Changes In Liver Function Research Articles

High variability in short and long-term recovery kinetic of blood cell count and blood chemistry in a partial body irradiation mouse model

Purpose In the aftermath of a nuclear disaster or accident, survivors will suffer from radiation-induced normal tissue damage. Recovery after radiation exposure is dictated by several factors, one of which is degree of shielding at time of exposure. This study aims to characterize the short and late term changes in kinetics and magnitude of pancytopenia and blood chemistry in a model of heterogeneous radiation exposure, or partial body irradiation (PBI), compared to whole body irradiation (WBI). Materials and methods Male C57BL/6 mice, 8-10 weeks of age, were WBI at 6 different doses (6, 6.1. 6.15, 6.2, 6.5, and 7.5 Gy) to establish the LD50. To determine the effect of shielding on blood cell counts and chemistry, animals were either WBI at 6 Gy (LD2230) or 6 Gy PBI with one leg shielding (LD030). Complete blood counts and chemistry were measured at 1, 5-, 10-, 20-, 30- and 120-days post-irradiation. Results and conclusions Irradiated animals had significant depletion of white blood cells, red blood cells and platelets up to 10 days post-irradiation. Separation between PBI and WBI were observed at 10- and 20-days post-irradiation at which point PBI animals showed sign of recovery while overall cell count remains depleted in WBI animals up to 30 days post-irradiation. In addition, significant changes were found in parameters indicative of hematopoietic injury including hemoglobin count, hematocrit count and white blood cell population. Significant changes were observed in kidney function with changes to blood urea nitrogen and calcium concentration at 5-days post-irradiation. At 10-days post-irradiation. liver function changes differentiated WBI from PBI animals. Long-term, irradiated animal’s chemistry values and many blood counts were not significantly different from Sham. In conclusion, partial shielding ensured complete survival and demonstrated a different recovery kinetics of blood and chemistry parameters after irradiation compared to survivors of whole body irradiation and no single hemopoietic parameter was able to consistently differentiate irradiated from Sham animals. This seems to indicate that there is no single robust hemopoietic parameter to differentiate those exposed from those who were not due to the inherent variability in individual responses. Furthermore, there were no significant long-term effects on these blood parameters between survivors of WBI and PBI except that shielding accelerated recovery.

P821 Multi-site analysis of upadacitinib effectiveness in Crohn's Disease patients: A UK perspective

Abstract Background Upadacitinib, a selective Janus Kinase inhibitor, is the newest advanced therapy in our armamentarium for the treatment of Crohn’s Disease (CD). It has been licensed for use in moderate-to-severely active CD. However, we have limited evidence of its effectiveness in a ‘real-world’ setting. Methods We undertook a retrospective cohort study on CD patients treated with upadacitinib in 24 UK hospitals. Clinical endpoints were reviewed at 12 weeks compared to baseline. Clinical remission was defined as Harvey-Bradshaw Index (HBI) <4 and response as HBI reduction ≥3 or sustained HBI <4. Biochemical remission using faecal calprotectin (FCal) and CRP was defined as FCal <200 µg/g and CRP ≤5, and response as FCal or CRP reduction of 50% and no increase in either parameter. Corticosteroid or exclusive enteral nutrition (EEN) use was documented. Results 170 patients (50% male) were included. The breakdown of disease location included 15% ileal, 21% colonic, 61% ileocolonic and 3% upper GI. Prior advanced therapy exposure was seen in 168 patients, with 117 having failed 3 or more agents. Clinically active disease as defined by HBI ≥4 was seen in 133 patients at baseline. Median HBI at baseline was 8 (5-10) and by week 12 this had fallen to 3 (2-6) (p<0.001). 51% received prednisolone and/ or EEN during induction. Of the 128 patients with paired clinical assessment at baseline and 12 weeks clinical remission was achieved in 41% (figure 1A), 96% of whom were in steroid free clinical remission. This also included 39% of those with 3 or more previous advanced therapy failures. A further 40% were noted to have clinical response at 12 weeks. The median faecal calprotectin reduced from 781 µg/g (354-1800) to 255 µg/g (79-655) (p<0.0001) (figure 1B). In a multivariate analysis (table 1), a higher number of previous resections (p=0.031) and use of steroids (p=0.006) increased clinical remission rate whilst disease location/ behaviour, number of prior advanced therapy failures and baseline HBI did not have an effect. There were three significant adverse events noted including: a reported malignancy, zoster reactivation (drug withdrawal required), and thrombosis. Mild lipid, liver function, and full blood count changes were noted in 29 (17%) of patients, not requiring drug withdrawal. Conclusion Upadacitinib was effective in inducing clinical response in our cohort of patients with previously refractory CD regardless of the number of previous advanced therapy failures. A higher number of prior resections may represent lower overall disease burden but further investigation into the relationship with remission is required, as well as to review real-world endoscopic response and maintenance of remission.

