Endoscopic ultrasound-guided tissue acquisition for focal liver lesions in patients with a history of multiple primary malignant neoplasms.

Objective: This study aimed to investigate the usefulness of endoscopic ultrasound-guided tissue acquisition (EUS-TA) for diagnosing focal liver lesions in patients with a history of multiple primary malignant neoplasms. Methods: Among patients who underwent EUS-TA for focal liver lesions between 2016 and 2022, those with a history of multiple malignant neoplasms were included. A histologically confirmed malignant tumor within the past 5 years before EUS-TA was defined as a history of malignant neoplasm. The primary outcomes were diagnostic ability and adverse events of EUS-TA. Results: This study included 16 patients (median age, 73 [33-90] years), the median tumor size was 32 (6-51) mm, 14 had a history of double malignant neoplasms, whereas two had triple malignant neoplasms. Malignant neoplasms were detected histologically or cytologically in all cases. Immunohistochemistry was performed in 75% (12/16), and the final diagnosis of EUS-TA was metastatic liver tumor in 12 patients, and primary malignant liver tumor in four patients. The primary site could be identified in 11 of 12 metastatic tumor cases. The diagnostic yield of EUS-TA was 100% (16/16) for differentiating benign and malignant tumors and 94% (15/16) for confirming the histological type including the primary site of metastatic lesions. No adverse events were associated with the procedure. Conclusion: EUS-TA is a useful diagnostic modality for focal liver lesions in patients with a history of multiple malignant neoplasms, allowing for the differential diagnosis of primary and metastatic tumors and identification of the primary site of metastatic lesions.

Gut microbiota causally affects drug-induced liver injury via plasma metabolites: a Mendelian randomization study.

Background: The gut microbiota and plasma metabolites play important roles in the progression of drug-induced liver injury (DILI). We investigated the causal associations between the gut microbiota, plasma metabolome, and DILI. Methods: The summary data for gut microbiota (n = 18,340), plasma metabolome (n = 8,299), and DILI (n = 366,838) were obtained from the large genome-wide association studies. A two-sample Mendelian randomization was performed to explore the associations between the gut microbiota, plasma metabolome, and DILI. Additionally, a two-step Mendelian randomization was performed to explore the potential metabolites. Results: Five taxa were causally associated with DILI, including Oscillospira [odds ratio (OR) = 2.257, 95% confidence interval (CI) = 1.110-4.590], Blautia (OR = 2.311, 95% CI = 1.010-5.288), Roseburia (OR = 2.869, 95% CI = 1.429-5.761), Fusicatenibacter (OR = 1.995, 95% CI = 1.024-3.890), and Prevotella 7 (OR = 1.549, 95% CI = 1.065-2.253). Moreover, 53 metabolites were causally associated with DILI. After mediation analysis, four taxa were found to affect DILI through five mediation metabolites. N6-carbamoylthreonyladenosine mediated the effect of Blautia on DILI. Acetylcarnitine mediated the effect of Fusicatenibacter on DILI. In addition, 4-cholesten-3-one mediated the effect of Prevotella 7 on DILI. Furthermore, 5,6-dihydrothymine levels and the salicylate-to-citrate ratio mediated the effect of Oscillospira on DILI. Conclusion: We found that the gut microbiota could affect DILI through plasma metabolites, which could serve as potential biomarkers for risk stratification and elucidate underlying mechanisms for further investigation of DILI.

Hepatic macrophage niche: a bridge between HBV-mediated metabolic changes with intrahepatic inflammation.

Hepatitis B Virus (HBV) is a stealthy and insidious pathogen capable of inducing chronic necro-inflammatory liver disease and hepatocellular carcinoma (HCC), resulting in over one million deaths worldwide per year. The traditional understanding of Chronic Hepatitis B (CHB) progression has focused on the complex interplay among ongoing virus replication, aberrant immune responses, and liver pathogenesis. However, the dynamic progression and crucial factors involved in the transition from HBV infection to immune activation and intrahepatic inflammation remain elusive. Recent insights have illuminated HBV's exploitation of the sodium taurocholate co-transporting polypeptide (NTCP) and manipulation of the cholesterol transport system shared between macrophages and hepatocytes for viral entry. These discoveries deepen our understanding of HBV as a virus that hijacks hepatocyte metabolism. Moreover, hepatic niche macrophages exhibit significant phenotypic and functional diversity, zonal characteristics, and play essential roles, either in maintaining liver homeostasis or contributing to the pathogenesis of chronic liver diseases. Therefore, we underscore recent revelations concerning the importance of hepatic niche macrophages in the context of viral hepatitis. This review particularly emphasizes the significant role of HBV-induced metabolic changes in hepatic macrophages as a key factor in the transition from viral infection to immune activation, ultimately culminating in liver inflammation. These metabolic alterations in hepatic macrophages offer promising targets for therapeutic interventions and serve as valuable early warning indicators, shedding light on the disease progression.

