Objectives: Prostate cancer is well known to express high levels of somatostatin receptors and preliminary data suggests that PET imaging with the somatostatin analog, 68Ga-DOTATATE, may allow for whole body staging of patients with metastatic castration resistant prostate cancer (mCRPC) and neuroendocrine prostate cancer (NePC). This study explores the utility of 68Ga-DOTATATE PET-CT to identify metastatic deposits in men with mCRPC and NePC and prognosticate disease progression. Methods: 68Ga-DOTATATE PET-CT was performed in 17 patients with mCRPC and of those 2/17 had NePC. Semiquantitative analysis with standardized uptake values (SUV) (e.g. SUVmax, SUVmean) was performed for each metastatic lesion and reference background tissues. 68Ga-DOTATATE uptake in metastatic deposits was further classified as: mild (less than liver), moderate (up to liver average), or marked (greater than liver). Serial prostate-specific antigen measurements and patient survival were followed up to 3 years after PET imaging to assess response to standard of care treatment. Results: All patients had at least one metastic lesion with identifiable 68Ga-DOTATATE uptake. Marked 68Ga-DOTATATE uptake was found in 7/17 patients, including both NePC patients, and all were non-responders to systemic therapy and died within the follow up period, with a mean time to death of 8.1 months. 3 patients had mild 68Ga-DOTATATE uptake, and all were responders to systemic therapy and were alive 36 months after 68Ga-DOTATATE imaging. Conclusions: 68Ga-DOTATATE is able to identify mCRPC and NePC metastatic deposits, and lesions with 68Ga-DOTATATE uptake > liver may portend poor outcomes in patients with mCRPC.

One of the most notable changes in the Esophageal Cancer (EC) epidemiology is the rising incidence and prevalence of esophageal adenocarcinoma (EAC) in developed countries, likely due to lifestyle and/or environmental factors that may play an important role in EAC onset. The aim of this systematic review was to collect and summarize all the available evidence regarding lifestyle, diet and EAC risk. We searched the PubMed and Scopus databases in January 2021 for studies providing information about lifestyle, diet, WCRF/AICR recommendations and EAC risk. A total of 106 publications met the inclusion criteria. Body mass index (BMI) and waist circumference (WC) are associated with increased EAC risk. Physical activity does not appear to have a significant direct role in EAC risk. A diet rich in fruit, vegetables, and whole grains appeared to be more protective than a diet rich in animal fat, red meat, and processed meat. Alcohol does not seem to be related to EAC whereas smokers, particularly heavy smokers, have an increased risk of EAC. Primary prevention remains the best option to avert EAC. BMI and WC, along with low consumption of red and processed meat, high consumption of plant food, and the avoidance of smoking are pivotal for EAC prevention.

Breakthrough cancer pain (BTcP) is a temporary exacerbation of pain that "breaks through" a phase of adequate pain control by an opioid-based therapy. The non-predictable BTcP (NP-BTcP) is a subtype of BTcP that occurs in the absence of any specific activity. Since NP-BTcP has an important clinical impact, this analysis is aimed at characterizing the NP-BTcP phenomenon through a multidimensional statistical technique. This is a secondary analysis based on the Italian Oncologic Pain multiSetting - Multicentric Survey (IOPS-MS) . A correlation analysis was performed to characterize NP-BTcP profile about its intensity, number of episodes per day, and type. The Multidimensional Correspondence Analysis (MCA) determined the identification of 4 groups (Phenotypes). A univariate analysis was performed to assess differences between the 4 Phenotypes and selected covariates. The four phenotypes represent the hierarchical classification according to the status of NP-BTcP: from the best (Phenotype 1) to the worst (Phenotype 4). The univariate analysis found a significant association between the onset time >10 min in the Phenotype 1 (37.3%) vs. the onset ≤ 10 min in Phenotype 4 (74.2%) (p<0.001). The Phenotype 1 was characterized by gastrointestinal type of cancer (26.4%) respect to Phenotype 4 where the most frequent cancer affected the lung (28.8%) (p<0.001). Phenotype 4 was mainly managed with rapid onset opioids, while in Phenotype 1 many patients were treated with oral, subcutaneous, or intravenous morphine (56.4% and 44.4%, respectively; p=0.008). The ability to characterize NP-BTcP can offer enormous benefits for the management of this serious aspect of cancer pain. This strategy can provide many indications for identifying the diagnostic and therapeutic gaps on NP-BTcP management.

Ongoing concerns regarding the morbidity and mortality from cancer-associated thrombosis led the European Cancer Patient Coalition (ECPC), the voice of cancer patients across Europe, to create a pan-European cancer-associated awareness patient survey to assess CAT knowledge among a large population of patients with cancer. The ECPC survey represents the largest of its kind amongst patients/caregivers with CAT and identified significant gaps in patient awareness and knowledge of CAT. It also identified a need for educational CAT-related discussions and interventions between healthcare professionals and patients with cancer and their caregivers. The aim of this paper is to highlight these gaps and to provide healthcare professionals with awareness of what information should be shared with patients/caregivers as well as how and when that information should be provided. Notably, the importance of providing information on CAT risk and risk factors, how to reduce their risk of CAT, the role of anticoagulant prophylaxis and treatment (short- and long-term) including possible side-effects, and finally how to early identify CAT symptoms. Here we outline what type of information should be provided, as well as when and how to best discuss CAT with our oncology patients and their caregivers along the cancer care continuum, to reduce the risk of CAT and associated complications with a goal of improving patient outcomes.

Despite advances in the understanding of its molecular pathophysiology, prostate cancer remains largely incurable, highlighting the need for novel therapies. We developed a chimeric antigen receptor (CAR) specific for prostate specific membrane antigen (PSMA), a glycoprotein that is overexpressed in prostate cancer, which expression involves neovasculature of several tumor entities, thus envisaging an additional antiangiogenic effect. To optimize the CAR design, we compared two CARs with signaling domains containing one or two T cell costimulatory elements, in addition to CD3ζ. Conversely, what has been described for other CARs, a third-generation CAR (containing CD28 and 41BB co-signaling domains) induced a potent antitumor effect similar to a second-generation CAR (containing CD28 co-signaling domain), though we observed a detrimental effect of the additional costimulatory domain that was attributed to increased activation-induced cell death (AICD). This “super-stimulation” resulted in exhaustion of cells, higher frequencies of cell death and, more importantly, the impossibility of sufficiently expanding the CAR cells to obtain the minimum number of cells requested for in vivo therapies. While the superiority of 2nd and 3rd generation over 1st generation CAR T cells has been clearly shown in both preclinical and clinical studies, the optimal combination of costimulatory domains for 3rd generation CAR-T cells must still be defined and should be evaluated case-by-case in order to fine-tune immunotherapy approaches.

Bladder cancer (BC) is the most common neoplasm of the urinary tract, which originates in the epithelium that covers the inner surface of the bladder. The molecular BC profile has led to the development of different classifications of non-muscle invasive bladder cancer (NMIBC) and muscle-invasive (MIBC). However, the genomic BC landscape profile of the Mexican population, including NMIBC and MIBC, is unknown. In this study, we aimed to identify somatic single nucleotide variants (SNVs) and copy number variations (CNVs) in Mexican patients with BC and their associations with clinical and pathological characteristics. We retrospectively evaluated 37 patients treated between 2012 and 2021 at the National Cancer Institute - Mexico (INCan). DNA samples were obtained from paraffin-embedded tumor tissues and ran exome sequencing. Strelka2 and Lancet packages were used to identify SNVs and insertions or deletions. FACETS was used to determine CNVs. We found a high frequency of mutations in TP53 and KMT2D, gains in 11q15.5 and 19p13.11-q12, and losses in 7q11.23. STAG2 mutations and 1q11.23 deletions were also associated with NMIBC and low histologic grade.

The central reason behind emergence of clinically-detectable tumors is evasion from immune surveillance due to lack of cancer cells surface membrane expression of tumor-specific peptides in association with MHC class I molecules, concealment of natural killer cells-activating molecules, and absence of inflammation resulting from inefficient stimulation of innate immunity receptors and co-stimulatory molecules. The tumor microenvironment (TME) also contributes to tumor initiation, progression and resistance to therapeutic interventions because of its dense, fibrogenic, barrier-like composition, aberrant vasculature, and production of cytokines and chemokines responsible for recruitment of immune suppressive cells, notably myeloid-derived suppressor cells, M2 macrophages, regulatory T cells, extracellular trap-forming neutrophils, and cancer-associated fibroblasts. We herein show that the relentless efforts and strategies to overcome the TME elusive tumor-promoting impact produced contrasting, opposed, controversial effects, characterized by limited efficacy and proven adversity, and most importantly deterred from attempts to discover and counteract the fundamental inherent mechanisms initiating, and not consequent to, carcinogenesis.

Background: Colorectal cancer (CRC) is prevalent globally, constituting 11.9% of cases in Mexico. Lymph node metastases are established prognostic indicators, with extracapsular lymph node extension (ENE) playing a crucial role in modifying prognosis. While ENE is associated with adverse factors, certain aspects, like lymph node conglomerates, are underexplored. Matted nodes, clusters of lymph nodes infiltrated by cancer cells, are recognized as an independent prognostic factor in other cancers. This study investigates the prognostic implications of lymph node conglomerates, particularly matted nodes, in colon cancer. Methods: A retrospective analy-sis of 502 colon cancer cases (2005–2018) identified 255 with lymph node metastasis. Cases were categorized into two groups: 1) lymph node metastasis alone (n=208), and 2) lymph node metas-tasis with matted nodes (n=47). A comparative survival analysis was performed. Results: Of the 255 patients, 38% had lymph node metastasis. Patients with matted nodes (18.4%) showed an association with higher pN stage and lymphovascular invasion. The 5-year survival rate for pa-tients with matted nodes was 47.7%, compared to 60% without; however, this association demonstrated only a statistical tendency. Multivariate analysis identified clinical stage and ad-juvant chemotherapy use as independent factors contributing to survival. Conclusion: This study underscores matted nodes as potential prognostic indicators in colon cancer, emphasizing their association with higher pN stage and reduced survival. Further research is essential for validat-ing these findings and integrating matted nodes into the broader context of colorectal cancer management.

Cancer theragnostics is a novel approach that combines diagnostic imaging and radionuclide therapy. It is based on the use of a pair of radiopharmaceuticals, one optimized for positron emission tomography imaging, through linkage to a proper radionuclide, and the other bearing a beta-emitter isotope that can induce significant damage to cancer cells. In recent years, the use of theragnostics in nuclear medicine clinical practice has increased considerably, and thus investigation has focused on the identification of novel radionuclides that can bind to molecular targets which are typically dysregulated in different cancers. The major advantages of the theragnostic approach include elimination of multi-step procedures, reduced adverse effects to normal tissues, early diagnosis, better predicting responses and personalized patient care. This review aims to discuss emerging theragnostic molecules that have been investigated in a series of human malignancies, including gliomas, thyroid cancer, neuroendocrine tumors, cholangiocarcinoma and prostate cancer, as well as potent and recently introduced molecular targets, like cell-surface receptors, kinases, and cell adhesion proteins. Furthermore, special reference has been made to copper radionuclides as theragnostic agents, and their radiopharmaceutical applications since they present promising alternatives to the well-studied gallium-68 and lutetium-177.

Deregulation of cell growth and development lead to cancer, a severe condition that claims millions of lives worldwide. Targeted or selective approaches used during cancer treatment determine the efficacy and outcome of the therapy. In order to enhance specificity and targeting and better treatment options for cancer, novel and alternative modalities are currently under development. Photodynamic therapy has the potential to eradicate cancer and combination therapy would yield even greater outcomes. Nanomedicine-aided cancer therapy shows enhanced specificity for cancer cells and minimal side-effects coupled with effective cancer destruction both in vitro and in vivo. Nanocarriers used in drug-delivery systems are well able to penetrate cancer stem cell niche, simultaneously killing cancer cells and eradicate drug-resistant cancer stem cells, yielding therapeutic efficiency up to 100 fold against drug-resistant cancer in comparison with free drugs. Safety precautions should be considered when using Nano-mediated therapy as the effects of extended exposure to biological environments are still to be determined.

Background: The endocannabinoid system (ECS) is a very heterogeneous array consisting of many proteins like ligands, enzymes and receptors synthetized in various tissues and immunity cells. The main endogenous ligands are unsaturated fatty acid derivatives like anandamide(AEA), 2-arachidonoylglycerol(2-AG), but many others are under study. Endocannabinoids are involved in both physiological and pathological conditions. ECS plays an important role in the regulation of main processes which lead to cancer and also in sex steroid hormone-related cancers. Methods: With focus on gynaecological cancers, main papers and review articles, up to April 2018, on the role of the ECS, were acquired by PubMed searches using the search terms: ‘cancer’, ‘cannabinoid’, ‘endocannabinoid’, ‘gynaecology’ and ‘malignancy’. Results: The review of recent literature data showed the involvement of the endocannabinoid system in numerous physiological and pathological conditions of the female genital tract up to the development of gynaecological malignancy as cervical, endometrial and ovarian cancer. Conclusions: The endocannabinoid system has an important role in antitumor actions involving different signalling receptor and receptor-independent pathways. It represents an exciting challenge to researchers for its potential use in diagnosis and treatment of all gynaecological malignancies

Pregnancy associated plasma protein-A (PAPP-A) plays an integral role in breast cancer (BC), especially triple negative breast cancer (TNBC). This subtype accounts for the most aggressive BC, possesses high tumor heterogeneity, is least responsive to standard treatments and has the poorest clinical outcomes. There is a critical need to address the lack of effective targeted therapeutic options available. PAPP-A is a protein that is highly elevated during pregnancy. Frequently, higher PAPP-A expression is detected in tumors than in healthy tissues. The increase in expression coincides with increased rates of aggressive cancers. In BC, PAPP-A has been demonstrated to play a role in tumor initiation, progression, metastasis including epithelial-mesenchymal transition (EMT), as well as acting as a biomarker for predicting patient outcomes. In this review, we present the role of PAPP-A, with specific focus on TNBC. The structure and function of PAPP-A, belonging to the pappalysin subfamily, and its proteolytic activity are assessed. We highlight the link of BC and PAPP-A with respect to the IGFBP/IGF axis, EMT, the window of susceptibility and the impact of pregnancy. Importantly, the relevance of PAPP-A as a TNBC clinical marker is reviewed and its influence on immune-related pathways are explored. The relationship and mechanisms involving PAPP-A reveal the potential for more treatment options that can lead to successful immunotherapeutic targets and the ability to assist with better predicting clinical outcomes in TNBC.

