Elevated ALT Levels Research Articles

Influence of sequential blood purification therapy on myocardial injury and serum inflammatory cytokine levels in patients with organophosphate poisoning.

To evaluate the impact of sequential blood purification therapy on myocardial injury and serum inflammatory cytokine levels in patients with organophosphorus poisoning. The clinical data of 67 patients hospitalized for organophosphorus poisoning from January 2020 to January 2021 in Anxi County Hospital were retrospectively analyzed. The patients were divided into a control group (n = 30, received conventional treatment plus hemoperfusion) and a research group (n = 37, received conventional treatment plus sequential blood purification therapy [hemoperfusion plus continuous veno-venous hemofiltration (CVVH)]). The clinical efficacy, myocardial injury indicators, inflammatory cytokine levels, liver and kidney function, incidence of complications, and mortality rate were compared between the two groups. The research group showed a significantly higher total effective rate of 94.59% compared to 73.33% in the control group (P < 0.05). Fewer doses of penehyclidine were administered in the research group, compared to the control group (P < 0.05). In addition, the duration of penehyclidinezation, wakefulness, recovery of CHE activity, mechanical ventilation and hospitalization in the research group was significantly shorter than those in the control group (all P < 0.05). After treatment, both groups exhibited decreased levels of serum NSE, cTnI, CK-MB, LDH, Myo, WBC, CRP, PCT and IL-6, with lower levels in the research group (P < 0.05). Conversely, both groups showed elevated levels of serum CHE, BUN, Scr, urine protein, AST, TBIL and ALT, with higher levels in the control group (P < 0.05). On the 1st and 2nd days after treatment, the serum NSE levels in the observation group were lower than those in the control group, while the serum CHE levels were higher than those in the control group (all P < 0.05). On the 3rd day after treatment, serum NSE and CHE levels were not significantly different between the two groups. The incidence of rebound in the research group was significantly lower (8.11% vs. 30.00%, P < 0.05) than that in the control group. The mortality rates did not show statistically significant differences between the two groups (10.00% vs. 2.70%, P > 0.05). Sequential blood purification therapy can effectively mitigate myocardial injury, reduce the expressions of inflammatory cytokines, and protect liver and kidney function in patients with organophosphorus poisoning, with a favorable safety profile.

Pomegranate fruit peel extract improves cardiac functions via suppressing oxidative stress, fibrosis, and myocardial infarction in Long-Evans rats

The pomegranate fruit (locally known as Dalim) is a rich source of various bioactive metabolites. The cardioprotective effect was aimed to investigate on polyphenol-rich pomegranate peel extract (PPE) that were administered isoproterenol, a synthetic catecholamine used to induce cardiac stress in rats. Twenty four adult rats were taken to evaluate the effects. The selected rats were divided into four groups, serving as the control (Group I), Isoproterenol (ISO) administered (Group II), PPE with ISO treatment (Group III) and gallic acid (polyphenol) along with ISO administration (Group IV). ISO administration increased inflammatory cell infiltration, fibrosis and lipid peroxidation. However, antioxidant enzyme activities were reduced in heart tissues by using isoproterenol. The findings of the study indicate that the various detrimental effects arose on the rat’s heart tissues by ISO administration which seemed to be protected by the administration of the polyphenol-rich PPE. This protection was associated with several positive outcomes, including: reduced inflammatory cell infiltration and fibrosis, reduction in free radicals by improving antioxidant enzymes activities (SOD, catalase), suppression of oxidative stress markers (MDA, NO, APOP), and reduction in inflammatory marker (MPO). Besides, PPE treatment normalized the elevated ALT, AST, ALP, and CK-MB levels. The cardioprotective effects shown by PPE may be due to the presence of polyphenolic compounds, as determined by HPLC analysis. Overall, the outcomes recommend that polyphenol enriched PPE may protect cardiac tissues in ISO-administered rats by suppressing oxidative stress, fibrosis, and myocardial infarction as well as enhancing antioxidant enzyme functions.

Empagliflozin: Potential Protective Effects on Hepatocytes and Liver Outcomes in Streptozotocin -Diabetic Rats.

