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Background: Occult hepatitis B infection (OBI) is characterized by the presence of hepatitis B virus (HBV) DNA at low levels in serum (<200 IU/mL) with a negative hepatitis B surface antigen (HBsAg) test. OBI remains a major challenge to blood safety, particularly in HBV-endemic regions like Cameroon, where HBV detection relies solely on HBsAg testing. This cross-sectional study aimed to investigate the actual incidence and genotype characteristics of OBI in Cameroonian blood donors. Methods: Between March and June 2023, samples were collected from 288 HBsAg-negative blood donors aged 18 to 55 years and analysed for antibodies against the HBV core (anti-HBc) and surface antigens (anti-HBs). Following DNA extraction from the serum samples, qualitative nested PCR and quantitative real-time PCR were used to detect HBV viral DNA and viral load respectively. For positive samples, sequencing of a fragment of the S gene was performed to identify the circulating HBV genotypes. Results: The findings revealed that 58% (n = 167/288) of blood donors tested positive for anti-HBc, 29% (n = 83/288) tested positive for anti-HBs, and 26% (n = 75/288) being positive for both anti-HBc and anti-HBs. Occult hepatitis was confirmed in 4.5% of the blood donors, all of whom belonged to either HBV genotypes A or E, which are predominant in Cameroon. The amino acid substitution sA184V associated with HBsAg detection failure in genotype E was observed in 70% of OBI sequences, and the HBsAg immune escape variants (sT131N and sS143L) implicated in OBI were also observed. The mutation rtN139K in the reverse transcriptase (RT) domain of the overlapping HBV polymerase (P) gene was present in 17% of OBI-positive sequences of genotype E, likely contributing to masking HBsAg secretion. Conclusion: The results suggest a considerable risk of transfusion-transmitted HBV in this region. Therefore, to ensure blood safety, nucleic acid testing (NAT) is recommended, as relying solely on HBsAg assays is insufficient to eliminate this risk. [ABSTRACT FROM AUTHOR]

Recent advancements in artificial intelligence (AI)-based design strategies for metamaterials have revolutionized the creation of customizable architectures spanning nano- to macro-scale dimensions. However, their increasing complexity poses challenges in generating diverse metamaterials, hindering widespread adoption. Here, we introduce an innovative design strategy for three-dimensional graph metamaterials through simple arithmetic operations within the latent space. By leveraging carefully designed hidden representations of disentangled latent space and diffusion processes, our method unravels design space complexity, generating diverse graph metamaterials with comprehensive understanding. This versatile methodology facilitates the creation of graph metamaterials ranging from repetitive lattices to functionally graded materials. We believe that this methodology represents a foundational step in advancing our comprehension of the intricate latent design space, offering the potential to establish a unified model for various traditional generative models in the realm of graph metamaterials. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) vaccination has been available for over four decades. However, a synthesis of the evidence regarding the effectiveness of this strategy on preventing hepatitis B infection in people who use drugs (PWUD) is lacking. A systematic search of the MEDLINE (via PubMed), SCOPUS, Web of Science, and Cochrane Library databases was conducted up to June 2024. Eight studies reported on the effectiveness of HBV vaccination, defined as a positive result for HBsAg or anti-Hbc in vaccinated versus non-vaccinated PWUD, with a pooled effect size of 52% (95% CI: 28.2–67.9) for HBsAg and 31.89% (95% CI: 14.8–45.5) for anti-Hbc. For sero-immunity, defined as the proportion of vaccinated PWUD with levels of anti-HBs ≥ 10 mIU/mL, we found that 66.2% (95% CI: 0.61–0.71; I2 = 94%) had protective levels of anti-HBs. The results of this meta-analysis indicate that the incidence of HBV infection is lower in vaccinated PWUD than in those who did not receive the vaccine. However, the effectiveness is lower than that observed in the general population. This highlights the need for a thorough review of the factors influencing the prevention of HBV infection in PWUD. [ABSTRACT FROM AUTHOR]

Introduction: Errors are very common in medical practice and in particular, in the healthcare of patients with inflammatory bowel disease (IBD); however, most of these can be prevented. Aim: To address common errors in the management of IBD. Methods: Our approach to this problem consists in identifying mistakes frequently observed in clinical practice (according to our experience) in the management of patients with IBD, then reviewing the scientific evidence available on the subject, and finally proposing the most appropriate recommendation for each case. Results: The most common mistakes in the management of IBD include those related to diagnosis and differential diagnosis, prevention, nutrition and diet, treatment with different drugs (mainly 5-aminosalicylates, corticosteroids, thiopurines, and anti-TNF agents), extraintestinal manifestations, anemia, elderly patients, pregnancy, and surgery. Conclusions: Despite the availability of guidelines for both disease management and preventive aspects of IBD care, a considerable variation in clinical practice still remains. In this review, we have identified common mistakes in the management of patients with IBD in clinical practice. There is a clear need for a greater dissemination of clinical practice guidelines among gastroenterologists and for the implementation of ongoing training activities supported by scientific societies. Finally, it is desirable to follow IBD patients in specialized units, which would undoubtedly be associated with higher-quality healthcare and a lower likelihood of errors in managing these patients. [ABSTRACT FROM AUTHOR]

Background: Despite centuries of traditional use of silymarin for hepatoprotection, current randomized controlled trial (RCT) studies on the effectiveness of silymarin in managing metabolic dysfunction-associated steatotic liver disease (MASLD) are limited and inconclusive, particularly when it is administered alone. The low bioavailability of silymarin highlights the possible influence of gut microbiota on the effectiveness of silymarin; however, no human studies have investigated this aspect. Objective: To determine the potential efficacy of silymarin in improving MASLD indicators and to investigate the underlying mechanisms related to gut microbiota. Method: In this 24-week randomized, double-blind, placebo-controlled trial, 83 patients with MASLD were randomized to either placebo (n = 41) or silymarin (103.2 mg/d, n = 42). At 0, 12, and 24 weeks, liver stiffness and hepatic steatosis were assessed using FibroScan, and blood samples were gathered for biochemical detection, while faecal samples were collected at 0 and 24 weeks for 16S rRNA sequencing. Results: Silymarin supplementation significantly reduced liver stiffness (LSM, -0.21 ± 0.17 vs. 0.41 ± 0.17, P = 0.015) and serum levels of γ-glutamyl transpeptidase (GGT, -8.21 ± 3.01 vs. 1.23 ± 3.16, P = 0.042) and ApoB (-0.02 ± 0.03 vs. 0.07 ± 0.03, P = 0.023) but had no significant effect on the controlled attenuation parameter (CAP), other biochemical indicators (aminotransferases, total bilirubin, glucose and lipid parameters, hsCRP, SOD, and UA), physical measurements (DBP, SBP, BMI, WHR, BF%, and BMR), or APRI and FIB-4 indices. Gut microbiota analysis revealed increased species diversity and enrichment of Oscillospiraceae in the silymarin group. Conclusion: These findings suggest that silymarin supplementation could improve liver stiffness in MASLD patients, possibly by modulating the gut microbiota. Trial registration: The trial was registered at the Chinese Clinical Trial Registry (ChiCTR2200059043). [ABSTRACT FROM AUTHOR]

