Increase In AST Research Articles

Biochemical, Histological, and Multi-Omics Analyses Reveal the Molecular and Metabolic Mechanisms of Cold Stress Response in the Chinese Soft-Shelled Turtle (Pelodiscus sinensis)

The Chinese soft-shelled turtle (Pelodiscus sinensis), a type of warm-water reptile, is frequently chosen as the model animal to understand how organisms respond to environmental stressors. However, the responsive mechanism of P. sinensis to natural cold stress is unclear, especially in terms of metabolic pattern and molecular pathways. Herein, plasma biochemical, hepatic morphological, apoptotic, transcriptomic, and metabolomic detection methods were performed to investigate the response of P. sinensis to acute cold stress. A consistent increase in plasma AST and ALT activities with a decline in ALP activity was found following 14 °C and 7 °C cold stress compared with the control group. Plasma GLU, TG, CHO, and HDL contents, reflecting energy metabolism, were decreased to lower levels from 2 to 16 days post cold stress (dps). Histological and TUNEL detection in the liver demonstrated that the 14 °C and 7 °C cold stress caused severe morphological damage and cell apoptosis in a time-dependent manner. DEGs in the biosynthesis of fatty acids (Acsbg2, Acsl3, Acsl4, Acsl5, Mcat, and Acacb), as well as unsaturated fatty acids (Hsd17b12, Elovl7, Scd, and Baat), starch and sucrose metabolism (Pgm1, Pgm2, and Treh), and apoptosis (Ddit3, Gadd45a, Lmnb1, Tuba1c, Tnf, Tnfsf10, Fos, Itpr1, and Ctso) were discovered in the transcriptome under cold stress. The metabolomic data showed that metabolites, including chenodeoxycholic acid, oleoylethanolamide, uric acid, fructose 1,6-bisphosphate, CMP, and S-(Hydroxymethyl)-glutathione, were remarkably altered in the cold stress groups. Combined transcriptomic and metabolomic data revealed that pyrimidine metabolism, amino acid metabolism, and pyruvate metabolism were the most significant pathways regulated by the low-temperature exposure. Overall, this work suggests that 14 °C and 7 °C cold stress could induce obvious morphological damage and apoptosis in the liver at 4 dps. Moreover, energy metabolism and amino acid metabolism were the main signaling pathways in response to cold stress for P. sinensis.

COVID-19 and liver

Abstract Background and aims The coronavirus disease 2019 (COVID-19) presents a significant health risk, affecting both healthy individuals and those with underlying health conditions, including liver diseases. This study aimed to evaluate the impact of COVID-19 on liver function in both hepatic and non-hepatic patients across varying degrees of disease severity, as confirmed by PCR testing. Methods In this prospective study, we included patients with confirmed COVID-19, both with and without liver conditions, who were admitted to the National Hepatology and Tropical Medicine Research Institute (NHTMRI) and Embaba Fever Hospital between November 2020 and July 2021. Results The study cohort consisted of 255 confirmed COVID-19 patients (mean age 52.16 years, 48.6% male, 24.3% with liver conditions). Among those with liver disease, 6.4% had mild symptoms, while 4.8%, 56.4%, and 33.8% experienced moderate, severe, and critical symptoms, respectively. Clinical characteristics were insignificantly different between hepatic and non-hepatic patients across the various COVID-19 severity grades, with the exception of the loss of taste and smell in severe cases and hepatic encephalopathy and oxygen saturation in critical cases. Laboratory findings similarly showed no significant differences, except that hepatic patients exhibited a notable decrease in platelet count and a significant increase in AST and bilirubin levels compared to non-hepatic patients. In critical COVID-19 cases, non-hepatic patients had significantly higher serum ferritin levels, while hepatic patients demonstrated increased serum bilirubin levels. Mortality was considerably higher in hepatic patients than in non-hepatic patients, particularly among those with severe and critical COVID-19. The study suggests that liver disease is associated with the progression to severe COVID-19, which includes a higher risk of mortality. Conclusion COVID-19 is linked to liver function impairment, with hepatic patients experiencing higher mortality rates compared to non-hepatic patients. Summary COVID-19, a novel coronavirus, presents a serious health threat to both healthy individuals and those with pre-existing health conditions. In this study, we evaluated its impact on individuals with liver disease compared to those without. The findings indicate that COVID-19 infection is associated with a decline in liver function and increased mortality rates in patients with liver disease.

First results of migoprotafib, a potent and highly selective Src homology-2 domain-containing phosphatase 2 (SHP2) inhibitor in patients with advanced solid tumors.