The current study investigated the potential positive impact of EMPA, an antidiabetic medication, on hepatocytes and liver outcomes in STZ-induced diabetic rats. Male Wistar rats were randomly assigned into four groups: control, DM (received 40mg/kg streptozotocin IP injection), DM+EMPA (received 40mg/kg streptozotocin and 10 mg/kg EMPA), and EMPA (received 10 mg/kg EMPA). Here, liver functional tests were assessed spectrophotometrically, while histological analysis of liver tissues was evaluated using light microscopy. Treated diabetic rats significantly reduced AST levels compared to treated control rats (p &lt; 0.05). DM rats, with or without EMPA treatment, showed significantly elevated ALT levels compared to control rats (p &lt; 0.005). Also, LDH levels were found to be lower in both treated and untreated diabetic rats compared to control rats (p &lt; 0.0001; p &lt; 0.05, respectively), while ALP levels were higher in both groups of diabetic rats relative to control rats (p &lt; 0.0001; p &lt; 0.005). Interestingly, the data showed clear trends indicating that empagliflozin-treated diabetic rats had improved liver parameters compared to untreated diabetic rats, although statistically significant differences were not observed. Remarkably, histological examination showed significant sinusoidal dilation and infiltration of inflammatory cells in hepatocytes in diabetic rats, whereas treated diabetic rats exhibited a normal hepatocyte arrangement with minor sinusoidal dilation. Altogether, the observed results suggest that EMPA may possess a protective effect on hepatocytes, thereby highlighting its potential as a therapeutic intervention for diabetes-related liver complications.

Exploring the effect and mechanism of cucurbitacin B on cholestatic liver injury based on network pharmacology and experimental verification

Ethnopharmacological relevanceCholestatic liver injury (CLI) is a pathologic process with the impairment of liver and bile secretion and excretion, resulting in an excessive accumulation of bile acids within the liver, which leads to damage to both bile ducts and hepatocytes. This process is often accompanied by inflammation. Cucumis melo L is a folk traditional herb for the treatment of cholestasis. Cucurbitacin B (CuB), an important active ingredient in Cucumis melo L, has significant anti-inflamamatory effects and plays an important role in diseases such as neuroinflammation, skin inflammation, and chronic hepatitis. Though numerous studies have confirmed the significant therapeutic effect of CuB on liver diseases, the impact of CuB on CLI remains uncertain. Consequently, the objective of this investigation is to elucidate the therapeutic properties and potential molecular mechanisms underlying the effects of CuB on CLI. Aim of the studyThe aim of this paper was to investigate the potential protective mechanism of CuB against CLI. MethodsFirst, the corresponding targets of CuB were obtained through the SwissTargetPrediction and SuperPre online platforms. Second, the DisGeNET database, GeneCards database, and OMIM database were utilized to screen therapeutic targets for CLI. Then, protein-protein interaction (PPI) was determined using the STRING 11.5 data platform. Next, the OmicShare platform was employed for the purpose of visualizing the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The molecular docking technique was then utilized to evaluate the binding affinity existing between potential targets and CuB. Subsequently, the impacts of CuB on the LO2 cell injury model induced by Lithocholic acid (LCA) and the CLI model induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) were determined by evaluating inflammation in both in vivo and in vitro settings. The potential molecular mechanism was explored by real-time quantitative polymerase chain reaction (RT-qPCR) and western blot (WB) techniques. ResultsA total of 122 CuB targets were collected and high affinity targets were identified through the PPI network, namely TLR4, STAT3, HIF1A, and NFKB1. GO and KEGG analyses indicated that the treatment of CLI with CuB chiefly involved the inflammatory pathway. In vitro study results showed that CuB alleviated LCA-induced LO2 cell damage. Meanwhile, CuB reduced elevated AST and ALT levels and the release of inflammatory factors in LO2 cells induced by LCA. In vivo study results showed that CuB could alleviate DDC-induced pathological changes in mouse liver, inhibit the activity of serum transaminase, and suppress the liver and systemic inflammatory reaction of mice. Mechanically, CuB downregulated the IL-6, STAT3, and HIF-1α expression and inhibited STAT3 phosphorylation. ConclusionBy combining network pharmacology with in vivo and in vitro experiments, the results of this study suggested that CuB prevented the inflammatory response by inhibiting the IL-6/STAT3/HIF-1α signaling pathway, thereby demonstrating potential protective and therapeutic effects on CLI. These results establish a scientific foundation for the exploration and utilization of natural medicines for CLI.