Lack of awareness and ethnic polarity is a major cause of metabolic associated fatty liver disease in high-risk diabetes population in South London.

Background: Metabolic associated fatty liver disease (MAFLD) stands as the leading cause of chronic liver disease globally. Notably, individuals with metabolic risk factors, such as diabetes and obesity, exhibit a staggering prevalence of MAFLD, with estimates reaching up to 70%. However, despite its widespread occurrence, there's a noticeable gap in understanding and awareness about MAFLD among these high-risk groups. Objectives: The main objective of this study was to assess the awareness and prevalence of MAFLD among diabetic patients who regularly receive secondary care focusing particularly on how multiethnic backgrounds and associated lifestyle preferences influence these health outcomes. Design: Cross-sectional study. Methods: Patients with type 2 diabetes (T2D) who regularly attend Lambeth Diabetes Intermediate Care Team clinics were invited to undergo MAFLD screening using FibroScan. Those who agreed to participate were provided with structured questionnaires on diet, physical activity, and MAFLD knowledge by a hepatologist. For each participant, anthropometric data, medical history, liver stiffness measurement, and controlled attenuation parameter (CAP) were documented. Steatosis was identified with a CAP value of ⩾275 dB/m, and advanced fibrosis was flagged at values of ⩾8 kPa. Results: The FibroScan data was valid in 96.4% (215), 53.5% (115/215) had steatosis and 26.2% (58/215) had liver fibrosis in this multiethnic high-risk group. Awareness of MAFLD was notably low at 30.9%. Alarmingly, 69% of patients diagnosed with liver fibrosis were unfamiliar with the condition. Additionally, understanding of MAFLD showed variation among different ethnic groups with highest levels were demonstrated in the Caucasian/White population (46%). Majority (96%) of these subjects were receiving specific lifestyle advice from healthcare professionals due to metabolic conditions and comorbidities. However, most patients preferred diets that were rich in carbohydrates (65.8%) and only 43% subjects performed moderate exercise daily highlighting lack of understanding regarding MAFLD and lifestyle management. Conclusion: There's a pressing need for increased awareness of MAFLD, especially in multiethnic high-risk groups. Additionally, the development of cost-effective strategies to stratify risk is essential to address this growing health concern.

Ethnic differences and lack of awareness increase fatty liver disease risk in South London diabetics Metabolic associated fatty liver disease (MAFLD) or more commonly fatty liver disease is the leading cause of chronic liver disease globally, particularly affecting individuals with diabetes and obesity. This study focuses on patients with type 2 diabetes in South London who regularly receive secondary care, examining the awareness and prevalence of MAFLD, especially across different ethnic groups. Participants, all with Type 2 Diabetes, attended clinics run by the Diabetes Intermediate Care Team where they underwent MAFLD screening using Fibroscan. This tool measures liver stiffness (fibrosis) and fat levels. In addition to the scans, participants answered questions about their diet, physical activity, and knowledge of MAFLD. Key findings include a low overall awareness of MAFLD, with only about 30.9% of patients aware of the disease. Among those diagnosed with liver fibrosis, 69% were unfamiliar with the condition, indicating a significant awareness gap. Interestingly, awareness levels varied among ethnic groups, with Caucasian/white patients showing the highest awareness at 46%. Despite receiving lifestyle advice from health professionals, many participants preferred carbohydrate-rich diets and only a minority engaged in daily moderate exercise. This behaviour highlights a general lack of understanding about MAFLD and its management through lifestyle changes. The study concludes that there is a critical need to raise awareness about MAFLD among high-risk, multi-ethnic groups in South London. It also highlights the necessity for developing cost-effective strategies to better identify and manage this growing health concern.

Nutrition and continuous nursing intervention following radical resection of esophageal cancer in a patient after liver transplantation: a case report.