Src homology-2 domain-containing phosphatase 2 (SHP2) promotes RAS-MAPK signaling and tumorigenesis and is a promising therapeutic target for multiple solid tumors. Migoprotafib is a potent and highly selective SHP2 inhibitor designed for the treatment of RAS-MAPK driven cancers, particularly in combination with other targeted agents. Here we report first-in-human study results of single agent migoprotafib in advanced solid tumor patients. We conducted a phase 1a, open-label, multi-center, dose-escalation and expansion study in adult patients with locally advanced or metastatic solid tumors. The key objectives were to evaluate safety, pharmacokinetics, pharmacodynamics (peripheral blood pERK) and preliminary anti-tumor activity. Fifty-six heavily pre-treated patients were treated with migoprotafib (10-150 mg QD). Migoprotafib had a rapid absorption rate (~0.5-2 hours) with dose-dependent increases in exposure and pathway modulation (pERK changes). The maximum tolerated dose was 100 mg and the recommended phase 2 dose (RP2D) was 60 mg daily (QD) based on safety, pharmacokinetics (PK), pharmacodynamics, and anti-tumor activity. Migoprotafib was generally well tolerated with the most frequent adverse events of diarrhea, peripheral edema, dyspnea, anemia, constipation, fatigue, AST increase and platelet count decrease. Stable disease was observed in 10 patients (18%). Migoprotafib had predictable, dose-dependent PK with an effective half-life that supports QD dosing and demonstrated promising safety, tolerability, and clinical activity at the RP2D. Further clinical testing of migoprotafib in combination with other targeted agents is warranted.

Ampelopsis grossedentata tea alleviating liver fibrosis in BDL-induced mice via gut microbiota and metabolite modulation

Liver fibrosis (LF) is a common sequela to diverse chronic liver injuries, leading to rising rates of cirrhosis and hepatocellular carcinoma (HCC). As the medicinal and edible homologous material, traditional teas have exhibited promising applications in the clinical management of liver fibrosis. Here, we generated a liver fibrosis mouse model to explore the potent therapeutic ability of Ampelopsis grossedentata (AG) tea on this condition by multi-omics analysis. The biochemistry results pointed towards mitigated increases of ALT, AST, TBIL, and ALP triggered by BDL in the AG-treated group. Examination using H&E and Sirius Red staining revealed severe liver injuries, inflammation infiltration, amplified fibrosed regions, and the creation of bile ducts, all of which were fallout from BDL. Immunohistochemistry findings also implicated a noteworthy upregulation of the HSC activation marker α-smooth muscle actin (α-SMA) and the fibrosis marker collagen I in the BDL group. However, these symptoms demonstrated a significant improvement in the group treated with 100 mg/kg AG. Findings from the Western Blot test corroborated the prominent elevation of TNF-α, col1a1, α-SMA, and TGF-β, instigated by BDL, while AG treatment meaningfully modulated these proteins. Furthermore, our study underscored the potential involvement of several microbiota, such as Ruminococcaceae UCG-014, Eubacterium Ruminantium, Ruminococcus 1, Christensenellaceae R-7, Acetatifactor, Dubosiella, Parasutterella, Faecalibaculum, and Defluviitaleaceae UCG-011, in the progression of liver fibrosis and the therapeutic efficacy of AG. This investigation shows that during the process of AG ameliorating BDL-induced liver fibrosis, bile acid derivatives such as CDCA, TCDCA, 3-DHC, UCA, DCA, among others, play significant roles. In this study, we identified that several non-bile acid metabolites, such as Deltarasin, Thr-Ile-Arg, etc., are entailed in the process of AG improving liver fibrosis.

Abstract 4138704: Safety and Efficacy of Generic Atorvastatin in Korean Dyslipidemia Patients: A Non-Interventional Observational Study

