Elevated Aspartate Aminotransferase Levels Research Articles

Assessing the Impact of Annona muricata Aqueous Extract on Liver Enzymes in Wister Rats Exposed to Paracetamol Over Dose

Aims: This study examines the effect of the aqueous leaf extract of Annona Muricata on liver enzymes in wister rats using the spectrophotometric method. Methodology: 20 Wister rats were divided into groups A, B, C, and D, of 5 rats each, housed, fed, and the experimental groups administered treatments orally in distilled water (10 ml/kg) by means of orogastric cannula for 14 days. 500g of the plant powder was submerged for 72 hours 1500ml of distilled water. The sample was taken with a rotating evaporator, an electrical evaporator extraction apparatus. With water heated to 45°C, the solvent was removed. Before use, a paste-like sample was made and kept in a refrigerator at 4 degrees Celsius. The animals in group A were used as the control. The animals in group B were given feeds + 20mg of paracetamol, and the animals in group C were administered 100mg of paracetamol + silymarin. In comparison, the ones in group D were given 150mg of paracetamol + Annona muricata extracts. The animals were then sacrificed 48 hours following the final dose. A blood sample was collected, allowed to coagulate, and then the serum was separated, while the liver was excised and utilized for biochemical analyses. Results: The alanine aminotransferase activities (ul) recorded 9.0±2.71, 14.67±1.5, 13.50±0.58, 15.75±2.50 for animals in groups A, B, C, and D respectively with corresponding activities of aspartate aminotransferase (ul) of 7.25±0.50, 27.33±4.04, 20.00±2.71, 17.25±1.71. Results revealed a significant difference (p<0.05) in the activities of ALT and AST of all the treated groups. Thus, the aqueous leaf extract of Annona muricata could be hepato-protective. The silymarin could also be hepatoprotective, but it is less effective than Annona muricata. The untreated group, B, showed elevated levels of alanine aminotransferase and aspartate aminotransferase, confirming paracetamol's hepatotoxic activity. Conclusion: The ethanol leaf extract of Annona muricata decreased the activities of liver enzymes in male wister rats, suggesting its hepato-protective tendency. It also does not encourage body weight loss.

Validation of MELD 3.0 in patients with alcoholic liver cirrhosis using prospective KACLiF cohort.

The Model for End-Stage Liver Disease (MELD) is a reliable prognostic tool for short-term outcome prediction in patients with end-stage liver disease. MELD 3.0 was introduced to enhance the predictive accuracy. This study assessed the performance of MELD 3.0, in comparison to MELD and MELD-Na, in patients with alcoholic liver cirrhosis. This multicenter prospective cohort study comprised patients with alcoholic cirrhosis admitted for acute deterioration of liver function in the Republic of Korea between 2015 and 2019. This study compared the predictive abilities of MELD, MELD-Na, and MELD 3.0, for 30-day and 90-day outcomes, specifically death or liver transplantation, and explored the factors influencing these outcomes. A total of 1096 patients were included in the study, with a mean age of 53.3±10.4years, and 82.0% were male. The mean scores for MELD, MELD-Na, and MELD 3.0 at the time of admission were 18.7±7.2, 20.6±7.7, and 21.0±7.8, respectively. At 30 and 90days, 7.2% and 14.1% of patients experienced mortality or liver transplantation. The areas under the receiver operating characteristic curves for MELD, MELD-Na, and MELD 3.0 at 30days were 0.823, 0.820, and 0.828; and at 90days were 0.765, 0.772, and 0.776, respectively. Factors associated with the 90-day outcome included concomitant chronic viral hepatitis, prolonged prothrombin time, elevated levels of aspartate transaminase, bilirubin, and creatinine, and low albumin levels. MELD 3.0 demonstrated improved performance compared to previous models, although the differences were not statistically significant.

Hepatoprotective effects of safranal on acetaminophen-induced hepatotoxicity in rats

Abstract This research aimed to explore the protective and therapeutic properties of safranal in mitigating inflammation and oxidative stress induced by elevated acetaminophen (APAP) doses in a rat model. The protective and therapeutic effects of safranal were determined by histopathologically and examining some biochemical parameters such as aspartate transaminase (AST), alanine transaminase (ALT), glutathione, glutathione peroxidase, catalase, malondialdehyde, interleukin-6, tumor necrosis factor-α, and interleukin-1β. Male Wistar–Albino rats were subject to random allocation, forming five groups, each comprising seven rats (n = 7) in the study. Group 1 was the control group. APAP was administered in Group 2 to induce hepatotoxicity. Rats in Groups 3, 4, and 5 received intraperitoneal injections of safranal at doses of 0.025, 0.05, and 0.1 mL/kg/day for 14 days, respectively. On the 15th day, to induce APAP-induced hepatotoxicity, four groups (Groups 2, 3, 4, and 5) acquired a single intraperitoneal injection of 600 mg/kg APAP. The presence of APAP-induced hepatotoxic effect was proven by elevated AST and ALT levels, which are typical biomarkers of liver function in addition to the demonstration of histopathological changes. The findings suggest that pre-treatment with safranal may offer a protective effect against hepatotoxicity by attenuating oxidative stress and the inflammatory response.