A 72-year-old man was referred to our hospital for the examination of a pancreatic head mass. Abdominal computed tomography revealed a contrasted 8-cm-diameter tumor extending from the dorsal pancreatic head to the porta hepatis. The preoperative diagnosis was challenging due to the absence of specific imaging findings and the inability to perform a biopsy. Positron emission tomography/computed tomography and diffusion-weighted imaging suggested a malignant tumor originating from the organs surrounding the pancreatic head. Subtotal stomach-preserving pancreaticoduodenectomy with regional lymph node dissection was performed, as dissection from the pancreatic head proved unfeasible. Pathological examination identified the tumor as an enlarged lymph node consisting of pleomorphic large cells forming clusters, positive for follicular dendritic cell markers cluster of differentiation (CD) 21 and CD23. No evidence of tumor capsule infiltration, other organ infiltration, or metastasis to other lymph nodes was observed. The final diagnosis was nodal follicular dendritic cell sarcoma (FDCS) originating from the pancreatic head lymph nodes. No recurrence occurred at 3 years postoperatively with no postoperative treatment. Intraperitoneal nodal FDCS is extremely rare, and occasionally, it can lead to postoperative recurrence and progression. It is crucial to differentiate neoplastic lymph node enlargement around the pancreatic head from nodal FDCS. [ABSTRACT FROM AUTHOR]

FoxO is a member of the evolutionary conserved family of transcription factors containing a Forkhead box, involved in many signaling pathways of physiological and pathological processes. In mammals, mutations or dysfunctions of the FoxO gene have been implicated in diverse diseases. FoxO homologs have been found in some invertebrates, including echinoderms. We have isolated the FoxO cDNA from the sea urchin Paracentrotus lividus (Pl-foxo) and characterized the corresponding gene and mRNA. In silico studies showed that secondary and tertiary structures of Pl-foxo protein corresponded to the vertebrate FoxO3 isoform, with highly conserved regions, especially in the DNA-binding domain. A phylogenetic analysis compared the Pl-foxo deduced protein with proteins from different animal species and confirmed its evolutionary conservation between vertebrates and invertebrates. The increased expression of Pl-foxo mRNA following the inhibition of the PI3K signaling pathway paralleled the upregulation of Pl-foxo target genes involved in apoptosis or cell-cycle arrest events (BI-1, Bax, MnSod). In silico studies comparing molecular data from sea urchins and other organisms predicted a network of Pl-foxo protein–protein interactions, as well as identified potential miRNAs involved in Pl-foxo gene regulation. Our data may provide new perspectives on the knowledge of the signaling pathways underlying sea urchin development. [ABSTRACT FROM AUTHOR]

Background and Objectives: The goal of this study was to assess the impact of supplementation with a combination of nutrients on metabolic-dysfunction-associated steatotic liver disease (MASLD)-related liver parameters, and other parameters related to metabolic syndrome in adults with obesity. These measurements included anthropometric and lipid profiling, and FibroScan technology (controlled attenuation parameter (CAP) and transient elastography (TE) values). Materials and Methods: A double-blind, placebo-controlled pilot clinical trial was conducted over a three-month treatment period. Adults with metabolic syndrome and obesity were allocated to receive either a cocktail of nutrients with defined daily dosages (5-MTHF, betaine, alpha-linolenic acid, eicosapentaenoic acid, choline bitartrate, docosahexaenoic acid, and vitamin B12) or a placebo. The participants were evaluated at the start and the end of the three-month treatment period. Results: A total of 155 participants entered the study, comprising 84 in the treatment group and 71 in the placebo group. The administration of the nutritional supplement resulted in a notable reduction in both CAP and TE scores when compared to the placebo group. The treatment group exhibited a mean reduction in CAP of 4% (p < 0.05) and a mean reduction in TE of 7.8% (p < 0.05), indicative of a decline in liver fat content and fibrosis. Conclusions: The supplementation over a period of three months led to a significant amelioration of liver fibrosis and steatosis parameters in adults with metabolic syndrome and obesity. These findings suggest that this supplementation regimen could be a beneficial adjunct therapy for improving liver health in adults with obesity-induced MASLD. [ABSTRACT FROM AUTHOR]

Recently, fish consumption has been increasing; subsequently, the number of by‐products has also increased. However, generated residues are frequently discarded, and an appropriate management is necessary to properly use all fish by‐products. Fishery by‐products are well known for their content of bioactive compounds, such as unsaturated fatty acids, amino acids, minerals, peptides, enzymes, gelatin, collagen, and chitin. Several studies have reported that fishery by‐products could provide significant properties, including antioxidant, antihypertensive, antimicrobial, anti‐inflammatory, and antiobesity. Consequently, fish discards are of considerable interest to different industrial sectors, including food, nutraceuticals, medical, and pharmacology. In the food industry, the interest in using fishery by‐products is focused on hydrolysates as food additives, collagen and gelatin as protein sources, chitin and chitosan to form edible films to protect food during storage, and oils as a source of Omega‐3 and useful as antioxidants. Although different studies reported good results with the use of these by‐products, identifying new applications in the food sector, as well as industrial applications, remains necessary. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a skin condition characterized by significant challenges and a substantial deterioration in the life quality for affected patients. The therapeutic landscape for AD has witnessed a transformative shift with the emergence of biologic therapies. Our focus centers on biologics currently undergoing phase III and IV clinical trials, deeming them to hold the highest potential for significant clinical relevance. To identify biologic drugs under development in phase III and IV clinical trials, we searched ClinicalTrials.gov. Additional relevant trials were identified through JapicCTI/ Japan Registry of Clinical Trials (jRCT) with a citation search. A search in MEDLINE and EMBASE was performed. There have been 76 clinical trials identified concerning biologic drugs: dupilumab (34 trials), lebrikizumab (14 trials), tralokinumab (10 trials), rocatinlimab (7 trials), amlitelimab (2 trials), nemolizumab (6 trials), MG-K10 (1 trial), CM310 (1 trial), 611 (1 trial). A search in MEDLINE revealed 132 articles concerning phase III and IV clinical trials for AD treatment. A total of 39 articles concerned biologic drugs covering 23 clinical trials. A search in EMBASE revealed 268 relevant articles, allowing us to identify results of an additional six clinical trials. The safety and efficacy of these biologics are comprehensively addressed in this review. This comprehensive review aims to explore the current landscape of biologic therapies for AD, delving into the latest research findings, clinical trial outcomes, and the diverse mechanisms of action employed by these novel interventions. [ABSTRACT FROM AUTHOR]

This review systematically examines gender differences in hepatocellular carcinoma (HCC), identifying the influence of sex hormones, genetic variance, and environmental factors on the disease's epidemiology and treatment outcomes. Recognizing the liver as a sexually dimorphic organ, we highlight how gender-specific risk factors, such as alcohol consumption and obesity, contribute differently to hepatocarcinogenesis in men and women. We explore molecular mechanisms, including the differential expression of androgen and estrogen receptors, which mediate diverse pathways in tumor biology such as cell proliferation, apoptosis, and DNA repair. Our analysis underscores the critical need for gender-specific research in liver cancer, from molecular studies to clinical trials, to improve diagnostic accuracy and therapeutic effectiveness. By incorporating a gender perspective into all facets of liver cancer research, we advocate for a more precise and personalized approach to cancer treatment that acknowledges gender as a significant factor in both the progression of HCC and its response to treatment. This review aims to foster a deeper understanding of the biological and molecular bases of gender differences in HCC and to promote the development of tailored interventions that enhance outcomes for all patients. [ABSTRACT FROM AUTHOR]

Pharmaceuticals are recognized as a serious threat to aquatic ecosystems due to their persistence or pseudo-persistence and their biological activity. Their increased consumption in human and animal medicine has led to a continuous discharge of such biologically active molecules in aquatic environments. Marine ecosystems have been poorly investigated, even though recent studies have confirmed that these emerging contaminants occur widely in these ecosystems. Due to their interaction with specific biochemical and physiological pathways in target organisms, pharmaceuticals can cause alterations in several marine species during their entire life cycle. In particular, marine fishes have shown the ability to bioaccumulate these compounds in their body, and they may be used as potential bioindicators of pharmaceutical contamination in seawater. The objective of this review was to provide a comprehensive overview of the current understanding of the sources and occurrence of pharmaceuticals in marine environments, illustrating the adverse biological effects of important classes of these compounds on marine fishes. [ABSTRACT FROM AUTHOR]

