Emerging evidence suggests that the severe-acute-respiratory-syndrome-related coronavirus (SARS- CoV-2) infection and anti-SARS-CoV-2 vaccines may trigger autoimmune responses in genetically predisposed individuals. Idiopathic inflammatory myopathies (IIMs) are a group of diseases with a broad spectrum of clinical manifestations featured by the presence of myositis autoantibodies (MAs). The diagnosis of IIM is challenging due to the limitations of current classification criteria and diagnostic assays. We conducted a multicenter observational study, whose main goal was to describe the incidence of IIM following exposure to SARS-CoV-2 infection and/or its specific vaccination, and to compare the rates of both. A total of 788 patients belonging to 11 different Spanish referral centers were analyzed, with a cumulative count of 1,209 MAs measured by line blot immunoassays (LIA). The study identified distinct patterns in the frequency of aminoacyl-tRNA synthetase (ARS) antibodies compared to pre-pandemic periods. Notably, the most prevalent ARS antibody identified associated to IIM was anti-PL-7 (14.85%), whereas anti-Jo1, traditionally the most frequent antibody documented, had a frequency of 7.23% in our cohort. Anti- MDA5, the most commonly described antibody in the literature associated with the SARS-CoV-2 infection, was identified in 11.68% of our patients. Our cohort displayed positive antinuclear antibodies (ANA) result in 61% of patients, which suggests an underlying autoimmune background. The most prevalent final diagnoses were anti- synthetase syndrome (ASSD) or IIM-non-ASSD (21.31% of total cases) and other systemic autoimmune diseases (SAID) with 13.57% of cases. 91.13% of patients received at least one dose of a messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccine, with a median of three doses per patient. It is noteworthy that patients with prior SARS-CoV-2 infection or heterologous vaccination demonstrated a higher frequency of multiple autoantibody positivity (p<0.05), which could reflect different humoral and cellular immune signatures. This collaborative work enhances our understanding of IIM and may facilitate the optimization of care through the implementation of standardized approaches. Further investigation is required to fully characterize the autoimmune risks and phenotypes following a diagnosis of SARS-CoV-2 infection or vaccination.Emerging evidence suggests that the severe-acute-respiratory-syndrome-related coronavirus (SARS- CoV-2) infection and anti-SARS-CoV-2 vaccines may trigger autoimmune responses in genetically predisposed individuals. Idiopathic inflammatory myopathies (IIMs) are a group of diseases with a broad spectrum of clinical manifestations featured by the presence of myositis autoantibodies (MAs). The diagnosis of IIM is challenging due to the limitations of current classification criteria and diagnostic assays. We conducted a multicenter observational study, whose main goal was to describe the incidence of IIM following exposure to SARS-CoV-2 infection and/or its specific vaccination, and to compare the rates of both. A total of 788 patients belonging to 11 different Spanish referral centers were analyzed, with a cumulative count of 1,209 MAs measured by line blot immunoassays (LIA). The study identified distinct patterns in the frequency of aminoacyl-tRNA synthetase (ARS) antibodies compared to pre-pandemic periods. Notably, the most prevalent ARS antibody identified associated to IIM was anti-PL-7 (14.85%), whereas anti-Jo1, traditionally the most frequent antibody documented, had a frequency of 7.23% in our cohort. Anti- MDA5, the most commonly described antibody in the literature associated with the SARS-CoV-2 infection, was identified in 11.68% of our patients. Our cohort displayed positive antinuclear antibodies (ANA) result in 61% of patients, which suggests an underlying autoimmune background. The most prevalent final diagnoses were anti- synthetase syndrome (ASSD) or IIM-non-ASSD (21.31% of total cases) and other systemic autoimmune diseases (SAID) with 13.57% of cases. 91.13% of patients received at least one dose of a messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccine, with a median of three doses per patient. It is noteworthy that patients with prior SARS-CoV-2 infection or heterologous vaccination demonstrated a higher frequency of multiple autoantibody positivity (p<0.05), which could reflect different humoral and cellular immune signatures. This collaborative work enhances our understanding of IIM and may facilitate the optimization of care through the implementation of standardized approaches. Further investigation is required to fully characterize the autoimmune risks and phenotypes following a diagnosis of SARS-CoV-2 infection or vaccination.

A rare neurological condition known as Dyke-Davidoff-Masson syndrome (DDMS) is characterized by cerebral hemiatrophy, facial asymmetry, contralateral motor impairment, and seizures. Cerebral hypoplasia, ventriculomegaly, paranasal sinus hyper-pneumatization, and compensatory osseous expansion are classic imaging findings. The relationship between clinical and neuroimaging findings provides the basis for the diagnosis of DDMS. DDMS is treated with anticonvulsant medication and physical therapy. This is the case of a 26-year-old male, with a known case of cerebral palsy and on antiepileptics for 15 years, who presented with complaints of generalized weakness, vomiting, difficulty walking, recurrent convulsions, and a recent episode of generalized tonic-clonic seizures. Neuroimaging revealed findings significant of Dyke Davidoff Masson Syndrome. Understanding its imaging and clinical characteristics facilitates prompt and precise diagnosis, permitting appropriate management.

The objective of this review is to do an overview about the current knowledge of Anti Iglon5 Syndrome, a disease that was first described in 2014. The IgLON proteins are a family of cell adhesion molecules and the presence of antibodies against IgLON5 are crucial for diagnosis of Anti IgLON5 Syndrome. This syndrome has an expanded clinical spectrum that involves prominent sleep disorder, progressive bulbar dysfunction, gait instability with abnormal eye movements reminiscent and cognitive deterioration sometimes associated with chorea. The main neuropathological finding is the neuronal loss with hyperphosphorylated tau (p-Tau) protein accumulation at hypothalamus, brainstem tegmentum, hippocampus, periaqueductal gray matter, medulla oblongata and upper cervical cord. The exact pathogenesis is still unclear and involves a neurodegenerative process and autoimmune response. The early diagnosis is important to avoid unnecessary tests and prevent complications. Important resources for diagnosis are the antibody testing of serum and CSF for IgLON5-IgG. The mortality of anti IgLON5 syndrome is high and new studies published described a good response to immune therapy. However, the response to immune therapy depends of some clinical and analytical characteristic. In addition, future studies are needed to thoroughly study the aspects of pathogenesis and treatment of this important pathological syndrome.

Polycystic Ovarian Syndrome (PCOS) is a common endocrine condition that affects 8–13% of women of reproductive age and is one of the leading causes of anovulation and infertility. In Kazakhstan, the prevalence of this syndrome is particularly high compared to other countries and the global average. Currently, the diagnosis of polycystic ovarian syndrome is based on internationally established Rotterdam criteria, using hyperandrogenism, i.e. high testosterone levels, as a key parameter. These criteria are applied to diagnose PCOS in all female patients, although obese patients may have excess testosterone produced by adipose tissue. To avoid possible false PCOS diagnoses, an additional criterion could be considered to diagnose PCOS among obese women. Anti-Müllerian hormone (AMH) is promising as a more effective diagnostic criterion, since its level represents the state of the ovarian reserve and adipose tissue does not produce AMH. Therefore, the use of AMH instead of hyperandrogenism as a diagnostic criterion for PCOS among obese women might improve diagnostic precision and patient treatment. In this study, data on the levels of various hormonal indicators such as estrogen, progesterone, and others were analyzed for a large cohort of female patients with and without PCOS to explore possible correlations between these indicators, AMH, and testosterone. The findings suggest that the absence of a negative correlation between AMH and follicle-stimulating hormone (FSH), and a positive correlation of AMH with testosterone could support the use of AMH as a reliable additional criterion for PCOS diagnosis among obese women.

Nitrogen (N) is an important mineral nutrient for plant growth, as well as a limiting factor for crop yield, and how to improve the utilization efficiency of N fertilizer by plants is currently a research hotspot. This article uses bioinformatics methods to identify and analyze members of the glutamine synthetase (GS) and glutamate synthase (GOGAT) gene families in pecan. A total of 6 GS genes and 4 GOGAT genes were identified, and their physicochemical properties, gene structures, and homologous evolutionary relationships were analyzed. Analysis of tissue-specific expression of GS and GOGAT genes based on transcriptome data from pecan. The enzyme activities of GS and GOGAT and the gene expression were quantitatively analyzed under different N form ratios in pecan. According to the results, the promoter cis-acting elements of GS and GOGAT genes can be roughly divided into three types: light-responsive elements, hormone-responsive elements, and stress-responsive elements. The results of homologous evolution showed that there was no tandem duplication event for the two gene families, and GS and GOGAT have undergone purification during the evolutionary process. CiGS2s and CiFd-GOGATs were expressed mainly in leaves, and CiNADH-GOGATs were expressed mainly in fruits. The qPCR analysis results showed that T4 treatment significantly increased the expression levels of CiGS and CiGOGAT genes in the leaves. The enzyme activities of GS and GOGAT in pecan were significantly increased under T3, T4, and T5 treatments. In summary, a higher proportion of ammonium nitrogen (NH4+) in the nutrient solution was profit to pecan NH4+ assimilation. This study determined the appropriate nitrogen ratio for pecan, promoting a theoretical basis for reducing environmental pollution caused by nitrogen fertilizer and improving the nitrogen utilization efficiency of pecan. In summary, both CiGSs and CiGOGATs exhibit tissue specificity, and an ammonium-nitrate mixture with a higher proportion of NH4+ is more favorable for NH4+ assimilation in pecan. This study provides a reference basis for further understanding the functions of CiGSs and CiGOGATs in pecan, and offers a theoretical foundation for improving N use efficiency in pecan.

Aminoacyl-tRNA synthetases (ARSs) are essential enzymes for translating amino acids for protein synthesis. Their function in pathogen-derived infectious diseases has been well established, which has led to development of small molecule therapeutics. The applicability of ARS inhibitors for other human diseases such as fibrosis has recently been explored in the clinical setting. There are active studies to find small molecule therapeutics for cancers. Studies on central nervous system (CNS) disorders are burgeoning as well. In this regard, we present a concise analysis of the recent development of ARS inhibitors based on small molecules from the discovery research stage to clinical studies as well as a recent patent analysis from the medicinal chemistry point of view.

Aspergillus montevidensis is an important domesticated fungus that has been applied to produce many traditional fermented foods under high osmotic conditions. However, the detailed mechanisms of tolerance to osmotic stress remain largely unknown. Here, we construct a target-deleted strain (ΔLeuRS) of A. montevidensis and found that the ΔLeuRS mutants grew slowly and suppressed the development of the cleistothecium compared to the wide-type strains (WT) under salt-stressed conditions. Furthermore, differentially expressed genes (P<0.0001) governed by LeuRS were involved in salt tolerance, ABC transporter, amino acid metabolism, sugar metabolism, and reproduction process. The ΔLeuRS strains compared to WT strains under short- and long-term salinity stress especially altered accumulation levels of metabolites, such as amino acids and derivatives, carbohydrates, organic acids, and fatty acids. The study provides new insights into the underlying mechanisms of salinity tolerance and lays a foundation for favor improvement of foods fermented with A. montevidensis.

The ultimate goal of our review is to draw clinician’s attention, especially of those who are managing pediatric patients with permanent, long-standing, ventriculoperitoneal or, less commonly, ventriculo-atrial shunts. This specific subgroup of patients may eventually suffer from severe, intractable headaches which may negatively impair their quality of daily living. In the absence of any other clinical condition that could be attributed as the cause of the headache, shunt overdrainage should not be overlooked but, on the contrary, should be seriously taken into consideration in the therapeutic armamentarium of such cases, that are difficult to be handled.

Purpose: To elucidate the mechanism of CXCR4/EAAT1/GS pathway in CXCL12 regulating invasion and migration in malignant pleural mesothelioma (MPM). Methods: Immunohistochemistry for CXCL12, CXCR4, EAAT1 and GS stainings and correlation analysis between them were conducted in MPM and normal tissues. Western blot and real-time PCR were performed to examine the CXCR4, EAAT1 and GS expression in H2052 cells. Wound healing and transwell assay were applied to determine the cell migration and invasion. MTT was utilized to assess cell viability. Results: CXCL12, CXCR4, EAAT1 and GS were highly expressed in MPM tissues and correlated with each other. CXCL12 upregulated both in protein and mRNA levels of CXCR4, EAAT1 and GS in H2052 cells. The EAAT1 and GS expression upregulated or not by CXCL12 were decreased by CXCR4 and EAAT1 knockdown. CXCR4 antagonist AMD3100 and EAAT1 antagonist TFB-TBOA also resulted in the same effects as CXCR4 and EAAT1 knockdown, respectively. CXCL12 promoted cell invasion and migration and increased the Matrix metalloproteinase 9 (MMP9) mRNA level. CXCR4 and EAAT1 knockdown suppressed all these functions. Furthermore, CXCL12 promoted H2052 cells growth in nude mice, both AMD3100 and TFB-TBOA inhibited this promotion. Conclusions: CXCL12 regulated the invasion and migration through CXCR4/EAAT1/GS pathway in H2052 cells.

Herbal cosmetics are cosmetics derived from plants. One example is bakuchiol. Bakuchiol is a meroterpene phenol from the seeds of the Psoralea corylifolia plant. Bakuchiol can be derived from Psoralea grandulosa, Pimelea drupaceae, Ulmus davidiana, Otholobium pubescens, and Piper longum. Bakuchiol has antioxidant, anti-inflammatory, and anti-aging activities such as retinol. Bakuchiol will replace retinol with much better safety. Bakuchiol and retinoids share similar cellular pathways, such as the regulation of retinoic acid, the expression of collagen, and extracellular matrix synthesis enzymes. Bakuchiol has many benefits for the skin, so cosmetics and skin therapy can use bakuchiol. This review aims to provide information about the activity of bakuchiol, which has benefits for facial skin, so that this review can be a reference in making cosmetics containing bakuchiol. Bakuchiol has many benefits for skincare such as anti-aging, anti-hyperpigmentation, anti-oxidant, anti-inflammatory, anti-acne, and anti-melanogenesis. Products containing bakuchiol on the market are cleansers, serum, nanoemulsion, and cream.

Objectives: Studies on the association between non-steroidal anti-inflammatory drugs (NSAIDs) and major adverse cardiovascular events (MACE) in the Arabian Gulf are scarce. The aim of this study was to evaluate the association between NSAIDs use and MACE in acute coronary syndrome (ACS) patients in the Arabian Gulf region. Methods: Data was analyzed from 3,007 consecutive patients diagnosed with ACS admitted to 29 hospitals in four Arabian Gulf countries from January 2012 to January 2013 as well as being on prior NSAIDs use during the index admission. MACE included stroke/transient ischemic attacks (TIAs), myocardial infarction (MI), all-cause mortality and readmissions for cardiac reasons. Results: The overall mean age of the cohort was 62 ± 12 years and 9.6% (n = 290) of the patients were on prior NSAID use during the index admission. At 12-months follow-up, after adjusting for confounding factors, those on NSAIDs were significantly more likely to have had MACE (adjusted OR (aOR), 1.89; 95% confidence interval (CI): 1.44-2.48; p < 0.001). Specifically, the higher event rates observed were stroke/TIA (aOR, 2.50; 95% CI: 1.51-4.14; p < 0.001) and readmissions for cardiac reasons (aOR, 2.09; 95% CI: 1.59-2.74; p < 0.001) but not MI (aOR, 1.26; 95% CI: 0.80-1.99; p = 0.320) and all-cause mortality (aOR, 0.79; 95% CI: 0.46-1.34; p = 0.383). Conclusions: NSAIDs use was associated with significant stroke/TIA events as well as readmissions for cardiac reasons. However, NSAIDs were not associated with increased MI or all-cause mortality rates in ACS patients in the Arabian Gulf.