Background: Reasonable nutritional intervention is very important to promote wound healing and rehabilitation in patients with radical esophagectomy for esophageal cancer. This report aims to summarize the experience of nutritional and continuous nursing intervention in a patient who underwent radical resection of esophageal cancer after liver transplantation, by testing a comprehensive approach to optimize nursing plans in similar clinical practice. We hope that the implementation of home enteral nutrition can improve the nutrition status and quality of life of postoperative patients. Case Description: A patient with liver transplantation was admitted to The Fourth Hospital of Hebei Medical University for postoperative care. The nursing intervention were subsequently summarized and analyzed. In July 2023, the patient successfully underwent radical resection for esophageal cancer. Following the operation, the patient received regular medication and on-site nutritional intervention with the consent of her family. At discharge, the prealbumin, albumin, total protein and hemoglobin values of the patient were low, and body weight was 91 kg. The patient's nutritional risk screening (NRS2022) score was 5 points, and the Patient-Generated Subjective Global Assessment (PG-SGA) score was 4 points. After discharge, the patient continued to receive family enteral nutrition treatment, dietary guidance and psychological nursing. A follow-up review conducted 4 weeks after discharge showed improvements in the patient's NRS2022, albumin, total protein, hemoglobin, and body weight. Conclusions: Strengthening postoperative nutritional intervention are vital for promoting rehabilitation in patients who undergo radical resection of esophageal cancer after liver transplantation.

Sonic hedgehog expression in steatohepatitic hepatocellular carcinoma and its clinicopathological significance.

Hedgehog (Hh) signaling pathway dysregulation is involved in the pathogenesis of metabolic dysfunction-associated steatohepatitis, and the sonic Hh (SHh) protein, a pivotal molecule in the Hh pathway, is expressed in ballooned hepatocytes. The present study aimed to investigate the clinicopathological significance of SHh expression in steatohepatitic hepatocellular carcinoma (SH-HCC). Reverse transcription-quantitative polymerase chain reaction and immunohistochemistry were performed to examine SHh gene and SHh protein expression in SH-HCC. Additionally, patients with conventional HCC (C-HCC) were included in the control group. Comparisons of patient and tumor characteristics were also performed. The prevalence of SH-HCC was 3% in the whole cohort, and it was significantly associated with a high prevalence of diabetes mellitus. SHh mRNA was detected in all patients with SH-HCC, but not in 23% of patients with C-HCC. Notably, SHh mRNA expression was not significantly different between patients with SH-HCC and those with C-HCC; however, high SHh protein expression was significantly more frequent in SH-HCC patients than in those with C-HCC. Although the prognosis was not significantly different between the SH-HCC and C-HCC groups, high SHh protein expression was an independent poor prognostic factor for HCC. In conclusion, SHh could potentially serve as a therapeutic target for patients with HCC.

Biliary stenosis after liver transplant is not associated with cytomegalovirus infection.

Background: Liver transplantation (LT) is the best treatment for end-stage liver disease; however, biliary complications (BCs) still pose a significant challenge. Among the post-transplant BC, strictures and biliary fistulas are the most common. Biliary strictures are classified as anastomotic and non-anastomotic. Some previous studies suggest an association between post-transplant biliary strictures and cytomegalovirus (CMV) infection. In this study, we aimed to identify whether there is an association between CMV infection and biliary strictures in patients undergoing LT. Methods: A retrospective study of 175 patients aged ≥18 years undergoing LT at Felicio Rocho Hospital between 2011 and 2017 was conducted. All included patients received grafts perfused with Institut Georges Lopez-1 (IGL-1) solution from brain-dead donors, survived post-transplantation for more than 120 days, and had a minimum follow-up of 12 months after LT. The diagnosis of CMV was made by antigenemia and biliary strictures by magnetic resonance cholangiopancreatography (MRCP). Results: The average age of the recipients was 54 years. Postoperative BCs occurred in 12% of transplants. The most common BC was stricture (9.1%), with a predominance of anastomotic strictures (AS) over non-AS (NAS) (87.5% vs. 12.5%, respectively). CMV infection was confirmed in 22.9% of patients. In the univariate analysis, post-transplant CMV infection correlated with the development of BCs (P=0.01), as well as biliary strictures (P=0.008). In the multivariate analysis, however, only model for end-stage liver disease (MELD) >21 was a risk factor for the development of BCs in general (P=0.02) and biliary strictures (P=0.01). Conclusions: CMV infection was not an independent risk factor for the development of non-anastomotic post-transplant biliary strictures in this study.

