the production of the bactericidal antibiotic Myxopyronin A from Myxococcus fulvus 124B02 isolated from different soil environments in Egypt.

Background: Across the world, antibiotic resistance is a critical challenge. To address such a problem, it has to be done to investigate new antibiotic sources. Aim of the study: Study of the antibacterial activity of Corallopyronin A in preclinical animal testing and randomized human clinical trials stages 1/2, as well as investigating the purification of Corallopyronin A from different soil conditions in Egypt. Type of the study: Screening experimental study. Methodology: Egypt's various soil conditions were tested to develop bacterial isolates that produced the antibiotic compound Corallopyronin A. Reversed phase HPLC was used to purify Myxopyronin A. The broth microdilution method and the paper disc diffusion assay determined the test antibiotic's minimum inhibitory concentration( MIC) and in vitro antibacterial activity. Moreover, in vivo antibacterial spectrum, adverse medication responses, and pharmacokinetics were found in phases 1/2 of randomized clinical studies involving humans and animal models. Results: Corallopyronin A was generated from the culture supernatant of the soil bacterial isolate Corallococcus coralloides M2, cultivated on a Casein yeast peptone( CYP) plate. The test antibiotic prevented the growth of several Gram-ve bacteria, including Escherichia coli, at MICs higher than 100 mcg/ ml; while blocking the development of many Gram +ve bacteria, with MICs ranging from 3 to 15 mcg/ ml. However, eukaryotic cells—such as those found in fungi and humans—were unaffected. A bactericidal consequence of the test antibiotic was detected in the inhibition of prokaryotic DNA-dependent RNA polymerase( RNLP). Conclusion: The synthesis of the bactericidal antibiotic Corallopyronin A from Corallococcus coralloides M2 isolated from different soil settings in Egypt intrigued the current investigation.

Graves' disease (GD) is an autoimmune disorder in which Thyrotropin Receptor Antibodies (TRAb) continuously stimulate thyroid receptors, leading to excessive production of thyroid hormones. TRAb also affect the orbital tissues, causing Graves' ophthalmopathy. Treatment to control Graves' disease consists of antithyroid drugs, radioiodine and thyroidectomy, and through such treatments, TRAb is reduced and the disease is alleviated. The mechanism by which TRAb, which play a critical role in the pathogenesis of Graves’ disease, decreases after GD treatment is still unknown. This paper presents a theoretical mechanism of how GD patients maintain a vicious cycle and how GD treatment can reduce the TRAb levels and breaks the cycle using stress-based ideas.

Litsea martabanica root's antioxidant and AChE activity showed promise as a pesticide detoxification agent in our previous study. In addition to roots, its leaves can help mitigate pesticide exposure, although there is limited scientific evidence supporting their efficacy. However, the use of roots in many countries, such as Thailand, could contribute to environmental degradation, as highland communities traditionally cut down whole trees to obtain them. This study aims to evaluate the antioxidant activity and anti-pesticide potential of water extracts from L. martabanica leaves instead of its roots through in vitro and in vivo investigations. The findings showed that L. martabanica water extracts and fractions demonstrated varied antioxidant activity. The water extract, obtained using traditional extraction methods, was chosen for in vivo experiments. Rats received the extract followed by chlorpyrifos exposure for 16 days. Results indicated reduced acetylcholinesterase activity in chlorpyrifos-exposed rats, while treatment with leaf extract led to increased activity, suggesting its potential as a detoxifying agent. Histopathological examination revealed no liver cell necrosis and showed liver cell regeneration, indicating potential protection against free radical-induced liver damage without affecting rat liver weight or biochemical profiles. Utilizing L. martabanica leaves for healthcare purposes holds promise without negative environmental impact.