Background: Statins are widely used for controlling dyslipidemia. However, most evidences for dyslipidemia prevention and treatment with statins are based on studies involving Caucasian populations, resulting in limited data on Korean patients. This study was conducted to evaluate the efficacy lipid profile and safety of generic atorvastatin in a real-world clinical setting among Korean dyslipidemia patients. Methods: This study was conducted as a non-interventional, multi-center observational study. It was carried out across 264 institutions and clinics from October 2017 to July 2021. Total 16,992 participants were enrolled. The safety and efficacy evaluation cohorts consisted of 16,803 and 11,035 subjects, respectively. The liver function evaluation cohort included 13,889 subjects. The main eligibility criteria were dyslipidemia patients prescribed generic atorvastatin according to approved indications. Adverse event rates were collected for safety evaluation, and lipid profiles, including LDL-C, were collected for efficacy evaluation. Results: In the safety endpoint evaluation, 1,612 adverse events were reported in 1,027 subjects (6.11%). Common adverse events such as dizziness, headache, and constipation, which were frequently observed in this study, were within the approved labels. Muscle pain occurred in 0.14% of subjects, and myopathy, myositis, rhabdomyolysis, and CK abnormalities or increases were reported in 0.01% of subjects, respectively. Most of the adverse events were confirmed to be mild or resolved, and the study was completed without changing the dose. All abnormal liver function test results were reported in less than 1% of subjects (AST increase: 0.14%, ALT increase: 0.1%, ALP increase: 0.01%, γ-GT increase: 0.01%). The mean LDL-C decreased from 117.31 mg/dL to 89.97 mg/dL, showing a statistically significant improvement in LDL-C levels (p < 0.0001). Conclusions: Generic atorvastatin demonstrated tolerable safety as well as significant efficacy on lipid profile. Generic atorvastatin might be safe and effective for Korean patients with dyslipidemia.

The effect of different definitions of hepatic injury on incidence and mortality rates in the ICU patient population with secondary hepatic injury

ObjectiveThe aim was to investigate how different hepatic injury (HI) definitions used in the same study population change incidence and mortality rates and which would best diagnose secondary HI. DesignSingle-centre retrospective observational cohort study. SettingTertiary hospital ICU, ANKARA, Turkey. PatientsFour hundred seventy-eight adult patients were included in the study. InterventionsNone. Main variables of interestThree definitions of HI were compared. Taking the SOFA hepatic criteria (SOFA: Total bilirubin (TBL) > 1.2 mg/dl) as the gold standard, sensitivity, specificity, positive and negative predictive values, and accuracy of the modified 2017 definition by the American College of Gastroenterology (ACG) and the 2019 European Association for the Study of the Liver (EASL) were calculated. ResultsIncidence rates ranged from 10% to 45% according to the definition (p < 0.005), while mortality rates ranged from 38% to 57%. When the SOFA1.2 (TBL > 1.2 definition was taken as the gold standard, the diagnostic value of the ACG definition was high, and HI was found to be an independent risk factor that increased mortality four times. ConclusionsAccording to this study’s results, the incidence and mortality rates of secondary HI vary greatly depending on the definition used. A definition that includes minimal increases in ALT, AST, and TBL predicts mortality with reasonable incidence rates.

Red herrings and zebras and TB, oh my! Unexpected bone marrow presentation of Mycobacterium tuberculosis

Abstract Introduction/Objective Epithelioid granulomas are uncommon and non-specific findings in bone marrow samples, and should prompt additional testing for appropriate diagnosis and treatment, especially in the immunocompromised patient. The differential diagnosis for bone marrow granulomas includes infections, neoplasia, autoimmune disease, sarcoidosis, and drug/therapy reaction. Although bone marrow workup to delineate the cause of granulomas should include staining to rule out both infection and lymphoma, morphologic review is often inconclusive. Final diagnosis requires clinical consultation and additional testing. Methods/Case Report A 76-year-old male was admitted to the hospital from the emergency department for a level 2 trauma after being found on the ground ~3 hours after a fall. The patient reported a recent increasing frequency of falls with associated weakness, as well as an almost 30 lb weight loss over the last 3.5 months and low grade fevers over several weeks. His past medical history was significant for treatment for urothelial carcinoma with transurethral resection and BCG therapy, hypertension, coronary artery disease, and peripheral vascular disease. Imaging showed hepatosplenomgaly, suspicious for early cirrhosis, and mild peripancreatic lymphadenopathy. Initial laboratory abnormalities demonstrated mild anemia, low albumin, and mild increase in ALT, AST, and alkaline phosphotase. Initial Infectious Diseases workup was negative for causative etiology (blood cultures, tick-borne parasites, and respiratory pathogens). Patient symptoms did not improve and cytopenias worsened. A bone marrow biopsy showed multiple non-necrotizing epithelioid granulomas. Despite low clinical concern for infectious etiology, mycobacteria blood culture isolated Mycobacterium tuberculosis complex. Final results were available 112 days after specimen collection. Results (if a Case Study enter NA) NA Conclusion Although tuberculosis is commonly associated with granulomatous pathology, infection is very uncommon in North American patients who have not traveled and alternative diagnoses might initially be favored. A high suspicion for mycobacterial infections is essential for diagnosis even in low-incidence populations with no known exposure or risk factor(s).