Hepatotoxic effects of Stevia rebaudiana leaf extract and commercial stevia on rats: a comparative study

The popularity of stevia is high, especially among diabetics and those looking to reduce their calorie-intake. The aim of this study was to compare the effects of a commercially-available stevia and of a Stevia rebaudiana leaf extract on the liver function and histology of rats. After preparing the Stevia rebaudiana leaf extract, 60 healthy adult male rats were randomly separated into three groups: untreated control, commercial stevia treatment (25 mg/kg), and Stevia rebaudiana leaf extract treatment (25 mg/kg). Our results show that after 60 days of treatment (oral administration), a significant elevation of the alanine aminotransferase (ALT) levels was observed in the commercial stevia-treated group, suggesting potential effects on liver function. The Stevia rebaudiana leaf extract-treated group also exhibited increased ALT levels. Moreover, the aspartate aminotransferase (AST) levels were found significantly increased in both of these treatment groups (when compared to the control group). Alkaline phosphatase levels were not found altered between groups. Histological-examinations, in spite of the elevated ALT and AST levels, exhibited no abnor¬malities in the liver. Although stevia is generally regarded as safe, this study underlines the importance of considering the type and form of stevia when evaluating its effects on liver health. Further study is warranted so as to elucidate the specific components and mechanisms responsible for the observed variations in liver enzymes, and to confirm the overall safety of stevia products.

Effect of Perilla seeds inclusion on the performance, egg quality characteristics, biochemical parameters and egg yolk fatty acid composition of laying hens.

This study investigates the effect of supplementation of Perilla seeds (PS) on the performance, egg quality, blood biochemical parameters, and egg yolk fatty acids composition in the diet of egg-laying chicken. A total of 1600 Lohmann laying hens were randomly assigned to four different groups with 4 replicates each (100 chickens/replicate) and were subjected to varying PS concentrations (PS0, PS6, PS12, and PS18; 0%, 6%, 12%, and 18%, respectively) for four weeks, including an acclimation period of one week. The results showed no significant differences among the groups for average egg weight (P > 0.005). The laying rate (%), feed conversion ratio (FCR) and average feed intake (AFI) decreased significantly for birds fed on 18% PS as compared to the other treatments (P < 0.005). Haugh unit, albumin height, egg-shape index and eggshell thickness among hens fed PS diets were greater averaging 80.53, 7.00, 1.29, 0.34 compared to 76.84, 6.86, 1.25 and 0.32 from Control hen eggs (P < 0.05). Serum analysis showed a trend towards elevated levels of glucose (Glu), total protein (TP) and aspartate aminotransferase (AST) among treatments. Total cholesterol (TC), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) decreased for the birds fed on 6% PS. The fatty acid composition of egg yolk showed a substantial reduction for α-linolenic acid and docosahexaenoic acid increased significantly by the incorporating PS in the diet (P < 0.001). PS incorporation in diets resulted in significant improvements in both performance indicators and greater amounts of α-linolenic acid and DHA in egg yolks. These findings indicate that PS at 6% inclusion has the potential to improve fatty acid profiles of egg yolk without anyadverse effect on performance of egg quality.

Assessment of Gastrointestinal Manifestations and Predictive Factors Associated with Their Occurrence in Kawasaki Disease Patients: A Cross-Sectional Study

Background: Kawasaki disease is an idiopathic febrile systemic vasculitis, recognized as the leading cause of acquired heart disease in pediatric patients. Gastrointestinal manifestations can lead to delayed treatment, underscoring the importance of identifying and predicting factors associated with these manifestations to enable timely intervention. Objectives: The primary objective of this study was to identify the aforementioned factors. Methods: This retrospective study collected demographic information, medical history, physical examination findings, and laboratory results of 359 children suspected of having Kawasaki disease and referred to Mofid Children’s Hospital between 2013 and 2022. The study assessed the frequency of gastrointestinal manifestations and their association with physical examination findings and laboratory data. Results: A total of 359 patients were included in the study, comprising 153 males and 206 females. The mean age of participants was 2.8 ± 2.6 years. Abdominal pain was the most common clinical manifestation, reported in 39% of patients. Elevated levels of aspartate aminotransferase (AST) were observed in 38.1% of patients, while 30.2% showed elevated alanine aminotransferase (ALT) levels, and 10.5% exhibited direct hyperbilirubinemia. Patients with elevated ALT and AST levels had a higher incidence of abdominal pain, nausea/vomiting, and anorexia. Moreover, patients with positive findings of red blood cell (RBC) and white blood cell (WBC) in their stool examination had a higher incidence of fever and abdominal pain. Conclusions: Based on our statistical analysis, elevated AST and ALT levels, hyperbilirubinemia, and positive stool findings of RBC and WBC appear to be predictive factors for gastrointestinal manifestations in Kawasaki disease.