Type 2 diabetes mellitus (T2DM), a multifactorial and complicated metabolic disorder, is a growing public health problems. Numerous studies indicated that bioactive compounds from herbal medicine have beneficial effects on T2DM prevention and treatment, owing to their numerous biological properties. Curcumin, the major curcuminoid of turmeric, is one of the most studied bioactive components of herbal supplements, which has a variety of biological activities. Clinical trials and preclinical research have recently produced compelling data to demonstrate the crucial functions of curcumin against T2DM via several routes. Accordingly, this review systematically summarizes the antidiabetic activity of curcumin, along with various mechanisms. Results showed that effectiveness of curcumin on T2DM is due to it being anti-inflammatory, anti-oxidant, anti-hyperglycemic, anti-apoptotic, anti-hyperlipidemia and other activities. In light of these results, curcumin may be a promising prevention/treatment choice for T2DM.

The evaluation of nanostructured biomaterials and medicines is associated with 2D cultures that provide insight into the biological mechanisms at the molecular level, while critical aspects of the tumor microenvironment (TME) are provided by the study of animal xenograft models. More realistic models that can histologically reproduce human tumors are provided by tissue engineering methodologies of co-culturing cells of varied phenotypes, to provide 3D tumor spheroids that recapitulate the dynamic TME in 3D matrices. The novel approaches of 3D tumor models are combined with tumor tissue engineering (TTE) scaffolds including hydrogels, bioprinted materials, decellularized tissues, fibrous and nanostructured matrices. This review focuses on the use of nanostructured materials in cancer therapy and regeneration, and the development of realistic models for studying TME molecular and immune characteristics. Tissue regeneration is an important aspect of TTE scaffolds for restoring the normal function of the tissues, while providing cancer treatment. Thus, this article reports recent advancements on the development of 3D TTE models for antitumor drug screening, studying of tumor metastasis, and tissue regeneration. Also, this review identifies the great opportunities of 3D TTE scaffolds in the evaluation of the immunological mechanisms and processes involved in the application of immunotherapies.

Chronic kidney disease (CKD) is a progressive condition that affects more than 10% of the world's population. Monitoring urine albumin and creatinine ratio (µACR) has become the gold standard for nephropathy diagnosis and control. The objective of the present study was to develop a simple, accurate, sensitive, and rapid point-of-care test (PoCT) device - MYμALBUMIN that community healthcare professionals can use in resource-limited facilities and by patients in their own homes for screening the risk and monitoring the progress of CKD. Albumin and creatinine concentrations in urine samples were determined using spectrophotometric dye (tetrabromophenol blue)-binding and colorimetric Jaffe’assay, respectively. Urine samples were diluted with distilled water (1:80) and mixed separately with albumin and creatinine reaction mixture. The creatinine reaction was incubated at room temperature (25oC) for 30 minutes before analysis. Optical density (OD) was measured at the wavelengths of 625 nm (albumin) and 515 nm (creatinine). All calibration curves (2-60 mg/L and 0.25-2 mg/dL for albumin and creatinine) yielded linear relationships with correlation coefficients (r2) of &gt; 0.999. Good accuracy (%DMV &lt; + 2.88%) and precision (%CV &lt; 3.0%) were observed from both the intra- or interday assays for the determination of albumin and creatinine by MYµALBUMIN. The limit of quantification (LOQ) of albumin and creatinine in urine samples determined by MYµALBUMIN and laboratory spectrophotometer were 2 mg/L and 0.1 mg/dL, respectively, using 37.5 μL urine samples. The device was well applied with clinical samples from 13 CKD patients. The median (range) of %DMV of the central (hospital) laboratory method (immune-based assay) was 3.18 (-10.11 to 14.12)%, with a high correlation coefficient (r2 &gt;0.99). In conclusion, MYμALBUMIN showed satisfactory test performance in terms of accuracy, reproducibility, sensitivity, and specificity. The device would have significant economic benefits besides obviously improving clinical decision-making processes.