Decidualization of the uterine endometrium is a critical process for embryo implantation in mammals, primarily occurring on gestational day 8 in pregnant mice. However, the interplay between the maternal gut microbiome, metabolism, and the uterus at this specific time point remains poorly understood. This study employed a multi-omics approach to investigate the metabolic, gut microbiome, and transcriptomic changes associated with early pregnancy (gestational day 8 (E8)) in mice. Serum metabolomics revealed a distinct metabolic profile in E8 compared to controls, with differential metabolites primarily enriched in amino acid metabolism pathways. Gut microbial composition showed that E8 mice exhibited higher alpha-diversity and a significant shift of beta-diversity. Specifically, the E8 group displayed a decrease in pathogenic Proteobacteria and an increase in beneficial Bacteroidetes and S24-7 taxa. Transcriptomics identified myriads of distinct gene between E8 and control mice. The differentially expressed genes were enriched in pathways involved in Alanine, Aspartate and Glutamate metabolism, PI3K-Akt signaling, and PPAR signaling pathway. Integrative analysis of the multi-omics data uncovered potential mechanistic relationships among the differential metabolites, gut microbiota, and uterine gene expression changes. Notably, the gene Asns showed strong correlations with specific gut S24-7 and metabolite L-Aspartatic acid, suggesting its potential role in mediating the crosstalk between the maternal environment and embryo development during early pregnancy. These findings provide valuable insights into the complex interplay between the maternal metabolome, gut microbiome, and uterine transcriptome in the context of early pregnancy, which may contribute to our understanding of the underlying mechanisms of embryo implantation and development.

Ophelia syndrome is characterized by the coincidence of severe neuropsychiatric symptoms, classical Hodgkin lymphoma, and the presence of antibodies to the metabotropic glutamate 5 receptor (mGluR5). Little is known about the pathogenetic link between these symptoms and the role that anti-mGluR5-antibodies play. We investigated lymphoma tissue from patients with Ophelia syndrome and with isolated classical Hodgkin lymphoma by quantitative immunocytochemistry for mGluR5-expression. Further, we studied the L-1236, L-428, L-540, SUP-HD1, KM-H2, and HDLM-2 classical Hodgkin lymphoma cell lines by FACS and Western blot for mGluR5-expression, and by transcriptome analysis. mGluR5 surface expression differed significantly in terms of receptor density, distribution pattern, and percentage of positive cells. Highest expression levels were found in the L-1236 line. RNA-sequencing revealed more than 800 genes that were higher expressed in the L-1236 line in comparison to the other classical Hodgkin lymphoma cell lines. High mGluR5-expression was associated with upregulation of PI3K/AKT and MAPK pathways and of downstream targets (e.g. EGR1) known to be involved in classical Hodgkin lymphoma progression. Finally, mGluR5 expression was increased in the classical Hodgkin lymphoma-tissue of our Ophelia syndrome patient in contrast to five classical Hodgkin lymphoma-patients without autoimmune encephalitis. Given the association of encephalitis and classical Hodgkin lymphoma in Ophelia syndrome, it is possible that mGluR5-expression on classical Hodgkin lymphoma cells not only drives tumor progression but also triggers anti-mGluR5 encephalitis even before classical Hodgkin lymphoma becomes manifest.

Premenstrual syndrome is characterized by pain and symptoms affecting the women´s quality of life. We aimed to evaluate the safety and effectiveness of an oral fixed dose combination containing naproxen 220 mg + paracetamol 300 mg + pamabrom 25 mg tablet (Analgen Fem®) during the routine clinical practice. A prospective, open-label, multicenter, observational post-marketing study was conducted from December 2017 to December 2019 including 270 women older than 18 years. Primary endpoint was the proportion of adverse events, meanwhile the pain intensity, premenstrual syndrome symptoms, and patient proportion with a pain score reduction by at least 50% were secondary endpoints. The mean age of population was 28.9 ± 8.8 years. Among the 270 women, 8 (3%) experienced 10 adverse events. These were headache (5/8), gastritis (2/8) dyspepsia (1/8), diarrhea (1/8) and nausea (1/8). The investigator discontinued the study medication in 3/8 patients because of adverse events. The median of differences between the pain intensity at baseline and at last observation (-4.5, 95%CI; -5, -4) demonstrated that naproxen 220 mg + paracetamol 300 mg + pamabrom 25 mg fixed dose combination reduced pain intensity (p<0.001). In addition, the proportion of patients with pain reduction by at least 50% at the end of the treatment was 70.7%. The study demonstrated that this drug represents a safe and tolerated treatment, reducing pain intensity and premenstrual symptoms.

Objectives: This study was undertaken to reveal therapeutic effects and the preliminary mechanism of Chinese medicine formula Qianlie Tongli decoction (QTD) in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Methods: A total of 50 male C57BL/6 mice were randomly divided into five groups. All groups except the control group were injected subcutaneously T2 peptide emulsion, which induced the CP/CPPS model. After the induction of CP/CPPS, the model group was given 0.9% NaCl by oral gavage while low-dose, medium-dose, and high-dose groups were treated with Chinese medicine formula. Micturition habits and pain behavior of mice were analyzed for each group. Hematoxylin and eosin staining were used to investigate prostate inflammation. The serum level of tumor necrosis factor-α (TNF-α) was measured by enzyme-linked immunosorbent assay (ELISA) kit. Key findings: Chinese medicine formula significantly reduced the number of urine spots and improved pain response frequency in the medium-dose and high-dose group. The high-dose group showed reduced considerably inflammatory lesion and inflammatory cell infiltration than the low-dose and medium-dose groups. Serum levels of TNF-α in the high-dose group were significantly reduced compared with the model group. Conclusions: The results demonstrated the therapeutic effects of Qianlie Tongli decoction in CP/CPPS mice by analyzing clinically relevant symptoms (urinary tract system, pelvic pain, and prostate inflammation), and preliminary explored the inflammatory-related treatment mechanisms by measuring TNF-α.

Low nasal nitric oxide (nNO) is a typical feature in Primary Ciliary Dyskinesia (PCD). nNO is part of the PCD diagnostic algorithm due to its discriminative power against other lung diseases such cystic fibrosis (CF). However, the underlying pathomechanisms are elusive. To better understand NO dysregulation in PCD, the L-arginine/NO (Arg/NO) pathway in patients with PCD (pwPCD) and CF (pwCF) and in healthy control (HC) subjects was investigated. In a prospective, controlled study, we measured in 24 pwPCD, 25 age-matched pwCF, and 14 HC the concentrations of the NO precursors Arg and homoarginine (hArg), the arginase metabolite ornithine (Orn), the NO inhibitor asymmetric dimethylarginine (ADMA), and the major NO metabolites (nitrate, nitrite) in sputum, plasma and urine by validated methods. In comparison to HC, the sputum contents (in µmol/mg) of L-Arg (PCD 18.43 vs. CF 329.46 vs. HC 9.86, p &lt; 0.001) and of ADMA (PCD 0.055 vs. CF 0.015 vs. HC 0.010, p &lt; 0.001) were higher. In contrast, the sputum contents (in µmol/mg) of nitrate and nitrite were lower in PCD compared to HC (nitrite 4.54 vs. 9.26, p = 0.023; nitrate 12.86 vs. 40.33, p = 0.008), but higher in CF (nitrite 16.28, p &lt;0.001; nitrate 56.83, p = 0.002). The metabolite concentrations in urine and plasma were similar in all groups. The results of our study indicate that PCD, unlike CF, is associated with impaired NO synthesis in the lung, presumably due to mechano-chemical uncoupling.

Coordination of cellular biological processes is regulated in part via metabolic enzymes acting to match cellular metabolism to current conditions. The acetate activating enzyme, acyl-coenzyme A synthetase short-chain family member 2 (Acss2) has long been considered to have a predominantly lipogenic function. More recent evidence suggests that this enzyme has regulatory functions in addition to its role in providing acetyl-CoA for lipid synthesis. We used Acss2 knockout mice (Acss2-/-) to further investigate the roles this enzyme plays in three physiologically distinct organ systems that make extensive use of lipid synthesis and storage including the liver, brain and adipose tissue. We examined the resulting transcriptomic changes resulting from Acss2 deletion and assessed these changes in relation to fatty acid constitution. We find that loss of Acss2 leads to dysregulation of numerous canonical signaling pathways, upstream transcriptional regulatory molecules, cellular processes, and biological functions, which were distinct in the liver, brain and mesenteric adipose tissues. The detected organ-specific transcriptional regulatory patterns reflect the complementary functional roles of these organ systems within the context of systemic physiology. While alterations in transcriptional states were evident, the loss of Acss2 resulted in few changes in fatty acid constitution in all three organ systems. Overall, we demonstrate Acss2 loss institutes organ-specific transcriptional regulatory patterns reflecting the complementary functional roles of these organ systems. Collectively, these findings provide further confirmation that Acss2 regulates key transcription factors and pathways under well-fed, non-stressed conditions, and acts as a transcriptional regulatory enzyme.

Eurotium rubrum is a halophilic marine ascomycete, which can bear the hypersalinities of the Red Sea and proliferate, while most living entities cannot bear this condition. Recently, a 26.2 Mb assembled genome of this fungus had become available. Marine fungi are fascinating organisms capable of harboring several biosynthetic gene clusters (BGCs), which enables them to produce several natural compounds with antibiotic and anticancerous properties. Understanding the BGCs are critically important for the development of biotechnological applications and the discovery of future drugs. There is no knowledge available on the BGCs of this halophilic marine ascomycete. Herein, we set out to explore and characterize BGCs and the corresponding genes from E. rubrum using bioinformatic methods. We deciphered 36 BGCs in the genome of E. rubrum. These 36 BGCs can be grouped into four non-ribosomal peptide synthetase (NRPS) clusters, eight NRPS-like (NRPSL) BGCs, eight type I polyketide synthase (T1PKS), 11 terpene BGCs including one β-lactone cluster, four hybrid BGCs, and two siderophore BGCs. This study is an example of marine genomics application into potential future drug-like compound discovery.

Single molecule de novo protein sequencing based on the 'superspecificity' of amino-acyl tRNA synthetases (aaRS) is proposed. An unfolded protein molecule is threaded through a nanopore in an electrolytic cell (e-cell) to expose the terminal residue in the e-cell's trans chamber. After the residue is cleaved with an exopeptidase, a set of tRNAs, their aaRSs, and ATP are added to trans. An aaRS charges a cognate tRNA molecule with the residue. The charged tRNA (along with the other reactants) is transferred to an extended e-cell with N (20 ≤ N ≤ 61) pores in N individual cis chambers and a single trans chamber. Each pore holds an RNA molecule ending in a unique codon that is exposed in trans. The charged tRNA's anticodon base-pairs with the terminal codon of an RNA. If tRNAs and residues are fluorescently tagged with two different colors, the residue can be identified from the observed position of the resulting color pair. As charging is 'superspecific' identification is unambiguous. The protein molecule in the first e-cell is advanced by one residue and the process repeated. In this approach there is no need for precise pore current or optical intensity measurements. Potential implementation issues are discussed. Other possibilities, including one in which the terminal residue is cleaved after charging, are also examined.

The growing worldwide cancer incidence, coupled to the increasing occurrence of multidrug cancer resistance, requires a continuous effort towards the identification of new leads for cancer management. In this work, two C-scorpionate complexes, [FeCl2(κ3-Tpm)] (1) and [Co(κ3-TpmOH)2] (2), (Tpm = hydrotris(pyrazol-1-yl)methane and TpmOH = 2,2,2-tris(pyrazol-1-yl)ethanol), are studied as potential scaffolds for future anti-cancer drug development. Their cytotoxicity and cell migration inhibitory activity are analyzed, and an untargeted metabolomics approach is em-ployed to elucidate the biological processes significantly affected by these two complexes, using two tumoral cell lines (B16 and HCT116) and a non-tumoral cell line (HaCaT). While [FeCl2(κ3-Tpm)] did not display a significant cytotoxicity, [Co(κ3-TpmOH)2] was particularly cy-totoxic against the B16 cell line. While [Co(κ3-TpmOH)2] significantly inhibited cell migration in all tested cell lines, [FeCl2(κ3-Tpm)] displayed a mixed activity. From a metabolomics perspective, exposure to [FeCl2(κ3-Tpm)] is associated with changes in various metabolic pathways involving tyrosine, where iron-dependent enzymes are particularly relevant. On the other hand, [Co(κ3-TpmOH)2] is associated with dysregulation of cell adhesion and membrane structural pathways, suggesting its antiproliferative and anti-migration properties can be due to changes in the overall cellular adhesion mechanisms.

Encephalitis is a condition with a variety of etiologies, clinical presentations and degrees of severity. The causes of these disorders include both neuroinfections and autoimmune diseases in which host antibodies are pathologically directed against self antigens. In autoimmune encephalitis, autoantibodies are expressed in the central nervous system. The incidence of this disease is approximately 4% of all reported cases of encephalitis. Autoimmune encephalitis can be induced by antibodies against neuronal surface antigens such as N-methyl-D-aspartate-activated glutamate receptors (NMDAR), ⍺-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors (AMPAR) or gangliosides GQ1b, DPPX, CASPR2, LGI1, as well as by antibodies against neuronal intracellular antigens. The paper presents a number of both mental and neurological symptoms of autoimmune encephalitis. Moreover, the coexistence of psychoses, neoplastic diseases and the methods of diagnosing autoimmune encephalitis are discussed. Attention was also drawn to the fact that early diagnosis, as well as early initiation of targeted treatment, increases the chance of a successful course of the therapeutic process.

Work reviews the new isolated isolated cembranoid diterpene derivatives from species belonging to the family Alcyoniidae, which comprises the genera Sarcophyton, Sinularia, and Lobophytum as well as their biological properties, during 2016–2017. The compilation permitted to conclude that much more new cembranoid diterpenes were found in the soft corals of the genus Sarcophyton sp. (33 new compounds) than in those belonging to the genera Lobophytum (17) or Sinularia (8). Several methods have been used for identifying these new compounds, after extraction with organic solvents and fractionation. The fractions obtained, in some cases, were followed by TLC, and again subjected to chromatographic procedures, including semi-preparative HPLC. Beyond the chemical composition, the biological properties were also evaluated, namely anti-microbial against several Gram-positive and Gram-negative bacteria and fungi, anti-inflammatory and anti-tumoral against several types of cancer cells. Although the biological activities detected in almost all samples, they were not outstanding ones.