Background: This study retrospective evaluates patients with stage IV melanoma treated with Nivolumab and Ipilimumab combination therapy from two regional oncology centers from Romania between the years of 2019 up to the end of 2022. Methods: The data were analyzed in SAS for Windows, V9.4. The survival curves were estimated using the Kaplan-Meier method, and survival distributions were compared with log-rank test. The effects of the main clinical and pathological variables on OS and PFS were investigated with Cox regression. Results: Kaplan-Meier curve of OS in all evaluable patients enrolled in the study resulted in a median OS of 346 days (95% CI: 150-NA) and a median PFS of 211 days (95% CI: 113-430). 45.3% of the patients experienced adverse events during the Nivolumab + Ipilimumab treatment with some of them having multiple organ systems involved. Discussion: The OS values were lower than that reported in approval clinical trials, but the results show a marked improvement when comparing to results obtained by chemotherapy regimens previously used in these scenarios. Conclusion: This study provides real-world insights into the survival data and safety profiles of combination therapy with anti-PD-1 antibodies and anti-CTLA-4 antibodies.

This thesis presents a comprehensive review of cancer, with a particular focus on its physical and biochemical basis. Cancer, a leading cause of mortality worldwide, is characterized by the uncontrolled growth and spread of abnormal cells. Understanding the fundamental differences between cancerous and normal cells is essential for developing effective diagnostic tools and therapeutic strategies. The review begins by exploring the physical anomalies of cancer cells, including their irregular shape, size, and structural organization. These cells often exhibit altered cell membranes, disrupted cytoskeletal architecture, and irregularities in cell adhesion and communication, which contribute to their invasive and metastatic potential. The biochemical basis of cancer is examined in detail, with an emphasis on the dysregulation of key metabolic pathways. Cancer cells undergo profound metabolic reprogramming, often referred to as the Warburg effect, where they preferentially utilize glycolysis over oxidative phosphorylation, even in the presence of oxygen. This metabolic shift supports the rapid proliferation of cancer cells and their survival in hypoxic conditions. Additionally, cancer cells produce abnormal proteins that contribute to tumor progression, such as mutant p53, and fail to produce critical tumor suppressor proteins like RB1, leading to unchecked cell division and evasion of apoptosis. Furthermore, the thesis reviews the role of oncogenes and tumor suppressor genes in cancer development, highlighting how mutations and epigenetic alterations drive the transformation of normal cells into malignant ones. The complex interplay between these genetic changes and the tumor microenvironment is also discussed, emphasizing the importance of signaling pathways, immune evasion, and angiogenesis in cancer progression. This detailed review synthesizes current research and insights from authoritative sources, including peer-reviewed journals and foundational medical texts, to provide a thorough understanding of the physical and biochemical underpinnings of cancer. The findings underscore the importance of continued research in these areas to advance the diagnosis, treatment, and prevention of cancer.

The immune system attempts to eliminate foreign substances, such as pathogens and viruses, that invade the body. As normal cells transform into cancerous cells, the immune system can eliminate these cells and suppress cancer onset. The immune system is regulated so that it does not become overactive or attack normal cells. When cancer cells transform from normal cells, they acquire various characteristics, and some cancer cells influence the regulatory function of the immune system to suppress it and escape immune attack. Therefore, treatments have been developed to eliminate the suppression of the immune system by cancer cells and to restore the immune system's ability to eliminate cancer cells. Immunotherapies include immune checkpoint inhibitors, cytokines, cancer vaccines, and effector cell therapies. Cytokine therapy activates the immune system by injecting substances produced by immune cells (such as interleukin 2 and interferon alpha) into the body, thereby increasing the ability of the immune system to attack cancer cells. Cancer vaccine therapy enhances the attack on cancer cells by injecting substances (antigens) that serve as markers for cancer cells into the body to make it easier for immune cells to detect the cancer. Depending on the type of antigen, cancer peptides, tumor cells, and dendritic cell vaccines are available. Effector cell therapy is a treatment method in which immune cells that directly attack cancer cells (CD8+ T cells, NK cells, etc.) are taken from the patient's body, expanded outside the body, activated, and returned to the body to attack cancer cells. To develop these treatments, it is essential to understand the cells and molecules related to immunity as well as the local tumor environment. In this article, we consider the factors related to antitumor immunity.

This bibliometric study analysed breast cancer research trends and outputs from 2014 to 1 2023, utilising data from the Scopus database. The primary objectives include analysing publication 2 growth, citation metrics, document type distribution, leading countries, preferred journals and 3 authorship patterns. The study reveals a significant increase in breast cancer research publications, 4 with a total of 12,073 documents and 216,769 citations over the ten-year period. The United States 5 leads in publication output and citation impact, followed by China and Japan. Articles are the 6 predominant document type for total 73.4% of publications, while reviews and book chapters also 7 contribute notably. The most preferred journals for publishing breast cancer research include Breast 8 Cancer Research and Treatment, Clinical Breast Cancer, and Breast Cancer Research. Authorship 9 patterns show a trend towards multi-authored papers, with a substantial number of papers having 10 more than five authors. The study underscores the global collaborative effort in advancing breast 11 cancer research and highlights key areas for future exploration.

Background/Objectives: The global burden of colorectal cancer (CRC) is projected to increase by 2040, highlighting the need for prevention strategies, early detection and adequate follow. The aim of this study was to provide an overview of the progress in personalized medicine of CRC in Serbia, with results and insights from the Institute for Oncology and Radiology of Serbia (IORS), and to propose guidance for tackling observed challenges in the future. Methods: Epidemiological data was derived from official global and national cancer registries and IORS electronic medical records. Germline genetic testing for Lynch syndrome was performed by Next Generation Sequencing. RAS and BRAF mutation analyses were performed using qPCR diagnostic kits. Results: Epidemiology and risk factors, prevention and early detection programs, as well as treatment options and scientific advances have been described in detail. Out of 103 patients who underwent germline testing for Lynch syndrome, 19 (18.4%) had a pathogenic or likely pathogenic mutation in one of the MMR genes, and 8 (7.8%) in other CRC-associated genes (APC, CHEK2, MUTYH). Of 6369 tested patients, 50.43% had a mutation in KRAS or NRAS genes, while 9.54% had the V600 mutation in the BRAF gene. Conclusions: Although significant improvements in CRC management have occurred globally in recent years, the high incidence of young-onset CRC and the growing elderly population due to a rise in life expectancy require a strategic approach leading to population-based systemic solutions, especially important for countries with limited health care resources as Serbia.

Introduction and Objectives: Multimorbidity, defined as the coexistence of two or more chronic conditions, poses significant challenges in healthcare by affecting patient outcomes and increasing costs. This study aimed to evaluate multimorbidity's impact on patients with genitourinary cancer (GUC) in Chile, focusing on prevalent comorbidities, their combinations, and their association with hospitalization severity. Materials and Methods: A retrospective, population-based study was conducted using data from the Fondo Nacional de Salud (FONASA) in Chile, including patients with bladder, prostate, kidney, and testicular cancer between 2019 and 2021. Diagnosis-related group (DRG) data were used to analyze comorbidity prevalence, hospitalization type (elective vs. emergency), severity (moderate/major vs. minor/none), length of stay, and associated costs. Results: Among 4,028,597 hospital events, 11.6% were related to GUC, involving 18,792 patients. Multimorbidity was present in 67.3% of patients, with hypertension and diabetes being the most common comorbidities. These patients accounted for 69.1% of total GUC care costs. Hospital mortality was higher in multimorbid patients (7.5% vs. 3.7%; P<0.001), who also had longer stays (mean 8 vs. 5 days). Most patients were admitted electively (60.3%), while 39.7% were admitted through the emergency room. Patients with multimorbidity had higher rates of moderate/major severity hospitalizations compared to those without (56.1% vs. 32.5%; P<0.001). Conclusions: In Chile, multimorbidity in GUC patients is linked to increased costs, longer hospital stays, higher mortality, and greater hospitalization severity. Comprehensive care strategies are needed to improve outcomes and reduce healthcare system burdens.

Gastroesophageal cancers, are among the most prevalent cancers globally and represent the third leading cause of cancer-related mortality worldwide. Surgical resection remains the primary curative approach for localized and locally advanced stages, but its effectiveness is limited for locally advanced diseases, evidenced by a low 5-year survival rate of around 25%. High relapse rates post-surgery, particularly in western populations, necessitate the use of neoadjuvant, adjuvant, or perioperative strategies involving chemotherapy and radiation to improve surgical outcomes. Neoadjuvant chemoradiation therapy has demonstrated a significant improvement in overall survival. Recent advances have identified several target genes and pathways involved in the pathogenesis and progression of these cancers, leading to the development of targeted drugs, including immunotherapy, anti-HER-2 antibodies, and anti-VEGFR antibodies. These targeted therapies are emerging as promising interventions for better patient outcomes and personalized treatment approaches and therefore could eventually evolve into a novel therapeutic regimen for gastroesophageal cancer.

Cancer stem cell (CSC) has paved the way to many fundamental and translational studies. Recent studies have highlighted differentiated breast cancer cells (non-CSCs) switching phenotype to CSCs in response to various stimuli, depicting the existence of cancer stem cell plasticity. Although strategies to reduce the phenotypic plasticity of non-CSCs into CSCs are likely to prevent treatment-resilient cancer cells driving recurrence, most phenotypic plasticity mechanisms involve Notch, Wnt or MAPK signaling pathways. In this study, breast cancer cells were irradiated to identify soluble reprogramming factors. Using conditioned medias, protein arrays analyses, flow cytometry and in cellulo/in vivo functional assays, we demonstrated, for the first time, that radiation-induced chemokine expression, especially CXCL1 and CCL5 and their receptors CXCR2, CCR1 and CCR5, stimulates reprogramming of breast non-CSCs into CSCs. Treatment of non-CSCs with recombinant CXCL1 and CCL5 is sufficient to induce cell reprogramming, while their inhibition can be used to prevent reprogramming and sensitize tumor to radiation. Moreover, analysis of gene expression profiles from 38 public merged databases demonstrated that combined over-expression of CXCL1/CXCR2, CCL5/CCR1 or CCL5/CCR5 has a poorer prognosis in patients treated with radiotherapy, suggesting a promising way for patient stratification, where individuals with elevated cytokine levels could benefit from radiotherapy in conjunction with cytokine inhibitors. Taken together, our findings provide a rationale to consider these axes as potential targets and predictive biomarkers in breast cancer patients.

Background and objectives: TSC1 is a crucial component of the mTOR pathway, impacting cell growth, proliferation, and autophagy, while TSC2 is a tumor suppressor gene that regulates cell growth and is associated with the mTOR signaling pathway. In the present study, we analyzed TSC1 and TSC2 mRNA expression levels in rectal cancer, and evaluated the clinicopathological and prognostic characteristics of TSC1 and TSC2. Materials and Methods: TSC1 and TSC2 mRNA expression was examined in various cancer types. We further evaluated survival to determine the prognostic significance of TSC1 and TSC2 mRNA in CRC using The Cancer Genome Atlas (TCGA) data. Results: The study focused on rectal cancer, as it exhibited the most promising results. The patients were split into two subgroups, each comprising 50% of the total, based on the TSC gene expression levels. This division was made to assess the clinical characteristics associated with the expression of TSC1 and TSC2 genes. In the study, lower TSC1 expression was linked to venous invasion in rectal cancer patients, and there was also a related trend with lymphatic invasion, although it didn't reach statistical significance. Lower TSC2 expression was observed in younger patients and had some associations with sex and M stage, but these correlations were not statistically significant. When it came to survival analysis, TSC1 expression did not significantly impact overall survival, while higher TSC2 expression was associated with a poorer prognosis in rectal cancer. To enhance our comprehension, additional research, especially in larger case studies, is needed to explore the molecular mechanisms and clinical characteristics of TSC genes in colorectal cancer.

(1) Background: China holds the highest esophageal squamous cell carcinoma (ESCC) incidence areas in the world, with some areas of incidence over 100 per 100,000. Despite extensive public health efforts, its etiology is still poorly understood. This study aims to review and summarize past research into potential etiologic factors for ESCC in China. (2) Methods: Relevant observational and intervention studies were systematically extracted from four databases using key terms, reviewed using Rayyan software, and summarized into Excel tables. (3) Results: Among the 207 studies included in this review, 130 studies were focused on genetic etiologic factors, followed by 22 studies focused on dietary-related factors, 18 studies focused on HPV-related factors, and 37 studies focused on other factors. (4) Conclusions: ESCC in China involves a variety of factors including genetic variations, gene-environment interactions, dietary factors like alcohol, tobacco use, pickled vegetables, and salted meat, dietary behavior such as hot food/drink consumption, infections like HPV, poor oral health, gastric atrophy, and socioeconomic factors. Public health measures should prioritize genetic screening for relevant polymorphisms, conduct comprehensive investigations into environmental, dietary, and HPV influences, enhance oral health education, and consider socioeconomic factors overall as integral strategies to reduce ESCC in high-risk areas of China.

Cancer is amenable to low-cost treatments, given that it has a significant metabolic component, which can be effected through diet and lifestyle change at minimal cost. The Warburg hypothesis states that cancer cells have altered cell metabolism towards anaerobic glycolysis. Given this metabolic reprogramming in cancer cells, it is possible to target cancers metabolically by depriving them of glucose. In addition to dietary and lifestyle modifications which work on tumors metabolically, there are a panoply of nutritional supplements and repurposed drugs associated with cancer prevention, and better treatment outcomes. These interventions and their evidentiary basis are covered in the latter half of this review to guide future cancer treatment.

Preferentially expressed Antigen in Melanoma (PRAME) is a cancer testis antigen (CTA) that is selectively expressed in certain somatic tissues, predominantly in the testis and is overexpressed in various cancers. PRAME family proteins are leucine rich repeat proteins, that are localized in the nucleus and cytoplasm, with multifaceted roles in immunity, during gametogenesis and in the overall reproduction process. It is a widely studied CTA and has been associated with the prognosis and therapeutic outcome in patients with epithelial and non-epithelial tumors. PRAME has also been studied extensively as a therapeutic target. Moreover, it has been found to play a role in most of the well-known cancer hallmarks. Interestingly, the role of PRAME in tumorigenesis is paradoxical. Over the last decade, PRAME has garnered substantial interest as a target for immunotherapy. There are multiple clinical trials and pre-clinical studies targeting PRAME alone or in combination with other tumor antigens. This review article is an attempt to update our knowledge and understanding of the context-dependent oncogenic functions of PRAME in various carcinomas, and the current immunotherapeutic strategies, challenges, and perspectives on developing newer strategies to target PRAME for a better outcome.