Global burden of adult non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) has been steadily increasing over the past decades and is expected to persist in the future.

Background: At present, there is a dearth of comprehensive data at the global, national, and regional levels regarding the adult non-alcoholic fatty liver disease (NAFLD) prevalence. This cross-sectional study aims at ascertaining the prevalence of NAFLD and non-alcoholic steatohepatitis (NASH), utilizing body mass index (BMI) as a determining factor. Methods: Based on the NHANES database, sigmoidal fitting curves were generated to establish the relationship between BMI and the risk of NAFLD/NASH. Utilizing BMI data from the NCD Risk Factor Collaboration (NCD-RisC) database at both global and regional levels, the prevalence of NAFLD/NASH among adults was estimated from 1975 to 2016, encompassing global, regional, and national perspectives. Additionally, projections were made to forecast the prevalence of adult NAFLD/NASH from 2017 to 2030. Results: In 2016, the global prevalence of NAFLD was 41.12% for males and 37.32% for females, while the global prevalence of NASH was 15.79% for males and 16.48% for females. The prevalence of NAFLD/NASH increased with higher BMI in both genders. Over the period from 1975 to 2016, there has been a gradual increase in the global prevalence of NAFLD/NASH in adults, and this trend is expected to continue between 2017 and 2030. In males, the prevalence of adult NAFLD/NASH was found to be highest in High-income Western countries, while it was highest in Central Asia, Middle East, and North African countries after 1995. Conclusions: The prevalence of adult NAFLD/NASH has been observed to increase annually, with significant variations in burden across different countries and regions.

Effects of elafibranor on liver fibrosis and gut barrier function in a mouse model of alcohol-associated liver disease.

BACKGROUND: Alcohol-associated liver disease (ALD) is a leading cause of liver-related morbidity and mortality, but there are no therapeutic targets and modalities to prevent ALD-related liver fibrosis. Peroxisome proliferator activated receptor (PPAR) α and δ play a key role in lipid metabolism and intestinal barrier homeostasis, which are major contributors to the pathological progression of ALD. Meanwhile, elafibranor (EFN), which is a dual PPARα and PPARδ agonist, has reached a phase III clinical trial for the treatment of metabolic dysfunction-associated steatotic liver disease and primary biliary cholangitis. However, the benefits of EFN for ALD treatment is unknown. AIM: To evaluate the inhibitory effects of EFN on liver fibrosis and gut-intestinal barrier dysfunction in an ALD mouse model. METHODS: ALD-related liver fibrosis was induced in female C57BL/6J mice by feeding a 2.5% ethanol (EtOH)-containing Lieber-DeCarli liquid diet and intraperitoneally injecting carbon tetrachloride thrice weekly (1 mL/kg) for 8 weeks. EFN (3 and 10 mg/kg/day) was orally administered during the experimental period. Histological and molecular analyses were performed to assess the effect of EFN on steatohepatitis, fibrosis, and intestinal barrier integrity. The EFN effects on HepG2 lipotoxicity and Caco-2 barrier function were evaluated by cell-based assays. RESULTS: The hepatic steatosis, apoptosis, and fibrosis in the ALD mice model were significantly attenuated by EFN treatment. EFN promoted lipolysis and ß-oxidation and enhanced autophagic and antioxidant capacities in EtOH-stimulated HepG2 cells, primarily through PPARα activation. Moreover, EFN inhibited the Kupffer cell-mediated inflammatory response, with blunted hepatic exposure to lipopolysaccharide (LPS) and toll like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signaling. EFN improved intestinal hyperpermeability by restoring tight junction proteins and autophagy and by inhibiting apoptosis and proinflammatory responses. The protective effect on intestinal barrier function in the EtOH-stimulated Caco-2 cells was predominantly mediated by PPARδ activation. CONCLUSION: EFN reduced ALD-related fibrosis by inhibiting lipid accumulation and apoptosis, enhancing hepatocyte autophagic and antioxidant capacities, and suppressing LPS/TLR4/NF-κB-mediated inflammatory responses by restoring intestinal barrier function.

Exploring non-invasive diagnostics for metabolic dysfunction-associated fatty liver disease.