Carbapenemase-producing Enterobacter spp. Serratia marcescens, Citrobacter freundii, Providencia spp. and Morganella morganii (CP-ESCPM) are increasingly identified as causative agents of nosocomial infections but are still not under systematic genomic surveillance. In this study, using a combination of whole genome sequencing and conjugation experiments, we sought to elucidate the genomic characteristics and transferability of resistance genes in clinical CP-ESCPM isolates from Bulgaria. Among the 36 sequenced isolates, NDM-1 (12/36), VIM-4 (11/36), VIM-86 (8/36) and OXA-48 (7/36) carbapenemases were identified; two isolates carried both NDM-1 and VIM-86. The majority of carbapenemase genes were found on self-conjugative plasmids. IncL plasmids were responsible for the spread of OXA-48 among E. hormaechei, C. freundii and S. marcescens. IncM2 plasmids were generally associated with the spread of NDM-1 in C. freundii and S. marcescens, and also of VIM-4 in C. freundii. IncC plasmids were involved in the spread of the recently described VIM-86 in P. stuartii isolates. IncC plasmids carrying blaNDM-1 and blaVIM-86 have been observed too. blaNDM-1 was also detected on IncX3 in S. marcescens and on IncT plasmid in M. morganii. The significant resistance transfer rates highlight the role of the ESCPM group as a reservoir of resistance determinants and stress the need for strengthening the infection control measures.

Frequent and excessive consumption of alcohol, be it episodic or sustained misuse, ranks among the top causes of mortality globally. This comprehensive analysis seeks to elucidate how alcohol misuse precipitates death, with a particular focus on associated cardiac anomalies. Notably, the phenomenon of "Holiday Heart Syndrome," linked to binge drinking, is recognized for inducing potentially fatal cardiac arrhythmias. Moreover, persistent alcohol consumption is implicated in the development of alcoholic cardiomyopathy, a condition that underlies heart failure and arrhythmic disturbances of the heart. Additionally, individuals undergoing withdrawal from alcohol frequently exhibit disruptions in normal heart rhythm, posing a risk of death. This review further delves into additional alcohol-related mortality factors, including the heightened likelihood of hypertension, cerebrovascular accidents (strokes), and the connection between excessive alcohol use and Takotsubo syndrome.

This perspective discusses the ongoing real-world practice using nitazxoanide, NSAIDs and/or azithromycin (Kelleni’s protocol) to manage the evolving manifestations of SARS CoV-2 Omicron EG.5.1, its descendant HV.1 as well as BA.2.86 and its descendant JN.1 subvariants in Egypt. These subvariants are well-known for their highly evolved immune-evasive properties and the manifestations include some peculiar manifestations as persistent cough besides high fever in young children as well as high fever, persistent severe cough, change of voice, loss of taste and smell, epigastric pain, nausea, vomiting, diarrhea, generalized malaise and marked bone aches in adults including the high risk groups. It’s suggested that the ongoing SARS CoV-2 evolution is continuing to mostly affect the high risk groups of patients, to some of whom we’ve also successfully prescribed nitazoxanide and/or NSAIDs for post-exposure prophylaxis of all household contacts. We also continue to recommend starting the immune-modulatory antiviral Kelleni’s protocol as soon as possible in the course of infection and adjusting it in a personalized manner to be more aggressive from the beginning for the high risk patients, at least until the currently encountered surge of infections subsides.

The aging of the population in developing and developed countries has lead to a significant increase in health burden of spinal diseases. These elderly patients often have a number of medical co-morbidities due to aging. The need for minimally invasive techniques to address spinal disorders in this elderly population group cannot be stressed enough. Minimally invasive spine surgery (MISS) has several proven benefits such as minimal muscle trauma, minimal bony resection, lesser post-operative pain, decreased infection rate and shorter hospital stay. Over the last 40 years, constant efforts are being made to develop newer techniques of spine surgery. Endoscopic spine surgery is one such subset of MISS which has all the benefits of modern MISS. Endoscopic spine surgery initially was limited only to treatment of lumbar disc herniations. With improvement in optics, endoscopes, endoscopic drills and shavers, irrigation pumps, there has been a paradigm shift. Endoscopic spine surgery can now be performed with high magnification thus allowing its application not only to lumbar spinal stenosis, but also to spinal fusion surgeries, cervical and thoracic pathology as well. There has been increasing evidence in support of these newer techniques of spine surgery. For the purpose of this review, we studied current available literature and outlined the historical evolution of endoscopic spine surgery, the various different endoscopic systems, and techniques available and the current applications of endoscopic techniques as an alternative to traditional spinal surgery.