Efficacy analysis of hepatic arterial infusion chemotherapy combined with targeted and immune therapy followed by 125I seeds implantation in the treatment of hepatocellular carcinoma with portal vain tumor thrombus

Objective: To investigate the safety and efficacy of Hepatic Arterial Infusion Chemotherapy(HAIC) combined with targeted and immune therapy followed by 125I seeds implantation in portal vain tumor thrombus (PVTT) in the treatment of hepatocellular carcinoma(HCC) with PVTT. Methods: A retrospective study was performed on the clinical data of 21 patients [ (11 men, 10 women) aged 34-73 (52.6±13.7) years] with HCC with PVTT in The First Affiliated Hospital of Zhengzhou University from October 2020 to October 2022, all of them were treated with HAIC plus targeted and immune therapy,and 125I seeds implanted into PVTT. The patients were followed up to January 2023, the efficacy was evaluated according to the modified version of the solid tumor efficacy evaluation criteria (mRECIST). The progression-free survival (PFS) rate, overall survival(OS) rate and portal tumor thrombus control rate at 3, 6, 12 and 18 months after treatment were recorded, and PFS and OS time were followed up. The changes of liver function, AFP, coagulation function and adverse events were observed. Results: Each patient received 2 to 7 (mean: 3.3±1.2) cycles of HAIC. 10-37 seeds (mean:16.6±6.7) were implanted per patients. The median follow-up time was 15 (range from 5 to 25) months.During the follow-up time, 15 patients showed progression and 6 patients died, and the PFS rates at 3, 6, 12, and 18 months after treatment were 90.5%, 71.4%, 42.9%, and 23.8%, respectively, and at 3, 6, 12, and 18-month OS rates were 100%, 100%, 81.0%, and 61.9%, respectively.The PVTT control rates at 3, 6, and 12 months were 90.5%, 90.5%, and 62.5%, respectively. Overall efficacy evaluation of CR rate 0, PR rate 47.6% (10/21), SD rate 38.1% (8/21), and PD rate 14.3% (3/21). The total incidence of treatment-related adverse events was 100%.Grade 3 treatment related adverse events were observed for 4 cases, the rest wereⅠtoⅡadverse events. Right upper abdominal pain, fever and hemorrhage in liver capsule related to the procedures were observed in 11(52.4%), 5(23.8%) and 3(14.3) patients, respectively. Conclusion: HAIC combined with targeted and immune therapy followed by 125I seeds implantation in PVTT is a safe and efficacy therapy for HCC with PVTT.

Therapeutic effect of autophagy induced by rapamycin versus intermittent fasting in animal model of fatty liver.