Glufosinate, a glutamine synthetase (GS) inhibitor, often provides variable weed control depending on environmental conditions such as light, temperature and humidity at the time of application. Midday applications normally provide improved efficacy compared to applications at dawn or dusk. We investigated the physiological, molecular, and biochemical basis for the time-of-day effect on glufosinate efficacy in Amaranthus palmeri. GS1 and GS2 gene expression and protein abundance were assessed in different parts (young leaves, old leaves, and roots) of plants incubated in the dark compared to those in the light. The turnover of GS total activity was also evaluated overtime following glufosinate treatment at midday compared to dusk application. The results suggest that GS in A. palmeri is less expressed and less abundant in the dark compared to in the light. Midday application of glufosinate under intense light conditions in the hours following application provide full control of A. palmeri plants. Consequently, these plants are unable to recover GS activity by de novo protein synthesis. Full activity of GS is required for complete inhibition by the irreversible inhibitor glufosinate. Therefore, glufosinate applications should always be performed in the middle of the day when sunlight is intense, to prevent weed escapes from the herbicide treatment.

Curcumin is the main secondary metabolites of Curcuma longa and other Curcuma spp, and has been reported to have some potential in preventing and treating some physiological disorders. This study investigated the effect curcumin in inhibiting high-fat diet and streptozotocin (STZ)-induced hyperglycemia and hyperlipidemia in rats. Twenty-six male Sprague-Dawley (SD) rats (170-190 g) were randomly divided into a standard food pellet diet group (Control group), a high-fat diet and streptozotocin group (HF+STZ group), and a high-fat diet combined with curcumin and STZ group (HF+ Cur +STZ group). Compared with the HF+STZ group, the HF+Cur+STZ group exhibited significantly reduced fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (AST) and aspartate transaminase (ALT) levels, and liver coefficients; in the livers of these rats, the expression of malondialdehyde (MDA) and Bax was downregulated, whereas that of superoxide dismutase (SOD) and Bcl-2 was upregulated. Moreover, the liver histology of these rats was improved and resembled that of the control rats. These results suggest that curcumin prevents high-fat diet and STZ-induced hyperglycemia and hyperlipidemia, mainly via anti-oxidant and anti-apoptotic mechanisms in the liver.

This retrospective study assesses the efficacy and tolerability of anti-CGRP therapy in adolescents and young adults (ages 12-21) with migraines and chronic daily headaches unresponsive to standard treatments. Migraines severely affect school performance, self-esteem, psychological well-being, and cognitive health in this demographic, who are also sensitive to the side effects of conventional medications often prescribed off-label and face high insurance denial rates. Medication overuse, including analgesics, triptans, and NSAIDs, is prevalent due to treatment failures. Elevated plasma CGRP levels during migraines suggest that anti-CGRP therapies, which have shown success in adults, might benefit this age group. Over three years, patients at a specialized headache center were evaluated for the impact of anti-CGRP treatments, including monoclonal antibodies (erenumab, fremanezumab, galcanezumab) and small molecule CGRP receptor antagonists (ubrogepant, rimegepant, atogepant), either alone or in combination with OnabotulinumtoxinA. The study found significant improvements in migraine management, especially among older adolescents, with reduced rescue medication use and emergency visits. Longer treatment courses and combination therapy with traditional medications were more effective than monotherapy, reducing migraine intensity and frequency. Adverse effects were minimal, and no significant medication interactions were noted. Anti-CGRP therapy demonstrates substantial potential in improving outcomes for this age group with chronic and episodic migraines.

Inotodiol, a lanostane-type triterpenoid, and many phytochemicals from Chaga mushroom have been investigated for various allergic diseases. However, antiaging and anti-inflammatory activities of inotodiol under different types of oxidative stress and impact of inotodiol on collagen and hyaluronan synthesis are not sufficiently studied. Lanostane triterpenoids-rich concentrate, which contained 10% inotodiol as major (the inotodiol concentrate), was prepared from Chaga and compared with pure inotodiol in terms of anti-inflammatory activities on a human keratinocyte cell line, HaCaT cells, under various stimulation such as stimulation with ultraviolet (UV) B or tumor necrosis factor (TNF)-α. In stimulation with TNF-α, interleukin (IL)-1β, IL-6, and IL-8 genes were significantly repressed by 0.44~4.0 μg/mL of pure inotodiol. UVB irradiation induced overexpressions of pro-inflammatory cytokines, but those genes were significantly suppressed by pure inotodiol or inotodiol concentrate. Moreover, pure inotodiol/inotodiol concentrate could also modulate synthesis of collagen and hyaluronic acid by controlling COL1A2 and HAS2/3 expression, which implies a crucial role of pure inotodiol/inotodiol concentrate in prevention of skin aging. These results enlighten anti-inflammatory and anti-aging effect of pure inotodiol/inotodiol concentrate, and it is highly conceivable that pure inotodiol and inotodiol concentrate could be promising natural bioactive substances to be incorporated in therapeutic and beautifying applications.

Antibiotic failure is one of the most worrying health problems worldwide. Nowadays we are facing an international crisis where several issues are involved: new antibiotics are not being discovered any longer, resistance mechanisms become spread in nearly every clinical isolate of bacteria and the appearance of recurrent infections caused by persistent bacteria complicates the overcoming of infections. In this context, it has been explored new anti-infectious strategies against MDR and persistent bacteria as well as the rescue of FDA-approved compounds (drug repurposing). Among the highlighted new anti-infectious strategies we find anti-microbial peptides, anti-virulence compounds, phage therapy and new molecules. On the other hand, as drugs of repurposing that have been described, we have anti-inflammatory compounds, anti-psychotics, anti-helmintic drugs, anti-cancerous and statins.

Counterfeiting and theft have always been problems that incur high costs and results in considerable losses for the international markets. In this research paper, we will address the issue of counterfeiting while using RFID technology in retailer systems or other industries by presenting a new anti-counterfeiting and anti-theft system for the retailer market. This system will address the two above mentioned issues and provide a solution that can save the retailer systems millions of dollars yearly. This proposed system will achieve the objective of preventing or minimising the counterfeiting and theft of tagged products. At the same time, it will provide a strong indication for suspiciously sold or obtained items. Furthermore, we conducted a security analysis to prove the correctness of our protocol on the basis of the strand spaces.

A protocol was designed for plasmid curing using a novel counter-selectable marker, named pylSZK-pylT, in Escherichia coli. The pylSZK-pylT marker consists of the archaeal pyrrolysyl-tRNA synthetase (PylRS) and its cognate tRNA (tRNApyl) with modification, and incorporates an unnatural amino acid (Uaa), Nε-benzyloxycarbonyl-l-lysine (ZK), at a sense codon in ribosomally synthesized proteins, resulting in bacterial growth inhibition or killing. Plasmid curing is performed by exerting toxicity on pylSZK-pylT located on the target plasmid, and selecting only proliferative bacteria. All tested bacteria obtained using this protocol had lost the target plasmid (64/64), suggesting that plasmid curing was successful. Next, we attempted to exchange plasmids with the identical replication origin and an antibiotic resistance gene without plasmid curing using a modified protocol, assuming substitution of plasmids complementing genomic essential genes. All randomly selected bacteria after screening had only the substitute plasmid and no target plasmid (25/25), suggesting that plasmid exchange was also accomplished. Counter-selectable markers based on PylRS-tRNApyl, such as pylSZK-pylT, may be scalable in application due to their independence from the host genotype, applicability to a wide range of species, and high tunability due to the freedom of choice of target codons and Uaa’s to be incorporated.

Akt1 is a proto-oncogene that is over active in most cancers. Akt1 activation requires phosphorylation at Thr308; phosphorylation at Ser473 further enhances catalytic activity. Akt1 activity is also regulated via interactions between the kinase domain and the N-terminal auto-inhibitory pleckstrin homology (PH) domain. As it was previously difficult to produce Akt1 in site-specifically phosphorylated forms, the contribution of each activating phosphorylation site to auto-inhibition was unknown. Using a combination of genetic code expansion and in vivo enzymatic phosphorylation, we produced Akt1 variants containing programmed phosphorylation to probe the interplay between Akt1 phosphorylation status and the auto-inhibitory function of the PH domain. Deletion of the PH domain increased the enzyme activity for all three phosphorylated Akt1 variants. For the doubly phosphorylated enzyme, deletion of the PH domain relieved auto-inhibition by 295-fold. We next found that phosphorylation at Ser473 provided resistance to chemical inhibition by Akti-1/2 inhibitor VIII. The Akti-1/2 inhibitor was most effective against pAkt1T308 and showed 4-fold decreased potency with Akt1 variants phosphorylated at Ser473. The data highlight the need to design more potent Akt1 inhibitors that are effective against the doubly phosphorylated and most pathogenic form of Akt1.

Vaccine refusal and hesitancy pose a critical challenge to public health, leading to delays in vaccination and compromising herd immunity. To address this issue, we conducted a comprehensive observational study on the adult Spanish population in 2021. Through an online questionnaire, we explored the sociodemographic and sociocultural factors, beliefs, and opinions of those refusing or holding hesitancy about vaccines, and their vaccination behaviours by vaccine type and sex. Our findings revealed that vaccine refusal rates were relatively low (16.8%), and mainly associated with influenza vaccination (10.3%). Greater refusal of vaccination was observed in over 60 years old, in those expressing hesitancy due to vaccine components and opposing free and compulsory vaccination, unaware that vaccination protects the community and being against consuming cow’s milk and the use of infant formulas for breastfeeding. Vaccine hesitancy was greatest in individuals under 31 years old, women, parents of children under 15 years old, against compulsory vaccination, unaware that vaccination protects the community, with hesitancy due to vaccine costs, and in favour of alternative and complementary treatments. These insights underscore the need for strategies to improve education about vaccination and dispel misconceptions are crucial for effectively reducing vaccine refusal and hesitancy across the population.

Maslinic acid (MA) is a natural triterpene from Olea europaea whose pharmacological functions have been showed. The objective of this study was to examine MA effect on cell viability (by MTT assay), reactive oxygen species (ROS levels, by flow cytometry) and key anti-oxidant enzyme activities (by spectrophotometry) in murine skin melanoma (B16F10) cells compared to healthy cells (A10). MA induced cytotoxic effects in cancer cells (IC50 42 µM) whereas no effect was found in A10 cells treated with MA (up to 210 µM). In order to produce a stress situation in cells, 0.15 mM of H2O2 were added. Under stressful conditions, MA protected both cell lines against oxidative damage, decreasing intracellular ROS, being higher in B16F10 than in A10 cells. The treatment with H2O2 and without MA produced different responses in anti-oxidant enzymes activities depending on cell line. In A10 cells, all enzymes were up-regulated, but in B16F10 cells only superoxide dismutase, glutathione S-transferase and glutathione peroxidase increased their activities. MA restored the enzyme activities to similar levels than control group in both cell lines, highlighting that in A10 cells the highest MA doses induced values lower than control. Overall, these findings demonstrate the great anti-oxidant capacity of MA.

The storage of biochemical information, which is a prerequisite for the development of the first cell, is an unsolved problem affecting all concepts of the origin of life. However, if the protected environment in the continental crust is taken into account, completely new possibilities emerge for identifying processes that may have been crucial for the formation of the first cell. Under this background, we can hypothesize that cellular life began, with a self-sustaining cycle of molecular reaction steps and information storage of peptide sequences in RNA in a crustal depth of approximately 1000 m. This cycle was made possible in an open system bound to gas-permeable tectonic fracture zones with a high proportion of CO₂ and/or N₂. It can be assumed that a large number of RNA-like molecular strands formed in the crustal environment, from which a special RNA was selected by flotation processes, which formed the basis of a proto-tRNA. The formation of peptides and vesicles in supercritical CO₂ and the chemical evolution of peptides have already been proven at conditions of the upper continental crust. The behavior of individual amino acids in connection with vesicle formation deserves special interest. Hydrophobic amino acids accumulate in the vesicle membrane, with their position in the membrane depending on the degree of hydrophobicity. Selection of a proto-tRNA with an acceptor arm ending with the bases CCA resulted in a distinctive property. The position of adenine at the tip of the acceptor arm permitted it to penetrate the membrane, allowing it to be linked to an amino acid at the 3'-OH position of the terminal ribose. The penetration depth was controlled by the hydrophobicity of the opposite anti-codon, with adenine always occupying the middle position for the hydrothermally formed hydrophobic amino acids. When the vesicle membrane was closely occupied by proto-tRNAs, the anti-codons acted as templates and stored the sequence of the peptides that form. In the cases of hydrophilic anti-codons, the acceptor arm does not reach far enough into the membrane. This allowed hydrophilic amino acids to be linked to 2´-OH.

Immune-mediated necrotizing myopathy (IMNM) is a rare and severe disease that corresponds to a specific entity of idiopathic inflammatory myopathy. Patients with IMNM suffer from proximal muscle weakness, and present high levels of creatine kinase and necrotic myofibers. Anti-Signal Recognition Particle (SRP) and anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase autoantibodies (HMGCR) have recently been identified in two thirds of patients with IMNM and are used as a hallmark of the disease. In this review, we provide a detailed description of these antibodies and the tests used to detect them in the serum of patients. Based on in vitro studies and mouse models of IMNM, we will discuss the role of autoantibodies in the pathogenesis of the disease. Finally, in the light of the latest knowledge, we will conclude with a review of recent therapeutic approaches.

Three new polyketides (penidihydrocitrinins A–C, 1–3) and 14 known compounds (4–17) were isolated from the deep-sea-derived Penicillium citrinum W17. Their structures were elucidated by comprehensive analyses of 1D and 2D NMR, HRESIMS, and ECD calculations. Compounds 1–17 were evaluated for their anti-inflammatory and anti-osteoporotic bioactivities. All isolates exhibited significant inhibitory effects on microglial activation in LPS-stimulated BV-2 cells in a dose-response manner. Notably, compound 14 displayed the strongest effect with the IC50 value of 4.7 µM. Moreover, compounds 6, 7, and 8 not only suppressed osteoclastogenesis, but also promoted osteoblast mineralization.

Green products have excellent potential for discovering and producing new medicinal products. In recent years, there is a growing interest towards the green synthesis of metal nanoparticles, particularly from plants sources. This eco-friendly approach was used in the recent research to biosynthesize zinc oxide nanoparticles (ZnO NPs) from Cissus antractica plant. The present study aims to examine the cell cytotoxicity, cell death, and pathways of apoptosis in lung cancer cells (A549) and inflammation properties treated with biosynthesized ZnO NPs. Additionally, synthe-sized ZnO nanoparticles were characterized using UV–vis spectroscopy, X-ray diffraction (XRD), Transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FT-IR), and Energy-dispersive X-ray spectroscopy (EDS). The XRD and TEM analyses exhibited 31 nm as the size of synthesized nanoparticles, the pure crystal form of ZnO NPs, and the shape of the NPs as nearly spherical and hexagonal quartzite. The MTT assay used for cytotoxicity evaluation de-picted the significant toxic effect of CA-ZnONPs against the A549 lung cancer cells at concentra-tions up to 20 µg/mL than non-cancerous cells. Furthermore, we observed an elevated ROS level in cancer cells. These NPs also demonstrated dose-dependent ability to suppress colony for-mation and cell migration, which increases their potential as a lung cancer treatment. Further-more, The NPs formulation's ability to induce apoptosis in cancer cells was further supported by Hoechst and propidium iodide dye. Further, CA ZnO NPs increased the gene expression of BAX, Cyto-c, Caspase 3 and 9, but decreased the expression of Bcl-2, indicating that the nanoformulation triggered mitochondrial-mediated apoptosis. Besides, this study showed that NPs suppressed in-flammatory responses by subsequently decreasing reactive oxygen species (ROS) generation, downregulating the expression of the pro-inflammatory cytokines TNF-α, iNOS, COX-2, IL-6, IL-8, and NO. Moreover, the study's findings imply that Cissus antractica are a potential source with biosynthesize nanoparticles that can might be further investigated for the progress of an-ti-inflammatory and anti-cancer drugs with further study.