Lipid metabolism dysregulation can lead to dyslipidemia and obesity, which are major causes of cardiovascular disease and associated mortality worldwide. The purpose of the study was to obtain and characterize six plant extracts (ACE—Allii cepae extractum; RSE—Rosmarini extractum; CHE—Cichorii extractum; CE—Cynarae extractum; AGE—Apii graveolentis extractum; CGE—Crataegi extractum) as promising adjuvant therapies for the prevention and treatment of dyslipidemia and its related metabolic diseases. Phytochemical screening revealed that RSE was the richest extract in total polyphenols (39.62 ± 13.16 g tannic acid/100 g dry extract) and phenolcarboxylic acids (22.05 ± 1.31 g chlorogenic acid/100 g dry extract). Moreover, the spectrophotometric chemical profile highlighted a significant concentration of flavones for CGE (5.32 ± 0.26 g rutoside/100 g dry extract), in contrast to the other extracts. UHPLC-MS quantification detected considerable amounts of phenolic constituents, especially chlorogenic acid in CGE (187.435 ± 1.96 mg/g extract) and rosmarinic acid in RSE (317.100 ± 2.70 mg/g extract). Rosemary and hawthorn extracts showed significantly stronger free radical scavenging activity compared to the other plant extracts (p < 0.05). Pearson correlation analysis and the heatmap correlation matrix indicated significant correlations between phytochemical contents and in vitro antioxidant activities. Computational studies were performed to investigate the potential anti-obesity mechanism of the studied extracts using target prediction, homology modeling, molecular docking, and molecular dynamics approaches. Our study revealed that rosmarinic acid (RA) and chlorogenic acid (CGA) can form stable complexes with the active site of carbonic anhydrase 5A by either interacting with the zinc-bound catalytic water molecule or by directly binding Zn2+. Further studies are warranted to experimentally validate the predicted CA5A inhibitory activities of RA and CGA and to investigate the hypolipidemic and antioxidant activities of the proposed plant extracts in animal models of dyslipidemia and obesity. [ABSTRACT FROM AUTHOR]

Hepatitis C virus infection affects over 58 million individuals and is responsible for 290,000 annual deaths. The infection spread in the past via blood transfusion and iatrogenic transmission due to the use of non-sterilized glass syringes mostly in developing countries (Cameroon, Central Africa Republic, Egypt) but even in Italy. High-income countries have achieved successful results in preventing certain modes of transmission, particularly in ensuring the safety of blood and blood products, and to a lesser extent, reducing iatrogenic exposure. Conversely, in low-income countries, unscreened blood transfusions and non-sterile injection practices continue to play major roles, highlighting the stark inequalities between these regions. Currently, injection drug use is a major worldwide risk factor, with a growing trend even in low- and middle-income countries (LMICs). Emerging high-risk groups include men who have sex with men (MSM), individuals exposed to tattoo practices, and newborns of HCV-infected pregnant women. The World Health Organization (WHO) has proposed direct-acting antiviral (DAA) therapy as a tool to eliminate infection by interrupting viral transmission from infected to susceptible individuals. However, the feasibility of this ambitious and overly optimistic program generates concern about the need for universal screening, diagnosis, linkage to care, and access to affordable DAA regimens. These goals are very hard to reach, especially in LMICs, due to the cost and availability of drugs, as well as the logistical complexities involved. Globally, only a small proportion of individuals infected with HCV have been tested, and an even smaller fraction of those have initiated DAA therapy. The absence of an effective vaccine is a major barrier to controlling HCV infection. Without a vaccine, the WHO project may remain merely an illusion. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is a global public health problem that causes liver-related morbidity and mortality. It is also an independent risk factor for non-communicable diseases. In 2020, a proposal was made to refer to it as "metabolic dysfunction-associated fatty liver disease (MAFLD)", with concise diagnostic criteria. Given its widespread occurrence, its treatment is crucial. Increased levels of oxidative stress cause this disease. This review aims to evaluate various studies on antioxidant therapies for patients with MAFLD. A comprehensive search for relevant research was conducted on the PubMed, SCOPUS, and ScienceDirect databases, resulting in the identification of 87 studies that met the inclusion criteria. In total, 31.1% of human studies used natural antioxidants, 53.3% used synthetic antioxidants, and 15.5% used both natural and synthetic antioxidants. In human-based studies, natural antioxidants showed 100% efficacy in the treatment of MAFLD, while synthetic antioxidants showed effective results in only 91% of the investigations. In animal-based research, natural antioxidants were fully effective in the treatment of MAFLD, while synthetic antioxidants demonstrated effectiveness in only 87.8% of the evaluations. In conclusion, antioxidants in their natural form are more helpful for patients with MAFLD, and preserving the correct balance of pro-oxidants and antioxidants is a useful way to monitor antioxidant treatment. [ABSTRACT FROM AUTHOR]

Copyright of Revista Gênero e Interdisciplinaridade is the property of Instituto de Ensino e Pesquisa Periodicojs and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Across the wide range of clinical conditions, there exists a sex imbalance where biological females are more prone to autoimmune diseases and males to some cancers. These discrepancies are the combinatory consequence of lifestyle and environmental factors such as smoking, alcohol consumption, obesity, and oncogenic viruses, as well as other intrinsic biological traits including sex chromosomes and sex hormones. While the emergence of immuno-oncology (I/O) has revolutionised cancer care, the efficacy across multiple cancers may be limited because of a complex, dynamic interplay between the tumour and its microenvironment (TME). Indeed, sex and gender can also influence the varying effectiveness of I/O. Androgen receptor (AR) plays an important role in tumorigenesis and in shaping the TME. Here, we lay out the epidemiological context of sex disparity in cancer and then review the current literature on how AR signalling contributes to such observation via altered tumour development and immunology. We offer insights into AR-mediated immunosuppressive mechanisms, with the hope of translating preclinical and clinical evidence in gender oncology into improved outcomes in personalised, I/O-based cancer care. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to investigate the effects of aspirin eugenol ester (AEE) on ileal immune function in broilers under lipopolysaccharide (LPS)- induced immune stress. Methods: Two hundred and forty one-day-old male Arbor Acres chicks were randomly divided into four groups (saline, LPS, saline + AEE and LPS + AEE) with six replicates of ten broilers each. The saline group and LPS group were fed the normal diet, while the other two groups received normal diet plus 0.1 g/kg AEE. Broilers in the LPS and LPS + AEE groups were injected intraperitoneally with 0.5 mg/kg B. W LPS in saline for seven consecutive days beginning at 14 days of age, while broilers in the saline and saline + AEE groups were injected with saline only. Results: The results showed that AEE improved the ileal morphology and increased the ratio of villus height to crypt depth of immune-stressed broilers. LPS-induced immune stress significantly reduced the expression of the genes for the tight junction proteins occludin, zonula occludens-1 (ZO-1), claudin-1 and claudin-2, in the ileum, while AEE significantly up-regulated the expression of these genes. Compared with the saline group, the LPS-treated chickens showed significantly increased mRNA expression of the inflammatory factors tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10), cyclooxygenase-2 (COX-2), and microsomal Prostaglandin E Synthesase-1 (mPGES-1) in the ileum, while they were significantly decreased by AEE supplementation. In addition, analysis of the ileal bacterial composition showed that compared with saline and LPS + AEE groups, the proportion of Firmicutes and Lactobacillus in the LPS group was lower, while the proportion of Proteobacteria and Escherichia-Shigella was higher. Similarly, Line Discriminant Analysis Effect Size (LEfSe) analysis showed that compared with the LPS group, Brevibacillus was dominant in the saline group, while the LPS + AEE group was rich in Rhizobium, Lachnoclostridium, Ruminococcaceae, Faecalibacterium, Negativibacillus, Oscillospiraceae, and Flavonifractor. Conclusion: These results indicate that dietary supplementation with 0.1 g/kg AEE could protect the intestinal health by improving the intestinal villus morphology, enhancing the expression of tight junction genes and alleviating inflammation to resist the immune stress caused by LPS stimulation in broilers, and the mechanism may involve COX-2-related signal transduction and improved intestinal microbiota composition. [ABSTRACT FROM AUTHOR]