Redox imbalance and inflammation: A link to depression risk in brazilian pesticide-exposed farmers

This study aims to elucidate the mechanisms linking occupational pesticide exposure to depression among rural workers from Maravilha, Brazil. We assessed the mental health, oxidative, and inflammatory profiles of farmers exposed to pesticides (N = 28) and compared them to an urban control group without occupational exposure to pesticides (N = 25). Data on sociodemographic, occupational history, and clinical records were collected. Emotional states were evaluated using the State-Trait Anxiety Inventory (STAI) and Beck Depression Inventory (BDI). Biochemical, hematological, inflammatory, and redox parameters were examined in blood samples from both groups. Results showed educational disparities between groups and unveiled a concerning underutilization of personal protective equipment (PPEs) among farmers. Glyphosate was the predominant pesticide used by farmers. Farmers exhibited higher BDI scores, including more severe cases of depression. Additionally, elevated levels of creatinine, ALT, AST, and LDH were observed in farmers, suggesting potential renal and hepatic issues due to pesticide exposure. Oxidative stress markers, such as increased lipid peroxidation and superoxide dismutase (SOD) activity, along with decreased catalase (CAT) activity and ascorbic acid levels, were noted in the pesticide-exposed group compared to controls. Elevated levels of inflammatory cytokines, particularly IL-1β, IL-6 and TNF-α, were also observed in pesticide-exposed group. Our findings suggest that inflammation, oxidative distress and lower educational levels may be associated with depression in pesticide-exposed farmers. This study highlights the impact of occupational pesticide exposure on the mental health of rural workers. The underuse of PPEs and the link between depressive symptoms, inflammation, and oxidative stress underscore the urgent need for improved safety measures in agricultural practices. Addressing these issues will contribute to a deeper understanding of the intricate relationship between environmental exposures and mental health outcomes.

Alanine transferase levels (ALT) and triglyceride-glucose index are risk factors for type 2 diabetes mellitus in obese patients

AimsThe role of liver steatosis and increased liver enzymes (ALT) in increasing incident type 2 diabetes mellitus (T2DM) is debated, because of their differential effects on different ethnicities and populations. The aim of this study was to evaluate the role of elevated ALT in the development of T2DM in non-diabetic obese subjects receiving routine medical treatment.MethodsA total of 1005 subjects [296 men and 709 women, aged 45.7 ± 13.12 years, body mass index (BMI) 39.5 ± 4.86 kg/m2] were followed for a mean period of 14.3 ± 4.44 years. Subjects were evaluated for several metabolic variables, including the triglyceride-glucose index and the presence of metabolic syndrome (IDF 2005 definition), and were subdivided into ALT quartiles.ResultsT2DM developed in 136 subjects, and the difference was significant between the first and the fourth ALT quartile (p = 0.048). Both at univariate analysis and at stepwise regression, ALT quartiles were associated with incident T2DM. Traditional risk factors for T2DM coexisted, with a somehow greater predictive value, such as triglyceride-glucose index, age, arterial hypertension, LDL-cholesterol, and metabolic syndrome.ConclusionsThese data suggest an association between elevated ALT levels and the risk of incident T2DM in obesity.

Association between liver enzymes and metabolic syndrome: a study in Bangladeshi adults

ABSTRACT Background This study aimed to investigate the association between serum liver enzymes and the presence of metabolic syndrome (MetS) among Bangladeshi adults. Research design and methods A total of 602 participants (424 males and 178 females) were enrolled in this cross-sectional study. Serum levels of liver enzymes (ALT, AST, GGT and ALP) and other biochemical parameters were measured by standard colorimetric methods. The relationship between liver enzymes and MetS was assessed by multivariable logistic regression models. Results Overall, the prevalence of MetS was 34.9% among the participants. Of the four liver enzymes, the mean levels of serum ALT and GGT were significantly higher among subjects with MetS than those without MetS (p < 0.01). When liver enzyme levels were categorized into normal and elevated ranges, MetS and its component’s prevalence was higher in the elevated group except for ALP. Serum ALT and GGT showed a significant relationship with the maximum components of MetS. According to the logistic regression analysis, elevated levels of ALT and GGT were significantly associated with the prevalence of MetS (p < 0.01 and p < 0.001, respectively). Conclusions This study showed that elevated ALT and GGT levels were independently associated with MetS and its components.

FRI652 Type 2 Diabetes Management: More GLP1 Agonists And Less Metformin?