Much research has been conducted to determine how hair regeneration is regulated, as this could provide therapeutic, cosmetic, and even psychological interventions for hair loss. The current study focused on the hair growth effect and effective utilization of fatty oil obtained from Bryde's whales through high-throughput DNA microarray approach in conjunction with immunohistochemical observations. The research also examined the mechanisms and factors involved in hair growth. In an experiment using female C57BL/6J mice, the vehicle control group (VC: propylene glycol: ethanol: water), the positive control group (MXD: 3% minoxidil), and the experimental group (WO: 20% Whale Oil) were topically applied to the back of the mouse. The results showed that 3% MXD and 20% WO were more effective than VC in promoting hair growth, especially 20% WO. Furthermore, in hematoxylin and eosin-stained skin tissue, an increase in the number of hair follicles and subcutaneous tissue thickness was observed with 20% WO. Whole-genome transcriptomic analysis also showed that 20% WO may have lower stress- and inflammation-related responses than 3% MXD. Therefore, whale oil can be expected to be used as a safe hair growth agent.

mRNA-lipid nanoparticle (LNP) medicinal products can be considered a platform technology because the development process is similar for different diseases and conditions, with similar noncoding mRNA sequences and lipid nanoparticles and essentially unchanged manufacturing and analytical methods utilised often for different products. It is critical not to lose the momentum built using the platform approach during the development, regulatory approval and rollout of vaccines for SARS-CoV-2 and its variants. This Review proposes a set of modifications to existing regulatory requirements for mRNA products, based on a platform perspective for quality, manufacturing, preclinical and clinical data. For the first time, we address development and potential regulatory requirements when the mRNA sequences and LNP composition vary in different products as well. In addition, we propose considerations for self-amplifying mRNA, individualised oncology mRNA products and mRNA therapeutics. Providing a predictable development pathway for academic and commercial groups, so they can know in detail what product characterisation and data are required to develop a dossier for regulatory submission, has many potential benefits. These include reduced development and regulatory costs; faster consumer/patient access and more agile development of products in the face of pandemics; and for rare diseases where alternatives may not exist or to increase survival and the quality of life in cancer patients. Therefore, achieving consensus around platform approaches is both urgent and important. This approach with mRNA can be a template for similar platform frameworks for other therapeutics and vaccines to enable more efficient development and regulatory review.

Injury to the peritoneum during surgery is followed by a healing process that frequently results in the attachment of adjacent organs by a fibrous mass, referred to commonly as adhesions. Because injuries to the peritoneum during surgery are inevitable, one must understand the mechanisms of adhesion formation to prevent its occurrence. This requires a thorough understanding of the molecular sequence that results in the attachment of injured peritoneum and the development of fibrous tissue. Recent data show that fibroblasts from the injured peritoneum may play a critical role in forming adhesion tissues. Therefore, identifying changes in gene expression patterns in the peritoneal fibroblasts during the process may provide clues to the mechanisms by which adhesion develops. This review presents many papers discussing genes implied in peritoneal adhesion.