Nuclear transcription factor Y (NF-Y) is a CCAAT-binding trimeric protein. The overexpression of the DNA-binding subunit A (NF-YA) results in deregulation of many CCAAT-dependent pro-growth genes in multiple tumor types. Exon 3 alternative splicing of NF-YA results in two different isoforms, NF-YAs (short) and NF-YAl (long), which can promote tumor proliferation or metastasis, respectively. In this work, we developed an electrolyte-gated organic transistor (EGOT) biosensor to study the binding of a NF-YAl-composed NF-Y complex to its consensus sequence. We show that by using the target DNA sequence as a probe, the device detects NF-Y in the range of 1 pM to 10 nM. Control experiments performed with oligonucleotide probes mutated in the consensus sequence exhibit weaker, though not fully hindered, binding to NF-Y compared to the response to unmutated DNA. This behavior confirms that the base pairs near the CCAAT-box also have a role in the transcription factor recognition. Furthermore, we contributed to the advancement of the present state of the art by demonstrating the ability of the EGOT biosensor to detect NF-Y in cell lysate, a fundamental step towards the development of point-of-care (POC) devices for the analysis of biopsies. [ABSTRACT FROM AUTHOR]

Fiber-reinforced composites offer innovative solutions for architectural applications with high strength and low weight. Coreless filament winding extends industrial processes, reduces formwork, and allows for tailoring of fiber layups to specific requirements. A previously developed computational co-design framework for coreless filament winding is extended toward the integration of reciprocal design feedback to maximize design flexibility and inform design decisions throughout the process. A multi-scalar design representation is introduced, representing fiber structures at different levels of detail to generate feedback between computational design, engineering, and fabrication. Design methods for global, component, and material systems are outlined and feedback generation is explained. Structural and fabrication feedback are classified, and their integration is described in detail. This paper demonstrates how reciprocal feedback allows for co-evolution of domains of expertise and extends the existing co-design framework toward design problems. The developed methods are shown in two case studies at a global and component scale. [ABSTRACT FROM AUTHOR]

Oxidative stress plays a central role in most chronic liver diseases and, in particular, in metabolic dysfunction-associated fatty liver disease (MAFLD), the new definition of an old condition known as non-alcoholic fatty liver disease (NAFLD). The mechanisms leading to hepatocellular fat accumulation in genetically predisposed individuals who adopt a sedentary lifestyle and consume an obesogenic diet progress through mitochondrial and endoplasmic reticulum dysfunction, which amplifies reactive oxygen species (ROS) production, lipid peroxidation, malondialdehyde (MDA) formation, and influence the release of chronic inflammation and liver damage biomarkers, such as pro-inflammatory cytokines. This close pathogenetic link has been a key stimulus in the search for therapeutic approaches targeting oxidative stress to treat steatosis, and a number of clinical trials have been conducted to date on subjects with NAFLD using drugs as well as supplements or nutraceutical products. Vitamin E, Vitamin D, and Silybin are the most studied substances, but several non-pharmacological approaches have also been explored, especially lifestyle and diet modifications. Among the dietary approaches, the Mediterranean Diet (MD) seems to be the most reliable for affecting liver steatosis, probably with the added value of the presence of extra virgin olive oil (EVOO), a healthy food with a high content of monounsaturated fatty acids, especially oleic acid, and variable concentrations of phenols (oleocanthal) and phenolic alcohols, such as hydroxytyrosol (HT) and tyrosol (Tyr). In this review, we focus on non-pharmacological interventions in MAFLD treatment that target oxidative stress and, in particular, on the role of EVOO as one of the main antioxidant components of the MD. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Clinical Hepatology / Linchuang Gandanbing Zazhi is the property of Journal of Clinical Hepatology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: The California purple sea urchin, Strongylocentrotus purpuratus, relies solely on an innate immune system to combat the many pathogens in the marine environment. One aspect of their molecular defenses is the SpTransformer (SpTrf) gene family that is upregulated in response to immune challenge. The gene sequences are highly variable both within and among animals and likely encode thousands of SpTrf isoforms within the sea urchin population. The native SpTrf proteins bind foreign targets and augment phagocytosis of a marine Vibrio. A recombinant (r)SpTrf-E1-Ec protein produced by E. coli also binds Vibrio but does not augment phagocytosis. Methods: To address the question of whether other rSpTrf isoforms function as opsonins and augment phagocytosis, six rSpTrf proteins were expressed in insect cells. Results: The rSpTrf proteins are larger than expected, are glycosylated, and one dimerized irreversibly. Each rSpTrf protein cross-linked to inert magnetic beads (rSpTrf::beads) results in different levels of surface binding and phagocytosis by phagocytes. Initial analysis shows that significantly more rSpTrf::beads associate with cells compared to control BSA::beads. Binding specificity was verified by pre-incubating the rSpTrf::beads with antibodies, which reduces the association with phagocytes. The different rSpTrf::beads show significant differences for cell surface binding and phagocytosis by phagocytes. Furthermore, there are differences among the three distinct types of phagocytes that show specific vs. constitutive binding and phagocytosis. Conclusion: These findings illustrate the complexity and effectiveness of the sea urchin innate immune system driven by the natSpTrf proteins and the phagocyte cell populations that act to neutralize a wide range of foreign pathogens. [ABSTRACT FROM AUTHOR]

Objectives: Biosynthesis of silver nanoparticles using the fungus Aspergillus niger, isolated from the soil for the purpose of studying its ability to produce nanoparticles. Methods: Grown in a liquid fermentation medium in glass flasks for ten days. The biosynthesis process was detected by observing the color changes of the filtrate. The properties of silver nanoparticles were determined by UV-measurement. Use SEM to discover the size, shape and distribution of nanoparticles. The chemical groups responsible for the biosynthesis and encapsulation of nanoparticles were detected using FTIR for both the fungal biomass filtrate and the resulting particles, after turning them into powder. Silver nanoparticles produced from mushrooms using the Well-Diffusion-Method showed antibacterial activity against MDRbacteria for both Gram-positive and Gram-negative Bacteria, which are: (E. coli, K. Pneumonia, S. aureus, and P. aeruginosa), at two concentrations (50, 100). μg/ml) for AgNPs. Results: The biosynthesis was detected by observing the color changes of the filtrate from transparent to light yellow to dark brown. The properties of silver nanoparticles were determined by measurement (UV). Which showed absorbance values at wavelengths (450 nm). The results showed SEM The shape was spherical with dimensions ranging from (17.84-64.03) nanometers. Conclusions: The fungus Aspergillus niger showed the ability to biosynthesise silver nanoparticles after 24 hours of incubation of the fungal filtrate treated with AgNO3. [ABSTRACT FROM AUTHOR]