High-fructose, high-fat diet consumption (HFHF) is one of the primary causes of non-alcoholic fatt liver disease (NAFLD), which is due to impaired beta-oxidation or apolipoprotein secretion by hepatocytes. Activation of autophagy in hepatocytes could be a therapeutic method against hepatic complications. This study was designed to compare effects of rapamycin and intermittent fasting-inducing autophagy in rats with experimentally induced nonalcoholic fatty liver. Male rats were divided into five groups: C (control, n = 6), the experimental group (EX) subdivided, EXIa (HFHF, n = 6), EXIb (recovery, n = 6), EXII (rapamycin, n = 6) and EXIII (intermittent fasting, n = 6). All rats in the experimental group received HFHF diet for 8 weeks to induce nonalcoholic-fatty liver and obesity. Then, for the next 8 weeks the animals received either a daily oral dose of rapamycin (EXII group) or to intermittent fasting (IF) for 16 hours daily (EXIII group). Blood samples were drawn, and serum TG concentration as well as ALT and AST activities were determined. Hepatic sections were examined by light and electron microscopy. LC3B immunohistochemical staining, morphometric and statistical studies were performed. Subgroups EXIa (HFHF subgroup) and EXIb (Recovery subgroup) showed marked increase in TG, ALT, and AST levels associated with loss of normal hepatic architecture, cytoplasmic vacuolations and faint LC3B immunoreactivity. Ultrathin sections exhibited many autophagosomes in hepatocytes. On the other hand, rapamycin (EXII) and IF (EXIII) groups showed significant improvement to a variable extent in comparison to EXI groups. It could be concluded that rapamycin and intermittent fasting significantly improved NAFLD-induced changes of liver structure and function by inducing autophagy in hepatocytes.

Clinical characteristics of patients with advanced hepatocellular carcinoma who received long-term treatment with atezolizumab and bevacizumab for more than one year.

532 Background: Atezolizumab plus bevacizumab (Ate/Bev) has become the standard of care since 2020 as a first-line systemic therapy for unresectable hepatocellular carcinoma (HCC). However, studies on patients receiving long-term treatment with Ate/Bev are still lacking. In this study, we evaluated the clinical characteristics and impacts on patients receiving Ate/Bev treatment for more than one year. Methods: We prospectively enrolled 246 patients with unresectable HCC who received Ate/Bev treatment at three tertiary cancer centers in Korea between May 2020 and April 2022. Comparative analyses were performed between patients treated with Ate/Bev for more than one year and those treated for less than one year. Additionally, treatment-related adverse events (AEs), and changes in liver function were evaluated. Results: Of the 246 patients, 69 (28.0%) were treated with Ate/Bev for more than one year. The long-term treatment group showed better Eastern Cooperative Oncology Group performance status, liver function, and lower residual hepatic tumor burden at baseline, compared to the group treated for less than one year. Furthermore, the long-term treatment group had a higher incidence of atezolizumab-related thyroid dysfunction (30.4% vs. 10.7%, p ‹ 0.001), dermatologic toxicity (30.4% vs. 14.1%, p = 0.006), and bevacizumab-related hypertension (43.5% vs. 22.6%, p = 0.002) and proteinuria (68.1% vs. 39.0%, p ‹ 0.001), compared to the less than one-year treatment group. The median time to onset of thyroid dysfunction and dermatologic toxicity after Ate/Bev treatment was 2.8 months and 3.3 months, respectively, while the median time to onset of hypertension and proteinuria was 4.2 months and 6.8 months, respectively. In the long-term treatment group, 30 patients (43.5%) showed an increase in Child-Pugh score, 20 (29.0%) had an increase in Child-Pugh grade during Ate/Bev treatment. Conclusions: The Ate/Bev long-term treatment group had better performance status, liver function, and a lower residual hepatic tumor burden at baseline. Atezolizumab-related immunologic adverse events occurred mostly early in the course of treatment, whereas bevacizumab-related adverse events occurred relatively later. In addition, a fraction of patients experienced deterioration of liver function during long-term Ate/Bev treatment.

Effect of Per and Poly-Fluoroalkyl Substances on Pregnancy and Child Development.