Antibody-drug conjugates (ADCs), a groundbreaking advancement in cancer therapy, synergistically combine the precision of monoclonal antibodies with the potent destruction capabilities of cytotoxic drugs, signifying a new era in the targeted oncological treatments. This comprehensive paper delves into the evolving field of antibody-drug conjugates (ADCs) and their pivotal role in cancer therapy. We have conducted an in-depth exploration of the structural components of ADCs, including target antigens, monoclonal antibodies, chemical linkers, and cytotoxic payloads, each playing a crucial role in determining the efficacy and safety profile of these novel therapies. A detailed market analysis reveals the leading pharmaceutical companies shaping the ADC landscape, reflecting the growing interest and potential in this therapeutic approach. We further dissect the engineering intricacies of ADCs, focusing on their ability to target specific cancer cell antigens while minimizing off-target effects, thus offering a more focused treatment with reduced systemic side effects compared to traditional chemotherapy. This approach holds promise in a heightened therapeutic index and decreased toxicity. The mechanisms and effector functions of ADCs are explored, highlight- ing their multifaceted strategy in combating cancer. We include a comprehensive look at how ADCs operate from initial blood circulation to the induction of apoptosis in cancer cells. We also review several key ADCs currently in use or under investigation, offering insights into their unique mechanisms of action, pharmacokinetics, and clinical implications. The discussion extends to drug creation modalities, focusing on innovative conjugation techniques that enhance ADC homogeneity and therapeutic efficacy. In conclusion, the paper underscores the transformative potential of ADCs in the realm of cancer treatment, marking a shift towards more precise and targeted therapeutic approaches. By offering a thorough analysis of ADC technology, this paper sheds light on the prospects of these groundbreaking therapies in the ongoing fight against cancer.

To develop peptide drugs targeting integrin receptors, synthetic peptide ligands endowed with well-defined selective binding motifs are necessary. The snake venom KTS-containing disintegrins, that selectively block collagen α1β1 integrin, were used as lead compounds for the synthesis and structure-activity relationship of a series of linear peptides containing the KTS-pharmacophore and alternating natural amino acids and 3-aminobenzoic acid (MABA). To ensure a better stiffness and metabolic stability, one, two and three MABA residues, were introduced around the KTS pharmacophore motif. Molecular dynamics simulations have determined that the solution conformation of MABA peptide 4 is more compact, underwent larger conformational changes until convergence, and spent most of the time in a single cluster. The peptides’ binding affinity has been characterized by enzyme linked immunosorbent assay in which the most potent peptide 4 inhibited with IC50 of 324±8 µM and 550±45 µM the binding of GST-α1-A domain to collagen IV fragment CB3, and the cell adhesion to collagen IV using α1-overexpressor cells, respectively. Docking studies and MM-GBSA calculations confirmed that peptide 4 binds a smaller region of the integrin near the collagen- binding site and penetrated deeper into the binding site near Trp1. Peptide 4, inhibited tube formation by endothelial cell migration in the Matrigel angiogenesis in vitro assay. Peptide 4 was acutely tolerated by mice, showed stability in human serum, decreased tumor volume and angiogenesis, and significantly increased the survival of mice injected with B16 melanoma cells. These findings propose that MABA-peptide 4 can further serve as an α1β1-integrin antagonist lead compound for further drug-optimization in angiogenesis and cancer therapy.

(1) Background: Asthma and Chronic Obstructive Pulmonary Disease (COPD ) are major global health issues, impacting morbidity, mortality, and healthcare costs. Despite the proven benefits of pharmacist involvement in managing these conditions, their potential in hospitals remains underused. This study aimed to identify patients at high risk of rehospitalisation post-exacerbation of asthma or COPD, to target pharmaceutical interventions. (2) Methods: Data from the University Hospital for January-December 2019 on adult admissions for asthma/COPD were analyzed, focusing on demographics, hospitalization, and clinical outcomes. (3) Results: Among the 140 patients enrolled, a significant majority (91%) underwent adjustments in their treatment regimens during their hospital stay, and nearly 59% faced readmission within six months. A survival analysis highlighted a notable disparity in the rates of rehospitalisation-free survival between patients with asthma and those with COPD, identifying COPD patients as having a higher susceptibility to rehospitalisation. (4) Conclusion: The study found COPD pa-tients at greater risk but didn't specify a priority profile, suggesting the necessity for broad, cus-tomized interventions to improve outcomes and reduce healthcare strain.