Acemella oleracea is known as toothache plant belongs to the family of Asteraceae. It is treated as a medicinal remedy like tuberculosis, illness, cough, rheumatism, and illness. This study was concentrated on the antioxidant, cytotoxic, antimicrobial & thrombolytic activities of methanol extract of Acmella oleracea leaves using in vitro model. The antioxidant activity was estimated as trolox equivalent antioxidant capacity utilizing the DPPH and reducing power tests. The plant extract was tested for its cytotoxic action using a brine shrimp lethality bioassay, thrombolytic activity using clot disruption, and antibacterial activity using a disc diffusion assay technique against four distinct gram-positive and gram-negative bacteria. IC₅₀ value of standard ascorbic acid for DPPH was 7.8µg/ml and the IC50 of the methanol extract of Acmella oleracea leaves was 198.34µg/ml that was moderate effect at all compare with ascorbic acid. Thrombolytic assay of Streptokinase as a positive control showed 88.49% where the extract shows 18.69% lytic activity shows the assay. In this study, the sample of LC₅₀ results of cytotoxicity assay was 1.431 µg/mL which can be treated as less activity. Moreover, the extracts showed low to moderate antibacterial activity against both gram-negative and gram-positive bacterial stains (zone of inhibition-10-26 mm). Vibrio Mimicus bacteria stains exhibited the highest level of activity, with a range of 23 for the diameter of the growth inhibition zone. The current review shows leaf extracts of Acmella oleracea may be used as a source of antioxidant and thrombolytic activity, as well as a significant source of antibacterial and anticancer substances. Further research is required to evaluate in-vivo the pharmacological activity of Acmella oleracea leaves in order to identify the essential metabolites and potential mechanisms.

Methotrexate (MTX) is a potent drug for the treatment of various diseases globally amidst being a chemotherapeutic and immunosuppressant agent. However, hepatotoxicity induced by MTX could be life-threatening if left untreated. Folate supplementation is concurrently applied to reduce the adverse effects of MTX, albeit efficacy compromise. Therefore, there is the need to understand the process for the prevention and treatment strategies for MTX induced hepatotoxicity (MIH). In recent times, preliminary preclinical and clinical findings indicate the potential of natural phytobioactive compounds for MIH prevention and treatment. This mini review therefore summarizes proposed mechanisms of MIH and recent advances in the prevention and treatment prospects of natural phytobioactive compounds on MIH.

The use of plant extracts in the synthesis of metal nanoparticles is a very attractive approach in the field of green synthesis. To benefit from the potential synergy between the biological activities of the Moringa oleifera leaves extract and metallic bismuth, our study aimed at synthesizing bismuth nanoparticles using a hydroalcoholic extract of M. oleifera leaves as a means of green synthesis that yields nontoxic products and reduces the production of wasteful material. To this end, the M. oleifera leaves extract was treated with a bismuth nitrate pentahydrate solution. A color change from light brown to dark brown indicates the synthesis of bismuth nanoparticles. The total phenolic content in the M. oleifera leaves extract used was 23.0 ± 0.3 mg gallic acid equivalent/g of dried M. oleifera leaves powder. Antioxidant property of MO synthesised bismuth Nanoparticles was evaluated and in line with the extract used in the synthesis of NPs. The physical properties of the synthesized bismuth nanoparticles were characterized using UV-Vis spectrophotometer, FT-IR spectrometer, TEM, SEM, and XRD. The synthesized bismuth nanoparticles have a size in the range of 40.4-57.8 nm with amorphous morphology. Using DPPH and phosphomolybdate assays, our findings revealed that the M. oleifera leaves extract and the synthesized bismuth nanoparticles possess antioxidant properties. Using resazurin microtiter assay, we also demonstrate that the M. oleifera leaves extract and the synthesized bismuth nanoparticles exert potent anti-bacterial activity against Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus and Enterococcus faecalis, similarly to the inhibition exerted by Moringa extract, especially against Enterococcus faecalis (MIC values for the extract: 500, 250, 250, and 250 µg/mL; MIC values for the bismuth nanoparticles: 500, 500, 500, and 250 µg/mL, respectively). Similarly, the M. oleifera leaves extract and the synthesized bismuth nanoparticles display relatively stronger anti-fungal activity against Aspergillus niger, Aspergillus flavus, Candida albicans, and Candida glabrata (MIC values for the extract: 62.5, 62.5, 125, and 250 µg/mL; MIC values for the bismuth nanoparticles: 250, 250, 62.5, and 62.5 µg/mL, respectively). Thus, the hydroalcoholic extract of M. oleifera leaves was successfully used in the synthesis of bismuth nanoparticles, showing a positive antioxidant, anti-bacterial, and anti-fungal activity. Therefore, the synthesized bismuth nanoparticles can potentially be employed in the alleviation of symptoms associated with oxidative stress and in the topic treatment of Candida infections.

The synthesis of metal nanoparticles using plant extracts is a very promising method in green synthesis. The medicinal value of Moringa oleifera leaves and the anti-microbial activity of metallic copper were combined in the present study to synthesize copper nanoparticles having a desirable added-value inorganic material. The use of a hydroalcoholic extract of M. oleifera leaves for the green synthesis of copper nanoparticles is an attractive method as it leads to the production of harmless chemicals and reduces waste. The total phenolic content in the M. oleifera leaves extract was 23.0 ± 0.3 mg gallic acid equivalent/g of dried M. oleifera leaves powder. The M. oleifera leaves extract was treated with a copper sulphate solution. A color change from brown to black indicates the formation of copper nanoparticles. Characterization of the synthesized copper nanoparticles was performed using UV-Vis spectrophotometer, FT-IR spectrometer, TEM, SEM, and XRD. The synthesized copper nanoparticles have an amorphous nature and particle size of 35.8-49.2 nm. We demonstrate that the M. oleifera leaves extract and the synthesized copper nanoparticles display considerable antioxidant activity. Moreover, the M. oleifera leaves extract and the synthesized copper nanoparticles exert potent anti-bacterial activity against Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, and Enterococcus faecalis (MIC values for the extract: 500, 250, 250, and 250 μg/mL; MIC values for the cooper nanoparticles: 500, 500, 500, and 250 μg/mL, respectively). Similarly, the M. oleifera leaves extract and the synthesized copper nanoparticles exert relatively more potent anti-fungal activity against Aspergillus niger, Aspergillus flavus, Candida albicans, and Candida glabrata (MIC values for the extract: 62.5, 62.5, 125, and 250 μg/mL; MIC values for the cooper nanoparticles: 125, 125, 62.5, and 31.2 μg/mL, respectively). Our study reveals that the green synthesis of copper nanoparticles using a hydroalcoholic extract of M. oleifera leaves was successful. In addition, the synthesized copper nanoparticles can be potentially employed in the treatment of various microbial infections due to their potent antioxidant, anti-bacterial, and anti-fungal activities.

The anti-money laundering (AML) process has failed both in identifying suspicious cases in due time as in assisting the AML analysts in decision making. Starting from a new generic anti-fraud approach, this article presents the main aspects related to the development of a multi-agent system that goes beyond the capture of suspicious transactions, seeking to assist the human expert in the analysis of suspicious behaviour. First, a transactional behavioural profile of clients is obtained in a data mining process. A set of rules, obtained through data mining over a real database, in conjunction with specific rules based on legal aspects and in the expertise of the AML analysts make up the agents' knowledge base. The cases for which the system was unable to suggest a decision are flagged as requiring more detailed analysis. The system analysed 6 months of real transactions and indicated several suspicious profiles, a set of these suspects was investigated by the AML analysts who proved the suspicion of several cases, including some that had not been identified by the systems in execution.

Several vaccines against COVID -19 have been developed and licenced to enhance the immune response against SARS-CoV-2. Similarly, infection with SARS-CoV-2 before vaccination has been shown to provide significant protection against severe infection and hospitalisation. The aim of this study was to investigate the effect of three doses of Sinopharm vaccine and SARS-CoV-2 infection on the specific immune response in 103 volunteers, measuring neutralizing antibodies, anti-S1 IgG, anti-RBD IgM, anti-N IgM, anti-N IgG antibodies and interferon γ. Our results showed that the presence of cardiovascular diseases increased the level of anti-N-IgG antibodies, while endocrinological diseases decreased the level of neutralizing antibodies and anti-N-IgG antibodies, suggesting that these diseases alter the effect of vaccine immunity. In addition, there was a significant decrease in anti-S1 IgG levels 6 months and in anti-N IgG levels 18 months post-infection, while neutralizing antibody and interferon γ levels were constant at 3, 6 and 18 months post-infection. Therefore, our results confirm the importance of hybrid immunity as the strongest and most durable compared to exclusively natural or vaccine-induced immunity. Significant positive correlations were found between humoral and cellular immunity markers: neutralizing antibodies, anti-S1 IgG, anti-N IgG and interferon γ, indicating a unique coordinated response specific to COVID-19.

Across different cultures around the globe, human beings have historically depended largely on medicinal plants for managing diseases that have hitherto threatened their optimal health, survival, and longevity. Evidently, the health-derived benefits of medicinal plants can be strongly attributed to the presence of secondary metabolites, particularly polyphenols. The health-promoting effects of Sorghum bicolor supplement Jobelyn® (SBSJ) —a unique supplement derived from the leaf sheaths of a West African variety of Sorghum bicolor (L.) Moench—have also been ascribed to its high levels of polyphenols. This review seeks to gather and synthesize findings from various experimental and clinical studies on the health benefits of SBSJ in arthritis, cancer, chronic viral infections, stroke, anaemia, and aging. SBSJ has been reported to contain potent bioactive polyphenolic compounds with polyvalent biological activities, including antioxidant, anti-inflammatory, immunomodulatory, chemopreventive, and neuroprotective activities. Moreover, the probable benefits of SBSJ in chronic viral infections (e.g., HIV/AIDS and COVID-19) have been attributed to its potent anti-inflammatory and immunomodulatory activities. As this supplement is increasingly becoming one of the fastest-selling herbal medicines in Nigeria, there is a need for more robust studies (including clinical trials) in order to replicate and validate the prior insights gleaned from experimental studies.

Hydrogenated water has emerged as a novel approach in the field of health and wellness. It is be-lieved to have potent antioxidant properties that can neutralize harmful free radicals in the hu-man body. It has also been shown to be beneficial in mitigating oxidative stress-induced damage through its anti-inflammatory and anti-apoptotic pathways. We aim to conduct a systematic re-view to evaluate the potential benefits of hydrogenated water. The review protocol was uploaded on PROSPERO. After the initial search criteria, the articles were reviewed by two blinded inves-tigators, and a total of 25 articles were included in the systematic review. The potential benefits of hydrogenated water on various aspects of health, including exercise capacity, physical endurance, liver function, cardiovascular disease, mental health, COVID-19, oxidative stress, and anti-aging research, are a subject of growing interest and ongoing research. Although preliminary results in clinical trials and studies are encouraging, further research with larger sample sizes and rigor-ous methodologies is needed to substantiate these findings. Current research needs to fully ex-plain the mechanisms behind the potential benefits of hydrogenated water. Continued scientific exploration will provide valuable insights into the potential of hydrogenated water as an adjunc-tive therapeutic approach in the future.

A healthy cornea is a nonvascularized, transparent tissue. It is nourished by diffusion through the tear film, aqueous fluid and neurotrophins supplied by the corneal innervation. The cornea is devoid of both blood and lymphatic vessels, which makes it an immunologi-cally privileged tissue. Corneal neovascularization develops due to an imbalance between angiogenic and anti-angiogenic factors and can lead to a significant decrease in visual acui-ty. It may cause scarring, lipid keratopathy, and corneal edema. The resulting pathological vascularization of the cornea reduces its immune privilege and significantly worsens the prognosis after subsequent penetrating keratoplasty, increasing the risk of rejection of the transplanted flap. Neovascularization is favored by many disease processes, including auto-immune diseases, viral inflammations, mainly herpes and varicella-zoster, and blepharitis [1]. There are several options to treat corneal neovascularization, both pharmacological and surgical. Angiostatic treatment involves inhibiting the growth of new vessels by suppressing inflammatory responses. VEGF inhibitors, steroids, cyclosporine A, and amniotic membrane grafts secured to the cornea work this way. VEGF inhibitors are the agents with the direct and most potent angiostatic effect. Angioregressive treatment, on the other hand, results in the regression of already existing pathological vessels. This therapy is also based on VEGF inhibitors, which, however, have the most potent effect on newly formed and small vessels but are less effective in reducing large-caliber and mature vessels. A more effective method for such vessels is ablation, which involves surgical closure. The most commonly used an-gio-occlusive method is needle diathermy and argon or yellow laser therapy. In advanced corneal neovascularization, corneal transplant surgery may be necessary. It is best performed after pretreatment with anti-VEGF preparations, often continued after corneal transplanta-tion to reduce the risk of transplant rejection [2]. This paper discusses the pathogenesis of corneal neovascularization and the current and future trends in its treatment.

Quinoa, known as the "golden grain" for its high nutritional value, is a significant source of essential nutrients, including proteins, minerals, vitamins, polyphenols, phytosterols, and flavonoids. However, the biological functions of quinoa polysaccharides remain understudied. In this research, two crude quinoa polysaccharides extracts (Q-40 and Q-60) were obtained extracting by 40% and 60% alcohol. The purity of Q-40 and Q-60 was 58.29% and 62.15%, with protein contents of 8.27% and 9.60%, respectively. Monosaccharide analysis revealed that Q-40 contained glucose (Glc), galacturonic acid (GalA), and arabinose (Ara) in a molar ratio of 0.967:0.027:0.006. Q-60 was composed of xylose (xyl), arabinose (Ara), galactose, and galacturonic acid (GalA) with a molar ratio of 0.889:0.036:0.034:0.020. The average molecular weight of Q-40 ranged from 47484 to 626488 Da, while Q-60 showed a range of 10025 to 47990 Da. Rheological experiments showed that Q-40 exhibited higher viscosity, while Q-60 demonstrated more elastic properties. Remarkably, Q-60 showed potent antioxidant abilities, with scavenging rates of 98.49% for DPPH and 57.5% for ABTS. Antibacterial experiments using the microdilution method revealed that Q-40 inhibited the growth of Methicillin-resistant Staphylococcus aureus (MRSA) and E. coli, while Q-60 specifically inhibited MRSA. At lower concentrations, both polysaccharides inhibited MDA cell proliferation, but at higher concentrations, they promoted proliferation. Similar proliferation-promoting effects were observed in HepG2 cells. The research provides important information in application of quinoa in food and functional food industries.