Investigating the protective effects of epigallocatechin-gallate against polystyrene microplastics-induced biochemical and hematological alterations in rats

BackgroundPolystyrene microplastics (PS-MPs) are widely used and found in drinking water and food, concerns have been raised about their potential health effects, especially in causing oxidative stress and inflammation in living organisms. ObjectivesThe aim of this study was to investigate the protective effects of epigallocatechin-gallate (EGCG), a natural antioxidant and anti-inflammatory compound, against PS-MPs-induced biochemical and hematological alterations in rats. MethodsMale Wistar rats were divided into four groups: control, EGCG-treated (80 mg∙ kg-1/d), PS-MPs-exposed (0.01 mg∙kg-1/d), and PS-MPs+EGCG-treated groups. PS-MPs were orally administered for 56 days, while EGCG was given concomitantly by gavage. At the end of the treatment period, blood samples were collected for hematological and biochemical analyses. Oxido-nitrergic stress markers, including malondialdehyde (MDA), nitric oxide (NO), reactive nitrogen species (RONS) and reduced glutathione (GSH), Superoxide dismutase (SOD), catalase (CAT), as well as inflammatory markers, such as tumor necrosis factor alpha (TNF-α), interferon gamma (IFY-γ) and interleukin-10 (IL-10), were also measured in serum. ResultsTreatment with PS-MPs caused a significant increase in MDA, RONS, NO levels and a decrease in SOD, CAT and GSH levels, indicating the induction of oxido-nitrergic stress. PS-MPs also caused an increase in the levels of TNF-α, IFY-γ, MPO and decreased IL-10, indicating the induction of inflammation. Additionally, PS-MPs caused alterations in hematological and serum transaminase parameters, including a decrease in red blood cell count, hemoglobin, and hematocrit levels, neutrophil and eaosinophil and an increase in white blood cell count, lymphocyte count, AST, ALT, ALP, LDH and GGT. PS-MPs also caused disturbances in electrolyte balance and renal function markers. However, treatment with EGCG significantly attenuated these alterations induced by PS-MPs, indicating its protective effects. ConclusionThe results of this study demonstrate that EGCG can protect against PS-MPs-induced biochemical and hematological alterations in rats, possibly through its antioxidant and anti-inflammatory properties.

Prognostic value of elevated transaminase levels as predictors of adverse outcomes in patients with acute myocardial infarction

Aim. To assess the prevalence of elevated serum liver transaminases (LTs), including alanine aminotransferase (ALT) and aspartate aminotransferase (ALT), and their impact on in-hospital and long-term mortality in patients with acute myocardial infarction (AMI).Materials and methods. The prospective observational study included 416 consecutive AMI patients (median age 65 years, 40.9% female, 46.9% with ST elevation) without prior liver diseases, who underwent coronary angiography within 24 hours after hospitalization. AST and ALT levels were measured upon admission. LTs were considered as abnormal when their levels exceeded the local upper limit of normal. Clinical endpoints were all-cause in-hospital and 18-month mortality. Associations between clinical endpoints and various risk factors, including LT levels, were assessed by the multivariate logistic regression analysis.Results. Elevated LT levels were seen in 28.6% of AMI patients: an isolated increase in ALT was noted in 17.8% of patients, while an isolated increase in AST was registered in 25% of cases. In-hospital and 18-month mortality was 5.8 and 11.3%, respectively. Abnormal LT levels were associated with the presence of ST elevation (odds ratio (OR) 1.873, 95% confidence interval (CI) 1.218–2.881, p = 0.004), lower systolic and diastolic blood pressure (OR 0.993, 95% CI 0.986–1.0, p = 0.04 and 0.979, 95% CI 0.964–0.994, p = 0.007, respectively), higher Killip class (OR 1.510, 95% CI 1.142–1.999, p = 0.004), and higher creatinine level (OR 1.010, 95% CI 1.003–1.016, p = 0.004). In the multivariate analysis, elevated LT levels were independently associated with in-hospital and 18-month mortality (OR 3.607, 95% CI 1.199–10.848, p = 0.022 and 2.182, 95% CI 1.011–4.708, p = 0.047, respectively).Conclusion. Elevated LT levels were present in about a third of patients with AMI. They were associated with specific clinical, biological, and prognostic features, including in-hospital and long-term mortality in AMI patients.