Abstract Disclosure: F.J. Lopez Maldonado: None. R.A. Cota: None. Case presentation: A 41-year-old male patient with family history of T2DM in both parents and brother, personal history of mild alcohol consumption and a sedentary job (public accountant), and obesity since age 30 presented to the endocrinology clinic due to failure to lose weight after 1 year of treatment with a nutritionist. During his first visit, the was asymptomatic and had acanthosis nigricans, his blood pressure was measured at 142/92 mmHg, weight was 100.8 kg, waist circumference was 128 cm, and serum glucose was at 280 mg/dL with an HbA1c of 11.9%. Further laboratory tests showed elevated levels of triglycerides (310 mg/dL), LDL (139 mg/dL), AST (96 U/L), and ALT (65 U/L). Two days later, glucose and HbA1c were repeated with similar results. A liver ultrasound was ordered which revealed diffuse hyperechogenicity of the liver and severe fatty liver disease. The ASCVD risk score was 5.4%. The patient was diagnosed with T2DM, obesity, mixed dyslipidemia, and fatty liver disease. The patient received education, nutrition support, exercise, and pharmacotherapy management with stepped-dose oral semaglutide without metformin. The dose was increased monthly starting at 3 mg and reaching the target dose of 14 mg QD. After three months, the patient demonstrated significant improvements in various parameters such as blood pressure (−10/−8 mmHg), weight (−9.8 kg), waist circumference (−25 cm), serum glucose (−179 mg/dL), HbA1C (−5.7%), triglycerides (−154 mg/dL), LDL (−18 mg/dL), AST (−60 U/L), and ALT (−38 U/L), along with an increase in HDL (+6 mg/dL). After approximately 4 months on the target dose the patient showed further improvements in several parameters including ASCVD risk score (2.1%), blood pressure (−20/12 mmHg), weight (−14.8 kg), waist circumference (−30 cm), serum glucose (−183 mg/dL), HbA1C (−6%), LDL (−25 mg/dL), AST (−63 U/L), and ALT (−40 U/L), and HDL (+10 mg/dL), except for triglyceride levels (−130 mg/dL). Follow-up liver ultrasound showed significant improvement in fatty liver disease. Real-world experiences with newly introduced drugs should be reported, as they may have beneficial effects beyond the ones studied. Oral semaglutide, the first oral GLP-1 analog, has been shown to be non-inferior to other subcutaneous GLP-1 analogs. In this case, improvements were observed in glycemic control, weight loss, lipid levels, and a reduction in cardiovascular risk, as well as an improvement in fatty liver disease. Presentation: Friday, June 16, 2023

The prevalence and impact of small intestine bacterial overgrowth in biliary atresia patients.

Acute cholangitis is an ominous complication in biliary atresia (BA) patients. We investigated the prevalence of small intestine bacterial overgrowth (SIBO) in BA patients and its role in predicting acute cholangitis. There are 69 BA patients with native liver recruited into this study prospectively. They received hydrogen and methane-based breath testing (HMBT) to detect SIBO after recruitment and were followed prospectively in our institute. There are 16 (23.19%) subjects detected to have SIBO by HMBT. BA subjects with SIBO were noted to have higher serum alanine aminotransferase levels than others without SIBO (P = 0.03). The risk of acute cholangitis is significantly higher in BA patients with SIBO than in others without SIBO (62.50% vs. 15.09%, P < 0.001). The logistic regression analysis demonstrated that BA subjects with SIBO have a higher risk of acute cholangitis than others without SIBO (odds ratio = 9.38, P = 0.001). Cox's proportional hazard analysis further confirmed the phenomena in survival analysis (hazard ratio = 6.43, P < 0.001). The prevalence of SIBO in BA patients is 23.19% in this study. The presence of SIBO is associated with the occurrence of acute cholangitis in BA patients. What is the key message of your article? Acute cholangitis is common in BA, and is associated with SIBO after hepatoportoenterostomy in this study. What does it add to the existing literature? This study demonstrated that SIBO is common in BA after hepatoportoenterostomy, and is predictive of acute cholangitis and elevated serum ALT levels in BA. What is the impact? This prospective cohort study provides data regarding the significance of SIBO on the risk of acute cholangitis in BA patients.

Association Between Pre-Transplant Oral Health and Post-Liver Transplant Complications.