Rhizophora mangle L. is a well-known medicinal plant found in mangroves worldwide used to treatment diabetes. This study evaluated the chemical composition of the acetonic extract from Rhizophora mangle barks (AERM), by HPLC-PDA and FIA-ESI-IT-MS/MS and the effects on high-fat diet induced obesity in mice and its mechanism of action by gene expression of inflammatory markers (Pparg, Ppara, Srebf1, Cd36, Tnf, Ccl2, Lep, Il10, Il6, Fasn, 18s). High-fat diet fed mice during 12 weeks was used as model of obesity and associated alterations. The results were very satisfactory, the extract, rich in polyphenolic compounds, flavonoids and phenolic acids, displayed intense antioxidant activity in vitro (608 µmol Trolox/g), and showed excellent activity against non-alcoholic fatty liver disease (NAFLD) and reverse insulin resistance in a model of diet-induced obesity. We can registered a modulatory effect of AERM in liver PPAR-γ mRNA expression associated to an important inhibition of CD36 mRNA expression suggesting that AERM induces the down regulation of CD36 mRNA via PPAR-gamma inhibition. These results support the traditional knowledge about the use of R. mangle for the treatment of type 2 diabetes and reveal the potential of AERM for the treatment of NAFLD and management of obesity and comorbidities.

Evolutionary, sequence and structural analyses of tRNA variable (V) loops provides a new understanding. Type I tRNA V loops have a primordial length of 5 nt, and type II tRNA V loops have a primordial length of 14 nt. Sequence-based alignments of type I and type II V loops gave deceptive results. Type II V loops are characterized by the trajectory of the V arm, the size and sequence of the loop and the first and last V loop nucleotides and their known contacts. Depending on the V arm trajectory, type II V stems and loops can be interaction sites for aminoacyl-tRNA synthetases. So, type II V arms for tRNALeu, tRNASer and tRNATyr (found in Bacteria) were coevolved and selected to distinguish determinants to support cognate tRNA charging. The alignment of type I and type II V loops was adjusted based on tRNA evolution. Results are consistent with Archaea being an older and simpler life form than Bacteria. TRNAome sequences were derived from radiation of an ordered tRNAPri (Pri for primordial) sequence comprised of known RNA repeats and inverted repeats. V loop and tRNA sequences, therefore, convey a history of the primary successful pathway in the origin of life.

Abstract: Oleuropein, the major compound of olive leaves, has been reported to exert numerous pharmacological properties, including anti-inflammatory, antidiabetic and anticancer. The purpose of this study is to evaluate, for the first time, the effect of oleuropein-rich leaf extracts (ORLE) in already-developed colon tumours colon tumours arising in an Apc (adenomatous polyposis coli) mutated PIRC rats (F344/NTac-Apcam1137). Here, we were able to investigate in parallel the anti-cancer effect of ORLE, both in vivo and in vitro, and its anti-inflammatory effect on macrophages, which represents a critical and abundant population in most solid tumours microenvironment. We found that in vivo ORLE treatment promoted apoptosis and attenuated iNOS activity both in colon tumours as in peritoneal macrophages of PIRC rats. We confirmed in vitro using primary RAW264.7 cells: ORLE reduced iNOS activity in parallel with COX-2 and pro-inflammatory cytokines, such as IL-1, IL-6 and TGF-. These findings suggest that ORLE possess a strong anti-inflammatory activity, which could be crucial for dampening the pro-tumourigenic activity elicited by a chronic inflammatory state generated by either tumour cells or tumour-associated macrophages.

Obesity, a chronic disorder of global prevalence, is associated with major health problems leading to mortality. Because of the presence of diverse types of bioactive molecules in plants, attention is being concentrated on the exploration of plant-based drugs to treat the disease. Inhibition of pancreatic lipase by the natural compounds in plants is one of the popular mechanisms for the management of obesity. The current study investigates the mechanism of the anti-obesity effect of the ethanol extract of seeds of Syzygium cumini seeds and roots of Dioscoria bulbifera in fatty diet-induced obese white albino Wister rats (age 8-9 weeks, average weight 110±8 gm). The total phenolic substances present in the ethanol extract of S. cumini was 103.79±3.45 and that of and D. bulbifera was 69.31 ± 2.99 mg GAE/g of dry extract. Correlating the phenolic contents, we also got the DPPH antioxidant activity of the plant extracts. The IC50 value of ethanol extract of S. cumini, D. bulbifera and standard Butyrated hydroxyl toluene (BHT) was found to be 93.03±6.23, 177.13±7.52, and 10.84±0.92 µg/mL, respectively. The body weight of fatty diet-induced rats was significantly reduced by S. cumini, D. bulbifera ethanol extract with a dose of 500 mg/kg bw during 12 weeks of treatment. The anti-obesity effect of the plant extracts is comparable to that of Orlistat with a dose of 10 mg/kg bw. The Orlistat at a concentration of 0.1 mg/ml could be able to inhibit 95.71% activity of Porcine pancreatic lipase while the ethanol extract of S. cumini, D. bulbifera with a concentration of 1.0 mg/ml showed 60.84% and 54.59% of anti-lipase activity. Moreover, the increased TG, LDL and cholesterol in HFD induced rats were significantly reduced by the plant extract as well as Orlistat. Molecular Docking study reveals that quercetin and isoquercetin bind with the rat lipase enzyme at the same site as that of orlistat with high affinity. Taken together, we can conclude that the ethanol extracts of causes anti-obesity effect by inhibiting the pancreatic lipase enzyme.

Our report presents the findings from a treatment program that involved plant-based diets (PBDs) and supplements for 1,750 elderly cardiology patients diagnosed with COVID-19 between April 2020 and June 2023. At the start of the program, there was no published data supporting the use of PBDs for COVID-19 patients. However, after 18 months, studies were released that indicated the effectiveness of PBDs in decreasing the incidence and severity of COVID-19. Our treatment protocol differed from these studies in several ways. We carefully controlled the quality, quantity, and processing method of the foods we provided, opting for raw instead of cooked vegetables. Additionally, we incorporated supplementation that complemented the nutrients lacking in a PBD and enhanced the anti-viral, anti-inflammatory, antioxidant, antithrombotic, and immunomodulatory properties of a PBD. Our patients recovered faster (12±1.4 days vs. 20.9±4.3 days), with lower severity (2% vs. 10-20%), hospitalizations (0 vs. 5-10%), and deaths (0 vs. 15-17%) compared to the general population. These favorable outcomes are particularly noteworthy given Indonesia's high COVID-19 morbidity and mortality rates, among the highest in Asia. The findings of this report provide valuable insights for practitioners in managing high-risk elderly COVID-19 patients, particularly in avoiding severity and mortality.

The goal of this study was to develop a rapid diagnostic kit for rheumatic disease and systemic lupus erythematosus (SLE) screening. A novel rapid vertical flow assay (VFA) was engineered and used to assay anti-nuclear (ANA) and anti-dsDNA (αDNA) autoantibodies from systemic lupus erythematosus (SLE) patients and healthy controls (HC). Observer scores and absolute signal intensities from the VFA were validated by ELISA. The rapid ten minute point of care VFA test engineered demonstrated a limit of detection of 0.5 IU/ml for ANA and αDNA autoantibodies in human plasma with inter-operator CV of 19% for ANA and 12% for αDNA. Storage stability was verified over a three-month period. When testing anti-dsDNA and ANA levels in 22 SLE and 18 HC serum samples, the duplex VFA revealed 95% sensitivity, 72% specificity and 84% accuracy in discriminating disease groups, comparable to the gold standard, ELISA. The rapid αDNA/ANA duplex VFA can potentially be used in primary care clinics for evaluating patients or at-risk subjects for rheumatic diseases and for planning follow-up testing. Given its low cost, ease and rapid turnaround, it can also be used to assess SLE prevalence estimates.

Neuromyelitis Optica Spectrum Disorder (NMOSD) is a rare immune-mediated relapsing-remitting disease of the central nervous system. The usage of rituximab, to prevent NMOSD relapses, is common in Sweden, but the knowledge on long-term efficacy and risk for severe infections are limited. We performed a retrospective cohort study with medical chart review of rituximab-treated NMOSD patients at the Karolinska University Hospital, Sweden, to assess the occurrence of relapses and severe infectious events (SIE). Furthermore, we collected data on CD19+ lymphocyte, and IgG levels during therapy. A total of 42 NMOSD patients; 24 with aquaporin -4 antibodies (AQP4+), eight with myelin oligodendrocyte glycoprotein antibodies (MOG+) and 10 with absence of antibodies (double-seronegative) were included. During a mean treatment time of 4.4 years, 37% AQP4+, 75% MOG+, and 60% double-seronegative patients experienced 1 relapse. SIEs were common with 46% of AQP4+, 25% of MOG+, and 40% of double-seronegative patients affected. Incomplete CD19+ lymphocyte suppression did not predict a relapse and there was no correlation between IgG levels and SIEs. In conclusion, our data demonstrated a high risk for both relapses and SIEs in rituximab-treated NMOSD patients highlighting the need for close clinical vigilance of disease activity and infections during treatment.

More than 15,000 prescriptions and over the counter drugs are available according to the US Food and Drug Administration website. Moreover, several herbal medicines and dietary supplements are readily available to add to the list of possible drugs, which can potentially cause adverse drug interactions. These are a pressing concern for all as they can interfere with many dental procedures. Additionally, the number of geriatric patients seen in routine dental practice has increased over time. This implies that there are more patients with multiple diseases and health conditions like hypertension, diabetes, problems associated with the cardiovascular, renal and gastrointestinal systems, arthritis, osteoporosis, etc. All these require patients to be on certain medications. Furthermore, advancement in the dental field has led to more complex dental procedures (implants, grafts) being carried out in a general dental practice. These advanced and slightly more invasive treatments require the use of certain drugs before, during and after the treatment like local anesthetics, vasoconstrictors, anxiolytics, analgesics and antibiotics. All of these can possibly interact with medications a patient is already taking and can also interfere with the current dental treatment and create complications. This article aims to provide necessary information about commonly encountered systemic diseases and associated treating medications, their mechanism of action, possible complications and their management. The classes of drugs discussed include anti-platelet agents, vitamin K antagonists, novel oral anticoagulants, bisphosphonates, disease-modifying anti-rheumatic drugs and oral contraceptives.

Abstract: This study reviewed aspects of the biology of two members of the glucosinolate family, namely sinigrin and glucoraphanin and their anti-tumour and anti-microbial properties. Sinigrin and glucoraphanin are converted by the β-sulphoglucosidase myrosinase or the gut microbiota into their bioactive forms, allyl isothiocyanate (AITC) and sulphoraphanin (SFN) which constitute part of a sophisticated defence system plants developed over several hundred million years of evolution to protect them from parasitic attack from aphids, ticks, bacteria or nematodes. Delivery of these components from consumption of cruciferous vegetables rich in the glucosinolates also delivers many other members of the glucosinolate family so the dietary AITCs and SFN do not act in isolation. In-vitro experiments with purified AITC and SFN have demonstrated their therapeutic utility as antimicrobials against a range of clinically important bacteria and fungi. AITC and SFN are as potent as Vancomycin in the treatment of bacteria listed by the World Health Organisation as antibiotic-resistant "priority pathogens" and also act as anti- cancer agents through the induction of phase II antioxidant enzymes which inactivate potential carcinogens. Glucosinolates may be useful in the treatment of biofilms formed on medical implants and catheters by problematic pathogenic bacteria such as Pseudomonas aeruginosa and Staphylococcus aureus and are potent antimicrobials against a range of clinically important bacteria and fungi. The glucosinolates have also been applied in the prevention of bacterial and fungal spoilage of food products in advanced atmospheric packaging technology which improves the shelf-life of these products.

Evolving or "re-emerging" viral deviation remains to pretense substantial worldwide public health threats. Influenza A virus (IAV), the main contributor to respiratory infections and related death in humans, is a prime example. Universally well-known as ‘flu’, it has disturbed our daily breathing, leaving a breakthrough till now. This virus can transmit from animals to humans and familiarize human hosts, resulting in ongoing transmission and the rise of novel viral strains. The processes through which viruses evolve within one host, cause animal-to-human transmission, and acclimatize to different host species are not yet fully understood. This review scans influenza antiviral resistance, highlighting the fundamental concepts behind its development and clinical impact. Influenza A represents a significant burden on healthcare systems and communities. While antiviral drugs are crucial for managing influenza effectively, healthcare providers and policymakers may need to be cautious due to the potential for antiviral-resistant strains to develop. Adamantanes and neuraminidase inhibitors targeting the viral components of the M2 ion channel and NA have been approved to treat IAV. However, the ongoing dissemination of drug-resistant virus variants due to mutation of these viral components poses a challenge and could undermine the effectiveness of primary antiviral therapies. Therefore, this review provides the susceptibility status of IAV subtypes to currently available antiviral drugs, factors to anti-IAV resistance, and soon-to-be-available control measures to emerging drug resistance IAV.

The 3 31 nucleotide minihelix tRNA theorem describes evolution of type I and type II tRNAs to the last nucleotide. In databases, type I and type II tRNA V loops (V for variable) were improperly aligned, but alignment based on the theorem is accurate. Type II tRNA V arms were a 3’-acceptor stem (initially CCGCCGC) ligated to a 5’-acceptor stem (initially GCGGCGG). The type II V arm evolved to form a stem-loop-stem. In Archaea, tRNALeu and tRNASer are type II. In Bacteria, tRNALeu, tRNASer and tRNATyr are type II. The positioning of the type II V arm is determined by the number of unpaired bases just 5’ of the Levitt base (Vmax). For Archaea, tRNALeu has 2 unpaired bases, and tRNASer has 1 unpaired base. For Bacteria, tRNATyr has 2 unpaired bases, tRNALeu has 1 unpaired base and tRNASer has 0 unpaired bases. Thus, the number of type II tRNAs is limited by the possible set points of the arm. From analysis of aminoacyl-tRNA synthetase structures, contacts to type II V arms appear to adjust allosteric tension communicated primarily via tRNA to aminoacylating and editing active sites. To enhance allostery, it appears that type II V arm end loop contacts may tend to evolve to V arm stem contacts.