Unraveling the hepatoprotective and anti-pancreatic cancer potential of Caralluma europaea: a comprehensive in vivo, in vitro and in silico evidence

Caralluma europaea Guss. (C. europaea) is a medicinal plant used for cancer treatment. However, these treatments may be associated with complications that need to be investigated. This work aims to evaluate not only the chemical composition but also the hepatoprotective and anticancer properties of C. europaea extracts. The chemical constitution of the hydroethanolic extract was explored using gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC). The hydroethanolic extract, flavonoids, and polyphenols-rich extract at 100, 15, and 50 mg/kg, respectively, were administered to acetaminophen-treated rats for seven days. We used Western blotting and Real-Time quantitative Polymerase Chain Reaction (RT-qPCR) to determine the protein and the mRNA levels of cancer stemness markers in pancreatic cancer cell lines MIA PaCa-2 and BxPC-3 exposed to increasing doses of C. europaea extracts. In silico analysis was used to evaluate the effects of phenolic compounds revealed in C. europaea on caspase-3 and HSP90, and on liver damage on CYP2E1. The primary phenolics detected by GC-MS and HPLC were ferulic acid and benzofurazan. The positive control group showed an increase in AST, ALT, ALP, triglycerides, and VLDL levels. C. europaea extracts demonstrated hepatoprotective effects by ameliorating acetaminophen-induced alterations of biochemical and hispathological parameters. Immunoblotting and RT-qPCR profiling of cancer stemness markers indicated a reduction in the expression levels of Oct-4 and Nanog proteins, as well as a reduction in the mRNA levels of CD133 by 50–60% and Sox2 by 80–90% in pancreatic cancer cells. Molecular docking showed that naringenin presented the highest docking Gscore on CYP2E1 (−8.199) and HSP90 (−7.742). In conclusion, C. europaea extracts could be considered as a safe and promising therapeutic strategy to sensitize pancreatic cancer cells to chemotherapy.

Hepatic adenosquamous carcinoma with sarcomatous transformation: a case report and review of the literature.

Adenosquamous carcinoma (ASC) with the presence of a sarcomatous component is exceptionally uncommon in intrahepatic cholangiocarcinoma (iCCA). We report a case of hepatic ASC with rhabdoid transformation, one variation of sarcomatous change. A 72-year-old man was admitted to our hospital after being diagnosed with a 45mm-diameter neoplastic lesion in the right hepatic duct on abdominal computed tomography. Laboratory findings showed increases in AST, ALT, ALP, gamma-GT, CA19-9 and DUPAN-II. The patient then underwent an extended right hepatectomy. Histopathologically, the tumor was composed of an ASC component within an abundant fibrous stroma and a sarcomatoid carcinoma component. By immunohistochemistry, keratin 7 and keratin 19 were expressed by all tumor cells. Expression of keratin 5/6, p40 and p63 was restricted to the squamous component. The sarcomatoid component was immunoreactive for vimentin with no loss of INI1 expression. This component also showed a loss of membranous E-cadherin expression and a reduction of membranous β-catenin expression. Staining for desmin, myoglobin and HepPar1 was negative in any tumor cells. The patient died of liver failure 3months after surgery. This report aims to provide a better understanding of the clinicopathological characteristics and disease progression of the rare variants of iCCA to aid diagnosis and treatment.

Parâmetros bioquímicos e morfológicos em ratos diabéticos tratados com extratos de Ora-Pro-Nóbis (Pereskia aculeata)

Diabetes mellitus (DM) is a serious global public health problem. DM complications corroborate with high morbidity and mortality rates. Thus, several plant species have been studied regarding their medicinal properties with potential use in the treatment of DM and/or its complications. This study evaluated the effects of leaf (LE-OPN) and bark (BE-OPN) extracts from ora-pro-nóbis (Pereskia aculeata) on biochemical parameters (glycemia, triglycerides, total cholesterol, creatine, urea, AST and ALT, and lipid peroxidation) and histology (heart, liver and kidneys) in animals with DM. Induction of type 1 DM (glycemia &gt; 200 mg/dl) in male Wistar rats was performed with Alloxane (150 mg/kg/ml). The animals were divided into 4 groups: (1) without DM, (2) with DM, (3) with DM treated with LE-OPN and (4) with DM treated with BE-OPN. The treatment was done by gavage (300 mg/kg/day) for 4 weeks. After this period the parameters were evaluated. BE-OPN prevented the increase in triglycerides, AST, ALT, and urea, in addition to lipid peroxidation (p &lt; 0.05). The results suggest a potential for BE-OPN to prevent typical complications of DM, improving the lipid profile, liver, and kidney, as well as attenuating oxidative stress.