Oral disease is linked with systemic inflammation and various systemic conditions, including chronic liver disease. Liver transplantation (LT) candidates often need dental infection focus eradication, and after LT, there is high risk of many inflammation-related complications. We studied whether pre-LT dental status is associated with the occurrence of post-LT complications. This study included 225 adult LT recipients whose teeth were examined and treated before LT, and 40 adult LT recipients who did not have pre-LT dental data available. Data on post-LT complications were collected from the national liver transplant registry and followed up until the end of July 2020. Worse pre-LT dental status was associated with a higher risk of acute rejection post-LT compared to patients with good dental status. Worse dental status was also associated with higher 1-year-post-LT ALT levels and lower albumin levels. In conclusion, poor pre-LT oral health seems to associate with an increased risk of post-LT acute rejection and with elevated ALT levels and decreased albumin levels, suggesting an effect on post-LT liver health. Therefore, prevention and treatment of oral and dental diseases should be promoted early in the course of liver disease.

Assessing risks of hepatobiliary disorders in children under combined exposure to persisting herpes and technogenic chemicals

Chronic persistent viral infection leads to developing immune deficiency and may induce lesions in many organs, the hepatobiliary system included. This, in its turn, may facilitate the onset of diseases of the digestive system under exposure to technogenic chemicals, especially those able to produce hepatotoxic effects. In this study, our aim was to examine risks of developing hepatobiliary disorders in children under combined exposure to persisting herpes infection and technogenic chemicals. We conducted a clinical examination of 324 children aged between 6 and 17 years living either in a large industrial city or on a territory where the sanitary-hygienic situation was favorable. The examination included a clinical checkup, laboratory diagnostic tests identifying herpes markers, chemical analyses aimed at establishing levels of technogenic chemicals in blood, and ultrasound scanning of hepatobiliary organs. We established that exposure to airborne technogenic chemicals created elevated levels of aromatic hydrocarbons and formaldehyde in 64.9–97.6 % of the exposed children; elevated manganese and chromium levels, in 20.8–34.6 % of them. Markers of cytomegalovirus (CMV) and Epstein Barr virus (EBV) were detected in 75 % of the exposed children; each second child had HSV-1 or HSV-2; each third child had human herpesvirus 6. Hepatobiliary disorders occurring under combined exposure to persistent herpes and echnogenic chemicals were represented by structural liver changes in 30.8 % of the examined children; abnormally shaped gallbladder or reactive changes in its walls and dyscholia, in 15.7–48.8 %. These disorders entail elevated levels of direct bilirubin and greater ALT against imbalance of oxidant and antioxidant systems and manifest themselves as biliary pathology in 69.5 % of cases. Exposed children with persistent herpes infection have 1.2–2.3 times higher likelihood of developing structural changes in the liver and gallbladder pathology and up to 4.3 times higher risks of biliary dysfunction and chronic gastroduodenitis.

Parameters of Complete Blood Count and Blood Chemistry during Treatment of Patients with MDR/XDR Pulmonary Tuberculosis with a Short-Course Regimen Containing Bedaquiline, Pretomanid, and Linezolid

The objective: assessment of changes in the parameters of complete blood count, clinical urine tests, and blood chemistry during chemotherapy of patients with MDR/XDR pulmonary tuberculosis receiving the short-course regimen containing bedaquiline, pretomanid, and linezolid (B-Pa-L).Subjects and Methods. 18 patients with MDR/pre-XDR/XDR pulmonary tuberculosis were enrolled into the study. They all received treatment at Central Tuberculosis Research Institute from 2015 to 2022.Results. In the course of chemotherapy of these patients, changes in laboratory test results were noted at different times. Abnormal changes in complete blood count were detected in 10/18 (55,6%) patients during chemotherapy for the 1st time. Hemoglobin levels, erythrocyte and leukocyte counts decreased. Hematuria and bacteriuria were detected by clinical urine test. Proteinuria was observed in almost in half of the patients. Elevated serum potassium level was frequently noted. Blood chemistry demonstrated elevated levels of ALT and AST, which is typical of cytolytic effect on hepatocytes of drugs within chemotherapy. In most cases, all above abnormalities were degree 1 of toxicity and resolved within 2-4 weeks after they were detected. Abnormalities in grade 2-3 of toxicity were mainly observed in patients receiving linezolid at the dose of 1200 mg/day. In most cases, the above abnormalities were detected during the first 4 weeks of chemotherapy.