Gastric inflammation-related disorders are commonly observed digestive system illnesses char-acterized by the activation of proinflammatory cytokines, particularly tumor necrosis factor-α (TNF-α). This results in the induction of cyclooxygenase-2 (COX-2)/prostaglandin E2 (PEG2) and matrix metallopeptidase-9 (MMP-9). These factors contribute to the pathogenesis of gastric in-flammation disorders. We examined the preventive effects of Lonicera japonica Thunb. ethanol ex-tract (Lj-EtOH) on gastric inflammation induced by TNF-α in normal GES-1 cells. The GES-1 cell line was used to establish a model that simulated the overexpression of COX-2/PGE2 and MMP-9 proteins induced by TNF-α, to examine the anti-inflammatory properties of Lj extracts. The re-sults indicated that Lj-EtOH exhibits significant inhibitory effects on COX-2/PEG2 and MMP-9 ac-tivity, attenuates cell migration, and provides protection against TNF-α-induced gastric inflam-mation. The protective effects of Lj-EtOH are associated with the modulation of COX-2/PEG2 and MMP-9 through activation of TNFR–ERK 1/2 signaling pathways as well as the involvement of c-Fos and nuclear factor kappa B (NF-κB) signaling pathways. Based on our findings, Lj-EtOH ex-hibits a preventive effect on human gastric epithelial cells. Consequently, it may represent a novel treatment for the management of gastric inflammation.

Nano- and microparticles are increasingly widely used in biomedical research and applications, particularly as specific labels and targeted delivery vehicles. Silica has long been considered the best material for such vehicles, but it has some disadvantages limiting its potential, such as the proneness of silica-based carriers to spontaneous drug release. Calcium carbonate (CaCO3) is an emerging alternative, being easily available, cost-effective, biocompatible material with high porosity and surface reactivity, which makes it an attractive choice for targeted drug delivery. CaCO3 particles are used in this field in the form of either bare CaCO3 microbeads or core/shell microparticles representing polymer-coated CaCO3 cores. In addition, they serve as removable templates for obtaining hollow polymer microcapsules. Each of these types of particles has its specific advantages in terms of biomedical applications. CaCO3 microbeads are primarily used due to their capacity for carrying pharmaceutics, whereas core/shell systems ensure better protection of the drug-loaded core from the environment. Hollow polymer capsules are particularly attractive because they can encapsulate large amounts of pharmaceutical agents and can be so designed as to release their contents in the target site in response to specific stimuli. This review focuses first on the chemistry of the CaCO3 cores, core/shell microbeads, and polymer microcapsules. Then, systems using these structures for the delivery of therapeutic agents, including drugs, proteins, and DNA, are outlined. The results of systematic analysis of available data are presented. They show that the encapsulation of various therapeutic agents in CaCO3-based microbeads or polymer microcapsules is a promising technique of drug delivery, especially in cancer therapy, enhancing drug bioavailability and specific targeting of cancer cells while reducing side effects. To date, research in CaCO3-based microparticles and polymer microcapsules assembled on CaCO3 templates has mainly dealt with their properties in vitro, whereas their in vivo behavior still remains poorly studied. However, an enormous potential of these highly biocompatible carriers for in vivo applications is undoubted. This last issue is addressed in depth in the Conclusion and Outlook sections of the review.

Analysing the human body by direct observation can lead to misinterpretation of underlying trends, whereas in vitro organ models facilitate their understanding. Likewise, in vitro organ models serve as valuable tools for assessing the toxicity of compounds. However, none of the existing models had the features we considered critical for toxicity assessment, so we developed an in vitro liver model for toxicity assessment. We used four different types of primary liver cells: Hepatic sinusoidal endothelial cells, hepatic stellate cells, Kupffer cells and hepatocytes. We cultured them in different combinations of composition and volume of cell medium, hepatocyte proportion of total cells, and addition of extracellular matrix. We added rifampicin, ibuprofen and 5-fluorouracil to this model and observed the microanatomy and physiology changes for a week with preclinical and clinical instruments. Among the different model configurations, we selected the feature combination of the in vitro model that had similar biomarker values to those measured by the clinical instruments used in clinical diagnostics. When we exposed the selected model configuration to rifampicin, ibuprofen and 5-fluorouracil, the viability of Kupffer cells and liver sinusoidal endothelial cells was significantly lower than in the untreated samples. In contrast, we observed negligible viability of hepatocytes compared to the untreated samples. We have built an in vitro liver model that resembles the liver microenvironment and we have analysed it with clinical instrumentation to facilitate the data translation. In this sense, we have established that Kupffer and LSEC cells are suitable candidates for the search for clinical diagnostic markers of liver function.