Growth performance, physiological response, and tissue microarchitecture of the carp Labeo rohita challenged with AFB1 are improved by supplementing with turmeric

Aim of study: To examine the impact of dietary supplementation with turmeric (TM) (Curcuma longa) on growth, haematological, biochemical parameters, and histoarchitecture in rohu (Labeo rohita) challenged with aflatoxin B1 (AFB1). Area of study: Ludhiana, Punjab, India. Material and methods: A completely randomized design involved the utilization of 225 fingerlings distributed across five treatments with three replicates each. Diets were allocated as follows: T1 denoted the negative control diet, T2 comprised AF100, while T3, T4, and T5 were formulated with AF25TM, AF50TM, and AF100TM, respectively. Main results: The results indicated a negative correlation between AFB1 dosage in feed and fish growth, with higher doses resulting in decreased growth. Significant changes were observed in haematological parameters, including reductions in total erythrocyte count, total leukocyte count, haemoglobin, and packed cell volume, alongside alterations in biochemical parameters, such as decreases in total protein, albumin, and globulin levels, and an increase in glucose levels and albumin/globulin ratio. Additionally, elevated levels of aspartate aminotransferase, alanine aminotransferase, catalase and superoxide dismutase were noted in T2 and T5 compared to other treatments. AFB1 exposure also led to damage in the microarchitecture of the brain, kidney, and liver tissues, although inclusion of TM at 25 ppb AFB1 showed signs of recovery. Research highlights: The changes observed were dose-dependent, and supplementation of TM showed increased resistance against AFB1 and the greatest improvement in T3. Therefore, a diet containing 5 g TM kg-1 would lower AFB1 contamination of 25 ppb compared to 50 and 100 ppb. In conclusion, supplementing TM in fish feeds can help regulating the AFB1, which in turn can improve sustenance-based output.

The Impact of Prenatal Alcohol Exposure on the Autonomic Nervous System and Cardiovascular System in Rats in a Sex-Specific Manner.

Fetal Alcohol Spectrum Disorder (FASD) is a consequence of prenatal alcohol exposure (PAE) associated with a range of effects, including dysmorphic features, prenatal and/or postnatal growth problems, and neurodevelopmental difficulties. Despite advances in treatment methods, there are still gaps in knowledge that highlight the need for further research. The study investigates the effect of PAE on the autonomic system, including sex differences that may aid in early FASD diagnosis, which is essential for effective interventions. During gestational days 5 to 20, five pregnant female Wistar rats were orally administered either glucose or ethanol. After 22 days, 26 offspring were born and kept with their mothers for 21 days before being isolated. Electrocardiographic recordings were taken on the 29th and 64th day. Heart rate variability (HRV) parameters were collected, including heart rate (HR), standard deviation (SD), standard deviation of normal-to-normal intervals (SDNN), and the root mean square of successive differences between normal heartbeats (RMSSD). Additionally, a biochemical analysis of basic serum parameters was performed on day 68 of the study. The study found that PAE had a significant impact on HRV. While electrolyte homeostasis remained mostly unaffected, sex differences were observed across various parameters in both control and PAE groups, highlighting the sex-specific effects of PAE. Specifically, the PAE group had lower mean heart rates, particularly among females, and higher SDNN and RMSSD values. Additionally, there was a shift towards parasympathetic activity and a reduction in heart rate entropy in the PAE group. Biochemical changes induced by PAE were also observed, including elevated levels of alanine transaminase (ALT) and aspartate aminotransferase (AST), especially in males, increased creatinine concentration in females, and alterations in lipid metabolism. PAE negatively affects the development of the autonomic nervous system, resulting in decreased heart rate and altered sympathetic activity. PAE also induces cardiovascular abnormalities with sex-specific effects, highlighting a relationship between PAE consequences and sex. Elevated liver enzymes in the PAE group may indicate direct toxic effects, while increased creatinine levels, particularly in females, may suggest an influence on nephrogenesis and vascular function. The reduced potassium content may be linked to hypothalamus-pituitary-adrenal axis overactivity.