The population with metabolic dysfunction-associated fatty liver disease (MAFLD) is increasingly common worldwide. Identification of people at risk of progression to advanced stages is necessary to timely offer interventions and appropriate care. Liver biopsy is currently considered the gold standard for the diagnosis and staging of MAFLD, but it has associated risks and limitations. This has spurred the exploration of non-invasive diagnostics for MAFLD, especially for steatohepatitis and fibrosis. These non-invasive approaches mostly include biomarkers and algorithms derived from anthropometric measurements, serum tests, imaging or stool metagenome profiling. However, they still need rigorous and widespread clinical validation for the diagnostic performance.

Impact of neoadjuvant multimodal therapy in the setting of locally advanced hepatocellular carcinoma.

Immunotherapy and the implementation of more aggressive treatment schemes for locally advanced hepatocellular carcinomas have expanded the boundaries of curative options. Because of these advancements, patients who were once considered beyond the aim of a cure are now eligible for liver transplantation and resection.

The protective effects of aqueous extract of Schisandra sphenanthera against alcoholic liver disease partly through the PI3K-AKT-IKK signaling pathway.

Purpose: This study aimed to investigated the key chemical components and the effect of the aqueous extract of Schisandra sphenanthera (SSAE) on alcoholic liver disease (ALD) and the related molecular mechanism. Methods: This study employed UPLC-Q-TOF-MS/MS to identify the chemical compositions in SSAE. ALD rat model was established through oral administration of white spirit. Transcriptome sequencing, weighted gene co-expression network construction analysis (WGCNA), and network pharmacology were used to predict key compositions and pathways targeted by SSAE for the treatment of ALD. Enzyme-linked immunosorbent assay (ELISA), biochemical kits, hematoxylin-eosin (HE) staining, Western blotting (WB) analysis, and immunohistochemical analysis were used to validate the mechanism of action of SSAE in treating ALD. Results: Active ingredients such as schisandrin A, schisandrol A, and schisandrol B were found to regulate the PI3K/AKT/IKK signaling pathway. Compared to the model group, the SSAE group demonstrated significant improvements in cellular solidification and tissue inflammation in the liver tissues of ALD model rats. Additionally, SSAE regulated the levels of a spartate aminotransferase (AST), alanine aminotransferase (ALT), alcohol dehydrogenase (ADH), and aldehyde Dehydrogenase (ALDH) in serum (P < 0.05); Western blotting and immunohistochemical analyses showed that the expression levels of phosphorylated PI3K, AKT, IKK, NFκB, and FOXO1 proteins were significantly reduced in liver tissues (P < 0.05), whereas the expression level of Bcl-2 proteins was significantly increased (P < 0.05). Conclusion: The active components of SSAE were schisandrin A, schisandrol A, and schisandrol B, which regulated the phosphorylation levels of PI3K, AKT, IKK, and NFκB and the expression of FOXO1 protein and upregulated the expression of Bcl-2 protein in the liver tissues of ALD rats. These findings indicate that SSAE acts against ALD partly through the PI3K-AKT-IKK signaling pathway. This study provided a reference for future research and treatment of ALD and the development of novel natural hepatoprotective drugs.

Bile acids attenuate hepatic inflammation during ischemia/reperfusion injury.