Modern organic synthesis is majorly focused on developing environmentally benign synthetic protocols by employing green chemistry principles. Accordingly, in our recent research work, we herein report the use of modified supramolecular host cyclodextrin as an effective solid based green catalyst for accessing structurally diverse and medicinally relevant pyrimidone architectures. The catalyst and the synthesized compounds 4 (a-r) were characterized using FT-IR, NMR and GC-Mass spectroscopy. Major highlights of the reported work include: atom economical process, extremely milder reaction conditions, operational simplicity, high isolated yields, and excellent catalyst turnover number. The molecular docking studies suggest that the compound 4n has the hydrogen bonding, hydrophobic and π-pair interactions with the active site of active sites of CXT M 15 receptor.

Post-operative chemotherapy is still required for the treatment of glioblastoma (GBM), and nanocarrier-based drug delivery has been identified as one of the most effective methods. However, the blood-brain barrier (BBB) and non-specific delivery to non-tumor tissues can significantly limit drug accumulation in tumor tissues and cause damage to nearby normal tissues. This study describes a targeted cancer therapy approach that uses AS1411 aptamer-conjugated nanospheres, 100-300 nm in size, loaded with doxorubicin (Dox) to selectively identify tumor cells overexpressing nucleolin (NCL) proteins. The study demonstrates that the active target model, which employs aptamer-mediated drug delivery, is more effective than nonspecific enhanced permeability and maintenance (EPR)-mediated delivery and passive drug delivery in improving drug penetration and maintenance in tumor cells. Additionally, the study shows the potential for anticancer effects through 3D spheroidal and in vivo GBM xenograft models. The DNA-protein hybrid nanospheres utilized in this study offer numerous benefits, such as efficient synthesis, structural stability, high drug loading, dye labelling, biocompatibility, and biodegradability. When combined with nanospheres, the 1411 aptamer has been shown to be an effective drug delivery carrier for precisely targeting tumors. This combination has the potential to produce anti-tumor effects in active targeted therapy of GBM.

Stem cell-based regeneration strategies have shown therapeutic efficacy in various fields of regenerative medicine. These include bone healing after bone augmentation, often complicated by pain, that is managed by using non-steroidal anti-inflammatory drugs (NSAIDSs). Information is limited about how NSAIDSs affect the therapeutic potential of stem cells. Therefore, we investigated the effects of ibuprofen and diclofenac in low and high therapeutic doses on the properties of human mesenchymal stromal cells isolated from the dental pulp (DPSCs) and cultured in vitro. Ibuprofen and diclofenac significantly reduced the viability of DPSCs, while the expression of mesenchymal stem cell surface markers was unaffected. Both ibuprofen and diclofenac treatment significantly upregulated the expression of HGF, while the expression of VEGFA remained unchanged. Ibuprofen significantly altered the expression of several apoptosis-related genes, including upregulation of CASP9 and BCL2, with decreased CASP3 expression. BAK, CASP3, CASP9, and BCL2 expressions were significantly increased in the diclofenac-treated DPSCs, while no difference was demonstrated in BAX expression. Our results suggest that concomitant use of the NSAIDSs ibuprofen or diclofenac with stem cell therapy may negatively impact cell viability and alter the expression of apoptosis-related genes, which can affect the efficacy of stem cell therapy.