Prevalence and Associated Factors of Liver Enzyme Abnormalities Among Bangladeshi Women: A Cross-Sectional Study.

Background Liver enzyme abnormalities can indicate underlying liver health issues and are influenced by various factors. This study aimed to investigate the prevalence of liver enzyme abnormalities and their associated factors among nonpregnant and nonlactating (NPNL) women in Bangladesh. Methodology A cross-sectional study was conducted among 251 NPNL Bangladeshi women. Data on demographic, socioeconomic, and health-related variables were collected. Logistic regression analysis was used to determine the association between liver enzyme abnormalities and associated factors. Results The prevalence of liver enzyme abnormalities among participants was determined, with associated factors such as age, body mass index (BMI), monthly income, and food security status examined. Elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were observed in 54 (21.5%) and 47 (18.7%) of participants, respectively, with 116 (46.2%) exhibiting an AST/ALT ratio exceeding 1.00. Food insecurity was significantly associated with a higher prevalence of elevated ALT levels (24.4% vs. 8.7%, P = 0.02), as well as low monthly income (18.8%, 14.7% vs. 36.7%, P < 0.01) and higher BMI (11% vs. 27.7% and 25.6%, P = 0.02). Similar trends were observed for AST levels. Moreover, participants with a higher BMI exhibited significantly higher rates of at least one abnormal liver function enzyme (15.9% vs. 34.9%, P = 0.01). Logistic regression analysis revealed a significant association between abnormal liver enzyme levels and certain demographic and socioeconomic factors, specifically BMI and age. Conclusions This study provides insights into the prevalence of liver enzyme abnormalities and their associated factors among NPNL Bangladeshi women. The findings underscore the importance of addressing factors such as BMI and age in mitigating liver health issues in this population. Further research and targeted interventions are warranted to address these concerns effectively.

Chemical characterization and effect of Ziziphora clinopodioides green-synthesized silver nanoparticles on cytotoxicity, antioxidant, and antidiabetic activities in streptozotocin-induced hepatotoxicity in Wistar diabetic male rats.

The present research studied the cytotoxicity, antioxidant, and antidiabetic activities of biogenically synthesized silver nanoparticles (AgNPs) using Ziziphora clinopodioides (Z. clinopodioides) as a green mediator. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), and ultraviolet-visible spectroscopy (UV-Vis) were employed to determine AgNPs. In the invivo experiment, the model rats were categorized into different groups receiving 50, 100, 200, and 400 μg/kg of AgNPs and diabetic, positive, and normal groups (n = 10) using a random division. A single dose of streptozotocin (STZ) at 60 mg/kg was administered to induce diabetes and hepatotoxicity in rats. The administration of AgNPs was performed via intragastric administration for 25 days. On the final day, the levels of glucose and biochemical enzymes, namely aspartate aminotransferase (AST), alkaline phosphatase (ALP), alanine transaminase (ALT), and gamma-glutamyltransferase (GGT), were assessed in the serum. Following tissue processing, liver sections with a thickness of 5 μm were prepared. Later, the total volume of different liver components, such as hepatocytes, sinusoids, portal vein, central vein, hepatic arteries, and bile ducts, was measured. The portal vein and bile duct volumes did not vary significantly in groups treated by AgNPs. However, the volume of the central vein and hepatic arteries exhibited noticeable variations in groups treated by AgNPs. After administration of streptozotocin, the volume of hepatocytes and sinusoids increased significantly. However, treatment with a high dose of AgNPs significantly decreased the volume of hepatocytes and sinusoids. In diabetic rats, administering AgNPs reduced the fasting blood glucose levels compared to the model group. In addition, AgNPs decreased the elevated levels of AST and ALP enzymes in a manner that depended on the dosage of AgNPs used. This research demonstrates the hepatoprotective and antidiabetic properties of AgNPs, suggesting their potential implications as hepatoprotective and antidiabetic supplements to prevent diabetes.

O-sialoglycoprotein Endopeptidase (OSGEP) Suppresses Hepatic Ischemia-Reperfusion Injury-Induced Ferroptosis Through Modulating the MEK/ERK Signaling Pathway.