Study of Risk Factors in Patient with Persistant Elevation of Liver Enzymes after Treatment of Chronic HCV by Direct Acting Antiviral Drugs (DAADs)

Abstract Background Hepatitis C virus (HCV) infection is a major global health challenge; it is estimated that more than 80 million people are chronically infected worldwide, with 3- 4 million new infections and 350000 deaths occurring each year because of HCV- related complications. Egypt is the country with the highest HCV prevalence in the world. Aim of the Work The aim of this study is to determine risk factors that cause persistent elevation of liver enzymes in hepatitis c virus patients treated by direct acting antiviral drugs (dyslipidemia, high BMI, type2 diabte, NAFLD). Patients and Methods This retrospective cross sectional study was conducted on 128 Egyptian candidates achieved SVR after 12 weeks with elevated liver enzymes before treatment by (DAAds) Results In this study, we found that there were correlations between the elevated ALT levels and most metabolic risk factors. There were increase in TG, BMI, and decreased. HDL-c, which were components of metabolic syndrome, were associated with high ALT levels in patients. Metabolic syndrome (MS) components are highly prevalent in NAFLD lack of biochemical response was associated with a higher risk to develop liver related complications (decompensation and cancer), indicating that these patients should undergo further hepatological followup. Conclusion Further large-scale studies employing larger number of patients are needed to evaluate risk factors that cause persistent elevated liver enzymes after eradication of hepatitis c viral infection with DAAds.

Comparison analysis of PD-1/PD-L1 inhibitors plus lenvatinib or gemcitabine/cisplatin as first-line treatment for patients with advanced intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive primary liver cancer, with increasing incidence worldwide. Effective first-line treatments for advanced ICC patients are currently limited. Therefore, our study aimed to assess the efficacy and safety of programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors in combination with gemcitabine/cisplatin (GC) and lenvatinib as first-line treatment in advanced ICC patients. This retrospective cohort study included 51 advanced ICC patients, among whom 25 patients were administered with PD-1/PD-L1 plus lenvatinib and 26 patients were administered with PD-1/PD-L1 plus GC. Baseline characteristics including demographic information, medical history, clinical characteristics, laboratory data, and imaging examination were collected. The primary endpoints were progression-free survival (PFS) and sixth- and ninth-month overall survival (OS) rate. Survival curve was plotted by the Kaplan-Meier method. A Cox proportion risk model was performed to investigate independent risk factors of PFS and OS. The secondary outcomes were objective response rate (ORR), disease control rate (DCR), and adverse events. The median age of advanced ICC patients in our study was 58.0 (95% confidence interval [95% CI] = 48.0-72.4) years, with 33 male and 18 female patients. Patients in the PD-1/PD-L1 inhibitors plus lenvatinib group were more likely to be in ECOG grade above 1, develop ascites, and have an elevated level of ALT. The ORR was 16.0% in the PD-1/PD-L1 inhibitors plus lenvatinib group and 23.1% in the GC group (p = 0.777). The DCR was 52.0% in the lenvatinib group and 46.2% in the GC group (p = 0.676). The combination treatment of PD-1/PD-L1 inhibitors plus lenvatinib was associated with longer PFS than the GC group; however, it was not statistically significant (lenvatinib: 9.5 months, GC: 5.1 months, p = 0.454). The sixth-month and ninth-month OS rates were 82.0% and 76.9% in the lenvatinib group and 87.4% and 71.5% in the GC group. After adjusting for confounders, multivariate Cox regression analysis showed that ECOG grade above 1 was an independent risk factor for PFS (hazard ratio [HR]= 3.388, 95% CI = 1.312-8.746, p = 0.012) and OS (HR = 4.220, 95% CI = 1.131-15.742, p = 0.032). PD-1/PD-L1 inhibitors in combination with lenvatinib or GC all demonstrated significant efficacy and safety as first-line treatment in patients with advanced ICC. As for patients who refuse or are intolerant to chemotherapy, PD-1/PD-L1 plus lenvatinib would be recommended.

Suspicion of Duchenne Muscular Dystrophy in A 7-Year-Old Madurese Boy: A Rare Case Report

Introduction: Duchenne Muscular Dystrophy (DMD) is an X-linked disorder presenting in early childhood and characterized by proximal muscle weakness and calf hypertrophy in affected boys associated with a functional deficiency of dystrophin. The incidence of these cases reached 1 in 3500-6000 male births. Research at RSUPN Dr Cipto Mangunkusumo (RSCM) showed that DMD is the second most frequent neuromuscular disorder in children regardless there is no prevalence data available yet in Indonesia. It is quite complicated to diagnose DMD due to the limited facilities of genetic testing and its high cost. Case Presentation: A 7-year-old boy came with the main complaint of weakness in both legs progressively two years before admission. He had to hold onto the floor and then both knees when started to stand. There was a history of motor and speech delay but family history was denied. Vital signs and nutritional status were within normal. Laboratory examination revealed significantly elevated levels of CK, ALT, and AST. The EMG result supported the presence of myopathy. Due to a lack of facilities, genetic testing or muscle biopsy could not be done. He received prednisone once a day with a 14 mg dose and was scheduled to attend regular physiotherapy. Conclusion: In a limited facilities area, the clinician should have a suspicion of DMD not only by anamnesis and clinical features, but also by considering the elevated levels of CK and myopathies on EMG.