Investigation of the specific toxicity of an analgesic agent for wild ungulates based on meloxicam

Laboratory studies were conducted to determine the subacute toxicity of the veterinary drug Loksidev on white rats and dogs. The meloxicam-based Loxidev drug is used for diseases of the European doe animal treatment system for non-infectious diseases of the musculoskeletal system (acute aseptic myositis to reduce the symptoms of lameness and inflammation), as well as for diseases of the respiratory organs (in case of appropriate antibiotic therapy). Red deer: treatment of animals for non-infectious diseases of the musculoskeletal system (arthritis of the metatarsal joint to reduce symptoms of lameness and inflammation). When administered subcutaneously to rats, the drug Loxidev (for injections), under the conditions of a subacute toxicological experiment, in doses of 0.03; 0.15 and 0.3 ml/kg of body weight, does not cause hemo-, hepato- and nephrotoxic effects on the body of laboratory animals. The exception was the tendency to decrease the concentration of total hemoglobin and the hematocrit indicator, as well as a probable decrease (P &lt; 0.05) in the number of erythrocytes and leukocytes by 6.5 and 7.2 %, respectively, relative to the control in the blood and an increase (P &lt; 0.05) enzymatic activity of ALT and AST and concentration of urea in blood serum of rats, after three days of administration of the drug, at a dose of 0.30 mg/kg of body weight by 11.8; 11.0 and 10.3 %, respectively. However, after 7 days, after stopping the administration of the drug, these indicators probably did not differ from the control. Subcutaneous administration of the drug Loxidev (for injections) to dogs in doses of 0.03; 0.15 and 0.3 ml/kg of body weight for 3 days generally does not affect the clinical and biochemical parameters of the blood and does not cause hepatotoxic and nephrotoxic effects on the animal body, under the conditions of a subacute toxicological experiment. The exception was the tendency to decrease the concentration of total hemoglobin, the hematocrit index and the number of erythrocytes, as well as a probable decrease (P &lt; 0.05) in the number of leukocytes by 6.6 %, respectively, relative to the control in the blood and an increase (P &lt; 0.05) in enzymatic activity ALT and AST and the concentration of urea in the blood serum of dogs, after three days of administration of the drug at a dose of 0.30 mg/kg of body weight by 19.4; 19.3 and 14.5 %, respectively, but 7 days after stopping the administration of the drug, these indicators probably did not differ from the control. Further studies will be the next stage of pre-registration tests aimed at studying the irritant effect, allergenic properties of “Loksidev”, which is mandatory material of the “Safety and residue studies” section of the dossier for this veterinary drug.

A comparison of the potential of melatonin and tryptophan to ameliorate CCl4-induced hepatic and renal toxicity in Wistar rats

CCl4 causes oxidative injury, fatty degeneration, fibrosis of the liver, renal failure, and even hepatocellular and renal carcinoma. Certain substances have the potential to neutralize the harmful effects of CCl4, so it will lead to numerous beneficial effects. Melatonin (MEL) is a powerful antioxidant that regulates circadian rhythm and has beneficial effects on organism; tryptophan (TRP) is its precursor necessary for the synthesis of MEL. The aim of the current study was to determine whether MEL and TRP, have protective effects during subchronic application of CCl4 to the liver and kidneys. Results suggest that CCl4 led to decrease of total proteins, albumins, globulins, erythrocytes, hemoglobin, and hematocrit; and increase of creatinine, AST, ALT values, and leukocytes. MEL and TRP both showing protective effects on regulation of serum proteins, albumins, globulins, A/G, AST, ALT, and creatinine levels. TRP had been shown to have potential in regulation of disbalanced hematological parameters caused by CCl4. TRP had beneficial effects on hepatocyte morphology in term of beaded chromatin and preserved cell morphology. Overall, oral supplementation of TRP had better protective effects on liver/kidneys compared to MEL.

Efficacy and Safety of Levilimab in Combination with Methotrexate in Patients with Active Rheumatoid Arthritis: 56-Week Results of Phase III Randomized Double-Blind Placebo-Controlled Trial SOLAR.