Like living organisms, cancer cells require energy to survive and interact with their environment. Mitochondria are the main organelles for energy production and cellular metabolism. Recently, investigators demonstrated that cancer cells can hijack mitochondria from immune cells. This behavior sheds light on a pivotal piece in the cancer puzzle, the ‘dependence’ on the normal cells. This article illustrates the benefits of new, functional mitochondria for cancer cells that urge them to hijack mitochondria. It describes how functional mitochondria help cancer cells’ survival in the harsh tumor microenvironment, immune evasion, progression, and treatment resistance. Recent evidence has put forward the pivotal role of mitochondria in cancer stem cells’ metabolism. This theory highlights the mitochondria in cancer biology and explains how targeted anti-mitochondrial treatments can improve oncological outcomes.

SAMHD1 is a deoxynucleotide triphosphate (dNTP) triphosphohydrolase with important roles in the control of cell proliferation and apoptosis, either through the regulation of intracellular dNTPs levels or the modulation of the DNA damage response. However, SAMHD1 role in cancer evolution is still unknown. We performed the first in-depth study of SAMHD1 role in advanced solid tumors, by analyzing samples of 128 patients treated with chemotherapy agents based on platinum derivatives and/or antimetabolites and developing novel in vitro knock-out models to explore the mechanisms driving SAMHD1 function in cancer. Low or no expression of SAMHD1 was associated with a positive prognosis in breast, ovarian and non-small cell lung cancer (NSCLC) cancer patients. A predictive value was associated to low-SAMHD1 expression in NSCLC and ovarian patients treated with antimetabolites in combination with platinum derivatives. In vitro, SAMHD1 knock-out cells showed increased γ-H2AX and apoptosis suggesting that SAMHD1 depletion induces DNA damage leading to cell death. In vitro treatment with platinum-derived drugs significantly enhanced γ-H2AX and apoptotic markers expression in knock-out cells, indicating a synergic effect of SAMHD1 depletion and platinum-based treatment. SAMHD1 expression represents a new strong prognostic and predictive biomarker in solid tumors and thus, modulation of SAMHD1 function may constitute a promising target for the improvement of cancer therapy.

Background: There is ongoing debate regarding the usefulness of laparoscopic pancreaticoduodenectomy. This study aimed to analyze all the randomized control trials published including the most recent one. Material and methods: The study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and MOOSE guidelines. Heterogeneity was measured using Q tests and I2. The random-effects models were used to summarise the relative risks, odds ratios, and mean differences as appropriate.Results:4 RCTs were included consisting of 818 patients. 411 patients were in the laparoscopic group and 407 in the open pancreaticoduodenectomy group. Weighted baseline patient characteristics were similar except more patients with pancreatic adenocarcinoma and more males were there in the open pancreaticoduodenectomy group. There was no difference in-hospital stay,90 days complications rate, 90 days mortality, R1 resection, postoperative pancreatic fistula, delayed gastric emptying, post pancreatectomy hemorrhage, bile leak between the two groups. Operative time was more in the laparoscopic group. Blood loss [mean difference -132.12 ml (-172.60,-91.65)] and surgical site infection [Risk ratio 0.41 ( 0.17-1.0)] were significantly lesser in laparoscopic group.Conclusion:There was no benefit in-hospital stay or clinical outcomes after laparoscopic pancreaticoduodenectomy. Blood loss and surgical site infection were lesser in laparoscopic pancreaticoduodenectomy.

The majority of cellular responses to external stimuli are mediated by receptors such as G protein-coupled receptors (GPCRs) and systems including endoplasmic reticulum stress (ER stress). Since GPCR signalling is pivotal in numerous malignancies, they are widely targeted by a number of clinical drugs. Cancer cells often negatively modulate GPCRs in order to survive, proliferate and to disseminate. Similarly, numerous branches of the unfolded protein response (UPR) act as pro-survival mediators and are involved in promoting cancer progression via mechanisms such as epithelial to mesenchymal transition (EMT). However, there are a few proteins among these groups which impede deleterious effects by orchestrating the pro-apoptotic phenomenon and paving a therapeutic pathway. The present review exposes and discusses such critical mechanisms and some of the key processes involved in carcinogenesis.

Ovarian cancer is the most lethal gynecological malignancy. Poor overall survival, particularly for patients with high grade serous (HGS) ovarian cancer, are often attributed to late stage at diagnosis and relapse following chemotherapy. HGS ovarian cancer is a heterogenous disease in that few genes are consistently mutated between patients. Additionally, HGS ovarian cancer is characterized by high genomic instability. For these reasons personalized approaches may be necessary for effective treatment and cure. Understanding the molecular mechanisms that contribute to tumor metastasis and chemoresistance are essential to improve survival rates. One favored model for tumor metastasis and chemoresistance is the cancer stem cell (CSC) model. CSCs are cells with enhanced self-renewal properties that are enriched following chemotherapy. Elimination of this cell population is thought to be a mechanism to increase therapeutic response. Therefore, accurate identification of stem cell populations that are most clinically relevant is necessary. While many CSC identifiers (ALDH, OCT4, CD133, and side population) have been established, it is still not clear which population(s) will be most beneficial to targeted in patients. Therefore, there is a critical need to characterize CSCs with reliable markers and find their weaknesses that will make the CSCs amenable to therapy. Many signaling pathways are implicated for their roles in CSC initiation and maintenance. Therapeutically targeting pathways needed for CSC initiation or maintenance may be an effective way of treating HGS ovarian cancer patients. In conclusion, the prognosis for HGS ovarian cancer may be improved by combining CSC phenotyping with targeted therapies for pathways involved in CSC maintenance.

Although several plant-derived drug groups (vinca alkaloids, taxanes, podophyllotoxin derivatives and camptothecins) continue to be widely used in cancer therapy, the anticancer potential of the Plant Kingdom remains largely unexplored. In this work, we have carried out a random screening for selective anticancer activity of 57 extracts from 45 plants collected in Grazalema Natural Park, an area in the South of Spain of high plant diversity and endemism. Using lung cancer cells (A549) and lung non-malignant cells (MRC-5), we found that several extracts were more cytotoxic and selective against the cancer cell line than the standard anticancer agent cisplatin. Five active extracts were further tested in cancer and normal cell lines from other tissues, including three skin cell lines with increasing degree of malignancy. An extract from the leaves of Daphne laureola L. (Thymelaeaceae) showed a striking potency and selectivity on lung cancer cells and leukemia cells; the IC₅₀ values against these cancer cells were approximately 10000-fold lower than against the normal cells. Daphnane-type diterpene orthoesters may be responsible for this highly selective anticancer activity.

Gastrointestinal (GI) cancers are the most common causes of global cancer burden and cancer-related deaths. Chronic inflammation is a hallmark feature of GI tumors and plays an important role in tumor initiation, progression, and therapeutic response. The genetic makeup of cancer cell, as well as epigenetic alterations, and biological processes constitute an inflammatory tumor microenvironment (TME) that provides an essential nich for cancer initiation and progression. Cancer-associated inflammation, a key component of TME, displays protumoral or antitumoral activity depending on the composition, spatial distribution, and functional status of the immune cells involved, thus adversely affecting response to cancer treatment and clinical outcomes, whereas acute inflammation supports T-cell priming, activation, and infiltration into malignant tissues, thereby conferring anti-tumoral immunity. Inflammatory cells and proinflammatory molecules within the TME act as a bridge between inflammation and cancer. The majority of cells involved in the inflammatory process in the TME are innate immune cells, which play a critical role in shapping both the cellular composition of the TME and the plasticity of cancer cells and stromal cells. Activation of innate immune cells in the TME initiates the production of inflammatory, regenerative, and anti-inflammatory soluble molecules, resulting in adaptive immune response to the cancer. Additionally, aberrant activation of intracellular signaling pathways, inflammatory molecules, and metabolites have critical roles in the development and healing of inflammation during carcinogenesis. Cancer-associated inflammation may inhibit the effectiveness of anti-cancer agents by causing enzymatic degradation of drugs and modulating the immun activity, thus affecting survival of patient. In this review article, we highlight the genetic and cellular mechanisms involved in the formation of the inflammatory component of the TME in GI cancers, the soluble molecules, the cancer cell-immune cell interactions, and the implications of all these for clinical outcomes. We also comprehensively address the mechanisms linking chronic inflammation to cancer, with a focus on the most frequent GI cancers.

Long noncoding RNAs (lncRNAs) are known to play key roles in breast cancers; however, detailed mechanistic studies of lncRNA function have not been conducted in large cohorts of breast cancer tumors, nor have inter-donor and inter-subtype variabilities been taken into consideration. Here we provide the first identification and annotation of the human BORG lncRNA gene. Using multiple tumor cohorts of human breast cancers, we show that while BORG expression is strongly induced in breast tumors as compared to normal breast tissues, the extent of BORG induction varies widely between breast cancer subtypes and even between different tumors within the same subtype. Elevated levels of BORG in breast tumors are associated with the acquisition of core cancer aggression pathways, including those associated with basal tumor and pluripotency phenotypes, and with epithelial-mesenchymal transition (EMT) programs. While a subset of BORG-associated pathways was present in high BORG-expressing tumors across all breast cancer subtypes, many were specific to triple-negative breast cancer tumors. Finally, we show that genes induced by heterologous expression of BORG in murine models of TNBC both in vitro and in vivo strongly overlap with those associated with high BORG levels in human TNBC tumors, indicating that human BORG is a novel driver of the highly aggressive basal TNBC tumor phenotype.

Colorectal cancer (CRC) is a weighty cause of mortality worldwide, with growing incidence in the Middle East. Understanding the level of awareness about CRC screening among the Syrian pop-ulation is crucial public health interventions. A cross-sectional study was conducted from Sep-tember 22, 2023, to October 15, 2023, involving 928 participants from six major governorates in Syria. An online questionnaire containing socio-demographic, knowledge, and attitude sections was used to collect data. Descriptive statistics and chi-square tests were employed for data analysis using (SPSS) v28.0. The survey revealed a lack of awareness regarding CRC screening among the Syrian population, with only 499(53%) of the proportion demonstrating adequate knowledge about the disease and its screening methods. Significant associations were observed between the level of knowledge and socio-demographic factors including gender, work status, and economic status (p < 0.05). The findings emphasize the need for public health initiatives to enhance awareness and knowledge about CRC and its early screening methods in Syria. Education is essential for improving early detection and reducing the burden of colorectal cancer in the region. Efforts to increase public understanding of CRC screening are critical for reducing the incidence and mortality.

Background: Despite recent advances in epithelial ovarian carcinoma (EOC) treatment, recur-rence and mortality rates have not improved significantly. DNA hypermethylation has generally been associated with ominous prognosis and chemotherapy resistance, but the role of DNMTs in EOC remains to be investigated. Methods: In the current study, we systematically retrieved gene expression data from patients with EOC and studied the immunohistochemical expression of DNMTs in 108 primary and 26 relapsed tumors. Results: Our results showed that DNMT1, DNMT3A, DNMT3B and DNMT3L RNA levels were higher and DNMT2 lower in tumors compared to non-neoplastic tissue, and DNMT3A and DNMT2 expression decreased from Stage II to Stage IV carcinomas. Proteomic data also suggested that DNMT1 and DNMT3A levels were increased in tumors. Similarly, DNMT1, DNMT3A and DNMT3L protein levels were overex-pressed and DNMT2 expression was reduced in high grade carcinomas compared to non-neoplastic tissue and low-grade tumors. Moreover, DNMT1 and DNMT3L were increased in relapsed tumors compared to their primaries. DNMT3A, DNMT1 and DNMT3B mRNA lev-els were correlated with overall survival. Conclusions: Our study demonstrates that DNMT1 and DNMT3L are upregulated in primary high grade EOC and further increase in relapses, whereas DNMT3A is upregulated only in the earlier stages of cancer progression. DNMT2 downregulation highlights a presumptive tumor-suppressor activity of this gene in ovarian car-cinoma.

Cancer is fundamentally a disease of perturbed genes. Although many mutations can be marked in the genome of a cancer or transformed cell, the initiation and progression were shown to be driven by only a few mutational events viz. driver mutations that progressively govern and execute the functional impacts. The driver mutations are thus believed to dictate and dysregulate the subsequent cellular proliferative function/decisions thereby producing a cancerous state. Therefore, identifying the driver events from the genomic alterations in a patient’s cancer cell gained large attention recently for designing better targeting therapies towards paving way for the precision cancer medicine. With rolling advancements in high-throughput omics technologies, analysis of genetic variations and gene expression profiles for cancer patients has become a routine clinical practice. However, it is anticipated that protein structural alterations resulting from such driver mutations can provide more direct and clinically relevant evidence of disease states than genetic signatures alone. This review comprehensively discusses various aspects and approaches that have been developed for the prediction of cancer drivers using genetic signatures and protein structures, and their potential application in developing precision cancer therapies.Keywords:

Formalin-Fixed Paraffin Embedded (FFPE) tissues are a valuable resource in studying different markers and mechanistic molecules (protein, DNA and RNA) in order to understand the etiology of different cancers as well as many other diseases. Degradation and modification of RNA is the major challenge in utilizing FFPE tissue samples in medical research. Recently, non-protein coding transcripts long non-coding RNAs (lncRNAs), have gained significant attention due to their important biological actions and potential involvement in cancer. There is no validated method except qRTPCR or RNAseq to evaluate and study lncRNA expression. We have standardized and are reporting a sensitive Z probe based in situ hybridization method to identify, localize and quantitate lncRNA in FFPE tissues. This assay is sensitive to single transcript and localizes lncRNA in individual cells within tumor. We have characterized a tumor suppressor lncRNA-NRON (non coding repressor of NFAT), which is scarcely expressed, a moderately expressed oncogeneic lncRNA UCA1 (urothelial cancer associated 1), and a highly studied and expressed lncRNA MALAT1 (metastasis associated lung adenocarcinoma transcript1) in different cancers. High MALAT1 staining was found in colorectal, breast and pancreatic cancer. MALAT1 expression increased with the progression of the stage in colorectal cancer and invasiveness in breast cancer.