Hepatic ischemia-reperfusion injury (HIRI) was widely accepted as a critical complication of liver resection and transplantation. A growing body of evidence suggested that O-sialoglycoprotein endopeptidase (OSGEP) was involved in cell proliferation and mitochondrial metabolism. However, whether OSGEP could mediate the pathogenesis of HIRI has still remained unclarified. This study investigated whether OSGEP could be protective against HIRI and elucidated the potential mechanisms. The OSGEP expression level was detected in cases undergoing ischemia-related hepatectomy and a stable oxygen-glucose deprivation/reoxygenation (OGD/R) condition in hepG2 cells. Additionally, it was attempted to establish a mouse model of HIRI, thus, the function and mechanism of OSGEP could be analyzed. At one day after hepatectomy, the negative association of OSGEP expression level with the elevated serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) was noted. Moreover, it was attempted to carry out gain- and loss-of-function analyses of OSGEP in hepG2 cells to reveal its influences on OGD/R-induced injury and relevant signaling pathways. The findings suggested that OSGEP overexpression significantly protected hepG2 cells against ferroptotic cell death, while OSGEP consumption had opposite effects. Consistent with in vitro studies, OSGEP deficiency exacerbated liver functions and ferroptoticcell death in a mouse model of HIRI. The results also revealed that OSGEP mediated the progression of HIRI by regulating the MEK/ERK signaling pathway. Rescue experiments indicated that ERK1/2 knockdown or overexpression reversed the effects of OSGEP overexpression or knockdown on hepG2 cells under OGD/R condition. Taken together, the findings demonstrated that OSGEP could contribute to alleviate HIRI by mediating the MEK-ERK signaling pathway, which may serve as a potential prognostic marker and a therapeutic target for HIRI.

Copper Intoxication in South American Camelids-Review of the Literature and First Report of a Case in a Vicuña (Vicugna vicugna).

Copper (Cu), an essential trace element in the metabolism of mammals, plays a central role in various metabolic processes. However, overdosing can lead to severe symptoms and even fatalities. Chronic Cu intoxication continues to be a problem in grazing and domestic animals, with sheep being particularly sensitive. There are few comparative studies on its impact on South American camelids (SACs). Therefore, this work presents the results of literature research combined with a case report on a 3-year-old female vicuña (Vicugna vicugna) presented to the clinic from a zoological garden in northern Germany. The animal showed reduced food intake, recumbency, bruxism, icteric mucous membranes and sclera. Auscultation revealed atony of the third compartment and the digestive tract. Similar to cases described in the literature, the animal showed rapid deterioration of its condition with unspecific symptoms of liver failure and rapid death. However, in contrast to descriptions in sheep, clinical icterus has not been previously reported in cases of other SACs. Laboratory findings from EDTA and serum samples revealed neutrophilia with a left shift, hypoproteinaemia, lymphopaenia, azotaemia, elevated levels of creatine kinase (CK), aspartate aminotransferase (AST) and glutamate dehydrogenase (GLDH) in the serum. Hyperbilirubinaemia and significantly elevated serum and liver Cu levels were observed. Subsequent blood samples from the remaining vicuñas and alpacas in the same enclosure showed no remarkable abnormalities. To the best of the authors' knowledge, this case report represents the first documented case of Cu intoxication specifically in vicuñas.

Assessment of hepatoprotective and nephroprotective effects of Vitis vinifera leaf extract on carbon tetrachloride induced toxicity in rats

Background: Vitis vinifera is known for its antimicrobial activity; however, the hepatoprotective activity of aqueous extracts of aerial parts has also been reported, but the nephroprotective and hepatoprotective activity of ethanolic extracts have not yet been evaluated. Objective: To evaluate Vitis vinifera's hepatoprotective and nephroprotective activities against CCl4-induced toxicity in rats. Methods: Two doses of ethanolic extract of Vitis vinifera (100 and 200 mg/kg/day) were evaluated and compared with silymarin 100 mg/kg. Biochemical blood parameters like aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), Gamma-glutamyltranspeptidase (GGT), bilirubin, urea, uric acid, total protein and creatinine, and histopathologic changes of liver and kidney were studied and evaluated. Results: Vitis vinifera reduced the elevated blood levels of ALT, AST, ALP, urea, and creatinine, with the ethanol extract to 200 mg/kg/day being more effective. The histopathologic evaluation suggested that Vitis vinifera decreased hepatic and renal necrosis induced by CCl4. The more significant dose resulted in reductions in AST, ALT, GGT, ALP, and bilirubin of 54, 27, 56, 36, and 17%, respectively. Ethanolic extract 200 mg/kg/day also shows a reduction in elevated levels of Creatinine, Urea, Uric Acid, and Total Protein by 61%, 58%, 29%, and 9%, respectively. Conclusion: Hepatoprotective and nephroprotective activities of ethanol extract of Vitis vinifera were demonstrated, with ethanol extract to 200 mg/kg/day being the most effective. This presents scientific evidence for using medicinal plants such as Vitis vinifera in managing liver and kidney disorders.