Background & Aims: Persistent cholestasis has been associated with poor prognosis after orthotopic liver transplantation. In this study, we aimed to investigate how the accumulation of tauro-beta-muricholic acid (TßMCA), resulting from the reprogramming of bile acid (BA) metabolism during liver ischemia/reperfusion (IR) stress, attenuates liver inflammation. Methods: Ingenuity Pathway Analysis was performed using transcriptome data from a murine hepatic IR model. Three different models of hepatic IR (liver warm IR, bile duct separation-IR, common bile duct ligation-IR) were employed. We generated adeno-associated virus-transfected mice and CD11b-DTR mice to assess the role of BAs in regulating the myeloid S1PR2-GSDMD axis. Hepatic BA levels were analyzed using targeted metabolomics. Finally, the correlation between the reprogramming of BA metabolism and hepatic S1PR2 levels was validated through RNA-seq of human liver transplant biopsies. Results: We found that BA metabolism underwent reprogramming in murine hepatocytes under IR stress, leading to increased synthesis of TßMCA, catalyzed by the enzyme CYP2C70. The levels of hepatic TßMCA were negatively correlated with the severity of hepatic inflammation, as indicated by the serum IL-1ß levels. Inhibition of hepatic CYP2C70 resulted in reduced TßMCA production, which subsequently increased serum IL-1ß levels and exacerbated IR injury. Moreover, our findings suggested that TßMCA could inhibit canonical inflammasome activation in macrophages and attenuate inflammatory responses in a myeloid-specific S1PR2-GSDMD-dependent manner. Additionally, Gly-ßMCA, a derivative of TßMCA, could effectively attenuate inflammatory injury in vivo and inhibit human macrophage pyroptosis in vitro. Conclusions: IR stress orchestrates hepatic BA metabolism to generate TßMCA, which attenuates hepatic inflammatory injury by inhibiting the myeloid S1PR2-GSDMD axis. Bile acids have immunomodulatory functions in liver reperfusion injury that may guide therapeutic strategies. Impact and implications: Our research reveals that liver ischemia-reperfusion stress triggers reprogramming of bile acid metabolism. This functions as an adaptive mechanism to mitigate inflammatory injury by regulating the S1PR2-GSDMD axis, thereby controlling the release of IL-1ß from macrophages. Our results highlight the crucial role of bile acids in regulating hepatocyte-immune cell crosstalk, which demonstrates an immunomodulatory function in liver reperfusion injury that may guide therapeutic strategies targeting bile acids and their receptors.

Financial burden and social implications of chronic liver disease in a patient population group in Pakistan.

Objective: To assess economic and social issues faced by cirrhotic patients & its financial burden for developing nations like Pakistan. Method: This cross-sectional study was carried out at the Department of Gastroenterology & Hepatology, Shaikh Zayed Hospital, Lahore, Pakistan during the period between July & December 2019. Patients with liver cirrhosis were recruited and information regarding disease, financial status, treatment expenses & dependency was recorded. Results: A total of 450 patients were recruited, 272 (60%) were males & 178 (40%) were females, with mean age 55.4±6.2 years. HCV was cause of cirrhosis in 86% of cases, 65% were diagnosed incidentally and 39.6% were illiterate. About 82.7% were urban while only 28.7% own their own home. Co-morbid conditions including diabetes, hypertension & ischemic heart disease were present in 54% of cases. Monthly income was

Assessing anticancer, antidiabetic, and antioxidant capacities in green-synthesized zinc oxide nanoparticles and solvent-based plant extracts.

Cancer and diabetes represent significant challenges in the field of biomedicine, with major and global impacts on public health. Acacia nilotica, commonly called 'gum arabic tree,' is recognized for its unique biomedical properties. The current study aimed to investigate the pharmacological potential of A. nilotica-based zinc-oxide nanoparticles (ZnO-NPs) in comparison to the ethanol and methanol-based extracts against cancer, diabetes, and oxidative stress. Green synthesis of ZnO-NPs was performed using barks of Acacia nilotica. Different techniques for the characterization of ZnO-NPs, including UV-Visible spectroscopy, Scanning Electron Microscopy, Fourier Transmission Infrared (FT-IR) spectroscopy, and X-ray Diffraction (XRD), were utilized. The morphological analysis of ZnO-NPs revealed that the fine NPs have mean particle sizes of 15 ± 1.5 nm. For the solvent based-extraction, leaves and barks were utilized and dissolved into ethanol and methanol for further processing. The MTT assay revealed that the optimum concentration of ZnO-NPs to inhibit the proliferation of liver cancer cell line HepG2 was 100 µg/mL where 67.0 % inhibition was observed; and both ethanol- and methanol-based extracts showed optimum inhibition at 100 µg/mL. The DPPH assay further demonstrated that 250 µg/mL of ZnO-NPs and 1000 µg/mL of both ethanol- and methanol-based extracts, as the optimum concentration for antioxidant activity (with 73.1 %, 68.9 % and 68.2 % inhibition respectively). The α-Glucosidase inhibition assay revealed that 250 µg/mL of ZnO-NPs and 10 µg/mL of both ethanol- and methanol-based extracts as the optimum concentration for antidiabetic activity (with 95 %, 93.7 % and 93.4 % inhibition respectively). The study provided interesting insights into the efficacy and reliability of ZnO-NPs for potential pharmacological application. Further research should be focused on examining specific pathways and the safety of ZnO-NPs in comparison to solvent-based extracts.