The sulfur-containing amino acids methionine (Met), cysteine (Cys) and taurine (Tau) are common dietary constituents with important cellular roles. Met restriction is already known to exert in vivo anticancer activity. However, since Met is a precursor of Cys, and Cys produces Tau, the role of Cys and Tau in the anticancer activity of Met-restricted diets is poorly understood. In this work, we screened the in vivo anticancer activity of several Met-deficient artificial diets supplemented with Cys, Tau or both. Diet B1 (6% casein, 2.5% leucine, 0.2% Cys and 1% lipids) and diet B2B (6% casein, 5% glutamine, 2.5% leucine, 0.2% Tau and 1% lipids) showed the highest activity and were selected for further studies. Both diets induced a marked anticancer activity in two animal models of metastatic colon cancer, which were established by injecting CT26.WT murine colon cancer cells in the tail vein or peritoneum of immunocompetent BALB/cAnNRj mice. Diets B1 and B2B also increased the survival of mice with disseminated ovarian cancer (intraperitoneal ID8 Tp53 -/- cells in C57BL/6JRj mice) and renal cell carcinoma (intraperitoneal Renca cells in BALB/cAnNRj mice). The high activity of diet B1 in mice with metastatic colon cancer may be useful in colon cancer therapy.

A brand-new approach to the understanding of breast cancer (BC) is urgently needed. In this contribution, the etiology, pathogenesis, and treatment of this disease is approached from the new pH-centric anticancer paradigm. Only this Unitarian perspective based upon that the hydrogen ion (H+) dynamics of cancer, allows understanding and integrating the many dualisms, confusions, and paradoxes of the disease. The new H+-related wide range model can embrace under a unique frame of mind the many aspects of the disease and at the same time therapeutically interfere with most, if not with all, the hallmarks of cancer known to date. The pH-related armamentarium available for the treatment of BC here reviewed may be beneficial for all types and stages of the disease. In this vein, we have attempted a mega synthesis of traditional and new knowledge in the different areas of breast cancer research and treatment based upon the wide range approach afforded by the hydrogen ion dynamics of cancer. The concerted utilization of a pH-related drugs nowadays available for the treatment of breast cancer is advanced.

It has been declared repeatedly that cancer is a result of molecular genetic abnormalities. However, there has been no working model describing the specific functional consequences of the deranged genomic processes that result in the initiation and propagation of the cancer process during carcinogenesis. We no longer need to question whether or not cancer arises as a result of a molecular genetic defect within the cancer cell. The legitimate questions are: how and why? This article reviews the preeminent data on cancer molecular genetics and subsequently proposes that the sentinel event in cancer initiation is the aberrant production of fused transcription activators with new molecular properties within normal tissue stem cells. This results in the production of vital oncogenes with dysfunctional gene activation transcription properties, which leads to dysfunctional gene regulation, the aberrant activation of transduction pathways, chromosomal breakage, activation of driver oncogenes, reactivation of stem cell transduction pathways and the activation of genes that result in the hallmarks of cancer. Furthermore, a novel holistic molecular genetic model of cancer initiation and progression is presented along with a new paradigm for the approach to personalized targeted cancer therapy, clinical monitoring and cancer diagnosis.

Telomerase presents over-expression in most of cancer cells and has been a near-universal marker of cancer. Studies revealed that inhibiting telomerase activity by utilizing oligonucleotides to down-regulate the expression of intracellular human telomerase reverse transcriptase (hTERT) mRNA was an effective method to achieve anti-tumor therapy. Considering oncogenic microRNA-21 has been proved to indirectly up-regulate hTERT expression and drive cancer metastasis and aggression through increased telomerase activity, here we constructed a AS1411-functionallized oligonucleotide-conjugated gold nanoprobe (Au-nanoprobe) to simultaneously down-regulate intracellular microRNA-21 and hTERT mRNA by using anti-sense oligonucleotide technology to explore their targeted anti-tumor therapy effect. In vitro cell studies demonstrated that Au-nanoprobes could effectively induce apoptosis and inhibit the proliferation of cancer cells through down-regulating intracellular hTERT activity. In vivo imaging and anti-tumor studies revealed that Au-nanoprobes could accumulate at the tumor site and inhibit the growth of MCF-7 tumor xenografted on balb/c nude mice, thus exert the potential of anti-tumor therapy.

Anthocyanins, known for their antioxidant properties and potential health benefits, are prone to degradation due to environmental factors such as light, temperature, and pH. Microencapsulation, a technique involving the entrapment of anthocyanins in a protective matrix, is used to enhance their stability and bioavailability. This study investigates the bioactive properties of microencapsulated anthocyanins derived from Vaccinium floribundum (Andean blueberry) and Rubus glaucus (Andean blackberry). The extracts from V. floribundum and R. glaucus were microencapsulated using maltodextrin as the carrier agent through a spray-drying process. The microcapsules were characterized using Fourier Transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscopy (SEM) to assess their chemical and morphological properties. The biological activities of these microencapsulated anthocyanins were evaluated for their antibacterial, antioxidant, and anti inflammatory effects. The results demonstrated enhanced bioactivity of the microencapsulated anthocyanins, highlighting their potential use in developing functional foods and pharmaceuticals. This study provides insights into the effectiveness of microencapsulation in preserving anthocyanins' functional properties and enhancing their health-promoting effects.

Geothermal energy generation faces challenges in efficiency, partly due to restrictions on reinjection temperatures caused by scaling issues. Therefore, developing strategies to prevent scaling is critical. This study aims to simulate the scaling tendencies and corrosion effects of geothermal fluids on various construction materials used in scaling reactor/retention tank systems. A range of materials, including carbon steel, austenitic stainless steel, duplex stainless steel, two proprietary two-part epoxy coatings, and thermally sprayed aluminium (TSA), were tested in a simulated geothermal brine. Experiments were conducted in a laboratory vessel designed to replicate the wall shear stress conditions expected in a scaling reactor. The tests revealed varying scaling tendencies among the materials, with minimal corrosion observed. The dominant scale formed was calcium carbonate, consistent with geochemical modelling. The findings suggest that despite the high operating temperatures, the risk of corrosion remains low due to the brine's low chloride content, while the wettability of materials after immersion may serve as a useful indicator for selecting those that promote scaling.

One of the main objectives of developing new anti-cancer vaccine strategies is to effectively induce CD8+ T cell-mediated anti-tumor immunity. Live recombinant vectors, notably Listeria mono-cytogenes, have been shown to elicit a robust in vivo CD8+ T cell response in preclinical settings. Significantly, it has been demonstrated that Listeria induces inflammatory/immunogenic cell death mechanisms such as pyroptosis and necroptosis in immune cells that favorably control immunological responses. Therefore, we postulated that the host's response to Listeria-based vec-tors and the subsequent induction of CD8+ T cell-mediated immunity would be compromised by the lack of regulatory or effector molecules involved in pyroptosis or necroptosis. To test our hy-pothesis, we used recombinant L. monocytogenes carrying the ovalbumin gene (LM.OVA) to vac-cinate wild-type (WT), caspase-1/11-/-, gsdmd-/-, ripk3-/-, and mlkl-/- C57Bl/6 mice. We performed an in vivo cytotoxicity assay to assess the efficacy of OVA-specific CD8+ T lymphocytes in eliminat-ing target cells in wild-type and genetically deficient backgrounds. Furthermore, we evaluated the specific anti-tumor immune response in mice inoculated with B16F0 and B16F0.OVA mela-noma cell lines. Our findings demonstrated that while caspase-1/11 and GSDMD deficiencies in-terfere with the rapid control LM.OVA infection, of the KO seems to contribute to the early acti-vation of OVA-specific CTL responses. In contrast, individual deficiency of each one of these pro-teins negatively impact the generation of long-lasting effector CD8+ T cells.

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

Obesity is a highly prevalent chronic disease characterized by excessive weight gain and fat accumulation. There is growing evidence that Lactiplantibacillus plantarum strains with bile salt hydrolase (BSH) activity are effective in preventing and alleviating obesity. However, few of them has confirmed the anti-obesity effect of BSH by gene deletion. In this study, 23 BSH-positive Lp. plantarum strains were screened by bile salt precipitation halo assay. Among these strains, Lp. plantarum Lp20 showed the highest BSH activity with a hydrolysis rate to glycodeoxycholic acid (GDCA) by 91.62%. Genomic sequencing and bioinformatics analysis indicated that gene bsh1 was associated with BSH activity of Lp. plantarum Lp20 and gene deletion of bsh1 confirmed the role of Bsh1 in GDCA hydrolysis. To investigate if the Bsh1 from Lp. plantarum Lp20 could alleviate obesity, the wild type and bsh1 deletion mutant strains were administered daily for 8 weeks to diet-induced obese mice, respectively. Compared with mutant strain, the wild type strain Lp20 significantly reduced body weight gain, inguinal white adipose tissue and mesenteric fat mass in obese mice. In addition, Lp20 also reduced serum total cholesterol levels and LDL-C by 20.8% and 33.3%, respectively. Furthermore, the recovered liver steatosis was only observed in Lp. plantarum Lp20 treated mice. Taken together, the bile salt hydrolase Bsh1 from Lp. plantarum Lp20 was a key functional factor on ameliorating HFD-induced obesity by reducing cholesterol levels and suppressing adipogenesis in mice.

Postbiotic is a preparation of inanimate microorganisms and/or their components that confers a health benefit on the host. Different bacterial strain and preparation method result in different functions. Herein, a postbiotic preparation named Postbiotic-P by intercepting 1-5 KD of the cell-free supernatants of L. caseiparacasei P6 fermentation broth was prepared, and its multifunctional activities were evaluated. The results showed that Postbiotic-P exerted good antihemolytic (10%-50% Postbiotic-P resulted in 4.9%-48.1% antihemolytic rate), anti-inflammatory (8% to 40% Postbiotic-P is comparable to 259.1-645.4 μg/mL of diclofenac sodium equivalents), antioxidant [reducing power (1.25%-12.5% Postbiotic-P resulted in the increase of OD700 from 0.279-2.322), DPPH free radical scavenging activity (2.5%-50% Postbiotic-P resulted in 38.9%-92.4% free radical scavenging rate), and hydroxyl radical scavenging activity (0.5%-4% Postbiotic-P resulted in 4.66%-10.38% hydroxyl radical scavenging rate)], and antimicrobial activities (against 2 Gram-positive, 8 Gram-negative and 1 fungus). Furthermore, it was proved that Postbiotic-P could significantly inhibit the increase of the peroxide value and the malondialdehyde content in cookies, indicating the application potential of Postbiotic-P in food preservation. Taken together, Postbiotic-P has good application potential for the development of health care products and functional foods. However, further studies are needed to determine their precise mechanism of action, to clarify the active components responsible for the function, and to validate the biological activities in animal models or clinical trials.

Compared to the general population, patients with inflammatory bowel disease (IBD) are less likely to be vaccinated, putting them at an increased risk of vaccine-preventable illnesses. This risk is further compounded by the immunosuppressive therapies commonly used in IBD management. Therefore, developing new treatments for IBD that maintain immune function is crucial, as successful management can lead to better vaccination outcomes and overall health for these patients. Here, we investigate the potential of recombinant banana lectin (rBanLec) as a supporting therapeutic measure to improve IBD control and possibly increase vaccination rates among IBD patients. By examining the therapeutic efficacy of rBanLec in a murine model of experimental colitis, we aim to lay the foundation for its application in improving vaccination outcomes. After inducing experimental colitis in C57BL/6 and BALB/c mice with 2,4,6-trinitrobenzene sulfonic acid, we treated animals orally with varying doses of rBanLec 0.1-10 µg/ml (0.01 – 1 µg/dose) during the course of the disease. We assessed the severity of colitis and rBanLec’s modulation of the immune response compared to control groups. rBanLec administration resulted in a dose-dependent reduction in colitis severity (less pronounced weight loss, less shortening of the colon) and an improved recovery profile, highlighting its therapeutic potential. Notably, rBanLec-treated mice exhibited significant modulation of the immune response, favoring anti-inflammatory pathways (primarily reduction in a local [TNFα]/[IL-10]) crucial for effective vaccination. Our findings suggest that rBanLec could mitigate the adverse effects of immunosuppressive therapy on vaccine responsiveness in IBD patients. By improving the underlying immune response, rBanLec may increase the efficacy of vaccinations, offering a dual benefit of disease management and prevention of vaccine-preventable illnesses. Further studies are required to translate these findings into clinical practice.

Arguably the most important parameter in treating cognitive decline associated with Alzheimer’s disease is the length of time in which improvement, if achieved at all, is sustained. However, monotherapies such as donepezil and memantine are associated with a more rapid decline than no treatment in patients over multi-year follow-ups {Kennedy, 2018 #535}. Furthermore, anti-amyloid antibody treatment, which at best simply slows decline, is associated with accelerated cerebral atrophy [2], resulting in earlier dementia-associated brain volumes for those treated at the MCI stage than untreated patients. In contrast, a precision medicine approach, in which the multiple potential drivers of cognitive decline are identified for each patient and then targeted with a personalized protocol (such as ReCODE), has led to documented improvement in patients with cognitive decline [3]; [4]; [5], but long-term follow-up (>5 years) has not been reported previously. Therefore, we report here sustained cognitive improvement, in some cases for over a decade, in patients treated with a precision medicine protocol—something that has not been reported in patients treated with anti-cholinesterase, glutamate receptor inhibitory, anti-amyloid, or other therapeutic methods. These case studies warrant long-term cohort studies to determine how frequently such sustained cognitive improvements occur in patients treated with precision medicine protocols.

Global navigation satellite system (GNSS) array antenna receivers are widely used to suppress wideband interference in navigation countermeasures. However, existing array antenna receivers all adopt digital array structure and digital beamforming technique, and it has limited analog-front-end (AFE) dynamic range. In strong interference scenarios, AFE saturation will occur, which limits the maximum interference suppression ability of the array receiver. Aiming at this issue, this paper proposes a robust wideband interference suppression method for GNSS array antenna receivers based on hybrid beamforming technique. Firstly, a novel fully connected hybrid array receiver structure is proposed; Secondly, the corresponding hybrid beamforming method is proposed at the same time, and it realizes the complete elimination of strong interference by jointly suppression in analog domain and digital domain. After mathematical simulation experiments, it is verified that compared to the digital beamforming-based anti-jamming technique, the proposed method can effectively suppress strong wideband interference, and the maximum interference suppression ability is improved by 36 dB.