. To evaluate the efficacy and safety of levilimab in combination with methotrexate (MTX) in subjects with MTX resistant active RA. : The study was conducted at 21 clinical sites in Russia and Belarus. All randomized subjects have completed the study between November 2019 and October 2021. Adult subjects (154) aged ≥18years with confirmed diagnosis of RA1 were randomly assigned (2 : 1) to receive either levilimab (162 mg, SC, QW) + MTX (n = 102) or placebo + MTX (n = 52). After W24 of the study all subjects continued toreceive open label levilimab. Subjects who have achieved DAS28-CRP ≤ 2.6 at W24 were switched to maintenance (Q2W) regimen of levilimab at W28 (LVL QW/Q2W and PBO/LVL Q2W arms). Those with DAS28-CRP > 2.6 at W28 continued with QW regimen (LVL QW and PBO/LVL QW arm). The PBO/LVL Q2W arm contained only one subject, thus not included in the analysis. The efficacy analysis was performed in a population of all randomized subjects. Those with missing data due to study discontinuation or rescue therapy prescription were considered non-responders. Otherwise, the analysis was performed on complete cases. Safety was assessed through monitoring of adverse events (AEs) in a population of those, who received at least on dose of LVL (n = 152). : Better response to treatment was observed in LVL QW/Q2W as it composed of those who reach DAS28-CRP ≤ 2.6 at W24. At this time point 15/27 (55.6%) of them achieved ACR70; 23/27 (85.2%) achieved DAS28-CRP remission (<2.6) and 7/27 (25.9%) achieved ACR/EULAR2011 remission of RA. After switching to LVL Q2W, rates of ACR70 and DAS28-CRP<2.6 did not significantly changed until W52: 17/27 (63.0%) and 21/27 (77.8%), respectively, yet the proportion of subject with ACR/EULAR 2011 remission further increased and reached 12/27 (44.4%). LVL QW arm was diminished by subjects who achieved high response to treatment at W24 and composed LVL QW/Q2W arm. Thus, ACR70, and remissions rate in this arm was close to zero at W24. However, continuation of LVL QW in those who not achieved DAS28-CRP ≤ 2.6 at W24 induced ACR70 response in 37/75 (36.0%), DAS28-CRP remission in 35/75 (46.7%) and ACR/EULAR 2011 remission in 8/75 (10.7%) at W52. The most common adverse events (reported in ≥5% of subjects) were blood cholesterol increase (30.3%), ALT increase (23.0%), lymphocyte count decrease (17.1%), ANC decrease (16.4%), blood triglycerides increase (13.8%), bilirubin increase (11.2%), AST increase (9.9%), WBC decrease (9.9%), IGRA with Mycobacterium tuberculosis antigen positive (7.2%), and injection site reactions (5.9%). No deaths occurred. : Open label period confirmed the lasting efficacy and safety of levilimab in combination with MTX in subjects with MTX resistant active RA and suggested the possibility of switching to levilimab maintenance regimen (once every 2 weeks) (Q2W) in those who achieved remission of RA at week 24.

Evaluation of transmission routes in patients with acute hepatitis B

Aims: In this study, we aimed to determine the possible transmission routes in patients diagnosed with acute hepatitis B virus (HBV) infection by anamnesis, physical examination and serologic tests. Methods: For this purpose, 44 patients hospitalized with acute hepatitis B in the Infectious Diseases and Clinical Microbiology Clinic of Ankara Numune Training and Research Hospital were included in the study. Patients were questioned about possible transmission routes. The diagnosis of acute hepatitis B was based on anamnesis, physical examination findings, anti-HBcIgM positivity by ELISA, absence of HBsAg positivity for more than 6 months and an increase in liver enzymes AST and ALT values 8-10 times above normal levels. HBsAg, HBeAg, AntiHBe serologic tests and Anti-HDV antibody against hepatitis delta virus (HDV) were also investigated in the sera of patients with acute hepatitis B. Possible transmission forms were questioned and recorded in the patient follow-up forms. All serologic markers were analyzed by ELISA (Organon, Netherlands). Results: Of the 44 patients included in the study, 29 (66%) were male and 19 (34%) were female. The mean ages of male and female patients were 36.6 (24-66 years) and 31.6 (23-60 years), respectively. When the patients with acute hepatitis B were evaluated in terms of possible transmission routes, 8 (18.2%) of the patients had HBsAg positive spouses, 3 patients had a history of surgical intervention in the last 6 months, 3 patients had a history of dental intervention, 2 patients had a history of blood transfusion in the last 6 months, and 2 patients had more than one possible transmission risk. Twenty-six (59.3%) patients had no possible route of transmission. Conclusion: Our findings revealed that possible transmission routes could not be identified in more than half of acute hepatitis B patients. In addition, we determined that 18.2% HBsAg positivity in the spouses of acute hepatitis B patients may be a possible route of transmission. In conclusion, we believe that patients with acute HBV infection should be evaluated for possible transmission routes, family members of acute hepatitis B patients should be screened for HBV infection, those with negative anti-HBs antibodies should be vaccinated, and relatives of HBsAg positive patients should be checked periodically.