A Comparative Study of Novel Fibrosis Index and Other Non-invasive Serum Indices for Predicting Fibrosis in Patients of Chronic Liver Disease.

Introduction Chronic liver disease progression leads to liver fibrosis/cirrhosis. Transient Elastography is used for staging liver fibrosis but ascites, obesity, and operator experience limit its applicability. In this study, we compared various non-invasive serum indices in predicting fibrosis in chronic liver disease patients. Materials and methods A total of 142 cases of confirmed Chronic Liver Disease were included. Quantitative determination of liver stiffness by Transient Elastography and relevant blood investigations was done. We compared the liver stiffness measurement by Transient Elastography and fibrosis indices, i.e., Aspartate Transaminase (AST) to Alanine Transaminase (ALT) Ratio (AAR), AST to Platelet Ratio Index (APRI), Fibrosis Index (FI), Fibrosis-4 (FIB-4) Index, Age-Platelet Index (API), Pohl score, and Fibrosis Cirrhosis Index (FCI) with Novel Fibrosis Index (NFI), to predict liver fibrosis stages. Results The optimum cutoff of NFI for the F4 stage was ≥ 6670 with a sensitivity of 75.8% and specificity of 81.8%, for the F3 stage was ≥ 2112 with a sensitivity of 63.6% and specificity of 72.7%, and for the F2 stage was ≥ 1334 with a sensitivity of 100% and specificity of 56.3%. The NFI had the maximum area under the curve compared to other indices in predicting fibrosis stages. Conclusion The Novel Fibrosis Index was the best in predicting fibrosis stages in Chronic Liver Disease patients, with good performance in predicting the F4 stage.

Unveiling the therapeutic potential of epigallocatechin gallate in liver cancer: insights from network pharmacology and in vitro assays.

Epigallocatechin gallate (EGCG) is a prominent catechin found in green tea polyphenols and has shown promising anti-tumor properties. However, the exact regulatory mechanism of EGCG on liver cancer is not fully revealed. In this study, we conducted integrative analyses using the SwissTargetPrediction and GeneCards repositories, which identified 98 targets. These targets were used to construct a protein-protein interaction network using STRING and visualised with Cytoscape. Central to this network are hub proteins, notably TNF and PIK3CA, suggesting pivotal roles in the therapeutic landscape. Gene Ontology (GO) enrichment analysis unveiled 1,570 biological terms with a notable preponderance within oxidative stress response processes. Complementary pathway enrichment via the Kyoto Encyclopaedia of Genes and Genomes (KEGG) highlighted 134 pathways, with the PI3K-Akt pathway emerging as prominent. In silico molecular docking supported these findings, revealing binding energies of EGCG-target complexes below -7.0 kcal/mol, indicative of robust interactions. Moreover, cellular assays including CCK-8, wound-healing, and Transwell modalities, established EGCG's inhibitory concentration-dependent effects on HepG2 cell proliferation, migration, and invasion. Apoptotic assays affirmed by FACS, evidenced enhanced apoptosis with escalating EGCG concentrations, underpinned by modulations in caspase activity and apoptotic protein levels. Notably, Western blot analysis demonstrated the attenuation of the PI3K/AKT signalling cascade by EGCG, paralleling the inhibitory profile of LY294002. These multifaceted inhibitory effects underscore EGCG's potential as an anti-tumor agent, deploying a strategic blockade of oncogenic pathways and augmenting apoptotic mechanisms, which provide a strong rationale for its application in liver cancer therapeutics.

Global prevalence of nonalcoholic fatty liver disease: an updated meta-analysis on 78 million population over 38 countries.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a global health challenge, with a rising rate in line with other metabolic diseases. We aimed to assess the global prevalence of NAFLD in adult and pediatric populations. METHODS: PubMed, Scopus and Web of Science databases were systematically searched up to May 2023. Heterogeneity was assessed using Cochran's Q test and I2 statistics, and random-effects model was used for meta-analysis. Analyses were performed using STATA version 18. RESULTS: A total of 479 studies with 78,001,755 participants from 38 countries were finally included. The global prevalence of NAFLD was estimated to be 30.2% (95% CI: 28.7-31.7%). Regionally, the prevalence of NAFLD was as follows: Asia 30.9% (95% CI: 29.2-32.6%), Australia 16.1% (95% CI: 9.0-24.8%), Europe 30.2% (95% CI: 25.6-35.0%), North America 29% (95% CI: 25.8-32.3%), and South America 34% (95% CI: 16.9-53.5%). Countries with a higher human development index (HDI) had significantly lower prevalence of NAFLD (coefficient = -0.523, p = 0.005). Globally, the prevalence of NAFLD in men and women was 36.6% (95% CI: 34.7-38.4%) and 25.5% (95% CI: 23.9-27.1%), respectively. The prevalence of NAFLD in adults, adults with obesity, children, and children with obesity was 30.2% (95% CI: 28.8-31.7%), 57.5% (95% CI: 43.6-70.9%), 14.3% (95% CI: 10.3-18.8%), and 38.0% (95% CI: 31.5-44.7%), respectively. CONCLUSION: The prevalence of NAFLD is remarkably high, particularly in countries with lower HDI. This substantial prevalence in both adults and children underscores the need for disease management protocols to reduce the burden.