Opuntia ficus-indica (L.) Mill. belongs to the Cactaceae family and the genus Opuntia; it is a succulent plant that adapts to extreme climatic conditions. The aerial part of the plant consists of the cladodes, morphological changes of branches that appear green, are covered with thorns, and are essential to reduce excessive perspiration of water. The composition of cladodes is very varied, and the main constituents are water, fibers, polysaccharides, proteins, fatty acids, vitamins, sterols, minerals, and polyphenols. Polyphenols are responsible for many beneficial activities for human health, such as antioxidant, anti-inflammatory, antitumor, and nutritional properties. The purpose of this manuscript was to compare the properties of cladodes belonging to the same plant but with different stages of maturity. Relative extracts were tested both in vitro and on a cell line and antioxidant and anti-apoptotic properties were found. The antioxidant activity was tested by the ORAC test, the DPPH test, and the measurement of cellular accumulation of ROS. Anti-apoptotic activity was evaluated by the annexin/PI assay and measurement of caspases 9 and 3 expression. The results obtained have shown that the extracts considered possess antioxidant and anti-apoptotic properties. However, the different stages of maturity of cladodes are essential for the performance of both functions. In addition, important variations have been made in the dissolution of extracts that have brought greater safety in their use. In conclusion, this manuscript provides further information on cladodes of Opuntia ficus-indica, which can be used as adjuvants in many human pathologies.

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.

In all mammals, the circulating pool of MLT is synthesized in the pineal gland, during the night darkness hours. Its main function is that of synchronizing the organism in the photoperiod. In contrast, extra-pineal MLT is synthesized in peripheral organs, does not follow any circadian rhythm nor circulates and plays a detoxifying and cytoprotective action. Circulating MLT may stimulate both innate and acquired immune responses by its circadian action and by activating high affinity receptors on immunocompetent cells. Extra-pineal MLT may have anti-oxidant and anti-inflammatory effects dampening the innate immune response. These two seemingly divergent roles may be considered as two faces of the same coin. In fact, the integration of both circulating and extra-pineal MLT functions might generate a balanced and effective immune response against microbial pathogens. The studies described in this review investigated the effect of exogenous MLT in various models of infectious diseases using extremely different doses and treatment schedules. None of them evaluated the possibility to integrate the non-circadian anti-inflammatory effect with the circadian immunoenhancing action of MLT. As a consequence, in spite that most studies agree that MLT has a beneficial effect against infections, it seems difficult to draw any definite conclusion about its possible therapeutic use.

Stallion mules have been used as working equids in several countries. Aggressiveness, under the influence of testosterone, resulted in the necessity for surgical castration before work training. The gonadotropin-releasing hormone (GnRH) vaccine may be an alternative method for immunocastration in mules. The objectives were to evaluate the effect of GnRH vaccine on anti-GnRH antibody production, serum testosterone level, clinical adverse effects, and behavior toward human manipulation. Twenty-five mules were separated into 3 groups: Control-intact, Control-castrated, and Treatment. Treatment was further divided into subgroups according to condition (intact or unilateral cryptorchid) and age. Treatment received 195 µg GnRH vaccine intramuscularly at week 0, 4, and 8. Anti-GnRH antibody increased at week 6 and 10, then gradually decreased to baseline at week 22. Treatment-intact-young had the highest anti-GnRH antibody, resulting in lower serum testosterone levels during week 2-6 and 12-16 compared to Control-intact. Subcutaneous edema adjacent to the injection site was detected only in Treatment-intact after booster vaccination. During week 6-22, the behavioral scores of Treatment significantly changed toward at ease with human contact compared to a score before vaccination. In conclusion, mules responded to GnRH vaccine, which could temporarily suppress testosterone for up to 16 weeks.

Inflammation is a cause of number of disorders. Many anti-inflammatory drugs are available to cure and prevent inflammation and its related disorders. Some of the drugs are from plant and animal origin. Among animals snake venom is also utilized as treatment option of certain disorders. In the current study the venom of N. oxiana from Northern areas of Pakistan is assayed to determine its anti-inflammatory activity. The Naja oxiana is also called central Asian cobra is endemic to Central Asia. Naja oxiana belong to family Elapidae and it is highly venomous snake. The venom has many enzymatic proteins as well as nonenzymatic proteins that is neurotoxins. The venom is lethal having very high mortality rate and the death may occur due to respiratory failure in 45 minutes to 24 hrs depending upon the nature and amount of venom. As the venom is highly toxic so initially after venom milking its protein estimation was done and toxicity profile and LD50 was determined to find out its therapeutic dose at which anti-inflammatory activity was observed. The toxicity and anti-inflammatory activity was determined on mice model. Inflammation was induced by carrageenan induced peritonitis method. The inflammatory markers ROS, TNF-α and IL-β were determined by ELIZA in peritoneal fluid. The LD50 of crude venom, fraction 1 and fraction 2 was found as 34 µg/kg, 7.4 µg/kg and 416 µg/kg respectively. Anti-inflammatory activity crude venom, fraction 1 and fraction 2 was found at dose 19 µg/kg, 1.8 µg/kg and 267 µg/kg respectively. The levels of inflammatory markers reduced after therapeutic dose administration of venom and its fractions that indicates that it can be utilized as anti-inflammatory agent and so can be effective in various disorders.

Inflammation is an important biological response to any tissue injury. The immune system responds to any stimulus, such as irritation, damage, or infection, by releasing pro-inflammatory cytokines. Overproduction of pro-inflammatory cytokines, including TNF-α and IL-1b, can lead to several diseases eg.,, cardiovascular diseases, joint disorders, cancer, and allergies. Emerging science suggests that whole grains may lower the markers of inflammation. Whole grains are a significant source of dietary fibres and phenolic acids that have inverse association with the risk of inflammation. The dietary fibres and phenolic acids composition of whole grains is very distinct over different grains. Whole grains (cereals and pseudo-cereals) are rich in both dietary fibres e.g., arabinoxylan, β-glucan and phenolic acids e.g., hydroxycinnamic acids, hydroxybenzoic acids, which are predominantly present in the bran layer. Although the biological mechanisms underlying widely reported association between whole grains consumption and a lower risk diseases are not fully understood. The modulatory effects of whole grains on inflammation also likely to be influenced by several mechanisms, including the effect of dietary fibres and phenolic acids, while some of these effects are direct, others involve gut microbiota, which transform important bioactive substances into more useful metabolites that moderate inflammatory signaling pathway. Thus, the aim of this review is two folded: first is to discuss the types of dietary fibres and phenolic acids commonly found in cereals and pseudo-cereals, and their health benefits observed in animal and human studies. Second, we review existing literature on the linkage between consumption of whole grains and markers of subclinical inflammation, the role of dietary fibres, phenolic acids, and gut microbiota on the anti-inflammatory activity of whole grains intake. Altogether, scientific data on the ant-inflammatory properties of whole grains are encouraging, further researches are needed to cover the gap between the emerging sciences of whole grains dietary fibres, phenolic acids and inflammation.

ABO incompatibility is not considered a contraindication for hematopoietic stem cell transplantation (HSCT). Approximately 30% of transplants from related donors and up to 50% of transplants from unrelated donors are ABO-incompatible. The immuno-hematologic investigationsmay evaluate donor/recipient ABO mismatch and anti-A/B isohemoagglutinins (IHAs) titration in pre-HSCT phase. Immediate hemolysis or delayed complications (passenger lymphocyte syndrome and pure red cell aplasia) can appear post-HSCT. Some preventive treatmentstake into consideration the manipulation of the product and decision-making algorithms based on the titration of IHAs in the recipient with clinical protocols for the removal/reduction of IHAs through plasma exchange or immunoadsorption procedures. Currently, the best approach in the managementof ABO-incompatibletransplant is not defined in expert consensus documents or with solid evidence. In addition, the methods for IHAs titration are not standardized. The transfusion strategy must consider both the blood group systems of the recipient and the donor until the RBC engraftment and the confirmed ABO conversion (forward and reverse typing) on two consecutive and independent samples. Therefore, ABO incompatibility in the HSCT is an important immuno-hematologic challenge and request all necessary preventive measures including the appropriate selection of ABO blood components for transfusion.

Objective: The study aimed to evaluate the effects of monoclonal antibodies (mAbs) acting on the calcitonin gene-related peptide (CGRP) or its receptor (anti-CGRP/R mAbs) on comorbid symptoms of depression, anxiety, and fatigue in migraine patients resistant to traditional prophylaxis. Methods: The study was an open-label prospective study assessing comorbidities in patients with high frequency (HFEM) and chronic migraine (CM), medication overuse headache (MOH), and resistance to traditional prophylaxis treated with anti-CGRP/R mAbs for 3 months. Results: 77 patients were enrolled with either HFEM (21%) or CM (79%) with or without MOH (56% and 44% respectively). We identified 21 non-responders (27%) and 56 responders (73%), defined on the reduction ≥ 50% of headache frequency. The two groups were highly homogeneous for investigated comorbidities. Disease severity in terms of headache frequency, migraine-related disability, and affective comorbid symptoms were reduced in both groups with different thresholds; allodynia and fatigue were ameliorated only in responders. Conclusion: anti-CGRP/R antibodies improve pain together with affection, fatigue, and sensory sensitization in migraine patients.

Inflammation which has important functions in human defense systems and in maintaining the dynamic homeostasis of the body has become a major risk factor for the progression of many chronic diseases. Although the applied medical products alleviate the general status, they still exert adverse effects in the long term. For this reason, the solution should be sought in more harmless and affordable agents. Microorganisms offer a wide range of active substances with anti-inflammatory properties. They propose important advantages such as renewable and inexhaustible nature. This review aims at the most recent updates on the microorganisms of different type and genera being carriers of anti-inflammatory activity.

Obesity is a global health concern. Recent research has suggested that the development of anti-obesity ingredients and functional foods should focus on natural products without side effects. We investigated the anti-obesity efficacy and mechanisms of action of Brassica juncea extract (BJE) using in vitro and in vivo obesity models. In in vitro experiments, BJE treatment downregulated adipogenic-related proteins CCAAT/enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), adipocyte protein 2 (aP2), and lipid synthesis-related protein acetyl-CoA carboxylase (ACC). It also upregulated the heat generation protein peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) and fatty acid oxidation protein carnitine palmitoyltransferase-1 (CPT-1). Oral administration of BJE decreased body weight, alleviated liver damage, and inhibited lipid accumulation in high-fat diet (HFD)-induced obese mice. Inhibition of lipid accumulation by BJE in vivo was associated with decreased expression of adipogenic and lipid synthesis proteins and increased expression of heat generation and fatty acid oxidation proteins. BJE administration improved obesity by decreasing adipogenesis and activating heat generation and fatty acid oxidation in 3T3-L1 cells and in HFD-induced obese C57BL/6J mice. These findings indicate that BJE is a promising natural means of preventing obesity-related metabolic diseases.

Overweight and Obesity are global health and economic concerns. According to the World Health Organization, the number of individuals with obesity has nearly tripled since 1975. This health issue is currently considered an epidemic, affecting over 1.9 billion adults and 340 million children and adolescents. It contributes to more than 5 million deaths each year and has a global economic burden that will reach $4.32 trillion annually by 2035, according to the World Obesity Federation. This disease can affect every system of the human body and can lead to complications such as metabolic syndrome, diabetes, cancer, dyslipidemia, cardiovascular diseases, and hypertension, among others. Treatment may sometimes include diet, exercise, drugs, and bariatric surgery. Nonetheless, not all people have access to these treatments, and public health strategies consider prevention the most important factor. In this regard, recent investigations are aiming to find alternatives and adjuvants for the treatment of obesity, its prevention, and the reversion of some of its complications, using natural sources of anti-obesogenic compounds like polyphenols, terpenes, alkaloids, saponins, among others. In this review, we gather the most current information using PubMed, Google Scholar, Scopus, Cochrane, and Web of Science. We present and discuss the current information about natural products that have shown anti-obesogenic effects at a molecular level. We also consider the impact of dietary habits and lifestyle in preventing overweight and obesity due to the evidence of the benefits of certain foods and compounds consumed regularly. We discuss mechanisms, pathways, and receptors involved in the modulation of obesity, especially those related to inflammation and oxidative stress linked to this disease, due to the relevance of these two aspects in developing complications.

Acne vulgaris is a prevalent dermatological disorder that impacts the quality of life for millions of people around the world. The multifactorial nature of this disorder requires innovative and effective treatment strategies. Over time, there has been a growing interest regarding the use of natural topical therapies, with cannabinoids emerging as a promising group of compounds for investiga-tion. In the context of acne treatment, cannabinoids are of particular interest due to their anti-acne properties, namely, lipostatic, anti-inflammatory, antiproliferative, and antimicrobial activities. Among these bioactive compounds, cannabidiol stands out as a notable derivative, exhibiting a promising spectrum of therapeutic actions. Pre-clinical and clinical studies have proven its ability to modulate sebum production, reduce inflammation, and inhibit bacterial proliferation - all of which are critical components in the pathogenesis of this dermatosis. This review provides a comprehen-sive overview of cannabinoids' potential as a novel and holistic approach to acne vulgaris treatment and summarizes recent developments in this area.

The escalating reliance on revolutionary online web services has introduced heightened security risks, with persistent challenges posed by phishing despite extensive security measures. Traditional phishing systems, reliant on machine learning and manual features, struggle with evolving tactics. Recent advances in deep learning offer promising avenues for tackling novel phishing challenges and malicious URLs. This paper introduces a two-phase stack generalized model named AntiPhishStack, designed to detect phishing sites. The model leverages the learning of URLs and character-level TF-IDF features symmetrically, enhancing its ability to combat emerging phishing threats. In Phase I, features are trained on a base machine learning classifier, employing K-fold cross-validation for robust mean prediction. Phase II employs a two-layered stacked-based LSTM network with five adaptive optimizers for dynamic compilation, ensuring premier prediction on these features. Additionally, the symmetrical predictions from both phases are optimized and integrated to train a meta-XGBoost classifier, contributing to a final robust prediction. This work's significance lies in advancing phishing detection with AntiPhishStack, operating without prior phishing-specific feature knowledge. Experimental validation on two benchmark datasets, comprising benign and phishing or malicious URLs, demonstrates the model's exceptional performance, achieving a notable 96.04% accuracy. This research adds value to the ongoing discourse on symmetry and asymmetry in information security and provides a forward-thinking solution for enhancing network security in the face of evolving cyber threats.

This study evaluated the effects of high-temperature and high-pressure treatment on the antioxidant and anti-inflammatory activities of carrot extracts. The total polyphenol and flavonoid content of heated carrot extract increased as the heating temperature increased, with 403.93 mg GAE/100 g and 53.14 mg CE/100 g at 150°C. DPPH and ABTs radical scavenging activity (IC50) of heated carrot extract also increased as the heating temperature increased, with 4.65 mg/mL and 7.31 mg/mL, respectively, at 150°C. The reducing power increased with the heating temperature. Heated carrot extract did not exhibit any temperature- or concentration-dependent cytotoxicity. Nitric oxide (NO) generation was suppressed as the heating temperature and NO production increased. The heated carrot extract showed a decrease in the production of dose-dependent TNF-α, IL-1β, and IL-6 compared to the control group. The above results show that heated carrot extract had effective antioxidant and anti-inflammatory activities.