Toxicological safety evaluation of zengye granule through acute and 30-day toxicity studies in rats

Ethnopharmacological relevanceZengye granule (ZYG), a traditional Chinese medicine formula composed of Radix Scrophulariae, Radix Ophiopogonis, and Radix Rehmanniae in the ratio of 1.0:0.8:0.8, is listed in the Chinese Pharmacopoeia for treating diseases associated with yin deficiency, such as inner heat, dry mouth and pharynx, and dry bound stool. However, little information is available on its toxicological safety. Aim of the studyTo evaluate the acute and subacute toxicity of ZYG after oral administration in rats. Materials and methodsIn the acute toxicity study, ZYG was orally administered to rats at a single dose of 10 g/kg/day. In the subacute toxicity study, ZYG was administered orally to rats at repeated daily doses of 2.5, 5.0, or 10 g/kg/day for 30 days. The toxicological effects were evaluated by assessing the rats’ general behavior, body weight, food intake, water consumption, blood biochemical and hematological parameters, organ coefficients, and organ histopathology. ResultsNo obvious adverse reactions were found in the rats in the acute toxicity study, indicating that ZYG was non-toxic. In the subacute toxicity study, ZYG had no toxic effect on the rats at a dose of 2.5 g/kg/day but showed slight toxicity in the kidneys, and spleens of the rats at doses of 5 and 10 g/kg/day. Significant drug toxicity was observed in male and female rats at 5 and 10/kg/day; however, elevated WBCs counts, ALT, and LYMs levels were found in female rats. ConclusionsThe oral administration of ZYG at a dose of less than 10 g/kg/day for 1 day or 2.5 g/kg/day for 30 consecutive days can be considered safe, as these doses showed no distinct toxicity or side effects in the rats in this study. Therefore, the dosage should be set according to the clinically recommended dosage to ensure its safety.

α-amanitin induces autophagy through AMPK-mTOR-ULK1 signaling pathway in hepatocytes

Amanitin poisoning is one of the most life-threatening mushroom poisonings. α-Amanitin plays a key role in Amanita phalloides intoxication. α-Amanitin shows toxic effects on the liver. However, the mechanism by which α-amanitin induces liver injury has not been elucidated. Autophagy plays a crucial role in maintaining cellular homeostasis and is closely related to the occurrence of a variety of diseases. Studies have shown that autophagy may play an important role in the process of α-amanitin-induced liver injury. However, the mechanism of α-amanitin-induced autophagy remains unclear. Thus, this study aimed to explore the mechanisms of α-amanitin in inducing hepatotoxicity in Sprague Dawley (SD) rats and the normal human liver cell line L02 cells. The SD rats and L02 cells exposed to α-amanitin were observed to determine whether α-amanitin could induce the autophagy of rat liver and L02 cells. The regulatory relationship between autophagy and the AMPK-mTOR-ULK pathway by exposing the autophagy agonist (rapamycin (RAPA)), autophagy inhibitor (3-methylademine (3-MA)), and AMPK inhibitor (compound C) was also explored. Autophagy-related proteins and AMPK-mTOR-ULK pathway-related proteins were detected using Western blot. The results of the study indicated that exposure to different concentrations of α-amanitin led to morphological changes in liver cells and significantly elevated levels of ALT and AST in the serum of SD rats. Additionally, the expression levels of LC3-II, Beclin-1, ATG5, ATG7, AMPK, p-AMPK, mTOR, p-mTOR, and ULK1 were significantly increased in the rat liver. And we found that L02 cells exposed to 0.5 μM α-amanitin for 6 h significantly induced autophagy and activated the AMPK-mTOR-ULK1 pathway. Pretreated with RAPA, 3-MA, and compound C for 1 h, the expression levels of autophagy-related proteins and AMPK-mTOR-ULK pathway-related proteins significantly changed. Our results indicates that autophagy and the AMPK-mTOR-ULK pathway are involved in the process of α-amanitin-induced liver injury. This study may foster the identification of actionable therapeutic targets for A. phalloides intoxication.