Silymarin, salvianolic acids B, and puerarin were considered healthy food agents with tremendous potential to ameliorate non-alcoholic fatty liver disease (NAFLD). However, the mechanisms by which they interact with gut microbiota to exert benefits are largely unknown. After 8 weeks of NAFLD modeling, C57BL/6J mice were randomly divided into five groups and fed a normal diet, high-fat diet (HFD), or HFD supplemented with a medium or high dose of Silybum marianum extract contained silymarin or polyherbal extract contained silymarin, salvianolic acids B, and puerarin for 16 weeks, respectively. The untargeted metabolomics and 16S rRNA sequencing were used for molecular mechanisms exploration. The intervention of silymarin and polyherbal extract significantly improved liver steatosis and recovered liver function in the mice, accompanied by an increase in probiotics like Akkermansia and Blautia, and suppressed Clostridium, which related to changes in the bile acids profile in feces and serum. Fecal microbiome transplantation confirmed that this alteration of microbiota and its metabolites were responsible for the improvement in NAFLD. The present study substantiated that alterations of the gut microbiota upon silymarin and polyherbal extract intervention have beneficial effects on HFD-induced hepatic steatosis and suggested the pivotal role of gut microbiota and its metabolites in the amelioration of NAFLD. [ABSTRACT FROM AUTHOR]

Chronic intestinal pseudo-obstruction (CIPO) is a rare intractable disease with limited treatment options. Small intestinal bacterial overgrowth (SIBO) often co-occurs with several diseases, including CIPO. While rifaximin (RFX) is effective in treating SIBO, its efficacy for CIPO remains unclear. Here, we aimed to investigate the efficacy and safety of RFX in adult patients with CIPO. Twelve patients were randomly assigned to receive RFX (400 mg three times daily, n=8) or a placebo (PBO, n=4) for 4 weeks. The global symptom score for abdominal bloating (GSS-bloating) and an original whole gastrointestinal symptoms score (O-WGSS) were collected, and a glucose hydrogen breath test (GHBT) and abdominal computed tomography (CT) were performed. No significant differences were observed in the primary endpoint. GSS-bloating improved by 75% and 25% in the PBO and RFX groups, respectively, and O-WGSS improved by 25% in both groups. No significant differences were observed in secondary and other endpoints, including the SIBO eradication rate in the GHBT and small intestinal volume on CT. In a post hoc analysis of SIBO-positive patients with CIPO (4/4 and 4/8 in the PBO and RFX groups), SIBO was eradicated in 25% and 75% of the patients (PBO and RFX groups, respectively) at the end of treatment, indicating a high eradication rate in the RFX group. Furthermore, the small intestinal gas volume decreased in the RFX group, and no severe adverse events occurred. Although no significant improvements were observed in subjective indicators, RFX may be beneficial in alleviating SIBO and reducing the small intestinal gas volume in SIBO-positive patients with CIPO. [ABSTRACT FROM AUTHOR]

Introduction: The interferon pathway plays a critical role in triggering the immune response to SARS-CoV-2, and these gene variants may be involved in the severity of COVID-19. This study aimed to analyze the frequency of three gene variants of OAS and RNASEL with the occurrence of COVID-19 symptoms and disease outcome. Methods: This cross-sectional study included 104 patients with SARS-CoV-2 infection, of which 34 were asymptomatic COVID-19, and 70 were symptomatic cases. The variants rs486907 (RNASEL), rs10774671 (OAS1), rs1293767 (OAS2), and rs2285932 (OAS3) were screened and discriminated using a predesigned 5′-nuclease assay with TaqMan probes. Results: Patients with the allele C of the OAS2 gene rs1293767 (OR = 0.36, 95% CI: 0.15–0.83, p = 0.014) and allele T of the OAS3 gene rs2285932 (OR = 0.39, 95% CI: 0.2–0.023, p = 0.023) have lower susceptibility to developing symptomatic COVID-19. The genotype frequencies (G/G, G/C, and C/C) of rs1293767 for that comparison were 64.7%, 29.4%, and 5.9% in the asymptomatic group and 95.2%, 4.8%, and 0% in severe disease (p < 0.05). Conclusions: Our data indicate that individuals carrying the C allele of the OAS2 gene rs1293767 and the T allele of the OAS3 gene rs2285932 are less likely to develop symptomatic COVID-19, suggesting these genetic variations may confer a protective effect among the Mexican study population. Furthermore, the observed differences in genotype frequencies between asymptomatic individuals and those with severe disease emphasize the potential of these variants as markers for disease severity. These insights enhance our understanding of the genetic factors that may influence the course of COVID-19 and underscore the potential for genetic screening in identifying individuals at increased risk for severe disease outcomes. [ABSTRACT FROM AUTHOR]

Primary biliary cholangitis (PBC) is an autoimmune liver disease characterised by the immune-mediated destruction of small and medium intrahepatic bile ducts, with variable outcomes and progression. This review summarises the state of the art regarding the risk of neoplastic progression in PBC patients, with a particular focus on the molecular alterations present in PBC and in hepatocellular carcinoma (HCC), which is the most frequent liver cancer in these patients. Major risk factors are male gender, viral infections, e.g., HBV and HCV, non-response to UDCA, and high alcohol intake, as well as some metabolic-associated factors. Overall, HCC development is significantly more frequent in patients with advanced histological stages, being related to liver cirrhosis. It seems to be of fundamental importance to unravel eventual dysfunctional molecular pathways in PBC patients that may be used as biomarkers for HCC development. In the near future, this will possibly take advantage of artificial intelligence-designed algorithms. [ABSTRACT FROM AUTHOR]

Silymarin has ameliorated obesity, type 2 diabetes (T2DM), and insulin resistance (IR) in combination with standard therapy, diet, or exercise in recent studies. Obesity and IR are the main risk factors for developing T2DM and other metabolic disorders. Today, there is a need for new strategies to target IR in patients with these metabolic diseases. In the present longitudinal study, a group of non-diabetic insulin-resistant women with type 1 and type 2 obesity were given silymarin for 12 weeks, with no change in habitual diet and physical activity. We used the Homeostatic Model Assessment for Insulin Resistance Index (HOMA-IR) to determine IR at baseline and after silymarin treatment (t = 12 weeks). We obtained five timepoint oral glucose tolerance tests, and other biochemical and clinical parameters were analyzed before and after treatment. Treatment with silymarin alone significantly reduced mean fasting plasma glucose (FPG) and HOMA-IR levels at 12 weeks compared to baseline values (p < 0.05). Mean fasting plasma insulin (FPI), total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (Tg), indirect bilirubin, and C-reactive protein (CRP) levels decreased compared to baseline values, although changes were non-significant. The overall results suggest that silymarin may offer a therapeutic alternative to improve IR in non-diabetic individuals with obesity. Further clinical trials are needed in this type of patient to strengthen the results of this study. [ABSTRACT FROM AUTHOR]

Pulmonary fibrosis (PF) is a terminal change of a lung disease that is marked by damage to alveolar epithelial cells, abnormal proliferative transformation of fibroblasts, excessive deposition of extracellular matrix (ECM), and concomitant inflammatory damage. Its characteristics include short median survival, high mortality rate, and limited treatment effectiveness. More in-depth studies on the mechanisms of PF are needed to provide better treatment options. The idea of the gut-lung axis has emerged as a result of comprehensive investigations into the microbiome, metabolome, and immune system. This theory is based on the material basis of microorganisms and their metabolites, while the gut-lung circulatory system and the shared mucosal immune system act as the connectors that facilitate the interplay between the gastrointestinal and respiratory systems. The emergence of a new view of the gut-lung axis is complementary and cross-cutting to the study of the mechanisms involved in PF and provides new ideas for its treatment. This article reviews the mechanisms involved in PF, the gut-lung axis theory, and the correlation between the two. Exploring the gut-lung axis mechanism and treatments related to PF from the perspectives of microorganisms, microbial metabolites, and the immune system. The study of the gut-lung axis and PF is still in its early stages. This review systematically summarizes the mechanisms of PF related to the gut-lung axis, providing ideas for subsequent research and treatment of related mechanisms. [ABSTRACT FROM AUTHOR]