Microorganisms such as bacteria, viruses and fungi are frequently the cause of infections. Antimicrobial agents, such as antibiotics, antivirals, and antifungals, are used to target and eliminate these infectious agents. Treating infections is crucial to prevent them from spreading, causing complications, or becoming chronic. On the other hand, inflammation is a natural response of the immune system to injury, infection, or irritation. While acute inflammation is a natural and protective process, chronic inflammation can contribute to various health issues, including autoimmune diseases, allergies, and chronic conditions like arthritis. Although herbal remedies have been used for centuries and can be effective in certain situations, it is crucial to use them with caution. Not all herbal remedies are supported by scientific evidence, and their safety and efficacy can vary. Thus, we conducted this review to determine the potential health benefits of agarwood as an antimicrobial and anti-inflammatory agent. Original articles were searched in three databases (PubMed, Scopus and Google Scholar) from the year 2013 to 2023 using the Medical subject heading (MeSH) terms “antimicrobial” and/or “anti-inflammatory”, crossed with the term “agarwood”. Synonyms and relevant search terms were also searched.  The most studied agarwood for antimicrobial and anti-inflammatory agents is Aquilaria sinensis. Some studies have shown its potential application as a biopesticide for mosquito control and as a potent inhibitor for fungi, including Lasiodiplodia theobromae, Fusarium oxysporum, and Candida albicans. Moreover, it is capable of inhibiting Bacillus subtilis and Staphylococcus aureus activities. In conclusion, agarwood and its isolates are worthy of further biomedical investigation and could be developed as potential candidates for the treatment or prevention of various microbial and inflammatory diseases. This review reveals that despite the absence of clinical trials, agarwood exhibits antimicrobial and anti-inflammatory properties.

: Since the COVID-19 pandemic, people have become aware that materials (products) can transmit infection and have begun to focus on questions such as how bacteria and germs, the sources of in-fection, maintain their infectivity on material surfaces, and the extent to which materials can or cannot prevent this. and to what extent materials can and cannot prevent it. The SIAA, a non-profit organization of many Japanese companies, had created an entirely separate interna-tional standard for materials' antibacterial, antiviral, and antibiofilm properties (products). The authors have studied the academic basis for the operation of the standards and were deeply in-volved as researchers in establishing one of the standards. This paper describes the interna-tional standards and some representative examples of the authors' actual use of these standards and explains the current status and future problems.

Abstract: In the last decade, gypsogenin has widely grabbed the attention of medicinal chemists by virtue of its prominent anti-cancer potential. Despite its late identification, gypsogenin proved itself as a new an-ti-proliferative player battling for a front position among other classic pentacyclic triterpenes such as oleanolic acid, glycyrrhetinic acid, ursolic acid, betulinic acid, and celastrol. Herein, we present insights into the anti-cancer activity of gypsogenin and its semisynthetic derivatives and go further by introducing our perspective to judiciously guide the prospect rational design. The present article opens a new venue for better exploitation of gypsogenin chemical entity as a lead compound in cancer chemotherapy. To the best of our knowledge, this is the first review article exploring the anti-cancer activity of gypsogenin derivatives.

The synthesis of the presented benzo[d]thiazol-2-amine derivatives was performed by condensing-(4-chlorobenzylidene) benzo[d]thiazol-2-amine with a number of substituted phenols in the presence of potassium iodide and anhydrous potassium carbonate in dry acetone. IR spectroscopy, 1HNMRspectroscopy and spectroscopy methods were used to characterize the structural properties of newly synthesized derivatives. In order to observe the attributes of drug-like candidates of these derivatives, the number of their molecular properties was estimated. Benzo[d]thiazol-2-amine derivatives were molecularly docked with selective enzymes COX-1 and COX-2. Findings suggested that Compounds G3, G4, G6, G8 and G11 possess higher binding affinity than diclofenac sodium, when docking was performed with enzyme COX-1. Compounds G1, G3, G6, G8and G10 showed lower binding affinity than Indomethacin when docking performed with enzyme COX-2.In vitro evaluation of the COX-1 and COX-2 enzyme inhibitory activities were performed for synthesized compounds. Compounds 10 and 11 exhibited significant COX-1 and COX- enzyme inhibitory action with IC50 values of 5.0 and 10 µM, respectively. Using the hot plate method and the carrageenan-induced rat paw edema model, the synthesized compounds were screened for their biological activities, including analgesic and anti-inflammatory activities. The highest analgesic action was exhibited by derivative G11and the compound G10 showed the highest anti-inflammatory response.

Polyacetylene phytochemicals are emerging as potentially responsible for the chemoprotective effects of consuming apiaceous vegetables. There is some evidence suggesting that polyacetylenes impact carcinogenesis by influencing a wide variety of signalling pathways, which are important in regulating inflammation, apoptosis, cell cycle regulation, etc. Studies have shown a correlation between human dietary intake of polyacetylene-rich vegetables with reduced risk of inflammation and cancer. Polyacetylene supplementation can influence cell growth, gene expression, and immunological responses, and reduce tumour number in rat and mouse models. Cancer chemoprevention by dietary polyacetylenes involves several mechanisms, including effects on inflammatory cytokines, the NF-κB pathway, antioxidant response elements, UPR pathway, growth factor signalling, cell cycle progression, and apoptosis. This review summarises the published research on falcarinol-type polyacetylene compounds and their mechanisms of action regarding cancer chemoprevention and treatment, and also identifies some gaps in our current understanding of the health benefits of these polyacetylenes.

： Anti-MDA5 antibody bearing (anti-MDA5+)-dermatomyositis (DM) or polymyositis (PM) is notorious for causing rapidly progressive interstitial lung disease (RPILD) &amp;/or cancers with high mortality rate. However, anti-MDA5 antibodies (Abs) are also found in other connective tissue diseases and their link with RPILD especially with regards to the mortality rate are unknown. We retrospectively recruited 71 patients bearing anti-MDA5-Abs in serum, stratified them in terms of a presence or absence of RPILD, and evaluated their clinical features, laboratory findings, associated myositis antibodies, concurrent connective tissue disease (CTD) as well as newly developed malignancies. Thirty-nine (55%) patients presented with DM/PM but 32 (45%) didn’t. Twenty-two of the former and 11 of the latter developed RPILD eventually, accounting for a total of 46% of all MDA5 bearing patients. On the other hand, 15 of all 71 (21.1%) patients had cancers. Among 32 patients who didn’t have DM/PM, 27 (38.0% of all 71) had other CTDs, indicating that only 5 (7.0% of 71) patients did not have CTDs. Senility (odds ratio [OR]=1.816, P=0.032), presence of anti-Ro-52 antibody (OR=1.676, P=0.018), elevated C-reactive protein (CRP, OR= 4.354, P&lt;0.001) and carcinoembryonic antigen (CEA, OR=2.625, P=0.005) posed risks for RPILD. High lactose dehydrogenase (LDH, p=0.009), CRP (p=0.001), CEA (p=0.001), ferritin (p ≤ 0.001) and low albumin (p ≤ 0.001) were significantly associated with mortality. Anti-SAE antibodies were negatively correlated with RPILD as analyzed by univariate (OR=0.245, P=0.017) and multivariate (OR= 0.058, P=0.036) regressions, indicating that they may be a protective factor from RPILD (OR= 0.543, P=0.008) or fatality (OR= 0.707, P=0.012), which was also demonstrated in subgroup analyses. In contrast to various risk factors for RPILD or mortality, anti-SAE antibodies might be conversely a protective factor in anti-MDA5+ patients.

Plant hormones regulate the adaptive responses to various biotic and abiotic stress factors. Applied exogenously they trigger the natural plant defense mechanisms, a feature that could be implemented in strategies for supporting crop resilience. The potential of exogenous cytokinin-like acting compound (kinetin), the auxin analogue 1-naphtyl acetic acid (NAA), abscisic acid (ABA) and the ethylene-precursor 1-aminocyclopropane-1-carboxylic acid (ACC) to mitigate dehydration was tested on Lactuca sativa (lettuce) grown on 12% polyethylene glycol (PEG). Priming with different blends containing these plant growth regulators applied in bioequivalent concentrations was evaluated through biometric measurements and biochemical analyses. The combined treatment with the four plant hormones exhibited the best dehydration protective effect. The antioxidative enzyme profiling of the PGR-primed individuals revealed increased SOD, catalase and peroxidase activity in the leaves. Immunodetection of higher levels of the rate-limiting enzyme for proline biosynthesis (delta-pyroline-5-carboxylate synthase) in the primed plants coincided with a significantly higher content of the amino acid measured in the leaves. These plants also accumulated particular dehydrin types, which may have contributed to the observed stress-relieving effect. The four-component hormonal mix applied by spraying or through the roots exerted similar stress-mitigating properties on soil-grown lettuce subjected to moderate drought.

Utilizing bioinformatics tools, this study expands our understanding of secondary metabolism in Botrytis cinerea, identifying novel genes within polyketide synthase (PKS), non-ribosomal peptide synthetase (NRPS), sesquiterpene cyclase (STC), diterpene cyclase (DTC), and dimethylal-lyltryptophan synthase (DMATS) families. These findings enrich the genetic framework associ-ated with B. cinerea's pathogenicity and ecological adaptation, offering insights into uncharted metabolic pathways. Significantly, the discovery of previously unannotated genes provides new molecular targets for developing targeted antifungal strategies, promising to enhance crop pro-tection and advance our understanding of fungal biochemistry. This research not only broadens the scope of known secondary metabolites but also opens avenues for future exploration into B. cinerea's biosynthetic capabilities, potentially leading to novel antifungal compounds. Our work underscores the importance of integrating bioinformatics and genomics for fungal research, paving the way for sustainable agricultural practices by pinpointing precise molecular interven-tions against B. cinerea. This study sets a foundation for further investigations into the fungus's secondary metabolism, with implications for biotechnology and crop disease management.

Background: Antiphospholipid antibodies (aPL) are a laboratory criterion for the classification of antiphospholipid syndrome (APS), and are known to cause clinical symptoms: vascular thrombosis or obstetric complications. It is suggested that aPL may be associated with thromboembolism in severe COVID-19 cases. Aim: to combine clinical data with aPL findings at 4 time points (admission, worsening, discharge, 3-month follow-up) in patients hospitalized with COVID-19 pneumonia. Methods: current and past history of thrombosis and obstetric complications; aPL determined at 4 time points: anticardiolipin (aCL), anti-β2-glycoprotein I (anti- β2GPI) and antiphosphatidylserine/prothrombin (aPS/PT) of the IgM, IgG or IgA isotypes. Results: 111 patients with COVID-19 pneumonia were enrolled. During hospitalization, 7 patients died, 3 of them due to pulmonary artery thromboembolism (none was aPL positive). Only one of the five who developed pulmonary artery thrombosis was aPL positive. Of 9/101 patients with a history of thrombosis, 5 had arterial thrombosis and none was aPL positive at admission and follow-up; 4 had venous thrombosis and one was aPL positive at all time points (newly diagnosed APS). Of these 9/101 patients, 55.6% were transiently aPL positive at discharge only, compared to 26.1% without history of thrombosis (p=0.05). Conclusions: aPL were not associated with fatal outcomes and vascular thrombosis; aPL were transiently positive in more than half of patients with a history of thrombosis.

Background and Objectives: Age-related macular degeneration (AMD) is one of the major causes of central vision loss in the older age group and its dry form accounts for the majority of cases. Although several causes and mechanisms for the development and progression of AMD have previously been identified, the pathogenesis of this complex disease is still not entirely understood. As the inflammation and involvement of the immune system are strongly suggested to have a central role to promote the degenerative process and to stimulate the onset of complications, we aimed to analyze the prevalence of serum anti-retinal (ARA) and anti-endothelial cell antibodies (AECA) in patients with dry AMD and to determine their relationship with the clinical features of the disease, notably area of geographic atrophy (GA). Materials and Methods: We enrolled 41 patients with dry AMD and 50 sex- and age-matched healthy controls without AMD. The presence of ARA was determined by indirect immunofluorescence using monkey retina as an antigen substrate, while the presence of AECA was determined using cultivated human umbilical vein endothelial cells and primate skeletal muscle. Results: ARA were detected 36 (87.8%) AMD patients (titers range from 1:20 to 1:320) and in 16 (39.0%) (titers range from 1:10 to 1:40) of controls (p=0.0000). Twenty of the 41 patients (48.8%) were positive for AECA, while in a control group AECA were present only in 5 sera (10.0%). The titers of AECA in AMD patients ranged from 1:100 to 1:1000 and in the control group the AECA titers were 1:100 (p=0.0001). There were no significant correlations between the presence of AECA and disease activity. Conclusions: This study provides evidence for the possible involvement of an autoimmune process against retina and retinal vessel antigens in the pathogenesis of geographic atrophy associated with dry AMD.

The West-African variety of Sorghum bicolor leaf sheath (SBLS) Jobelyn® is a natural remedy, which has gained international recognition for its anti-anemic effect and energy boosting qualities in debilitating diseases. The widespread use of traditional medicine in the region usually confirms its safety, but not its efficacy or deep assessment of their pharmacological properties. The other major issue for herbal-based treatments is the lack of definite and complete information about the composition of the extracts. Despite limitations, efforts have been made in isolation and characterisation of active compounds in this specie of sorghum showing various subclasses of flavonoids including apigeninidin, a stable 3-deoxyanthocyanidin and potential fungal growth inhibitor, which accounts for 84% of the total extract. Non-clinical in vitro and in vivo studies support previous indications that this variety of Sorghum bicolor possesses several biologically active compounds with potent antioxidant, anti-inflammatory, anti-aging and neuro-protective properties. Clinical studies show that SBLS has the ability to boost hemoglobin concentrations in anemic conditions and most remarkably to increase CD4 count in HIV-positive patients. The multiple effects and high safety profiles of this extract may encourage its development as a therapeutic agent for the treatment of anemia, chronic inflammatory conditions or in the symptomatic management of HIV infections. This review describes the potential therapeutic aspects of SBLS extract and its potential benefits.

Despite extensive use of intravitreal anti-vascular endothelial growth factor (anti-VEGF) biologics for over a decade, neovascular age-related macular degeneration (nAMD) or choroidal neovascularization (CNV) continues to be a major cause of irreversible vision loss in developed countries. Many nAMD patients demonstrate persistent disease activity or experience declined responses over time despite anti-VEGF treatment. The underlying mechanisms of anti-VEGF resistance are poorly understood, and no effective treatment strategies are available to date. Here we review evidence from animal models and clinical studies that supports the roles of neovascular remodeling and arteriolar CNV formation in anti-VEGF resistance. Cholesterol dysregulation, inflammation, and ensuing macrophage activation are critically involved in arteriolar CNV formation and anti-VEGF resistance. Combination therapy by neutralizing VEGF and enhancing cholesterol removal from macrophages is a promising strategy to combat anti-VEGF resistance in CNV.

This study investigated the efficacy and safety of a propolis mangosteen extract complex (PMEC) on gingival health in patients with gingivitis and incipient periodontitis. A multi-centered randomized, double-blind, placebo-controlled trial involving 104 subjects receiving either PMEC or placebo for eight weeks was conducted. The primary focus was on changes in inflammatory biomarkers from gingival crevicular fluid (GCF), with clinical parameters as secondary outcomes. Results revealed that the PMEC group showed significantly reduced expression of all measured GCF biomarkers compared to the placebo group (p&lt;0.0001) at 8 weeks, including substantial reductions in IL-1β, PGE2, MMP-8, and MMP-9 levels compared to baseline. While clinical parameters trended towards improvement in both groups, inter-group differences were not statistically significant. No significant adverse events were reported, indicating a favorable safety profile. These findings suggest that PMEC consumption can attenuate gingival inflammation and mitigate periodontal tissue destruction by modulating key inflammatory mediators in gingival tissue. Although PMEC shows promise as a potential adjunctive therapy for supporting gingival health, the discrepancy between biomarker improvements and clinical outcomes warrants further investigation to fully elucidate its therapeutic potential in periodontal health management.