Protective potential of fresh orange juice against zinc oxide nanoparticles-induced trans-placental and trans-generational toxicity in mice.

Due to the emerging applications of nanoparticles, human exposure to nanoparticles is unavoidable, particularly to zinc oxide nanoparticles (ZnO NPs), owing to their wide range of usage. The ongoing study aimed to evaluate trans-generational toxic potential of ZnO NPs through exposure to F0 mothers, in F1 pups and F1 mature offspring and the protective potential of fresh orange juice (OJ). Twenty-eight F0 mothers were randomly allocated into four groups (n = 7), control; untreated, dose group; exposed to ZnO NPs, dose+antidote group; coadministered ZnO NPs + OJ, antidote group; OJ, during the organogenetic period. Fifty percent of F0 mothers were subjected to cesarean sections on the 18th day of gestation and F1 pups were recovered, macro-photographed, and dissected for liver evisceration, while 50% of F0 mothers underwent standard delivery. After parturition, F1 offspring were examined, and the liver and blood samples were extracted. Observations showed that ZnO NPs exposure in F0 mothers in preparturition and postparturition resulted in decreased body weight, increased liver weight, and elevated levels of ALT and AST significantly p ≤ .05 as compared to the control and antidote groups. Histopathological analysis of maternal livers intoxicated with NPs showed the disruptive structure of central vein, hepatocytes, and Kupffer cells in F0 mothers, while F1 pups showed morphological deviations and distorted development of the liver tissue and congestion, in contrast to the control. F1 offspring of NPs exposed mothers, even at postnatal week 8 showed pyknotic nuclei and activated Kupffer cells in the liver sections against control. But in the case of the Dose+antidote group, alterations were less severe than in the dose group. It can be concluded that exposure to ZnO NPs instigates teratogenicity and hepatotoxicity in F1 pups, F0 mothers, and F1 offspring, respectively, while fresh orange juice acts as a remedial agent against the abovementioned toxicities.

Down-regulating CD4+CD25+T Cells Could Benefit CHB Patient with Mildly Elevated Alanine Aminotransferase by Applying Chinese Traditional Medicine

The hepatitis B virus (HBV) causes hepatitis B, an acute liver illness that raises the risk of liver failure, liver cancer, and cirrhosis. Chronic refers to a condition that lasts longer than six months. Currently, treatment is more biased toward severe patients. However, the therapy for patients with elevated ALT is also necessary but needs to be addressed. This paper will explore how the Chinese Traditional Medicine Bushen formula could benefit CHB patients will elevate ALT by reducing the number of CD4+CD25+T Cells. This work will use Flourescence-Activated Cell Sorter (FACS) and real-time PCR to measure the percentage of T-reg cells in mice with elevated ALT levels after treatment with the Bushen formula. The effectiveness of the Bushen formula on CHB patients has been proved in this paper, which could help millions of patients to have a better life quality once the side effects and the dosage for each individual are explored further.

Sex-specific effect of perfluoroalkyl substances exposure on liver and thyroid function biomarkers: A mixture approach.

Although studies have investigated the effects of perfluoroalkyl substances (PFASs) on liver and thyroid function, little is known about its combined and sex-specific effect. A total of 688 participants were interviewed and serum PFASs concentration was measured using liquid chromatography/mass spectrometry. Five biomarkers of liver and thyroid function (ALT, GGT, TSH, FT3 and FT4) were chosen as outcomes. A restriction cubic spline function was applied to capture the dose-response relationship between PFASs and liver enzymes and thyroid hormones. Multivariable regression and Bayesian kernel machine regression (BKMR) models were performed to assess the single and overall associations of PFASs with targeted biomarkers. Single-pollutant analyses indicated that increased PFASs concentrations were associated with elevated ALT and GGT levels. BKMR models suggested positive dose-response relationships between PFASs mixtures and ALT and GGT levels. Significant associations were only detected between several PFASs and thyroid hormones, and joint effect of PFASs mixtures on FT3 levels was found at higher concentrations. Meanwhile, sex differences were found in the associations of PFASs with ALT and GGT levels, with significant results only in males. Our findings provide epidemiological evidence for combined and sex-specific effects of PFASs on ALT and GGT levels.