Evaluation of clinically relevant serum proteins as biomarkers for monitoring COVID-19 severity, and end-organ damage among hospitalized unvaccinated patients

BackgroundThe extensive variability and conflicting information in Coronavirus Disease 2019 (COVID-19) patient data have made it difficult for the medical community to gain a comprehensive understanding and develop clear, reliable guidelines for managing COVID-19 cases. As the world uncovers the diverse side effects of the pandemic, the pursuit of knowledge about COVID-19 has become crucial. The present study aimed to evaluate some clinically relevant serum proteins, providing analysis of the obtained results to employ them in the diagnosis, prognosis, and disease monitoring among COVID-19 patients.MethodsSamples were collected from 262 COVID-19 unvaccinated hospitalized patients. Measurement of certain serum proteins, namely C-reactive protein (CRP), ferritin, D-dimer, procalcitonin, interleukin-6 (IL-6), serum creatinine (SCr), alanine transaminase (ALT), aspartate transaminase (AST) was done using standard methods. Statistical analysis was performed on the obtained data and the results were correlated to the severity and prognosis.ResultsThe calculated Mortality rate was found to be 30% with a higher percentage observed among females. The results showed elevation in serum CRP, ferritin, D-dimer, and procalcitonin in most of the patients, also some patients had elevated SCr, ALT, and AST levels indicating end-organ damage. The statistical analysis displayed a strong correlation between serum levels of CRP and ferritin, between D-dimer and ferritin, and between ferritin and procalcitonin. No significant difference was observed between male and female patients’ serum levels of the tested serum proteins. A significant correlation between increased serum procalcitonin and mortality was observed.ConclusionThe levels of measured serum proteins were impacted by SARS-CoV-2 infection. Serum ferritin, CRP, D-dimer, and procalcitonin are good predicting tools for end-organ damage and acute kidney impairment in COVID-19. Procalcitonin is a strong indicator of severity and mortality in hospitalized COVID-19 patients.

Toxicity evaluation of processing Evodiae fructus based on intestinal microbiota.

With the development of healthcare services, drug efficacy, and safety have become the focus of drug use, and processing alters drug toxicity and efficacy, exploring the effects of processing on Evodiae fructus (EF) can guide the clinical use of drugs. Fifty male Kunming mice were randomly divided into the control group (CCN), raw small-flowered EF group (CRSEF), raw medium-flowered EF group (CRMEF), processing small-flowered EF group (CPSEF), and processing medium-flowered EF group (CPMEF). The CRSEF, CRMEF, CPSEF, and CPMEF groups were gavaged with aqueous extracts of raw small-flowered EF dry paste (RSEF), medium-flowered EF dry paste (RMEF), processing small-flowered EF dry paste (PSEF) and processing medium-flowered EF dry paste (PMEF), respectively, for 21 days at 5 times the pharmacopeial dosage. Upon concluding the experiment, histopathological sections of liver and kidney tissues were examined. Additionally, levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum creatinine (SCr), and blood urea nitrogen (BUN) were determined. DNA from the intestinal contents of the mice was extracted, and 16S rRNA full-length high-throughput sequencing was performed. After fed EF 21 days, mice exhibited a decreasing trend in body weight. Comparative analysis with the CCN group revealed an upward trend in SCr, BUN, AST, and ALT levels in both CRSEF and CRMEF groups. The CRMEF group displayed notably elevated BUN and AST levels, with an observed increasing trend in Scr and ALT. Kidney sections unveiled cellular edema and considerable inflammatory cell infiltrates, whereas significant liver damage was not evident. Compared with CRSEF, Bun levels were significantly lower while AST levels were significantly higher in the CPMEF group. Additionally, the intestinal microbiota diversity and the relative abundance of Psychrobacter decreased significantly, and the relative abundance of Staphylococcus, Jeotgalicoccus, and Salinicoccus increased significantly in the CPMEF group. AST, ALT, and SCr were positively correlated with Staphylococcus, Jeotgalicoccus, and Salinicoccus. In conclusion, PMEF significantly increased harmful bacteria (Staphylococcus, Jeotgalicoccus, and Salinicoccu) and decreased beneficial bacteria. SEF with 5 times the clinical dose showed nephrotoxicity and SEF nephrotoxicity decreased after processing, but EF hepatotoxicity was not significant, which may be due to insufficient dose concentration and time.