Background The evolution of treatment patterns in neovascular age-related macular degeneration (nAMD) warrants investigation into the impact of patients’ adherence to anti-vascular endothelial growth factor (VEGF) treatment on visual outcomes. This retrospective, non-randomized, non-comparative study aimed to investigate real-world adherence to anti-VEGF treatment. Methods Patients (eyes) (≥ 50 years) with a diagnosis of nAMD who had a first injection of aflibercept or ranibizumab between January 2016 and December 2018 and 12 months of follow-up were included. Visual acuity (VA; logarithm of the minimum angle of resolution letters) and duration of injection intervals were recorded. Adherence was defined as < 20% of visits deviating from the schedule by ≥ 14 days. Results Overall, 133 patient eyes were included: 129 adherent, 4 non-adherent. Mean (± standard deviation) baseline VA was 57.0 (± 23.6) and 53.8 (± 35.3) letters in adherent and non-adherent patient eyes, respectively. Mean change in VA by month 12 was higher in adherent (6.3 letters) than non-adherent patient eyes (−11 letters). In non-adherent patient eyes, no improvement in VA was recorded following completion of the loading period (month 3). Compared with the previous visit, adherent visits were associated with a mean increase in VA of 0.67 letters and non-adherent visits with a decrease of 2.30 letters. Conclusions These results emphasize the importance of adherence to appropriate dosing regimens to optimize visual outcomes in patients with nAMD.

Bangladeshi medicinal plants (BMP) have been used as traditional medicinal plants to treat chronic inflammatory diseases, but the antioxidant and anti-inflammatory effects of the bark of BMP are not yet known. The objective of this study was to determine antioxidant and anti-inflammatory activities using methanolic extracts of bark obtained from 15 medicinal spices of Bangladesh plants. The bark methanol extracts of BMP evaluated the total antioxidant activity and anti-inflammatory effect of lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophages. Among the 15 bark extracts of BMP, Albizia odoratissima (A. odoratissima), Engelhardia spicata (E. spicata), and Shorea robusta (S. robusta) showed the highest total phenolic contents and total antioxidant capacity by reducing free radicals scavenging activity. In particular, the three bark extracts significantly reduced the mRNA expression of LPS-induced inflammatory cytokines and inflammation-inducible enzymes in macrophages. Also, the mRNA expression of NADPH oxidase 2 was significantly suppressed by three bark extracts in LPS-induced RAW 264.7 macrophages. The results suggest that among the 15 bark extracts obtained from medicinal plant in Bangladesh, three bark extracts of A. odoratissima, E. spicata, and S. robusta exert total antioxidant capacity by reducing free radicals scavenging activity and inhibitory effects on LPS-stimulated inflammation in macrophages.

Two-dimensional (2D) ice I is an atomic-level ice that is composed of two interlocked atom-ic layers saturated with hydrogen bonds. It has recently been experimentally observed but its properties have yet to be clarified. Accordingly, we theoretically studied the hydrophobic properties of 2D ice I. On the contrary, simulation of a hydrogen fluoride molecule on a 2D ice surface manifested that it destroyed the 2d ice structure and connected new hydrogen bonds with water molecules. Investigations of the interfacial effect between 2D and three-dimensional (3D) ice films indicated that the network structure of 2D ice was not de-stroyed by a 3D ice surface, as the former was saturated with hydrogen bonds. However, the surface of 3D ice reorganized to form as many hydrogen bonds as possible. Thus, the 2D ice film was hydrophobic and inhibited the growth of 3D ice. This shows that if 2D ice can be produced on an industrial scale, it could be used as an anti-3D-icing agent under low tem-perature.

This work is based on identifying the analysis techniques used to evaluate the antioxidant and anti-inflammatory effects using the zebrafish model. In this context, a literature review was performed with the Web of Science database. We used the terms zebra fish, antioxidant, anti-inflammatory, model, and Danio rerio. Fifty articles were reviewed, of which thirty-three were chosen to perform this review and were classified according to the source of plant extracts, compounds extracted from plants, chemical compounds, and other sources. This paper is an effort to provide a literature review on zebrafish models and elucidate their pros and cons to evaluate anti-inflamatory and antioxidant activity.

The purpose of this scoping review was to examine the literature on the use of anti-gravity treadmill and its effects on lower limb motor functions in children and adolescents with locomotor impairments. Four databases (MEDLINE, CINAHL, Embase, Web of Science) were searched for articles from inception to August 2021. Inclusion criteria were: (1) experimental or quasi-experimental studies using the anti-gravity training as the primary intervention; (2) studies conducted in paediatricpediatric participants; (3) articles reporting outcomes related to the lower limb functions; and (4) studies published in French or English. Fifteen articles were included in the review. Studies included children and adolescents aged 4–18 years with locomotor impairments. The intervention duration was ranged from 2 and to 12 weeks, with 2-5 sessions per week. Included studies showed reported that anti-gravity training induces improvements in muscle strength, balance, spatiotemporal gait parameters, and walking endurance in children with locomotor impairments. This review provides relevant information about the modalities, outcomes and limits associated with the anti-gravity training protocol reported in the literature. Overall, the anti-gravity treadmill training could be viewed as a valuable training modality for children with cerebral palsy. However, more precise, and comprehensive description of anti-gravity rehabilitation protocols would be useful.

Acquired Immunodeficiency Syndrome (AIDS) which is chiefly originated by a retrovirus named Human Immunodeficiency Virus (HIV), has influenced about 70 million populations worldwide. Even though several advancements have been invented in the field of antiretroviral combination therapy, still HIV has become the dominant reason for death in South Africa, for example. The current antiretroviral therapies have achieved success in providing instant HIV suppression but with countless undesirable adverse effects. In the present day, the biodiversity of the plant kingdom is being explored by several researchers for the discovery of potent anti-HIV drugs with different mechanisms of action. The primary challenge is to afford a treatment that is free from any sort of risk of drug resistance and serious side effects. Hence, there is a strong demand to evaluate the drugs obtained from natural plants as well as the synthetic derivatives that have been derived from the natural compounds by various chemical reactions. Several plants such as Andrographis paniculata, Dioscorea bulbifera, Aegle marmelos, Wistaria floribunda, Lindera chunii, Xanthoceras sorbifolia and others have displayed significant anti-HIV activity showing more potent anti-HIV activity along with their structures, SARs & important key findings.

As the time passes the modification in technology world lead to the evaluation in mobile application as well. With evaluation in mobile industry it is an open challenge for software quality researcher that how to enhance software quality to meet the needs of changes? Quality assurance play a key role in differentiating good application from bed application. With the continuous evaluation of mobile application developing process should be quick and efficient to comply with user requirements and satisfaction. While the listed requirement leads to bad design choices known as antipatterns, which in turn affect the reliability of the code. A tool based method PAPRIKA is used in the proposed re-search to identify and monitor these antipatterns together with a two-step assessment model for software quality assurance and object oriented software quality matrix.

The iridoids of H. diffusa play an important role in the anti-inflammatory process, but the specific iridoid with anti-inflammatory effect and its mechanism is lack of study. An iridoid compound named scandoside (SCA) was isolated from H. diffusa and its anti-inflammatory effect was investigated in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Its anti-inflammatory mechanism was confirmed by in intro experiment and molecular docking analysis. As results, SCA significantly decreased the productions of nitric oxide (NO), prostaglandin E₂ (PGE₂), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and inhibited the levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α and IL-6 mRNA expression in LPS-induced RAW 264.7 cells. SCA treatment suppressed the phosphorylation of inhibitor of nuclear transcription factor kappa-B alpaha (IκB-α), p38, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). The docking data suggested that SCA had great binding abilities to COX-2, iNOS and IκB. Taken together, the results indicated that the anti-inflammatory effect of SCA is due to inhibition of pro-inflammatory cytokines and mediators via suppressing the nuclear transcription factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, which provided useful information for its application and development.

In vitro studies show that diclofenac inhibits enzymatic steroid glucuronidation. This study was designed to investigate the influence of diclofenac on the excretion of stanozolol and 3'-hydroxystanozolol via analyses in hair, blood and urine in vivo in a rat study. Brown Norway rats were administered with stanozolol (weeks 1-3) and diclofenac (weeks 1-6). Weekly assessment of steroid levels in hair was complemented with spot urine and serum tests. Levels of both stanozolol and 3'-hydroxystanozolol steadily increased in hair during stanozolol treatment and decreased post-treatment, but remained readily detectable for 6 weeks. In contrast, compared to control rats, diclofenac significantly reduced urinary excretion of 3’-hydroxystanozolol which was undetectable in most samples. This is the first report of diclofenac altering steroid metabolism in vivo, detrimentally affecting detection in urine, but not in hair which holds considerable advantages over urinalysis for anti-doping tests.

Background and Objectives: In the current Covid-19 pandemic, children below the age of 12 could manifest Covid-19 symptoms and serve as a reservoir for the virus in the community. The present study was conducted to evaluate the reactogenicity, and immunogenicity of BBIBP-CorV, prior to involving this age group in the vaccination program in the kingdom of Bahrain. Subjects and Methods: The study included 582 children from 3 to 12 years old of Bahraini and non-Bahraini nationality, all of which contributed to the reactogenicity study. Of those, 401 contributed to the immunogenicity study. All children received 2 doses of BBIBP-CorV inactivated virus 3 weeks apart. To assess reactogenicity, children were followed up for 5 weeks to evaluate any vaccine-related adverse events (AE). To assess immunogenicity, blood was collected on day 0 and day 35 to assess antibody titer against S, N, and neutralizing antibody. Results: Of the 582 participants, (45.4%) were female, (54.61%) were male, with 49% in 9-12 age group. Of the 401 children contributing to the immunogenicity study, 274 (68.3%) had no prior exposure to Covid-19. The overall incidence of AE was 27.7%. No significant difference was found among different age groups. The most frequent AE was local (at the injection site) and occurred in 16% of children, followed by fever in 9.3%. No serious adverse events were reported. The Seroconversion rate was 100% among children with no prior exposure to Covid-19. Children with previous Covid-19 exposure had higher averages of anti-S (2379 U/ml compared to 409.1), anti-N (177.6 U/ml compared to 30.9) and neutralizing antibody (93.7 U/ml compared to 77.1) than children with no prior exposure at day 35. Conclusions: Two doses of COVID-19 BBIBP-CorV on the subjects aged between 3 to 12 has good safety and tolerance and can induce an effective immune response and neutralizing antibody titer.

The simplistic morphological characteristics of the Carica papaya, papaya or ‘pawpaw’ should not be the cause for underestimating its potential as a nutraceutical. The market for papaya has been expanding at a staggering rate, partly due to its applicability as a biofortified product, but mostly for its phytochemical properties and traditional health benefits. Recent characterization studies have showed that the entirety of papaya or using a formulation of fermented papaya promotion (FPP) displays effective free radical scavenging abilities, thought to be influenced by its phenolic, carotenoids, flavonoid or amino acid profile. Aiming at reducing the impact of free radical-induced oxidative damage in the human system, the antioxidant properties of FPP have been found to potently target a broad spectrum of diseases ranging from neurological impairments such as senile dementia to systemic diseases, to its interference at the cellular level and support of normal biological ageing processes. FPP has thus been extensively investigated for its ability to exert cellular protective effects and reduce oxidative stress via mitigation of genetic damage, lipid peroxidation and enzymatic inactivation in diseases. Oxidative stress reduction strategies using FPP and its holistic approach in disease prevention and management, with a focus on diabetes, cancer and cognitive health, contributes unequivocally to wellness in an aging population.

The plethora of bio-functional compounds present in fermented alcoholic beverages like wine, as well as the valorization of bioactives from their wineries/breweries by-products like grape pomace and grape seed, has gained significant interest in the functional foods sector. Wine has always accompanied humanity, for religion or for health. For example, Christians are using wine in the “Holy Communion”, following what Jesus Christ himself did and said during the Last Supper, while the benefits of the wine consumption in moderation was embedded in all Mediterranean civilizations, as it is mentioned by the wise King-Prophet David in his psalms, but also by Hip-pocrates and other wise men, in a Greek-based philosophy of “All things in Moderation” (Cleobulus of Lindos; 6th century BC). In modern times, and after the outbreak of research on wine benefits since the 90’s, when the term “French Paradox” was introduced in the US public during a CBS show, recent evidence has outlined that these benefits are derived by the synergisms of its bio-functional compounds and their digestion-derived metabolites. Within this article, the proposed health benefits of moderate wine consumption, as a functional component of a balanced diet (i.e. the Mediterra-nean Diet), against inflammation-related chronic disorders, is thoroughly reviewed. The various bio-functional compounds of both wine and wineries’ by-products, such as their bioactive phe-nolics, unsaturated fatty acids, polar lipids, and dietary fibers, and their functional antioxidant, anti-inflammatory and antithrombotic health promoting properties are also thoroughly evaluated. The mechanisms of actions and synergism, by which the health benefits are elicited, are also ex-plored. Functional properties of non-alcoholic wine products are also introduced. Emphasis is also given to applications of wineries’ by-products bioactives, as ingredients of bio-functional foods, supplements and nutraceuticals. Limitations and future perspectives for this popular functional alcoholic beverage (wine) ant its rich in bioactives by-products are also addressed. .

In recent decades, there has been a startling rise in the number of cancer patients worldwide, which has led to an amazing upsurge in the development of novel anticancer treatment candidates. On a positive note, arylpiperazines have garnered attention in cancer research due to their potential as scaffolds for developing anticancer agents. These compounds exhibit a diverse array of biological activities, including cytotoxic effects against cancer cells. Indeed, one of the key advantages of aryl piperazines lies in their ability to interact with various molecular targets implicated in cancer pathogenesis. Here, we focus on the chemical structures of several arylpiperazine derivatives, highlighting their anti-proliferative activity in different tumor cell lines. The modular structure, diverse biological activities, and potential for combination therapies of arylpiperazine com-pounds make them valuable candidates for further preclinical and clinical investigations in the fight against cancer. This review, providing a careful analysis of different arylpiperazine deriva-tives and their biological applications, allows researchers to refine the chemical structures to improve potency, selectivity, and pharmacokinetic properties, thus advancing their therapeutic potential in oncology.