The Mediterranean purple sea urchin Paracentrotus lividus (Lamarck 1816) is a remarkable model system for molecular, evolutionary and cell biology studies, particularly in the field of developmental biology. We sequenced the genome, performed a de novo assembly, and analysed the assembly content. The genome of P. lividus was sequenced using Illumina NextSeq 500 System (Illumina) in a 2 × 150 paired-end format. More than 30,000 open reading frames (ORFs), (more than 8000 are unique), were identified and analysed to provide molecular tools accessible for the scientific community. In particular, several genes involved in complex innate immune responses, oxidative metabolism, signal transduction, and kinome, as well as genes regulating the membrane receptors, were identified in the P. lividus genome. In this way, the employment of the Mediterranean sea urchin for investigations and comparative analyses was empowered, leading to the explanation of cis-regulatory networks and their evolution in a key developmental model occupying an important evolutionary position with respect to vertebrates and humans. [ABSTRACT FROM AUTHOR]

Personnel rescheduling problems have typically been studied from a static perspective, assuming a single rescheduling decision to be taken for which all disruption information is known. However, companies operate in a dynamic environment and new disruptions arise at different moments in time during the course of the execution of the schedule. In response, the personnel planner resides to (multiple) rerostering and/or allocation decisions to reinstate the workability of the schedule. In this paper, we investigate the dynamic personnel shift and task rescheduling problem and propose different recovery strategies to efficiently restore the personnel schedule. To that purpose, we simulate the operational variability based on input probability distributions for different sources of uncertainty and conduct timely recourse actions whenever indicated by the studied recovery strategies. Insights are provided into the recourse actions with respect to the number and timing of rescheduling decisions, the type of rescheduling decision and the rescheduling time horizon. We assess the trade-off between the rescheduling quality and effort, mapping the efficient recovery strategies using a Pareto front. Based upon these insights, we devise well-performing rules-of-thumb, defining efficient recovery decision strategies that lead to reconstructed personnel schedules of high quality. In addition, we investigate the impact of the timeline uncertainty on the outcome of the recovery strategies. [ABSTRACT FROM AUTHOR]

The interleukins IL-4 and IL-13 are increasingly recognized contributors to the pathogenesis of cutaneous T cell lymphomas (CTCLs), and their role in disease-associated pruritus is accepted. The prevailing Th2 profile in advanced CTCL underscores the significance of understanding IL-4/IL-13 expression dynamics from the early stages of disease, as a shift from Th1 to Th2 may explain CTCL progression. Targeted agents blocking key cytokines of type 2 immunity are established therapeutics in atopic disorders and have a promising therapeutic potential in CTCL, given their involvement in cutaneous symptoms and their contribution to the pathogenesis of disease. IL-4, IL-13, and IL-31 are implicated in pruritus, offering therapeutic targets with dupilumab, tralokinumab, lebrikizumab, and nemolizumab. This review analyzes current knowledge on the IL-4/IL-13 axis in mycosis fungoides and Sezary syndrome, the most common types of CTCL, examining existing literature on the pathogenetic implications with a focus on investigational treatments. Clinical trials and case reports are required to shed light on novel uses of medications in various diseases, and ongoing research into the role of IL-4/IL-13 axis blockers in CTCL therapy might not only improve the management of disease-related pruritus but also provide in-depth insights on the pathophysiologic mechanisms of CTCL. [ABSTRACT FROM AUTHOR]

The liver is the main organ for metabolic and detoxification reactions in the body. Therefore, its diseases can be associated with both metabolic disorders, such as insulin resistance, obesity, diabetes, or dyslipidemia, and exogenous insults such as drugs, xenobiotics, or alcohol. Indeed, lifestyle changes are the primary approaches for the prevention and treatment of liver diseases. Since ancient times, herbals have also been used for preventive and therapeutic purposes, because of their anti-apoptotic, anti-inflammatory, and antioxidant effects. Here, the literature was reviewed for potential therapeutic effects of plants and their compounds by including in vitro and in vivo studies, as well as clinical trials. Although the available data imply some beneficial roles of herbals on the liver, the indications and posology of specific plants need to be clarified through multicenter, randomized clinical trials. [ABSTRACT FROM AUTHOR]

Artificial intelligence-based algorithms are becoming essential tools in materials science-related fields because of their excellent functionality in reflecting physics in the training database and predicting the properties of unexplored materials with outstanding accuracy. Designing novel materials with engineered properties, such as metamaterials, is the key to revolutionizing material discovery, and machine learning (ML) and deep learning (DL) can be powerful and indispensable tools for acceleration. This review focuses on the implementation of ML/DL-based approaches for designing metamaterials. Quantum–mechanical, atomistic, and macroscale simulation methods are also assessed as database construction processes. Forward and inverse design methods are summarized in detail, and breakthroughs in generative models are particularly introduced. Moreover, applications in fundamental property prediction and material structural design are reviewed. Finally, the remaining challenging tasks for future related work are presented. [ABSTRACT FROM AUTHOR]

Invertebrates show great diversity in their responses to neural damage. Numerous invertebrate phyla, including gastropods, can replace all or a portion of their nervous systems. Aplysia species have been utilized extensively in toxicology, ecology, and neuroscience because their neurological systems react to bodily harm by releasing trophic substances that can stimulate non-neural tissue regeneration and induce changes in the nervous system. This study aims to assess the putative role of hemocytes of Aplysia depilans (Gmelin, 1791) by analyzing the presence of Toll-like receptor 2, inducible nitric oxide synthetase, and, in particular, vimentin and α-tubulin, molecules potentially implicated in the process of neural regeneration. The results demonstrate that all the aforementioned proteins are present in hemocytes, suggesting their role in the defense response and their possible contribution to the neuronal regeneration process of this gastropod. These data provide deeper insight into the internal defense system of this mollusk. [ABSTRACT FROM AUTHOR]

The management of patients with diverticular disease remains challenging. The aim of this national survey was to assess how gastroenterologists and general practitioners use rifaximin to manage diverticulosis and diverticular disease. Members of the Italian Association of Hospital Gastroenterologists and Endoscopists (AIGO) and the Italian Federation of General Practitioners (FIMMG) were invited to complete a 39-item online survey concerning the use of rifaximin in five clinical settings: (1) diverticulosis; (2) reducing symptoms in symptomatic uncomplicated diverticular disease; (3) reducing the occurrence of diverticulitis in patients with symptomatic uncomplicated diverticular disease (primary prevention); (4) reducing the recurrence of diverticulitis in patients with previous attacks of diverticulitis (secondary prevention); (5) treatment of uncomplicated acute diverticulitis. A total of 1094 physicians completed the survey. Overall, 25.1%, 83.5%, 68%, 74.2%, and 63% of physicians prescribed rifaximin for the clinical settings 1, 2, 3, 4, and 5, respectively. In each clinical setting, the dosage of rifaximin most frequently used was 800 mg/day, the most common duration of therapy was 7 days, and the cyclic administration of treatment (expressed in months) most frequently used was > 24 months. These results highlight that a reappraisal of the use of rifaximin in patients with diverticulosis and diverticular disease is required to reduce the gap between the evidence available and the daily clinical practice, optimizing also the use of healthcare resources., (© 2024. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