This paper studies the dynamic response of corner supported modular steel buildings with a core wall system, under progressive collapse scenarios, associated with corner module removals. Since using secondary systems such as concrete core in mid- to high-rise buildings is currently una-voidable, understanding their impact on load transfer between modules during collapse scenarios becomes essential. The designated buildings with four-, eight- and twelve-story were modelled using the macro-model based finite element method in Abaqus. Also, three different locations are considered for the concrete shear core within the building plan, leading to nine various case scenarios. Each vertical and horizontal inter-module connection was modelled by one axial and two shear springs with predefined nonlinear force-displacement behaviour. The local and global buckling, which plays an essential role in the building's stability, was considered to obtain accurate results. Finally, parametric studies on the building response were carried out, including the intra-module connection rigidity and inter-module connection stiffness. The results demonstrated that the core wall could maintain the robustness of modular steel building through two mechanisms dependent on its location within the plan. Also, preventing plastic hinges from forming in beams could be introduced as an anti-collapse mechanism in the corner module removal scenarios

Currently, the use of medications during pregnancy in Latin America is common; studies with Latin American samples find that nearly 90% of pregnant women use some medication at least once during pregnancy. Furthermore, approximately 21% of the respondents self-medicated. Worldwide, the prevalence of this disease is 32%. The most common medications are nonsteroidal anti-inflammatory drugs and analgesics. Many of these drugs are available over the counter without a prescription. For this reason, a systematic review of the literature on the adverse effects on the woman and the fetus was performed. Objective: To determine the adverse effects associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) on pregnant women and fetuses during pregnancy. Methods: Systematic literature review. The following search strategy was used for the databases: Science Direct, PubMed, Scopus and Web of Science, through September 3, 2022. The population of pregnant women without previous comorbidities was defined. The intervention of interest was the use of NSAIDs during pregnancy. The outcomes of interest were adverse effects for the mother or fetus (weight of the newborn, congenital malformations present in the fetus, systemic effects in the pregnant woman during her gestation period). The types of studies included clinical trials, cohort studies and case‒control studies. Results: 1 study included 2,985 pregnant women without previous comorbidities. The use of aspirin more frequently during pregnancy stands out. The adverse effects on the fetus were preterm birth <37 weeks, low birth weight < 2500 g and increased admission to the neonatal intensive care unit. No adverse effects were found for the mother. Conclusions: There are not enough data indicating that the use of NSAIDs during pregnancy is safe. Some studies show that the use of NSAIDs during pregnancy could be related to problems in the development and growth of the fetus and health effects for the mother during pregnancy, so it is advisable to use these drugs under medical prescription and for the shortest possible time. in the gestation stage.

This work reports the isolation, purification, and anti-inflammatory evaluation of compounds from the plant species Ageratina pichinchesis. Using open-column chromatography, 11 known compounds were purified, whose chemical structures were elucidated by nuclear magnetic resonance techniques (1D and 2D). All compounds were evaluated in the in vitro model of RAW 264.7 mouse macrophage cells measuring nitric oxide inhibition as a determination of the anti-inflammatory effect. Outstandingly, the compound betuletol 3-O-β-glucoside (11) exhibited inhibition of nitric oxide with an IC50 of 75.08 ± 3.07% at 75 µM, additionally, it inhibited the secretion of interleukin 6 (IL-6) and activation of nuclear factor (NF-kβ). These results show that compound 11 could be considered as a potential anti-inflammatory agent in suppressing the expression of NF-kβ target genes such as the proinflammatory pathway and inducible nitric oxide synthase (iNOS). Consequently, the medicinal use attributed in traditional medicine to the A. pichinchensis species is due to the diversity of compounds that the plant biosynthesizes, demonstrating that its effect relates to anti-inflammatory effects associated with compound 11.

The therapeutic effectiveness of current neurodegenerative diseases treatments is still under debate because of problems with bioavailability and a range of side effects. Fungi, which are increasingly recognized as sources of natural antioxidants and AChE enzyme inhibitors, may thus serve as potent neuroprotective agents. Previous studies have associated the anti-AChE and antioxidant activities of fungi mostly with polysaccharides and phenolic compounds, while other secondary metabolites such as polyamines (PAs) have been neglected. This study aimed to investigate eight edible and medicinal fungi from Serbia, marking the initial investigation into the neuroprotective capabilities of Postia caesia, Clitocybe odora, Clitopilus prunulus, and Morchella elata. Neuroprotective activity was examined using Ellman assay, while antioxidant capacity was tested by conducting DPPH, NO, ABTS and FRAP tests. PAs levels were determined by HPLC coupled with fluorescent detection. Ganoderma applanatum and Lepista nuda exhibited the most robust anti-AChE (98.05 ± 0.83% and 99.94 ± 3.10%, respectively) and antioxidant activities attributed to the synergistic effects of total protein, total phenolic and PAs levels. Furthermore, P. caesia displayed significant AChE inhibition (88.21 ± 4.76%), primarily linked to elevated SPD (62.98 ± 3.19%) and PUT levels (55.87 ± 3.16%). Our results highlight the need of thorough research to comprehend the intricate relationships between distinct fungus species and AChE inhibition. However, it's important to recognize that more research is required to identify the precise substances causing the reported inhibitory effects.

Intrauterine adhesions (IUA) has become one of the main causes of female infertility, how to effectively prevent postoperative re-adhesion has been a clinical challenge. In this study, a mussel-inspired dual-network hydrogel was proposed for postoperative anti-adhesion of IUA. First, calcium alginate/polyacrylamide (CA-PAM) hydrogel was prepared by covalent and Ca2+ cross-linking. Benefiting from abundant phenolic hydroxyl groups, polydopamine (PDA) was introduced to further enhance the adhesion ability and biocompatibility. This CA-PAM hydrogel immersed in 10 mg/mL dopamine solution possessed remarkable mechanical strength (elastic modulus > 5 kPa) and super stretchability (with a breaking elongation of 720%). At the same time, it shown excellent adhesion more than 6 kPa. Surprisingly, the coagulation index of the hydrogel was 27.27 ± 4.91, demonstrating attractive coagulation performance in vitro and the potential for rapid hemostasis after surgery.

In recent years, the use of solid waste fillers to partially replace natural fillers in asphalt mixtures to produce high-performance asphalt mixtures has received widespread attention. However, differences in the material properties of solid waste fillers remain a problem for this recycling method. To address this issue, limestone powder in asphalt mixtures was replaced by three solid waste fillers (steel slag powder, tailings powder and calcium carbide slag powder) in this study. The chemical composition of the fillers was first characterized to assess the homogeneity of the material. Then, AC and SMA asphalt mixtures were designed and produced and characterized for wet stability. The results showed that asphalt mixtures with solid waste fillers were superior to LP asphalt mixtures in terms of resistance to water damage, and steel slag powder showed the best improvement in moisture stability of asphalt mixtures. The optimum substitution of solid waste filler for limestone filler was 25%. In addition, the moisture stability of asphalt mixture with limestone filler was significantly improved with the addition of anti-stripping agents. In contrast, the moisture stability of asphalt mixtures with solid waste filler was slightly improved. Solid waste fillers could be used in asphalt mixtures and have a similar function as the anti-stripping agent. In summary, the use of solid waste fillers to replace mineral fillers in asphalt mixtures is a reliable, value-added, recycling option.

Although the COVID-19 pandemic appears to be diminishing, the emergence of SARS-CoV-2 variants represents a threat to humans due to its inherent transmissibility, immunological evasion, virulence, and invulnerability to existing therapies. The previous COVID-19 pandemic affected more than 500 million people and caused over 6 million deaths. Vaccines are essential, but in circumstances when vaccination is not accessible or in individuals with compromised immune systems, drugs can give additional protection. Targeting host signaling pathways is recommended due to their genomic stability and resistance barriers. Plant-derived products, which have been used in traditional medicine for treating pathological conditions, offer structurally novel therapeutic compounds including anti-viral. In addition, plant-derived bioactive substances might serve as the ideal basis for developing sustainable/efficient/cost-effective anti-viral alternatives. Epigenetic modifications in the genome can affect gene expression without altering DNA sequence. Host cells can use epigenetic gene regulation as a mechanism to silence incoming viral DNA molecules, while viruses have recruited cellular epi transcriptomic (covalent modifications of RNAs) modifiers to increase the translational efficiency and transcript stability of viral transcripts to enhance viral gene expression and replication. Moreover, viruses manipulate host cells' epigenetic machinery to ensure productive viral infections. Environmental factors, such as natural products, may influence epigenetic modifications. In this review, we are exploring the potential of plant-derived substances as epigenetic modifiers for broad-spectrum anti-viral activity, reviewing modulation processes and anti-viral effects on DNA and RNA viruses, and addressing future research objectives in this rapidly emerging field.

A (2,6)-fullerene F is a 2-connected cubic planar graph whose faces are only 2-length and 6-length. Furthermore, it consists of exactly three 2-length faces by Euler's formula. The (2,6)-fullerene comes from Do\v{s}li\'{c}'s (k,6)-fullerene, a 2-connected 3-regular plane graph with only k-length faces and hexagons. Do\v{s}li\'{c} showed that the (k,6)-fullerenes only exist for k = 2, 3, 4 or 5, and some of the structural properties of (k,6)-fullerene for k = 3, 4 or 5 are studied. In this paper, we study the properties of (2,6)-fullerene. We obtain that the edge-connectivity of (2,6)-fullerenes is 2. Every (2,6)-fullerene is 1-extendable, but not 2-extendable. F is said to be k- resonant (k>0) if the deleting of any i (0=< i<= k) disjoint even faces of F results in a graph with at least one perfect matching. We have that every (2,6)-fullerene is 1-resonant. An edge set S of F is called an anti-Kekule set if F-S is connected and has no perfect matchings, where F-S denotes the subgraph obtained by deleting all edges in S from F. The anti-Kekule number of F, denoted by ak(F), is the cardinality of a smallest anti-Kekule set of F. We have that every (2,6)-fullerene F with |V(F)|>6 has anti-Kekule number 4. Further we mainly prove that there exists a (2,6)-fullerene F having f_{F} hexagonal faces, where f_{F} is related to the two parameters n, m.

The recently reported microbial natural product N-benzoyl-tryptophane (1) along with twenty-two diverse known bioactive compounds were isolated from the marine Aspergillus terreus LGO13 after its re-cultivation using liquid culture fermentation. Structures of the isolated compounds were established on the basis of HR-ESIMS 1D/2D NMR spectroscopy, and comparison with literature data. The antimicrobial, cytotoxicity, and antiviral activities of the microbial extract and the obtained compounds were investigated using a set of microorganisms, cervix carcinoma KB-3-1, non-small cell lung cancer (NSCLC) A549, and coronavirus (SARS-CoV-2), respectively. Molecular docking (MD) simulation was employed to explore the theoretical targets of the isolated metabolites as anti-SARS-CoV-2 agents. Chaetominine (2) seemed to be a potential candidate against papain-like protease (PLpro), one of the viral proteins being aimed by recent research as a possible target of anti-covid agents. Inspired by the MD results, we accordingly assessed the antiviral efficacy of chaetominine (2), fumitremorgin C (6), and azaspirofuran A (9) against SARS-CoV-2. Fumitremorgin C (6) showed a high selectivity index (SI = 20.3), while chaetominine (2) and azaspirofuran A (9) showed moderate selectivity index (SI = 6.6 and 3.2, respectively). These results showed a promising antiviral activity of Fumitremorgin C against SARS-CoV-2 virus.

Unmanned aerial vehicle (UAV) usage is increasing drastically worldwide as UAVs are used in various industries for many applications, such as inspection, logistics, agriculture, and many more. This is because performing a task using UAV makes the job more efficient and reduces the workload needed. However, for a UAV to be operated manually or autonomously, the UAV must be equipped with proper safety features. An anti-collision system is one of the most crucial and fundamental safety features that UAVs must be equipped with. The anti-collision system allows the UAV to maintain a safe distance from any obstacles. The anti-collision technologies are of crucial relevance to assure the survival and safety of UAVs. Anti-collision of UAVs can be varied in the aspect of the use of sensors and the system’s working principle. This article provides a comprehensive overview of anti-collision technologies for UAVs. It also presents drone safety laws and regulations that prevent a collision at the policy level. The process of anti-collision technologies is studied from three aspects: Obstacle detection, collision prediction, and collision avoidance. A detailed overview and comparison of the methods of each element and an analysis of their advantages and disadvantages have been provided. In addition, the future trends of UAV anti-collision technologies from the viewpoint of fast obstacle detection and wireless networking are presented.

This study aims to investigate the spectroscopic and structural properties of the compound Lumefantrine which is important in pharmacology because of its anti-malarial effect. The structural and spectroscopic properties of this molecule such as bond lengths, bond angles, FT-IR and NMR spectra were handled computationally using a computational chemistry suite: Spar-tan’14. Both HF and DFT methods were used with different basis sets for the calculations. The re-sults calculated by the software were compared to experimental results from the literature. Both Computational and experimental results were exhibited as tables. Also some calculated results such as HOMO-LUMO boundary orbitals and electrostatic potential map, were given as graphics and pictures.

Background: Sulforaphane (SFN) is an isothiocyanate of vegetables origin with potent antioxidant and immunomodulatory properties. The pleiotropic activities characterization in human dendritic cells (DCs) is poorly summarized. The aim of this work was the study of the immunomodulatory power of SFN in response to an inflammatory microenvironment on human monocyte derived DCs (moDCs). Methods: The immunological response induced by SFN was studied, evaluating apoptosis and autophagy assays by flow cytometry in moDCs and cancer cell line (THP-1), including moDCs maturation, lymphocyte proliferation and cytokines production under different experimental conditions associated or not with an inflammatory microenvironment, which was induced by lipopolysaccharide (LPS). Results: Our results demonstrated that SFN can interact with moDCs, significantly reducing autophagy process and enhancing apoptosis, such as THP-1 cells, in chronic inflammatory microenvironment. Under this chronic inflammation, SFN modulated the phenotypical characteristics of moDCs, which reduction the expression of all markers (CD80, CD83, CD86, HLA-DR and PD-L1), and significantly reduced the Th2 proliferative response together with the reduction of the IL-9 and IL-13 levels. Although we did not find changes in the regulatory proliferative response, we observed an increase in IL-10 levels. Conclusion: These findings demonstrate that SFN exerts protective effects against LPS-induced inflammation through moDCs/T-cells modulation towards a regulatory profile. Therefore, SFN may be a potential candidate for use in the treatment of pathologies with an inflammatory profile.