Clinical and biomarker analyses of hepatic arterial infusion chemotherapy plus lenvatinib and PD-1 inhibitor for patients with advanced intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive cancer with a dismal prognosis and few effective therapeutic approaches. This study aimed to investigate the efficacy, safety, and predictive biomarkers of hepatic arterial infusion chemotherapy (FOLFOX-HAIC) in combination with lenvatinib and PD-1 inhibitor for patients with advanced iCCA. Locally advanced or metastatic iCCA patients receiving the triple combination therapy of lenvatinib, PD-1 inhibitor, and FOLFOX-HAIC were included in this retrospective study. Primary endpoint was the progression-free survival, evaluated using the RECIST criterion. The secondary endpoints included overall survival, objective response rate, and safety. Whole exome and RNA sequencing of tumor biopsy tissues were performed for biomarker exploration. Between May, 2019 and December 2022, a total of 46 patients were included in this study. The primary endpoint showed a median progression-free survival of 9.40 months (95% CI: 5.28-13.52), with a 6-month progression-free survival rate of 76.1%. The median overall survival was 16.77 months (95% CI, 14.20-19.33), with an objective response rate of 47.8% and disease control rate of 91.3% per RECIST. In addition, 4.3% and 8.7% of patients achieved complete response of all lesions and intrahepatic target lesions per mRECIST, respectively. The most common treatment-related adverse events were neutropenia, thrombocytopenia, elevated aspartate aminotransferase and alanine aminotransferase level. Furthermore, integrated analysis of genetic, transcriptomic, and immunohistochemistry data revealed that pre-existing immunity (high expression level of immune-related signatures and intra-tumoral CD8+ T cell density) in baseline tumor tissues was associated with superior clinical benefits. However, the evaluation of tumor mutation burden did not show potential predictive value in this triple combination. FOLFOX-HAIC in combination with lenvatinib and PD-1 inhibitor demonstrated a promising antitumor activity with manageable safety profiles in patients with advanced iCCA. Moreover, our study also revealed new perspectives on potential biomarkers for clinical efficacy.

Relationship of shift work with liver enzyme abnormalities and nonalcoholic fatty liver disease: A retrospective cohort study of Thai workers in Bangkok, Thailand

Shift work, particularly night shift work, has several detrimental health outcomes. This retrospective study investigated the associations of shift work with the incidence rates of liver enzyme abnormalities and nonalcoholic fatty liver disease (NAFLD) using the annual health check-up database between 2009 and 2016 and self-administered questionnaires from two large organizations in Thailand. Among 10,205 participants, 3620 eligible participants, classified into three subgroups by their shift work status, were followed up until abnormal liver outcomes were observed. The incidence rate of abnormal outcomes was calculated, and Cox proportional hazard models were used to assess the associations. Current shift work was not associated with abnormal liver outcomes, including elevated alanine aminotransferase and aspartate aminotransferase levels, elevated lipid accumulation product (e-LAP), and elevated hepatic steatosis index (e-HSI). However, when the frequencies and duration of shift work were investigated, the duration of shift work was associated with NAFLD outcomes. Healthcare personnel with 10–20 years of shift work experience had a higher risk of e-LAP (adjusted hazard ratio [HR] = 1.31, 95% confidence interval [CI] = 1.04–1.65), while workers with more than 20 years of shift work had a lower risk of e-LAP (adjusted HR = 0.77, 95% CI–0.62–0.97). Nonhealthcare shift workers with fewer than 10 years of work exposure had a higher risk of e-HSI (adjusted HR = 4.30, 95% CI = 1.28–14.47). In summary, the shift work status was not associated with liver abnormalities, but the duration of shift work was associated with NAFLD.

Resurgence of influenza A after SARS-CoV-2 omicron wave and comparative analysis of hospitalized children with COVID-19 and influenza A virus infection.

The highly infectious Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have caused large-scale transmission from Dec 2022 to Feb 2023 in China. After this event, a remarkable surge of influenza A (Flu A) occurred from March to May 2023, especially in pediatric patients. This study aimed to investigate the differences between pediatric patients infected with COVID-19 Omicron and Flu A virus. A total of 1,063 hospitalized children who admitted into two tertiary general hospital of Guangdong province of China were included. Medical records were compared retrospectively in these patients during the pandemic periods of SARS-CoV-2 omicron and Flu A. A total of 592 Patients with Flu A were mostly preschool and school-aged (>3y, 76.0%), they showed higher ratio of high fever (≥39°C), cough, rhinorrhea, and vomiting than patients with SARS-CoV-2 omicron. Most of the 471 Omicron patients were young children (0-3y, 74.5%) and had more poor appetite and dyspnea symptom. Benign acute children myositis (BACM) was only observed in patients with Flu A, and a significant male predominance. Multisystem inflammatory syndrome in children (MIS-C) was only found in patients with SARS-CoV-2 Omicron. Compared to the SARS-CoV-2 Omicron group, for both age groups (0-3 years and > 3 years), the Flu A group showed significantly reduced lymphocyte (Lym) counts (P < 0.001), and elevated levels of aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and creatinine kinase-MB (CK-MB) in laboratory indexes (all P < 0.001). Additionally, it was found that more children hospitalized with COVID-19 had increased C-reactive protein (CRP) levels compared to those with Flu A. Influenza A infections have notably surged in children, coinciding with the relaxation of COVID-19 related social restrictions. During the epidemic periods of Omicron and Flu A virus infection, different clinical and laboratory characteristics were observed in hospitalized children.