Childhood obesity is significantly influenced by maternal exposure to Per- and Poly-Fluoroalkyl Substances (PFAS) during pregnancy. PFAS exposure occurs through the Peroxisome Proliferator-Activated Receptor (PPAR-γ) receptor, leading to increased fat deposition and profound health effects in child growth and development. Despite ongoing investigations, the relationship between maternal serum PFAS concentration and child obesity requires further exploration. This study aimedto review the possible effects of Per and poly-fluoroalkyl substances exposure and their mechanism in overweight/obese children from pregnant ladies. A detailed literature survey was conducted using online databases, including Science Direct, Google Scholar, Scopus, Cochrane, and PubMed. The study focused on the diverse effects of PFAS on maternal and child health, with particular emphasis on neurological complications. Child growth development depends upon breastfeeding and placenta health, which is disrupted by PFAS exposure, ultimately destroying the body mass index of the child. Neurotoxicity testing utilized the SH-SY5Y human-derived cell line as an in vitro model, revealing PFAS-induced increases in adipocyte number, reduced cell size, altered lipid conglomeration, increased adiposity, and changes in liver function. in vivo studies in mice and human cell lines indicated PPAR-γ and ER-α activation, leading to adiposity and weight gain through Estrogen signaling and Lipid metabolism. PFAS concentrations positively correlated in maternal sera, analyzed by liquid chromatography/quadrupole mass spectrometry. PFAS, with a long half-life of 3.5-8.5 years, is commonly found in the serum of pregnant women, crossing the placenta barrier. This exposure disrupts placental homeostasis, negatively impacting mechanisms of action and potentially leading to deterioration in pregnancy and child health. Further research is needed to comprehensively understand the complex interplay between PFAS exposure and its implications for maternal and child well-being.

The impact of epigallocatechin gallate, vitamin D, and D-chiro-inositol on early surgical outcomes of laparoscopic myomectomy: a pilot study.

A prospective investigation to assess the impact of 3months of treatment with epigallocatechin gallate (EGCG), vitamin D and D-chiro-inositol (DCI) in the treatment of uterine fibroids (UF) with laparoscopic myomectomy as evidenced by surgical outcomes and effect on liver function. Non-pregnant or lactating women aged between 30 and 40years were scheduled for laparoscopic myomectomy to treat symptoms or looking to conceive. After enrollment, patients were assigned to either (1) intervention group, assuming a total of 300mg EGCG, 50μg vitamin D, and 50mg DCI divided in 2 pills per day for 3months, or (2) control group, including untreated women scheduled to undergo laparoscopic myomectomy after 3months. 91 patients completed the study. The comparison of the surgical outcomes between the intervention (n = 44) and the control (n = 47) groups revealed that the treatment significantly reduces the duration of surgery (41.93 ± 7.56min vs 56.32 ± 10.63min, p < 0.001). Moreover, the treatment also reduced blood loss during surgery (149.09 ± 25.40mL vs 168.41 ± 21.34mL, p < 0.001), resulting in treated patients having higher Hb levels at discharge 11.27 ± 0.82mL vs 10.56 ± 0.82mL, p < 0.01). The surgery induced an increase in AST and in total bilirubin regardless of the assigned group, and the treatment induced no change in liver function. Our data suggest that EGCG plus vitamin D, and DCI could represent a safe option for women with UF scheduled for laparoscopic myomectomy, improving surgical outcomes without affecting liver functionality.

Azvudine versus paxlovid for oral treatment of COVID-19 in Chinese patients

PurposeTo explore the effect of azvudine as compared to paxlovid for oral treatment of hospitalized patients with SARS-CoV-2 infection.MethodsWe analyzed data from a cohort of patients with SARS-CoV-2 infection in Shandong provincial hospital between February 15 and March 15, 2023. The primary outcome was time to sustained clinical recovery through Day 28 and secondary outcomes included the percentage of participants who died from any cause by Day 28, the average hospitilization time and expenses, the changes in liver and kidney function and adverse events. The Kaplan–Meier method and Cox regression model was used for statistical analysis.ResultsThere was no significant difference between azvudine and paxlovid in terms of time to sustained clinical recovery (p = 0.429) and death rates (p = 0.687). As for hospitalization time and fee, no significant differences were observed between azvudine group and paxlovid group (Hospitalization time: p = 0.633; Hospitalization fee: p = 0.820). In addition, there were no significant differences in the effects of the two drugs on liver and kidney function (p > 0.05).ConclusionAmong adults who were hospitalised with SARS-CoV-2 infection, azvudine was noninferior to paxlovid in terms of time to sustained clinical recovery, death rates, hospitalization time and cost, with few safety concerns.Trial registrationChiCTR2300071309; Registered 11 May 2023.Level of evidenceLevel III; Retrospective cohort study.

2,4-D Herbicide-Induced Hepatotoxicity: Unveiling Disrupted Liver Functions and Associated Biomarkers.