Citation: Lastname, F.; Lastname, F.; Last-name, F. Title. Phar-maceuticals 2022, 15, x. https://doi.org/10.3390/xxxxx Academic Editor: Firstname Lastname Received: date Accepted: date Published: date Publisher’s Note: MDPI stays neutral with regard to jurisdic-tional claims in pub-lished maps and insti-tutional affiliations. Copyright: © 2023 by the authors. Submitted for possible open access publication under the terms and conditions of the Creative Commons 1Olga Gumkowska-Sroka, 2Kacper Kotyla, 3Ewa Mojs, 2Klaudia Palka, 1,2*Przemysław Kotyla 1. Department of Rheumatology and Clinical Immunology Voivodeship Hospital No5 in Sosnowiec Medical University of Silesia Katowice, Poland 2. Department of Internal Medicine Rheumatology and Clinical Immunology Medical University of Silesia Katowice , Poland 3. 3. Department of Clinical Psychology, Poznan University of Medical Sciences Poznan, Poland *Correspondence: Prof Przemysław Kotyla Department of Internal Medicine Rheumatology and Clinical Immunology Medical University of Silesia, Katowice, Poland- Summary Systemic sclerosis is a connective tissue disease of unknown origin and unpredictable course, with both cutaneous and internal organ manifestations. In spite of enormous progress in rheumatology and clinical immunology, the background of diseases is largely unknown and no specific therapy exists. The therapeutic approach to the disease is aimed to treat and preserve the function of internal organs, and this approach is commonly referred to as an organ-based treatment. However, in modern times data from the other branches of medicine may help to treat disease-related complications, making it possible to find a group of drugs to be utilized in the treatment of the disease. In this review, we present possible therapeutic options aiming to stop the progression of fibrotic processes, restore aberrant immune response, stop improper signalling from proinflammatory cytokines, and halt the production of disease-related autoantibodies.

The influence of the addition of 2.5, 5, 7.5, and 10.0% of dried Enoki and Maitake mushrooms on the content of bioactive compounds and some pro-health properties of pasta was studied. The qualitative and quantitative analysis of phenolic compounds performed using the LC-MS/MS technique indicated the highest amount of phenolic compounds in pasta supplemented with Maitake. However, all pasta enriched with Enoki mushrooms contained statistically significant-ly higher content of α-glucans in comparison to the control. In samples subjected to gastrointes-tinal digestion, the antioxidant, and potential anti-inflammatory activities were significantly higher than ethanolic and PBS extracts of samples. The ethanolic extracts from pasta fortified with dried Enoki and Maitake mushrooms had higher antioxidant activity (in some of the anti-radical and reducing power assays ) as well as a higher ability to inhibit lipoxygenase (E2.5 and E5 samples) compared to the control sample. Also some in vitro digested samples of pasta en-riched with dried Enoki and Maitake mushrooms showed higher chelating power (E10, M7.5 and M10); reducing power (E5, E7.5, and M10) and lipoxygenase inhibition (E7.5, E10 and M10) than the control. In conclusion, Enoki and Maitake mushrooms can be used for fortification of semo-lina pasta, conferring healthier characteristics of the product.

Regulatory macrophages (Mregs) are unique in that they have anti-inflammatory and immunosuppressive properties. Thus, treating inflammatory diseases using Mregs is an area of active research. Human Mregs are usually generated by culturing peripheral blood monocytes stimulated by macrophage colony-stimulating factor with interferon (IFN)-. Here, we generated Mregs with an elongated cell morphology from THP-1 cells stimulated with phorbol 12-myristate 13-acetate and cultured with arginylglycylaspartic acid and vitamin D3. These Mregs regulated macrophage function, and respectively downregulated and upregulated the expression of pro-inflammatory and immunosuppressive mediators. They also expressed Mregs-specific marker, such as dehydrogenase/reductase 9, even when exposed to inflammatory stimulants such as IFN-, lipopolysaccharide, purified xenogeneic antigen, and xenogeneic cells. The Mregs also exerted anti- inflammatory and anticoagulatory actions in response to xenogeneic cells and immunosuppressive effects on mitogen-induced Jurkat T-cell proliferation. Our method of generating functional Mregs in vitro without cytokines is simple and cost-effective.

Antisense oligonucleotides (ASONs) have proven potential for the treatment of various diseases. However, their limited bioavailability restricts their clinical application. New structures with improved enzyme resistance stability and efficient drug delivery are needed. In this work, we propose a novel category of ASONs bearing anisamide conjugation at phosphorothioate sites for oncotherapy. ASONs can be conjugated with the ligand anisamide very efficiently and flexibly in solution. The conjugation sites and ligand amount both influence anti-enzymatic stability and cellular uptake, resulting in changes in antitumor activity that are detectable by cytotoxicity assay. T6 (with double end AA-conjugation) was identified as the optimal conjugate, and its antitumor activity and the underlying mechanism were examined further in vitro and in vivo. This paper presents a new strategy for the design of nucleic acid–based therapeutics with improved drug delivery and biophysical and biological efficacy.

in this work formulations of "environmentally compatible" silicone-based antifouling synthesized in the laboratory and based on copper and silver on silica/titania oxides have been characterized, capable of replacing the non-ecological antifouling paints currently on the market. The texture properties and the morphological analysis of these powders with an antifouling action indicate that their activity is linked to the nanometric size of the particles and to the homogeneous dispersion of the metal on the substrate. The presence of two metal species on the same support limits the for-mation of nanometric species and therefore the formation of homogeneous compounds. The presence of the antifouling filler (specifically the one based on TiO2 and Ag) facilitates the achievement of a higher degree of cross-linking of the pure resin, and therefore a better compactness and completeness of the coating. This leads to a consequent better degree of adhesion to the tie-coat and therefore to the steel support used for the construction of the boats.

Alkaloids are the most diversified nitrogen-containing secondary metabolites having antioxi-dant, and antimicrobial properties and are extensively used in pharmaceuticals to treat different types of cancer. Nicotiana serves as a reservoir of anticancer alkaloids and is also used as a model plant for the de novo synthesis of various anti-cancer molecules through genetic engineering. Up to 4% of the total dry weight of Nicotiana was found to be composed of alkaloids where nicotine, nornicotine, anatabine, and anabasine are reported as the dominant alkaloids. And, among the alkaloids present in Nicotiana, β-carboline (Harmane and Norharmane), Kynurenines are found to show anti-tumor effects, especially in the case of colon and breast cancer. Creating new or shunting of existing biosynthesis pathways in different species of Nicotiana resulted in de novo or increased synthesis of different anti-tumor molecules or their derivatives or precursors includ-ing Taxadiane (~22.5 µg/g), Artemisinin (~120 μg/g), Parthenolide (~2.05 ng/g), Costunolide (~60 ng/g), Etoposide (~1 mg/g), Crocin (~400 µg/g), Catharanthine (~60 ng/g), Tabersonine (~10 ng/g), Strictosidine (~0.23 mg/g), etc. Enrich precursor pool especially Dimethylallyl Diphos-phate (DMAPP) and down-regulating of other bi-product pathways, compartmentalization or metabolic shunting, or organelle-specific reconstitution of the precursor pool might trigger the enhanced accumulation of the targeted anticancer alkaloid in Nicotiana.

Due to its built-up chemoresistance after prolonged usage, the demand for replacing platinum in metal-based drugs (MBD) is rising. The first MBD approved by the FDA for cancer therapy was cisplatin in 1978. Even after nearly four and a half decades of trials, there has been no significant improvement in osteosarcoma (OS) therapy. In fact, many MBD have been developed, but the chemoresistance problem raised by platinum remains unresolved. This motivates us to elucidate the possibilities of the copper and zinc (CuZn) combination to replace platinum in MBD. Thus, the anti-chemoresistance properties of CuZn and their physiological functions for OS therapy are highlighted. Herein, we summarise their chelators, main organic solvents, and ligand functions in their structures that are involved in anti-chemoresistance properties. Through this review, it is rational to discuss their ligands’ roles as biosensors in drug delivery systems. Hereafter, an in-depth understanding of their redox and photoactive function relationships is provided. The disadvantage is that the other functions of biosensors cannot be elaborated on here. As a result, this review is being developed, which is expected to intensify OS drugs with higher cure rates. Nonetheless, this advancement intends to solve the major chemoresistance obstacle towards clinical efficacy.

The skin acts as a protective barrier, guarding the body against microorganisms, chemicals, and several environmental factors. Accordingly, this all-important organ must be kept healthy to maintain its optimal functionality. One approach to maintain skin health is the application of multifunction bioactive sunscreens containing antioxidant molecule(s). Rosmarinic acid (RA), a phenolic compound, is known for its antioxidant activity. Herein, the safety and efficacy of a multifunction prototype sunscreen were investigated, aiming to probe putative synergies of this polyphenol with two known and widely used UV filters (bemotrizinol and octyl p-methoxycinnamate). Samples protected the DNA fragmentation compared to UV control, by the comet assay, and showed good skin compatibility in subjects. Formulations F1 and F3 were able to increase skin hydration, and, possibly, the RA interfered with this attribute. An increase in transepidermal water loss was observed for formulations F1, F2 and F4, which may be related to vehicle containing or not the RA. No decreases were observed in the inflammatory reaction caused by the ethyl nicotinate with any of the evaluated formulations. As a perspective, we suggest trials with a greater number of subjects or protocol modifications. Altering the vehicle qualitative and quantitative composition is also a pertinent perspective.

The introduction of tenofovir-derived prodrugs has revolutionised the prevention and management of HIV, which has coincided with 23% reduction in new HIV incidences globally. To date, there are two formulations of tenofovir-derived nucleoside reverse transcriptase inhibitor (NRTI): tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) and tenofovir alafenamide fumarate/emtricitabine (TAF/FTC). Although these prodrugs have shown favourable safety profile, their effects on cardiovascular health are differ from one another: TDF/FTC exhibits potential lipid-lowering effect, TAF/FTC demonstrates potential lipid-inducing effect, which is a major risk factor for cardiovascular diseases. However, this issue has not been previously elucidated, especially among the marginalised populations [lesbian, gay, bisexual and transgender (LGBT) and men who have sex with men (MSM)] who are likely be the main users of these prodrugs. This is of clinically significance as the cardiovascular health in these populations is often overlooked, in addition to a lack of appropriate cardiovascular risk prediction algorithm. Therefore, this review aims to (1) highlight the cardiovascular risks of tenofovir-derived prodrugs in the marginalized populations, and also to (2) establish the importance of having a cardiovascular risk prediction model that is specific to this particular populations so that their health management could be more comprehensive.

Hyperactivation of Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) signaling is an attractive therapeutic target for tumor therapy. Herein, forty-eight novel meridianin derivatives were designed and synthesized, and their anti-tumor activity were evaluated in vitro both for activity optimization and structure-activity relationship (SAR) study. The results indicated that most derivatives exhibited significantly improved anti-tumor activity, especially for compound 6e. The compound 6e contains an isothiouronium linked by an alkyl chain consisting of 6 carbon atoms with IC50 ranging from 1.11 to 2.80 μM on various cancer cell lines. Consistently, 6e dose dependently induced the apoptosis of A549 and DU145 cells, in which STAT3 are constitutively active. Western blotting assays indicated that the phosphorylation levels of JAK1, JAK2 and STAT3 were inhibited by 6e at 5 μM without significant change in total STAT3 level. Moreover, 6e also suppressed the expressions of STAT3 downstream genes, including c-Myc, Cyclin D1 and Bcl-XL at 10 μM. An additional in vivo study revealed that 6e at the dose of 10 mg/kg could potently inhibit the DU145 xenograft tumor without obvious body-weight loss. These results clearly indicate that 6e could be a potential anti-tumor agent by targeting JAK/STAT3 signaling pathway.

Obesity represents a major public health problem with a prevalence increasing at an alarming rate worldwide. Continuous intensive efforts to elucidate the complex pathophysiology and improve clinical management have led to a better understanding of biomolecules like gut hormones, an-tagonists of orexigenic signals, stimulants of fat utilization, and/or inhibitors of fat absorption. In this article, we will review the pathophysiology and pharmacotherapy of obesity including inter-section points to the new generation of antidiabetic drugs. We provide insight into the effective-ness of currently approved anti-obesity drugs and other therapeutic avenues that can be explored.

Surface passivation, which has been intensively studied recently, is essential for the perovskite solar cells (PSCs), due to the intrinsic defects in perovskite crystal. A series of chemical or physical methods have been published for passivating the defects of perovskite, which effectively suppressed the charge recombination and enhanced the photovoltaic performance. In this study, the n-type semiconductor of [6,6]-phenyl-C61-butyric acid methyl ester (PCBM) is dissolved in chlorobenzene (CB) for the surface passivation during the spin-coating process for depositing the two-dimensional (2D) perovskite film. This approach simplifies the fabrication process of 2D PSCs and benefits the film quality. As a result, the defects of perovskite film are effectively passivated by this method. A better perovskite/PCBM heterojunction is generated, exhibiting an increased film coverage and improved film morphology of PCBM. It is found that this technology results in an improved electron transporting performance as well as suppressed charge recombination for electron transport layer. As a result, PSCs based on the one-step formed perovskite/PCBM heterojunctions exhibit the optimized power conversion efficiency of 15.69% which is about 37% higher than that of regular perovskite devices. The device environmental stability is also enhanced due to the quality-improved electron transport layer.

Objectives: To determine the prevalence of controlled systemic hypertension and its associated risk factors among the hypertensive patients who attended the clinic at Mbeya Zonal Referral Hospital in Tanzania. Methods: A descriptive cross-sectional quantitative study was used determine the prevalence of co to 252 hypertensive patients were recruited during clinic visit from September to November 2020 and participant was randomly selected interviews using structured self-administered questionnaires. Data was analyzed using chi square test to find the risk factors associated with controlled hypertension. Results: Among 252 participants, 94(39.7%) individuals with controlled hypertension giving the prevalence of controlled hypertension. The proportion of females with controlled hypertension was slightly higher than male (49 females to 45 males). The prevalence of uncontrolled hypertension was 152(60.3%) participants. The prevalence of controlled hypertension was higher among patients who have regular clinic visit (p< .05) and have daily adherence to their anti-hypertensive medication. A similar trend was observed among participants without financial challenges to attend clinic, short duration of illness, higher level of education and there was no association between age, sex, marital status, smoking, alcohol consumption, having health insurance and having chronic illness. Conclusion: Prevalence of controlled hypertension is higher among patients who have regular clinic visit and have daily adherence to their anti-hypertensive medication. Also, it is higher among participants without financial challenges to attend clinic so they can have regular clinic visit and checkup. Reinforcement on regular drug intake and clinic visit, good nutrition and reduced salt intake and modifying lifestyles of patient with hypertension is important.