Recovery between physical efforts is essential for optimal performance in sports. Dietary supplements like cannabidiol (CBD) have been proposed to facilitate recovery and performance optimization. This systematic review aimed to: a) systematize the scientific evidence on CBD for recovery, b) associate CBD's biomedical properties with those required for optimal fatigue recovery, and c) recommend a future research agenda. Searches across databases identified 70 relevant studies from 1990-2022, including 38.6% preclinical, 31.4% clinical trials, and 30.0% reviews/meta-analyses across various populations like mice, rats, epileptics, and athletes. CBD demonstrated potentially beneficial properties for athlete recovery such as anti-inflammatory, neuroprotective, anxiolytic, and analgesic effects with doses ranging from 5-600mg administered orally, intravenously, and via other routes. However, rigorous confirmatory research specifically in athlete populations is lacking. While CBD appears promising for facilitating recovery and performance optimization, further randomized placebo-controlled trials are needed to test the acute and chronic effects of different CBD dosing regimens in athletes. Future research should focus on elucidating CBD's physiological mechanisms of action as they relate to post-exercise recovery, as well as its comparative effectiveness versus conventional medications and therapies. Advancing our understanding of CBD's role in athlete recovery could provide new therapeutic strategies to optimize recovery and performance.

Lactococcus lactis subsp. cremoris C60 is a probiotic strain of lactic acid bacteria (LAB) which induces various immune modifications in myeloid lineage cells. These modifications subsequently reg-ulate T cell function, resulting in enhanced immunity both locally and systemically. Here, we report that C60 suppresses tumor growth by enhancing macrophage function via metabolic al-terations, thereby increasing adenosine triphosphate (ATP) production in a murine melanoma model. Intragastric (i.g.) administration of C60 significantly reduced tumor volume compared to saline administration in mice. The anti-tumor function of intratumor (IT) macrophage was up-regulated in mice administered with C60, as evidenced by an increased inflammatory phenotype (M1) rather than an anti-inflammatory/reparative (M2) phenotype, along with enhanced anti-gen-presenting ability, resulting in increased tumor antigen-specific CD8+ T cells. Through this functional modification, we identified that C60 establishes a glycolysis-dominant metabolism, rather than fatty acid oxidation (FAO), in IT macrophages, leading to increased intracellular ATP levels. To address the question of why orally supplemented C60 exhibits functions in distal places, we found a possibility that bacterial cell wall components, which could be distributed throughout the body from the gut, may induce stimulatory signals in peripheral macrophages via Toll-like receptors (TLRs) signaling activation. Thus, C60 strengthens macrophage anti-tumor immunity by promoting a predominant metabolic shift towards glycolysis upon TLR-mediated stimulation, thereby increasing substantial energy production.

Abstract Background: Periodontitis is associated with systemic chronic inflammatory diseases. There is limited evidence on the influence of anti-cytokine therapies on the periodontal condition and microbiome in the tooth pocket of such patients, so the aim of this study was to elucidate this issue. Methods: In this observational trial, the periodontal status and the gingival crevicular fluid of 13 patients with different chronic inflammatory diseases were obtained before initiation of anti-cytokine treatment and 14 weeks after. Gingival crevicular fluid was collected for 16S rRNA gene sequencing from a clinically healthy tooth and the deepest measured pocket. Results: In participants with advanced attachment loss at baseline, the clinical attachment level significantly decreased from 2.9 (2.3-3.4) to 2.4 (1.3-3.0) mm (p = 0.04), and the bleeding- on-probing index dropped from 19.4 (10.0-21.0) to 7.3 (6.9-9.9) mm (p = 0.02) without any further periodontal treatment. Shannon’s diversity index significantly increased in the deepest pockets of patients (p = 0.039). Conclusion: The data showed alterations in diversity of the subgingival microbiome and improvement of periodontal parameters over the course of the study, implying a shift towards a healthier condition after starting anti-cytokine therapy. Additional investigations are needed to analyze whether the administration of selective biologicals can improve periodontal conditions in patients with or without chronic inflammatory diseases.

Since ancient times, various scientists and doctors have utilized different herbs to heal diseases. Due to the rise in drug resistance and the negative effects of chemosynthetic drugs, researchers and the general public around the world have become more interested in medicinal herbs and plant metabolites/extracts. This is due to its non-toxicity and several health benefits when used to treat diseases in clinical and medical settings. Ocimum basilicum is one such plant, possessing a wide range of bioactive phytochemicals including alkaloids, phenolics, flavonoids, tannins, saponins, reducing sugars, cardiac glycosides, steroids and glycosides, as well as complex pharmacological activities including anti-inflammatory, antifungal, antibacterial, antioxidant, wound healing and antiviral properties. The results of many studies on Ocimum basilicum plant extracts are collected and presented in this review. The plant extracts have an excellent potential to be used as medicinal raw materials and exhibit an extensive variety of therapeutic capacities, including antibacterial, antioxidant, wound healing, anti-inflammatory, antifungal, and antiviral properties.

Inflammation is natural protective response of the body tissue caused by various stimuli. Macrophages start and control the inflammatory response. Microalgae have high value of ingredients including carotenoids which are well known for anti-inflammatory properties and used for various products in functional food industries. A green microalgal, Tetraselmis species contains a various type of carotenoids such as lutein, violaxanthin, astaxanthin, fucoxanthin, α-carotene and β-carotene. Therefore, we studied whether carotenoids isolated from Tetraselmis sp. with different culture conditions in Raw 264.7 cells and zebrafish (Danio rerio) have an anti -inflammatory effect. Carotenoid extracts of natural seawater (NS) and magma seawater (MS) showed inhibitory activity of nitric oxide (NO) overproduction without toxicity. In addition, carotenoid extracts of NS and MS inhibited pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)- 1β and IL-6. Inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, which are inflammatory mediators also decreased by pretreatment of NS and MS. Carotenoid extracts of NS and MS pretreatment also reduced phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kB (NF-kB). In conclusion, the carotenoid extract of Tetraselmis sp. has an anti -inflammatory effect and can be potential industrial ingredient.

A series of pyrazolopyrimidines derivatives 4– 11 were synthesized using 1-(6-(3-methoxyphenyl)-4-methylpyridazin-3-yl)-1H-pyrazolo [3,4-d] pyrimidin-4-amine 3 as a starting material. The detailed synthesis, structure assignments of the novel compounds based on chemical and spectroscopic evidence, spectroscopic data, pharmacological properties and molecular docking are reported. The pharmacological evaluation illustrated that many of these compounds have good analgesic, anti-inflammatory and antimicrobial activities.

Lipofuscin is indigestible garbage that accumulates in the autophagic vesicles and cytosol of post-mitotic cells with age. Drs. Brunk and Terman postulated that lipofuscin accumulation is the main or at least a major driving factor in aging. They even posited that the evolution of memory is the reason why we get lipofuscin at all, as stable synaptic connections must be maintained over time, meaning that the somas of neurons must also remain in the same locale. In other words, they cannot dilute out their garbage over time through cell division. Mechanistically, their position certainly makes sense given that rendering a large percentage of a post-mitotic cell’s lysosomes useless must almost certainly negatively affect that cell and the surrounding microenvironment. It may be the case that lipofuscin accumulation is the main issue with regard to current age-related disease. Degradation in situ may be an insurmountable task currently. However, a method of systemic lipofuscin removal is discussed herein.

Hydroxamic acid (HA) derivates displayed antibacterial and antifungal activities. HA with various numbers of carbon atoms (C2, C6, C8, C10, C12 and C17), complexed to different metal ions Fe(II/III), Ni(II), Cu(II) and Zn(II) were evaluated for their antimycobacterial activities and their anti-biofilm activities. Some derivates, among others HA12Fe2, inhibited the development of Mycobacterium tuberculosis, Mycobacterium bovis BCG and Mycobacterium marinum biofilms and could even attack pre-formed Pseudomonas aeruginosa biofilm. Proteomic profiles showed that the potential targets of HA10FeCl were mainly related to mycobacteria stress adaptation, involving cell wall lipid biosynthesis, drug resistance and tolerance, siderophore metabolism. This study provides new insights regarding the antimycobacterial activities of the HA and their complexes, especially about their potential antibiofilm activities.

Food and drinks can be contaminated with pollutants such as lead and strontium and this poses a serious danger to human health. For this reason, a number of effective sensors have been developed for the rapid and highly selective detection of such contaminants. TBA, a well-known aptamer developed to selectively target and thereby inhibit the protein of clinical interest -thrombin, is receiving increasing attention for sensing applications, particularly for the sensing of different cations. Indeed, TBA, in the presence of these cations, folds into the stable G-quadruplex structure. Furthermore, different cations produce small but significant changes in this structure that result in changes in the electrical responses that TBA can produce. In this article we produce an overview of the expected data regarding the use of TBA in the detection of lead and strontium, calculating the expected electrical response using different measurement techniques. Finally, we conclude that the TBA should perform better as a detector of strontium rather than lead.

Cancer is a catchall term that refers to a collection of more than one chronic disease that can adversely affect the body, including the organs of the body. These diseases can be grouped together under the umbrella term "cancer." Cancer is a catch-all term that is used to refer to a number of different diseases. During the process of looking for new chemical entities, it was found that certain compounds with a basic nucleus of benzoic acid (BA) exhibit a remarkable anticancer potential. This was discovered while the researchers were looking for new chemical entities. In the sixteenth century, the aromatic chemical known as BA, which is also known as an aromatic carboxylic acid, was discovered. BA is also referred to as an aromatic carboxylic acid. When it comes to the chemical synthesis of a wide range of different active molecules, the utilization of a sizeable quantity of BA as a raw material is absolutely necessary. In addition to being present in a variety of other naturally occurring compounds, the BA moiety is the component that is responsible for the activity of the naturally occurring compounds vanillin, gallic acid, and syringic acid. In the synthesis of a wide variety of synthetic bioactive molecules, the BA scaffold is utilized as a building block. The drugs furosemide, bumetanide, benzocaine, tetracaine, and bexarotene are all examples of molecules that fall into this category. The scope of this review article allows for the discussion of a number of noteworthy and recent achievements of BA derivatives in terms of their effectiveness against cancer.

The ethanol extract (EE) prepared from the leaves of Tibouchina granulosa, and its fraction in ethyl acetate (fEA) were evaluated concerning their capacity to reduce inflammation in different experimental models. fEA was also studied concerning its chemical constituents. EE and fEA were assayed for their anti-inflammatory potential, using formalin-induced licking behaviour and carrageenan-induced inflammation into the subcutaneous air pouch (SAP) models. Reduction in polymorphonuclear cells (PMN) activation was performed in freshly isolated PMN. Chromatographic analysis of fEA was done by HPLC. Hispiduloside was isolated as the main constituent in fEA and its quantity was estimated to be 11.75% in fEA, 3.05% in EE, and 0.2% (w/w) in the plant. EE (30 mg/kg) significantly reduced the second phase of formalin-induced licking. fEA demonstrated a reduction in leukocyte migration into the SAP. EE and fEA drastically reduced cytokines (TNF-α, IL-1β, and IFN-γ), nitric oxide (NO) production, in vitro PMN migration induced by C5a and IL-8, and TNF-α and IL-1β gene expression. Taken together our data indicate that either ethanol extract or its fEA fraction from leaves of T. granulosa present an anti-inflammatory effect contributing to the pharmacological and chemical knowledge of this species and confirming the rationale behind its traditional use.

Polysaccharides from marine algae exhibit beneficial biological activities. In this study, we examined the effect of polysaccharides from Codium fragile (PCF) on prebiotic and anti-obesity activity. PCF increases the growth of specific beneficial microbial populations with concomitant decrease in pathogenic microbes. Further, total phenolic content (TPC), total flavonoid content (TFC), and DPPH radical scavenging activity (DPPH activity) after fermentation with PCF as carbon source were higher than for the glucose as control. Moreover, PCF inhibited adipocyte differentiation by inducing differentiation-related factors when the induction of 3T3-L1 preadipocytes into adipocytes was induced. Therefore, we suggest that PCF can be used as prebiotic material with anti-obesity for human health.

Diabetes mellitus remains a major risk factor for developing cardiovascular diseases, resulting in increased morbidity and mortality associated with cardiovascular complications. Given the burden of diabetes-related cardiovascular complications, there is a need to identify strategies, safe and effective therapeutic agents that could effectively prevent and control diabetes. Presently, many patients living with diabetes depends on traditional medicines as an alternative cure. Channa striatus (Haruan) is a freshwater fish traditionally used to treat wounds, inflammations, and pains. Several pharmacological investigations have supported the folkloric claims of C. striatus extracts, including hypoglycemic, hypolipidemic, antioxidant, anti-inflammatory, and pro-platelet aggregation activities. The therapeutic potentials of C. striatus were demonstrated to be associated with the presence of high content essential amino acids and good fatty acids known to improve cell growth and facilitate wound healing. Therefore, C. striatus bioactive compounds have great potentials to serve as lead candidates in developing novel therapeutic agents for the management of diabetes and related cardiovascular diseases. This review aims to provide a comprehensive overview of the pharmacological properties and therapeutic potentials of C. striatus for the management of diabetes and associated cardiovascular complications.

Abstract: As a risk factor, obesity is a threat to human well-being and related metabolic disorders such as diabetes mellitus and dyslipidemia. adipogenesis is defined as the proliferation and maturation of adipocyte predecessor cells to adipocyte. As the adipogenesis process decides adipocyte production, it may be considered a therapeutic target for obesity and obesity-related disorders. White adipose tissue abnormal expansion increases the size and number of adipocytes. For that reason, this review aims to spot the molecular mechanisms implicated in adipogenesis that lead to application in the therapeutic targets. Keywords: adipogenesis, signaling pathways, anti-obesity treatment, obesity

Since the financial crisis in 2008, the U.S. economy has weakened, and the world economy has slowly developed. As the world's leading country, the United States has used many methods to restore the economy. But it does work efficiently. However, there are many issues in developed countries such as domestic social, economic, immigration in the United States/United Kingdom; those are not optimistic. Developed countries have entered a dilemma. The neoliberalism financial system has been unable to move forward. Populists have pointed out that those problems have been causing by globalization. Under the leadership of the Brexit Referendum, President Trump has caused a wave of anti-globalization. Under a series of systems such as the China-US trade war and the US-Mexico border wall repairs, the anti-globalization trend is getting stronger. This article mainly analyzes the in-depth reasons and mechanism research of globalization and anti-globalization alternately—the data obtained from an international method performance study. The results show that anti-globalization is temporary, along with globalization. There are three main factors affecting globalization: the situation of the dominant country, natural disasters, and wars. After so much literature review, I believe that the United States' globalization is gradually weakening, and globalization may return to regionalization under the United States' opposition.

Product counterfeiting is an on-going problem in supply chains and retail environments, Recently an anti-counterfeiting protocol to address this issue via cost-effective use of auto-identification technologies such as radio-frequency identification (RFID) was proposed by researchers.Yet the use case of re-selling the same product was not been fully addressed which might cause serious problem for the exciting and proposed schemes and transactions. This paper proposes an extended RFID-based anti-counterfeiting to address the use case of the original buyer reselling the same item to a second buyer. The extended scheme will be followed by a formal security analysis to show that the proposed protocol satisfies the requirements of security correctness and is resistant to compromise through security attacks.

A novel approach has been suggested to use isoelectric points of viral and human proteins to quickly identify proteins that are effective in not allowing virus particles to attach to human receptor cells by virtue of their electrical charge. The method has been applied to SARS CoV-2 to suggest potentially important human proteins that can be suitable for making anti-viral drugs.