2,4-dichlorophenoxyacetic acid (2,4-D) is a widely used herbicide worldwide and is frequently found in water samples. This knowledge has prompted studies on its effects on non-target organisms, revealing significant alterations to liver structure and function. In this review, we evaluated the literature on the hepatotoxicity of 2,4-D, focusing on morphological damages, toxicity biomarkers and affected liver functions. Searches were conducted on PubMed, Web of Science and Scopus and 83 articles were selected after curation. Among these studies, 72% used in vivo models and 30% used in vitro models. Additionally, 48% used the active ingredient, and 35% used commercial formulations in exposure experiments. The most affected biomarkers were related to a decrease in antioxidant capacity through alterations in the activities of catalase, superoxide dismutase and the levels of malondialdehyde. Changes in energy metabolism, lipids, liver function, and xenobiotic metabolism were also identified. Furthermore, studies about the effects of 2,4-D in mixtures with other pesticides were found, as well as hepatoprotection trials. The reviewed data indicate the essential role of reduction in antioxidant capacity and oxidative stress in 2,4-D-induced hepatotoxicity. However, the mechanism of action of the herbicide is still not fully understood and further research in this area is necessary.

Change in liver function and fat during pre-operative chemotherapy for colorectal liver metastases: results from the CLiFF study

Change in liver function and fat during pre-operative chemotherapy for colorectal liver metastases: results from the CLiFF study

Impact of Omicron variant infection on the liver, kidney, and coagulation system in patients undergoing elective surgery: a retrospective case-control study.

Purpose: We aimed to investigate the impact of Omicron variant infection on the perioperative organ function in patients undergoing elective surgery. Methods: A total of 5029 patients who underwent elective surgery between October 2022 and January 2023 at our hospital were enrolled. Among them, the patients who underwent elective surgery between October 2022 and November 2022 composed Group 1 (not infected with the Omicron variant) the control group; those who underwent elective surgery between December 2022 and January 2023 composed Group 2 (one month after Omicron variant infection) the experimental group. We further divided the patients into two subgroups for analysis: the tumor subgroup and the nontumor subgroup. Data on organ system function indicators, including coagulation parameters, liver function, complete blood count (CBC), and kidney function, were collected before and after surgery. Differences between the two groups were subsequently analyzed via binary logistic regression analysis. Results: Compared with those in the uninfected patient group, the following changes were observed in patients with Omicron variant infection who underwent elective surgery one month after infection: prothrombin activity (PTa), prothrombin time (PT), fibrinogen, albumin/globulin, alanine aminotransferase (ALT), mean corpuscular hemoglobin concentration (MCHC), platelet (PLT), and anemia were increased AST/ALT, indirect bilirubin (IBILI), eosinophils, and uric acid were decreased before surgery; and lung infection/pneumonia and fibrinogen were increased, while AST/ALT, globulin, total bilirubin (TBIL), white blood cell count (WBC), and uric acid were decreased after surgery. There was no significant difference in the mortality rate or length of hospital stay (LOS) between the two groups. Subgroup analysis revealed elevated monocyte, PLT, and fibrinogen classification, levels and decreased globulin, prealbumin (PBA), eosinophil, and uric acid levels in the tumor subgroup of patients who underwent elective surgery one month after Omicron infection compared with those in the uninfected patients. Compared with the nontumor subgroup, fibrinogen levels, lung infection/pneumonia, TBIL, and PLT count were increased in the uninfected patients, while the globulin and eosinophil levels were decreased. Conclusion: Compared with uninfected patients, patients who underwent elective surgery one month after Omicron variant infection exhibited minimal changes in perioperative coagulation parameters, liver function, CBC counts, and kidney function. Additionally, no significant differences in postoperative mortality or LOS were observed between the two groups.

Analysis of Biodistribution and in vivo Toxicity of Varying Sized Polystyrene Micro and Nanoplastics in Mice.