Amino acid derivatives are molecules of interest for medicinal chemistry and drug design studies due to their important chemical properties. In this study, the inhibition effects of some non-proteinogenic amino acid derivatives (hippuric acid (A), N-(9-Fluorenylmethoxycarbonyl)-D-valine (B), N-Z-(1-Benzotriazolylcarbonyl) methylamine (C), (S)-N-Z-1-Benzotriazolylcarbonyl-2-phenylethylamine (D)) on carbonic anhydrase I (hCA-I), II (hCA-II) isoenzymes and acetylcholinesterase (AChE) activity, whose inhibitors are of vital pharmacological importance, were examined. While carbonic anhydrase (CA) inhibitors are effective molecule candidates for the treatment of many diseases from glaucoma to cancer, acetylcholinesterase inhibitors are target molecules for the treatment of Alzheimer's disease. According to the results of this study, compound D had a strong inhibitory effect on hCA-I (IC 50 : 0.836 μM) and hCA-II (IC 50 : 0.661 μM), while compound B (IC 50 : 100 μM) showed a strong inhibitory effect on AChE activity. In addition, inhibition results were supported by molecular modeling studies. We hope that the obtained results will contribute to the synthesis of new and effective amino acid derivative inhibitors for CA and AChE., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

This study reports a rapid and efficient synthesis of four novel aryl Schiff base derivatives. Biological activity and molecular modeling studies were conducted to evaluate the inhibitory effects of these compounds on human carbonic anhydrases (hCA) and cholinesterases. The results indicate that the triazole-ring-containing compounds have strong inhibitory effects on hCA I, hCA II, acetylcholinesterase (AChE), and butyrylcholinesterase (BuChE) targets. Besides comparing the Schiff bases synthesized in our study to reference molecules, we conducted in silico investigations to examine how these compounds interact with their targets. Our studies revealed that these compounds can occupy binding sites and establish interactions with crucial residues, thus inhibiting the functions of the targets. These findings have significant implications as they can be utilized to develop more potent compounds for treating the diseases that these target proteins play crucial roles in or to obtain drug precursors with enhanced efficacy., (© 2024 The Authors. Archiv der Pharmazie published by Wiley-VCH GmbH on behalf of Deutsche Pharmazeutische Gesellschaft.)

Liver fibrosis is a dynamic pathological process that can be triggered by any chronic liver injury. If left unaddressed, it will inevitably progress to the severe outcomes of liver cirrhosis or even hepatocellular carcinoma. In the past few years, the prevalence and fatality of hepatic fibrosis have been steadily rising on a global scale. As a result of its intricate pathogenesis, the quest for pharmacological interventions targeting liver fibrosis has remained a formidable challenge. Currently, no pharmaceuticals are exhibiting substantial clinical efficacy in the management of hepatic fibrosis. Hence, it is of utmost importance to expedite the development of novel therapeutics for the treatment of this condition. Various research studies have revealed the ability of different natural flavonoid compounds to alleviate or reverse hepatic fibrosis through a range of mechanisms, which are related to the regulation of liver inflammation, oxidative stress, synthesis and secretion of fibrosis-related factors, hepatic stellate cells activation, and proliferation, and extracellular matrix synthesis and degradation by these compounds. This review summarizes the progress of research on different sources of natural flavonoids with inhibitory effects on liver fibrosis over the last decades. The anti-fibrotic effects of natural flavonoids have been increasingly studied, making them a potential source of drugs for the treatment of liver fibrosis due to their good efficacy and biosafety., (© 2024 John Wiley & Sons Ltd.)

Hepatocellular carcinoma (HCC) is the second lethal cancer. Short overall survival, low five-year survival rate, and unimproved treatment efficacy urge the need to improve HCC prognosis. Adiponectin is key protector against cancer and hepatic abnormalities. Hypoadiponectinemia occurs in and promotes carcinogenesis and hepatic diseases. Adiponectin reactivation by different methods showed impressive effect against cancer and hepatic diseases. Recently, AdipoRon, an adiponectin receptor agonist, can interact with both Adiponectin receptors. AdipoRon showed promising anti-cancer effect in some cancers, but no study on HCC yet. The in vitro effect of AdipoRon on HCC was investigated by cell viability, migration, invasion, colony formation and apoptosis assays. The signalling alteration was determined by RT-qPCR and Western blot. The effect of treatment was interpreted by comparison between treatments and control. The difference between two cell lines was relatively compared. Our results showed significant in vitro anti-cancer effect of AdipoRon via AMPK- and dose-dependent manner. Huh7 cells showed a lower level of AdipoR1/2 and a superior proliferation and aggressiveness, compared to Hep3B. In addition, Huh7 cells were more sensitive to AdipoRon treatment (lower IC 50 , less cell growth, migration, invasion and colonies upon AdipoRon treatment) than Hep3B cells. In conclusion, AdipoRon effectively inhibited HCC growth and invasiveness in vitro. The deficient expression of adiponectin receptors affects efficacy of AdipoRon and aggressiveness of HCC cells., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Primary liver cancer is a type of cancer that develops in the liver. Hepatocellular carcinoma is a primary liver cancer that usually affects adults. Liver cancer is a fatal global condition that affects millions of people worldwide. Despite advances in technology, the mortality rate remains alarming. There is growing interest in researching alternative medicines to prevent or reduce the effects of liver cancer. Recent studies have shown growing interest in herbal products, nutraceuticals, and Chinese medicines as potential treatments for liver cancer. These substances contain unique bioactive compounds with anticancer properties. The causes of liver cancer and potential treatments are discussed in this review. This study reviews natural compounds, such as curcumin, resveratrol, green tea catechins, grape seed extracts, vitamin D, and selenium. Preclinical and clinical studies have shown that these medications reduce the risk of liver cancer through their antiviral, anti-inflammatory, antioxidant, anti-angiogenic, and antimetastatic properties. This article discusses the therapeutic properties of natural products, nutraceuticals, and Chinese compounds for the prevention and treatment of liver cancer., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Many nucleoside triphosphate-diphosphohydrolases (NTPDases/APYRASEs, APYs) play a key role in modulating extracellular nucleotide levels. However, the Golgi-localized APYs, which help control glycosylation, have rarely been studied. Here, we identified AtAPY1, a gene encoding an NTPDase in the Golgi apparatus, which is required for cell wall integrity and plant growth under boron (B) limited availability. Loss of function in AtAPY1 hindered cell elongation and division in root tips while increasing the number of cortical cell layers, leading to swelling of the root tip and abundant root hairs under low B stress. Further, expression pattern analysis revealed that B deficiency significantly induced AtAPY1, especially in the root meristem and stele. Fluorescent-labeled AtAPY1-GFP localized to the Golgi stack. Biochemical analysis showed that AtAPY1 exhibited a preference of UDP and GDP hydrolysis activities. Consequently, the loss of function in AtAPY1 might disturb the homoeostasis of NMP-driven NDP-sugar transport, which was closely related to the synthesis of cell wall polysaccharides. Further, cell wall-composition analysis showed that pectin content increased and borate-dimerized RG-II decreased in apy1 mutants, along with a decrease in cellulose content. Eventually, altered polysaccharide characteristics presumably cause growth defects in apy1 mutants under B deficiency. Altogether, these data strongly support a novel role for AtAPY1 in mediating responses to low B availability by regulating cell wall integrity., (© 2024 Scandinavian Plant Physiology Society.)