Smart air filters are beneficial to provide highly efficient particle removal, treat multiple contaminants simultaneously and conserve energy during air filtration processes. Herein, a type of self-supporting smart air filter (SSSAF) was fabricated by sandwiching the VOC-responsive PZT/PVDF electrospun membrane with two metal mesh electrodes. Besides the high filtration efficiency for sub-micron particles, the SSSAF showed good responses to pressure drop in the range of 0 to 500 Pa via the electroactivity of PZT/PVDF membrane. In addition, the SSSAF achieved VOC sensing function via the swelling properties of PZT/PVDF membrane in organic vapors, demonstrated by its signal to 50 to 200 ppm ethanol gases. The SSSAF based nanogenerator was employed to harvest wind energy, which was further applied to inhibit bacterial growth without the need of additional power input. The results provide new insight into development of all-in-one smart air filters.

Purpose - Soil aggregates are of great significance to soil and water conservation and ecological environment construction in arid area of northwest district．Methods - Exploring the effects of different vegetation includes types and land use methods on the stability of soil aggregates in the Loess Plateau, and provide reference for the rational use and management of land, also the improvement of soil structure in the region. Select 9 types of samples of 0-30 cm of typical soil plots as the research objects, compare and analyze the particle size index, stability differences and anti-erodibility of soil aggregates under various vegetation cover. Results - The results show that P value, MWD value, GMD value, D value, and AI value of the 0-10cm surface soil all show the maximum value. As the depth increases, the size distribution of the above index values of each soil sample in the 10-20cm and 20-30cm layers is different; P value in the 0-30cm depth layer is linearly positively correlated with the AI value and MWD value, and linearly negatively correlated with the D value. The correlation coefficient R between each variable is in the range of 0.78-0.97, and the D value reflects the Loess Plateau area stability and erosion resistance of soil aggregates better. GMD and MWD value show an exponential relationship, the correlation coefficient R value of 10-20cm height layer is 0.46; AI and MWD value in 0-10cm, 20-30cm height layer have a power function relationship, 10-20cm height layer has a polynomial function, the correlation coefficient R value is 0.97. The scour coefficient of different soil samples has a high degree of dispersion, the maximum CV value is 1.92, and the minimum value is 0.49. Conclusions - The results of this study can provide a theoretical basis for the ecological and hydrological benefit evaluation of slope erosion control and vegetation restoration on the Loess Plateau.

Heparins, Unfractionated or Low Molecular Weight, are permanently at the spotlight of both clinical indications and laboratory monitoring. An accurate drug dosage is necessary for an effi-cient and safe therapy. The one-stage anti-FXa kinetics’ assays are the most widely and universally used with full automation for large series, without needing exogenous Antithrombin. WHO in-ternational standards are available for UFH and LMWH, but external quality assessment surveys still report a high inter-assay variability. This heterogeneity results from: assay formulation, designed without or with dextran sulfate to measure all heparin in blood circulation; calibrators for testing UFH or LMWH with the same curve; and automation parameters. The various factors which impact heparin measurements are reviewed, and we share our experience to optimize assays for completely testing plasma heparin. Evidence is provided on the usefulness of low molecular weight dextran sulfate to mobilize all drug present in blood circulation. Other key factors concern adjustment of assay conditions to obtain fully superimposable calibration curves for UFH and LMWH, and automation parameters. The study is illustrated by the performances of the various anti-FXa assays used for testing heparin on UFH or LMWH treated patients’ plasmas and obtained using citrate or CTAD anticoagulants. Comparable results are obtained only when CTAD anti-coagulant is used. Using citrate UFH is underestimated in the absence of dextran sulfate. Heparin calibrators, adjustment of automation parameters and data treatment contribute to other smaller differences.

Within the past several decades, the emergence of new viral diseases with severe health complications and mortality is evidence of an age-dependent, compromised bodily response to abrupt stress with concomitantly reduced immunity. The new severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, causes coronavirus disease 2019 (COVID-19). It has increased morbidity and mortality in persons with underlying chronic diseases and those with a compromised immune system regardless of age and in older adults who are more likely to have these conditions. While SARS-CoV-2 is highly virulent, there is variability in the severity of the disease and its complications in humans. Severe pneumonia, acute respiratory distress syndrome, lung fibrosis, cardiovascular events, acute kidney injury, stroke, hospitalization, and mortality have been reported that result from pathogen–host interactions. Hallmarks of aging, interacting with one another, have been proposed to influence health span in older adults, possibly via mechanisms regulating the immune system. Here, we review the potential roles of the hallmarks of aging coupled with host–coronavirus interactions. Of these hallmarks, we focused on those that directly or indirectly interact with viral infections, including immunosenescence, inflammation and inflammasomes, adaptive immunosenescence, genomic instability, mitochondrial dysfunction, telomere attrition, epigenetic alterations, and impaired autophagy. These hallmarks likely contribute to the increased pathophysiological responses to SARS-CoV-2 among older adults and may play roles as an additive risk of accelerated biological aging even after recovery. We also briefly discuss the role of anti-aging drug candidates that require paramount attention in COVID-19 research.

The new pandemic coronavirus disease 2019 (COVID-19) is a worldwide threatening health issue. Early progression of this disease starts in the lung airways with an exaggerated inflammation, triggered by the viral infection and characterized by a “cytokine storm” that can lead to lethal lung injuries. In the absence of an effective anti-viral molecule and until the formulation of a successful vaccine, anti-inflammatory drugs might offer a complementary tool for controlling the associated complications and thus decreasing the subsequent fatalities. Drug repurposing for several molecules has emerged as a rapid temporary solution for COVID-19. Among these drugs, Thalidomide, a historically emblematic controversial molecule that harbors an FDA approval for treating Erythema Nodosum Leprosum (ENL) and multiple myeloma (MM). Based on only one-case report of positive outcomes in a patient treated amongst others with Thalidomide, two clinical trials on the efficacy and safety of Thalidomide in treating severe respiratory complications in COVID-19 patients were registered. Conversely, the absence of any substantial, promising evidence on Thalidomide usage in that context along with the discontinued studies on the efficiency of this drug in similar pulmonary diseases might cause a significant obstacle for carrying on clinical studies. In this review, we will discuss the theoretical effectiveness of this drug in attenuating inflammatory complications that are encountered in patients with COVID-19 while pinpointing the lack of evidence that is needed to move forward with this drug.

COVID 19, a pandemic spread without any solid anti-viral antidote. Researchers worldwide are currently giving their best to make antidote for this virus with all available literatures and knowledge. Research carried out indicates sulfated polysaccharides (carrageenan) are selective inhibitors of several enveloped and non-enveloped viruses and act predominantly by inhibiting the binding or internalization of virus into the host cells. Polysaccharides produced from Porphyridium sp. are sulfated polysaccharides which are promising antiviral agents against respiratory viruses from the family of coronavirus. These biocompatible compounds can be used as a coating material on the sanitary items for COVID-19 prevention.

Field cricket (Gryllus bimaculatus) is newly emerged as an edible insect in several countries. Anti-inflammatory effect of glycosaminoglycan derived this cricket was not fully investigated on chronic disease animal model such as diabetic mouse. For potential therapeutic agents, anti-diabetic activities of field cricket glycosaminoglycan (GbG) was evaluated in diabetic mice based on their abilities to reduce glucose, ALT, AST, LDL-cholesterol, and BUN levels, compared with dung beetle (Catharsius molossus) glycosaminoglycan (CaG) as a positive control glycosaminoglycan. Db mice were orally administered for one month according to their groups: Db Hetero (normal), Db Homo (type-2 diabetic), CaG (5 mg/kg), GbG (5 mg/kg), and metformin (10 mg/kg). Blood glucose level was decreased after 1^st week treatment with GbG. It also inhibited LDL-cholesterol and alkaline phosphatase levels. Regarding oxidative damage of diabetic state, levels of hepatocellular biomarkers levels and protein carbonyl content were reduced in db mice treated with GbG. Especially anti-oxidative activities of catalase, superoxide dismutase, and glutathione peroxidase were significantly increased in GbG treated group compared to those in the control. GbG was composed of heparin disaccharides and main N-glycan was identified as Hex₉GlcNAc₂ (m/z 1905.7) of with neutral mono-sugar mainly comprising of hexose, L (+) rhamnose by mass spectroscopy. These results from sero-biochemical, hepatocellular anti-oxidant assay in db mice data suggest cricket (G. bimaculatus) glycosaminoglycan might play a role in its anti-diabetic action.

Globally, public acceptance of waste-to-energy (WtE) incinerators is a crucial factor in implementing national waste-to-energy policies. This study adds to the literature on anti-incinerator sentiment by drawing upon an extended psychological-emotional model that integrates place-, trust-, and fairness-based pathways. A total of 338 residents in the Asuwei area in North Beijing completed a survey on a proposal to construct a WtE incinerator in the vicinity. Hierarchical regression analyses indicate that place attachment positively enhances anti-incinerator sentiment through direct effects, as well as through moderation and mediation effects between risk perception and opposing willingness. Further, institutional trust negatively moderates the impact of perceived risk on anti-incinerator sentiment, in addition to directly reducing perceived risk. Trust also influences anti-incinerator sentiment via risk perception, attesting to the effectiveness of a casual model of trust. Likewise, fairness perception acts as another determinant of opposing sentiment, similar to trust. We further reveal that procedural fairness plays a more significant role in predicting anti-incinerator sentiment than does distributional fairness. These findings demonstrate the importance of using a range of instrumental and more affective strategies to promote social acceptance of renewable energy infrastructure.

In this study, we evaluated the effects of Cyclosporine A (CsA) on Lipopolysaccharide (LPS)-induced cytokine production in the genital tract of female rabbits. Twelve sexually mature and healthy female rabbits were randomly divided into four groups (n = 3 each). The rabbits in the LPS group were given an intrauterine infusion of Escherichia coli LPS (4 mg/kg body weight (BW)). Rabbits in the CsA group were given CsA (20 mg/kg BW). Rabbits in the LPS + CsA group were given LPS (4 mg/kg BW) and CsA (20 mg/kg BW). The control group received only LPS and CsA carrier. The gene expression and protein levels of pro- and anti-inflammatory cytokines were observed using qRT-PCR and immuno-histochemical (IHC) assay, respectively. Our study showed that IL-1β, IL-6, IL-8, TNF-α, IFN-γ, IL-4, IL-10, IL-13, and TGF-β were expressed in female genital organs. The LPS challenge increased the mRNA expression of IL-6 and TNF-α in the uterine body and IL-1β in the uterotubal junction compared to the control group. CsA increased the basal mRNA expression of anti-inflammatory cytokines (i.e., IL-4 in the uterine body, uterotubal junction, and oviductal ampulla; IL-10 in the cervix, oviductal isthmus, and ampulla; and TGF-β in the uterotubal junction and oviductal ampulla) and pro-inflammatory cytokines (i.e., IL-6 and IL-8 in the cervix; IL-1β in the oviductal isthmus; TNF-α in the oviductal ampulla; and IFN-γ in the uterine body compared to the control group). In addition, CsA inhibited the mRNA expression of pro-inflammatory cytokines, such as IL-6 in the uterine body, uterotubal junction, and oviductal isthmus; TNF-α in the uterine body; and IFN-γ in the uterotubal junction and oviductal isthmus induced by the LPS challenge. The IHC assay showed the LPS-induced increase in protein production of IL-6 in the uterine body and oviductal isthmus. CsA increased the protein production of IL-10 in the cervix, uterine body, oviductal ampulla, and isthmus. Moreover, CsA decreased the protein production of IL-6 in the uterine body and oviductal isthmus induced by LPS.

In this present study, we conducted untargeted metabolic profiling using Gas Chromatography-Mass Spectrometry (GC-MS) analysis of ascidian Didemnum bistratum to assess the chemical constituents by searching in NIST library with promising biological properties against anti-bacterial and Zika virus vector mosquitocidal Properties. Metabolites, steroids and fatty acids are abundant in crude compounds of ascidian D. bistratum and showed potential zone growth inhibition against bacterial strains Kluyvera ascorbate (10 mm). The active crude compounds of D. bistratum exhibited prominent larvicidal activity against the Zika vector mosquitoes of Aedes aegypti and Cluex quinquefasciatus (LC₅₀ values of 0.4436 to 2.23 mg/mL). The findings of this study provide a first evidence of the biological properties exhibited by D. bistratum extracts, thus increasing the knowledge about the Zika virus vector mosquitocidal properties of ascidian. Overall, ascidian D. bistratum are promising and biocontrol or eco-friendly tool against A. aegypti and C. quinquefasciatus with prospective toxicity against non-target organisms.

An azaphenothiazine derivative, 6-chloroethylureidoethyldiquino[3,2-b;2’,3’-e][1,4]thiazine (DQT) has recently been shown to exhibit immunosuppressive activities in mouse models. It also inhibited the expression of CXCL10 at the protein level, at non-toxic concentrations, in the culture of KERTr cells treated with double-stranded RNA, poly(I:C). In this report, we demonstrated that DQT inhibits the transcription of the CXCL10 gene. Although CXCL10 is an IFNγ-inducible protein, we found that the CXCL10 protein was induced without the detectable release of IFNγ or IκB degradation. Hence, we concluded that IFNγ or NFκB were not involved in the regulation of the CXCL10 gene in KERTr cells transfected with poly(I:C) as well as in the inhibitory activity of DQT. On the other hand, we found that IFNβ was induced under the same conditions and its expression was inhibited by DQT. Kinetic analysis showed that an increase in IFNβ concentrations occurred 4-8 h after poly(I:C) treatment, while the concentration of CXCL10 was undetectable at that time and started to increase later, when IFNβ reached high levels. Therefore, DQT may be regarded as a new promising inhibitor of IFNβ expression and IFNβ-dependent downstream genes and proteins, e.g., CXCL10 chemokine, which is implicated in pathogenesis of autoimmune diseases.

Re-investigation of the chemical composition of the annual plant Mitracarpus scaber Zucc. led to the identification of clarinoside, a new pentalogin derivative containing a rare quinovose moiety, and the known compound harounoside. While the planar structure was fully determined using tandem MS and quantum mechanics calculations (QM), the tridimensional structure was unravelled after isolation and NMR analysis. The absolute configuration was assigned by comparison of experimental and theoretical SRCD spectra. Both compounds were tested for anti-inflammatory activity and compound 1 showed the ability to inhibit the production of interleukin-8 (Il-8) with an IC₅₀ of 9.17 µM.