Studies have shown that microplastics (MPs) and nanoplastics (NPs) could accumulate in the human body and pose a potential threat to human health. The purpose of this study is to evaluate the biodistribution and toxicity of MPs/NPs with different particle sizes comprehensively and thoroughly. The purpose of this study was to investigate the biodistribution and in vivo toxicity of polystyrene (PS) MPs/NPs with different sizes (50 nm, 100 nm, and 500 nm). The BALB/c mice were given 100 μL of PS50, PS100 and PS500 at the dosage of 1 mg/kg BW or 10 mg/kg BW, respectively, by gavage once a day. After 28 consecutive days of treatment, the biodistribution of differently sized PS MPs/NPs was determined through cryosection fluorescence microscopy and fluorescent microplate reader analysis, and the subsequent effects of differently sized PS MPs/NPs on histopathology, hematology and blood biochemistry were also evaluated. The results showed that the three different sizes of PS MPs/NPs were distributed in the organs of mice, mainly in the liver, spleen, and intestine. At the same time, the smaller the particle size, the more they accumulate in the body and more easily penetrate the tissue. During the whole observation period, no abnormal behavior and weight change were observed. The results of H&E staining showed that no severe histopathological abnormalities were observed in the main organs in the low-dose exposure group, while. Exposure of three sizes of PS MPs/NPs could cause some changes in hematological parameters or biochemical parameters related to heart, liver, and kidney function; meanwhile, there were size- and dose-dependencies. The biological distribution and toxicity of plastic particles in mice were more obvious with the decrease of particle size and the increase of concentration of plastic particles. Compared with MPs, NPs were easier to enter the tissues and produce changes in liver, kidney, and heart functions. Therefore, more attention should be paid to the toxicity of NPs.

Alterations of serum biochemical parameters and tyrosine phosphorylation in kidney and liver of chronic stress-induced rats

Abstract Chronic stress (CS) can contribute to dysfunction in several organs including liver and kidney. This study was performed to investigate the changes in serum biochemistry, histological structure, as well as in localization of tyrosine phosphorylated proteins (TyrPho) and Heat shock protein 70 (Hsp-70) in liver and kidney tissues of CS rats induced by two stressors (restrained and force swimming) for 60 consecutive days. Samples of blood, liver, and kidney were collected from adult male Sprague–Dawley rats in each group. Our results showed that serum biochemical parameters including corticosterone, blood sugar, urea nitrogen, creatinine, cholesterol, triglyceride, HDL-C, LDL-C, ALT, AST, alkaline phosphatase in CS group were significantly different from that in normal group in both liver and kidney tissues. Although histological structure was not changed. TyrPho expression was significantly increased in liver lysate but significantly decreased in kidney. Hsp-70 expression in liver increased whereas in kidney decreased. In conclusion, CS can induce changes in liver and kidney functions.

Efficacy of 1060 nm Diode Laser for Non-Invasive Subcutaneous Fat Reduction in Mini-Pigs.

To evaluate the efficacy and safety of abdominal fat reduction in mini-pigs, utilizing at 1060 nm diode laser with a wavelength of 1060nm. The laser system non-invasively disrupts adipose tissue; its effectiveness and safety were evaluated by ultrasound imaging and histological analysis. Laser irradiation was performed with various powers, and the cooling function was activated to prevent skin surface damage. The dermal tissue temperature increased to at least 43°C during laser exposure, leading to a decrease in abdominal fat thickness after 30days. Blood tests revealed no significant changes in kidney and liver function but showed increased blood levels of nonessential free acids (NEFAs), likely due to the release of fatty tissue-derived free fatty acids. Histological evaluation demonstrated rapid transformation of adipose tissue into collagen, muscle fibers, and intracellular fibrous tissue. The 1060nm laser showed promise as a non-invasive and safe tool for reducing abdominal fat.

Age-related changes in hematological biomarkers in common marmosets.