Background and Aims: Nonalcoholic fatty liver disease (NAFLD), currently referred to as metabolic dysfunction-associated steatotic liver disease (MASLD), affects approximately 38% of the world's population, yet no pharmacological therapies have been approved for treatment. We conducted a traditional and network meta-analysis to comprehensively assess the effectiveness of drug regimens on NAFLD, and continued to use the old terminology for consistency., Methods: Randomized, placebo-controlled trials (RCTs) investigating drug therapy in an adult population diagnosed with NAFLD with or without diabetes mellitus were included. We assessed the quality of RCTs via the Risk of Bias 2 (ROB 2) tool. When I 2 < 50%, we chose a random-effects model, otherwise a fixed-effects model was selected. A random effects model was applied in the network meta-analysis. The odds ratio (OR), weighted mean difference (WMD) or standard mean difference (SMD) with 95% confidence interval (CI) were used for outcome evaluation. The primary endpoint was the resolution of nonalcoholic steatohepatitis (NASH) without the worsening of liver fibrosis. Other endpoints included histological findings and metabolic changes. The PROSPERO Registration ID was CRD42023404309., Results: Thiazolidinediones (TZDs), vitamin E plus pioglitazone, glucagon-like peptide-1 (GLP-1) receptor agonists and fibroblast growth factor-21 (FGF-21) analogue had a higher surface under the cumulative ranking curve (SUCRA = 76.6, 73.0, 72.0 and 71.6) regarding NASH resolution. Improvement of liver fibrosis stage (≥ 1) was observed with obeticholic acid 25 mg/day (OR 2.01, 95% CI 1.35-2.98), lanifibranor 1200 mg/day (OR 2.39, 95% CI 1.19-4.82) and silymarin (OR 4.54, 95% CI 1.18-17.43) in traditional meta-analysis., Conclusions: The results of the comprehensive analysis suggested hypoglycemic drug therapy as an effective intervention for NAFLD, with or without diabetes mellitus. A prioritized selection of TZDs, vitamin E plus pioglitazone, GLP-1 receptor agonists and FGF-21 analogue may be considered for NASH resolution. Obeticholic acid, lanifibranor and silymarin could be considered for the improvement of liver fibrosis. Each medication was relatively safe compared with placebo., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Dendritic cells (DCs) are specialized antigen-presenting cells that initiate and regulate innate and adaptive immune responses. Solute carrier (SLC) transporters mediate diverse physiological functions and maintain cellular metabolite homeostasis. Recent studies have highlighted the significance of SLCs in immune processes. Notably, upon activation, immune cells undergo rapid and robust metabolic reprogramming, largely dependent on SLCs to modulate diverse immunological responses. In this review, we explore the central roles of SLC proteins and their transported substrates in shaping DC functions. We provide a comprehensive overview of recent studies on amino acid transporters, metal ion transporters, and glucose transporters, emphasizing their essential contributions to DC homeostasis under varying pathological conditions. Finally, we propose potential strategies for targeting SLCs in DCs to bolster immunotherapy for a spectrum of human diseases., (© 2023 Wiley-VCH GmbH.)

Objectives: We aimed to study hepatitis D virus (HDV) prevalence and risk of progression to severe liver-related events (SLRE) in HBsAg positive people living with HIV (PLWH) in Italy; role of HDV-RNA copy levels, HCV coinfection and nadir CD4 counts were also investigated., Methods: People living with HIV (PLWH) from Italian Foundation cohort Naïve antiretrovirals (ICONA) with available HBsAg and HDV Ab were enrolled. HBsAg, HDV Ab, HDV-RNA and HDV genotypes were tested., Primary End-Point: time from first HDV screening to Severe Liver Related Events (SLRE: decompensated cirrhosis, liver transplantation, HCC). Fine-grey regression models were used to evaluate the association of HDV Ab, HDV-RNA, HDV/HCV coinfection, CD4 nadir and outcome. Secondary end-points: time to SLRE or death; HDV Ab and HDV-RNA prevalence., Results: A total of 152/809 (18.8%) HBsAg positive PLWH showed HDV Ab reactivity; 63/93 (67.7%) were HDV-RNA positive. Being male, persons who inject drugs (PWID), HCV Ab positive, with FIB-4 > 3.25 were independent factors of HDV Ab positivity. In a median follow-up of 5 years, 37 PLWH (4.1% at 5-year) developed SLRE and 97 (12.0%) reached the SLRE or death end-point. HDV-RNA positive (independently from HDV-RNA copy level) PLWH had a 4.6-fold (95%CI 2.0-10.5) higher risk of SLRE than HDV negatives. PLWH positive for both HCV Ab and HDV Ab showed the highest independent risk of SLRE (ASHR: 11.9, 95%CI: 4.6-30.9 vs. HCV neg/HDV neg). Nadir CD4 < 200/mL was associated with SLRE (ASHR: 3.9, 95% 1.0-14.5)., Conclusions: One-fifth of the HBsAg positive PLWH harbour HDV infection, and are at high risk of progression to advanced liver disease. HCV contributes to worse outcomes. This population needs urgently effective treatments., (© 2023 The Authors. Liver International published by John Wiley & Sons Ltd.)

Co-infection with hepatitis delta virus (HDV) is a challenging health care problem worldwide, estimated to occur in approximately 5%-10% of patients with chronic hepatitis B virus (HBV) infection. While HBV prevalence is decreasing globally, the prevalence of HDV infection is rising in some parts mainly due to injection drug use, sexual transmission and immigration from high endemicity areas. Eastern Europe and the Mediterranean are among the regions with high rates of endemicity for HDV and the immigration from high endemicity areas to Central and Western Europe has changed the HDV epidemiology. We aimed to review the prevalence of HDV infection in Europe. A paucity of publication appears in many European countries. Prevalence studies from some countries are old dated and some other countries did not report any prevalence studies. The studies are accumulated in few countries. Anti-HDV prevalence is high in Greenland, Norway, Romania, Sweden and Italy. Belgium, France, Germany, Spain, Switzerland, Turkey and United Kingdom reported decreasing prevalences. Among cirrhotic HBV patients, Germany, Italy and Turkey reported higher rates of HDV. The studies including centres across the Europe reported that HIV-HBV coinfected individuals have higher prevalence of HDV infection. The immigrants contribute the HDV infection burden in Greece, Italy, and Spain in an increasing rate. Previous studies revealed extremely high rates of HDV infection in Germany, Greece, Italy and Sweden. The studies report a remarkably high prevalence of hepatitis delta among HIV/HBV-coinfected individuals, individuals who inject drugs, immigrants and severe HBV infected patients across Europe. The HDV infection burden still appears to be significant. In the lack of an effective HDV therapy, prevention strategies and active screening of HBV/HDV appear as the most critical interventions for reducing the burden of liver disease related to HDV infection in Europe., (© 2023 John Wiley & Sons Ltd.)

Background: Trypanosomiasis, caused by protozoan parasites of the Trypanosoma genus, remains a significant health burden in several regions of the world. Cysteine proteases play a crucial role in the pathogenesis of Trypanosoma parasites and have emerged as potential therapeutic targets for the development of novel antiparasitic drugs., Introduction: This review article aims to provide a comprehensive overview of the role of cysteine proteases in trypanosomiasis and their potential as therapeutic targets. We discuss the biological significance of cysteine proteases in Trypanosoma parasites and their involvement in essential processes, such as host immune evasion, cell invasion, and nutrient acquisition., Methods: A comprehensive literature search was conducted to identify relevant studies and research articles on the role of cysteine proteases and their inhibitors in trypanosomiasis. The selected studies were critically analyzed to extract key findings and provide a comprehensive overview of the topic., Results: Cysteine proteases, such as cruzipain, TbCatB and TbCatL, have been identified as promising therapeutic targets due to their essential roles in Trypanosoma pathogenesis. Several small molecule inhibitors and peptidomimetics have been developed to target these proteases and have shown promising activity in preclinical studies., Conclusion: Targeting cysteine proteases and their inhibitors holds great potential for the development of novel antiparasitic drugs against trypanosomiasis. The identification of potent and selective cysteine protease inhibitors could significantly contribute to the combat against trypanosomiasis and improve the prospects for the treatment of this neglected tropical disease., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)