The association of exposure to polychlorinated biphenyls with lipid profile and liver enzymes in umbilical cord blood samples

Evidence on prenatal exposure to polychlorinated biphenyls (PCBs) and its effects on newborns and potential biological mechanisms is not well defined yet. Therefore, this study aimed to examine whether PCBs are associated with lipid profile and non-invasive markers of hepatocyte injuries in samples of blood obtained from the umbilical cord. This study included 450 mothers-newborn pairs. Umbilical levels of PCBs were measured using Gas Chromatography/Mass Spectrophotometry (GC/MS). Lipid profile including low-density lipoprotein (LDL-C), total cholesterol (TC), triglycerides (TG), and high-density lipoprotein (HDL-C), as well as liver enzymes i.e., alanine amino transferase (ALT), aspartate amino transferase (AST), γ-glutamyl-transferase (GGT) and alkaline phosphatase (ALP) were determined from umbilical cord blood samples. Quantile g-computation analysis was applied to evaluate the collective influence of PCBs on both lipid profiles and liver enzymes, along with the impact of lipid profiles on liver enzymes. Exposure to the mixture of PCBs was significantly associated with increases in ALP, AST, ALT, and GGT levels in cord blood samples, with increments of 90.38 U/L (95%CI: 65.08, 115.70, p < 0.01), 11.88 U/L (95%CI: 9.03, 14.74, p < 0.01), 2.19 U/L (95%CI:1.43, 2.94, p < 0.01), and 50.67 U/L (95%CI: 36.32, 65.03, p < 0.01), respectively. Additionally, combined PCBs exposure was correlated with significant increases in umbilical TG, TC, and LDL-C levels, with values of 3.97 mg/dL (95%CI: 0.86, 7.09, p = 0.01), 6.30 mg/dL (95%CI: 2.98, 9.61, p < 0.01), and 4.63 mg/dL (95%CI: 2.04, 7.23, p < 0.01) respectively. Exposure to the mixture of lipids was linked to elevated levels of AST and GGT in umbilical cord blood samples. Furthermore, a noteworthy mediating role of TC and LDL-C was observed in the association between total PCBs exposure and umbilical cord blood liver enzyme levels. Overall our findings suggested that higher levels of umbilical cord blood PCBs and lipid profile could affect liver function in newborns.

Investigating the Potential Hepatoprotective Effect of Quercetin in Male Rats ‎Following Acute Exposure to Cyclophosphamide

This study aimed to assess the hepatoprotective efficacy of quercetin against ‎hepatotoxicity ‎induced by cyclophosphamide in a rat model. A total of 28 male ‎Wister albino rats (Rattus ‎norvegicus), with body ‎weights ranging from 195.5 to ‎‎198.2 g and approximately three months ‎of age, were randomized into four different ‎groups: the untreated Control group ‎received no interventions; the CYP group was treated with an intraperitoneal ‎injection of ‎cyclophosphamide at a dose of 200 mg/BW; the Qt group received an ‎‎oral administration of quercetin at 100 mg/kg BW daily for ten days; and the combined (Qt+CYP) group received quercetin orally for ten days, followed by a ‎cyclophosphamide ‎injection on the tenth day. Various biochemical markers, ‎including alanine aminotransferase ‎‎(ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and liver glutathione ‎‎(GSH), and malondialdehyde ‎‎(MDA), were analyzed, in addition to body weight and ‎prothrombin time. The ‎Untreated Control group exhibited baseline levels for all assessed ‎markers. In ‎contrast, the CYP group showed elevated levels of ALT, AST, ‎‎ALP, and MDA, coupled with a decrease in GSH. Notably, the Qt+CYP ‎group ‎demonstrated a statistically significant reduction (P‎‎&lt;0.05) in ALT, AST, ALP, ‎and MDA levels, ‎as well as an increase in GSH and prothrombin time, when ‎compared to the CYP group. No significant differences in body ‎weight were observed across all groups ‎‎(P‎‎&lt;0.05). The results of the study indicate that quercetin has the potential to be used as a ‎‎hepatoprotective agent, protecting liver tissues from the cytotoxic effects of cyclophosphamide.