Researchers and veterinarians often use hematology and clinical chemistry to evaluate animal health. These biomarkers are relatively easy to obtain, and understanding how they change across healthy aging is critical to clinical care and diagnostics for these animals. We aimed to evaluate how clinical biomarkers from a chemistry profile and complete blood count (CBC)change with age in common marmosets (Callithrix jacchus). We assessed blood samples collected during routine physical exams at the Southwest National Primate Research Center and the University of Texas Health San Antonio marmoset colonies from November 2020-November 2021. We found that chemistry and CBC profiles varied based on facility, sex, and age. Significant changes in albumin, phosphorus/creatinine ratio, albumin/globulin ratio, amylase, creatinine, lymphocyte percent, hematocrit, granulocytes percent, lymphocytes, hemoglobin, red cell distribution width,and platelet distribution widthwere all reported with advancing age. Aged individuals also demonstrated evidence for changes in liver, kidney, and immune system function compared with younger individuals. Our results suggest there may be regular changes associated with healthy aging in marmosets that are outside of the range typically considered as normal values for healthy young individuals, indicating the potential need for redefined healthy ranges for clinical biomarkers in aged animals. Identifying animals that exhibit values outside of this defined healthy aging reference will allow more accurate diagnostics and treatments for aging colonies.

Developmental Programming: Impact of Prenatal Exposure to Bisphenol A on Senescence and Circadian Mediators in the Liver of Sheep.

Prenatal exposure to endocrine disruptors such as bisphenol A (BPA) plays a critical role in the developmental programming of liver dysfunction that is characteristic of nonalcoholic fatty liver disease (NAFLD). Circadian and aging processes have been implicated in the pathogenesis of NAFLD. We hypothesized that the prenatal BPA-induced fatty-liver phenotype of female sheep is associated with premature hepatic senescence and disruption in circadian clock genes. The expression of circadian rhythm and aging-associated genes, along with other markers of senescence such as telomere length, mitochondrial DNA copy number, and lipofuscin accumulation, were evaluated in the liver tissue of control and prenatal BPA groups. Prenatal BPA exposure significantly elevated the expression of aging-associated genes GLB1 and CISD2 and induced large magnitude differences in the expression of other aging genes-APOE, HGF, KLOTHO, and the clock genes PER2 and CLOCK-in the liver; the other senescence markers remained unaffected. Prenatal BPA-programmed aging-related transcriptional changes in the liver may contribute to pathological changes in liver function, elucidating the involvement of aging genes in the pathogenesis of liver steatosis.

Analysis of Somatic Mutations in the TCGA-LIHC Whole Exome Sequence to Identify the Neoantigen for Immunotherapy in Hepatocellular Carcinoma.

There are numerous clinically proven methods for treating cancer worldwide. Immunotherapy has been used to treat cancer with significant success in the current studies. The purpose of this work is to identify somatically altered target gene neoantigens and investigate liver cancer-related immune cell interaction and functional changes for potential immunotherapy in future clinical trials. Clinical patient data from the Cancer Genome Atlas (TCGA) database were used in this investigation. The R maf utility package was used to perform somatic analysis. The 17-mer peptide neoantigens were extracted using an in-house Python software called Peptide.py. Additionally, the epitope analysis was conducted using NetMHCpan4.1 program. Neopeptide immunogenicity was assessed using DeepCNN-Ineo, and tumor immune interaction, association with immune cells, correlation, and survival analysis were assessed using the TIMER web server. Based on somatic mutation analysis, we have identified the top 10 driver genes (TP53, TNN, CTNNB1, MUC16, ALB, PCLO, MUC4, ABCA13, APOB, and RYR2). From the superfamily of 20 HLA (Human leukocyte antigens) allele epitopes, we discovered 5653 neopeptides. Based on T cell receptor face hydrophobic analysis, these neopeptides were subjected to immunogenicity investigation. A mutation linked to tumor growth may have an impact on immune cells. According to this study's correlation and survival analysis, all driver genes may function as immune targets for liver cancer. These genes are recognized to be immune targets. In the future, immune checkpoint inhibitors may be developed to prolong patient survival times and prevent hepatocellular carcinoma (HCC) through immunotherapy.

Physiological changes in captive elephants in Northern Thailand as a result of the COVID-19 tourism ban - muscle, liver, metabolic function, and body condition.