Conjoint transcriptomics and metabolomics analyses provide insights into the toxicity of acetamiprid to Lethenteron reissneri larvae.

The neonicotinoid pesticide acetamiprid has been widely used in agricultural pest control and was frequently detected in the water environment. There have been some studies of the toxic effects of acetamiprid on fish, but studies on aquatic lower vertebrates are still very limited. As a primitive jawless vertebrate, Lethenteron reissneri has a special position in evolution and is now listed as a national second level protected animal in China. The present study aimed to investigate the toxic effect of acetamiprid on the liver of L. reissneri larvae. A conjoint analysis of the transcriptomics and metabolomics was performed to determine the responses of L. reissneri larvae liver to acetamiprid at different concentrations (L for low concentration 25 mg/L and H for high concentration 100 mg/L). Even low concentrations of acetamiprid can cause significant liver damage to L. reissneri larvae in a short period. In omics analyses, 2141 differentially expressed genes (DEGs) and 183 differentially abundant metabolites (DAMs) were identified in the H/Control group, and 229 DEGs and 144 DAMs were identified in the L/C group. Correlation analyses revealed acetamiprid affected the metabolic pathways of L. reissneri larvae liver such as the glycerophospholipid metabolism and arachidonic acid metabolism. This study not only enriches the basis for understanding the toxic effect of acetamiprid exposure to L. reissneri larvae liver and provides more information on the breeding and conservation of L. reissneri, but also further causes attention on toxicity risk from acetamiprid to aquatic lower vertebrate species.

Nonlinear relationships of circulating polyunsaturated fatty acids with the complications of liver cirrhosis: A prospective, longitudinal cohort study.

BACKGROUND & AIMS: The role of circulating polyunsaturated fatty acids (PUFAs) in preventing liver cirrhosis complications remains unclear. METHODS: Between 2006 and 2010, 273,834 UK Biobank participants with plasma PUFA quantification data were enrolled and followed up until October 31, 2022. Plasma PUFAs were quantified using a high-throughput nuclear magnetic resonance-based metabolic profiling platform. Liver cirrhosis complications were defined as hospitalization for liver cirrhosis or presentation with hepatocellular carcinoma. RESULTS: During a median follow-up of 13.9 years, 2026 participants developed liver cirrhosis complications. Total plasma PUFAs, omega-3 PUFAs, docosahexaenoic acid (DHA), omega-6 PUFAs, and linoleic acid (LA) were inversely associated with the risk of liver cirrhosis complications, whereas the plasma omega-6/omega-3 ratio was positively associated. Nonparametrically restricted cubic spline regression showed nonlinear associations of plasma PUFAs with liver cirrhosis complications. The inflection points were 4.78 mmol/L for total PUFAs, 0.73 mmol/L for omega-3 PUFAs, 0.25 mmol/L for DHA, 4.07 mmol/L for omega-6 PUFAs, and 2.99 mmol/L for LA. Plasma omega-3 PUFAs were negatively associated with the risk of liver cirrhosis complications when omega-3 PUFAs were <0.73 mmol/L (adjusted hazard ratio [HR], 0.11 [0.08-0.16]), whereas the association was inverted when omega-3 PUFAs were ≥0.73 mmol/L (adjusted HR, 1.87 [1.20-2.92]). CONCLUSIONS: The protective effect of plasma omega-3 PUFAs on liver cirrhosis complications is reversed after passing the corresponding inflection point, suggesting an optimal dietary omega-3 PUFA supplementation dose.