The international travel ban initiated in March 2020 due to the COVID-19 pandemic greatly affected how captive elephants were managed in Thailand. A lack of tourists and associated income meant elephants were chained longer with reduced food provisions, had fewer mahouts, and limited exercise like riding, which likely affected health and welfare. Fifty-eight elephants from six tourist camps were assigned a body condition score (BCS) and blood samples were collected monthly for 2 years during the travel ban to measure: (1) muscle enzymes [creatine kinase (CK), aspartate aminotransferase (AST)]; (2) liver enzymes [aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT)]; (3) lipids [total cholesterol (TC), triglycerides (TG), low (LDL) and high (HDL) density lipoproteins]; and metabolic function [glucose, insulin, fructosamine]. Serum CK concentrations were lower at the end of the study, possibly due to no tourist activities like riding. Changes in liver function included increased AST and ALP, also possibly due to physical inactivity. Feeding less bananas and sugar cane was associated with fewer elephants in the obese category and lower TG concentrations. However, increases in glucose, insulin and fructosamine were observed as local people returned to feed elephants after lifting travel restrictions. In sum, changes in several health biomarkers were observed in association with restricted activities and food resources. Camps need better plans to meet the health and welfare needs of elephants during any future disruptions to the tourism industry, although reduced feeding of sweet treats appeared to have positive effects on body condition and metabolic function.

Safety evaluation of combination treatment of drug-eluting bead transarterial chemoembolization and immune checkpoint inhibitors for hepatocellular carcinoma: An increased risk of liver abscess with treatment interval less than one month

PurposeTo analyze the safety of combination treatment comprising drug-eluting bead transarterial chemoembolization (DEB-TACE) and immune checkpoint inhibitors (ICIs) in hepatocellular carcinoma (HCC). MethodIn total, 208 HCC patients receiving DEB-TACE were enrolled for this retrospective single-institution study. Among them, 50 patients who received ICIs at an interval less than one month from DEB-TACE were categorized into the DEB-ICI group; the remaining 158 patients were categorized into the DEB group. Albumin-bilirubin (ALBI) score before and at three months after DEB-TACE were recorded to evaluate liver function changes. Adverse events within three months after DEB-TACE were considered TACE-related and were compared between the two groups. ResultsThe DEB-ICI group had significantly higher incidence of liver abscess than the DEB group (14.0 % versus 5.1 %, p-value = 0.0337). No significant difference in the other TACE-related adverse events and change of ALBI score between the groups. Univariate logistic regression confirmed that combination with ICIs was an independent risk factor for liver abscess after DEB-TACE (odds ratio = 3.0523, 95 % confidence interval: 1.0474–8.8947, p-value = 0.0409); other parameters including subjective angiographic chemoembolization endpoint scale and combined targeted therapy were nonsignificant risk factors in this study population. In the DEB-ICI group, patients who received ICIs before DEB-TACE exhibited a trend toward liver abscess formation compared with those who received DEB-TACE before ICIs (23.8 % versus 6.9 %, p-value = 0.0922). ConclusionsCombination treatment involving DEB-TACE and ICIs at an interval less than one month increased the risk of liver abscess after DEB-TACE. Greater caution is therefore warranted for HCC patients who receive ICIs and DEB-TACE with this short interval.

Protein extracted from Moringa oleifera Lam. Leaves: Bio-evaluation and characterization as suitable plant-based meat-protein alternative

This study aimed to isolate and characterize moringa leaf protein (MLP) via HPLC and evaluate its consumption's effects through rat model. Four groups of Albino Wistar rats (n = 25 each) along with a control group (n = 25) were acclimatized. The isolated MLP was added to the basal diet (casein; control) in various percentages (25, 50, 75, 100%) for a 21-day experimental period. On three intervals (1st, 11th, 21st days), blood samples were collected and subjected for hematological and biochemical examination (Renal Function Test (RFT), Liver Function Test (LFT)). MLP contained a variety of essential and non-essential amino acids in substantial amounts. The Protein Efficiency Ratio (PER) of 50% MLP-treated group was the highest (1.72) among MLP treatments. Increases in feed intake and weight were observed in treated rats compared to the control. The hematological profile of the rats revealed increases in Hemoglobin (Hb) (7.9–14.0%), White Blood Cell (WBC) (35.9–51.5%), Red Blood Cell (RBC) (17.1–22.2%), Hematocrit (HCT) (13.1–22.9%), and platelets levels (36.5–40.6%) from day 1. Protein isolates decreased liver parameters but resulted in non-significant changes in liver and kidney functions in rats. Further investigation is needed to determine the safe daily intake of MLP.