Noninvasive assessment of liver fibrosis in mini pigs using an 18F–AlF-NOTA-RGD2 PET/CT molecular probe

To evaluate the efficacy of the 18F–AlF-NOTA-RGD2 positron emission tomography (PET)/computed tomography (CT) molecular probe for the noninvasive staging of liver fibrosis in mini pigs, a potential alternative to invasive diagnostic methods was revealed. This study used 18F–AlF-NOTA-RGD2 PET/CT imaging of mini pigs to assess liver fibrosis. The methods included synthesis and quality control of the molecular probe, establishment of an animal model of liver fibrosis, blood serum enzymatic tests, histopathological examination, PET/CT imaging, collagen content and expression, and mitochondrial reserve function assessment. The 18F–AlF-NOTA-RGD2 PET/CT molecular probe effectively differentiated various stages of liver fibrosis in mini pigs. Blood serum enzymatic tests revealed distinct stages of liver fibrosis, revealing significant increases in AST, ALT, TBIL, and DBIL levels as fibrosis advanced. Notably, ALT levels increased markedly in severe fibrosis patients. A gradual increase in collagen deposition and increasing α-SMA RNA expression and protein levels effectively differentiated between mild and severe fibrosis stages. Pathological examinations and Sirius Red staining confirmed these findings, highlighting substantial increases in collagen accumulation. PET/CT imaging results aligned with histopathological findings, showing that increased radiotracer uptake correlated with fibrosis severity. Assessments of mitochondrial function revealed a decrease in total liver glutathione content and mitochondrial reserve capacity, especially in patients with severe fibrosis. The 18F–AlF-NOTA-RGD2 PET/CT molecular probe is a promising tool for the noninvasive assessment of liver fibrosis, offering potential benefits over traditional diagnostic methods in hepatology.

Dietary curcumin supplementation attenuates hepatic damage and function abnormality in a chronic corticosterone-induced stress model in broilers

Chronic stress refers to the activation of the hypothalamic-pituitary-adrenal (HPA) axis and elevated blood contents of ACTH and corticosterone (CORT), exhibiting significant adverse effects on health outcomes. Currently, natural polyphenol compounds are increasingly being explored as potential therapeutic agents and have been considered as a treatment option for a variety of stress-induced diseases. Curcumin (CUR) is the main substance in Curcuma longa (Zingiberacea) rhizome that has strong health-beneficial properties. The study aimed to assess the potential protective effects of CUR on hepatic oxidative stress damage and abnormal lipid deposition in a chronic CORT-induced stress (CCIS) model in broilers. One hundred and twenty experimental broilers were randomly divided into 1) control group (CON), 2) CUR group (200 mg/kg feed), 3) CORT group (4 mg/kg BW CORT) and 4) CORT+CUR group (200 mg/kg feed plus 4 mg/kg BW CORT). The liver histology, glycolipid metabolism and oxidative stress were determined. In addition, qPCR was performed to identify shifts in genes expression. Compared with CON group, broilers under CCIS showed a decreased body weight, body weight gain and average daily gain, while dietary CUR significantly reversed these adverse effects. Furthermore, the plasma contents of TCH, TG, HDL-C, LDL-C, TP, GLB and AST were all significantly increased in CCIS broilers, while dietary CUR obviously alleviated the increase of TCH, HDL-C, LDL-C and AST, and relieved the hepatic lipid deposition disorder and liver injury. Moreover, CCIS significantly increased the contents of MDA in both liver and plasma, and decreased the content of plasma SOD, while CUR obviously reversed these changes, showing reduced oxidative stress damage. Finally, the mRNA expressions of FAS, ACC, SCD and the protein level of PPAR-γ were significantly increased, meanwhile the mRNA expression of lipolytic genes ACOX1, ATGL and CPT as well as two major intracellular antioxidant enzymes SOD1 and GPX1 were obviously decreased, while CUR effectively reversed these effects. These results showed that dietary CUR effectively alleviated CCIS-induced body weight loss, hepatic oxidative damage and lipid deposition disorder, suggesting the possible therapeutic effectiveness of CUR against hepatic damage and function abnormality caused by CCIS.

Effect of Exposure to Air Freshener on Some Hepatic Enzymes and Haematological Parameters of Albino Rats

Air fresheners, which are available as incense sticks, scented candles, aerosols, liquids, gels, and electric diffusers, are used to mask odors with refreshing scents. They are widely used in homes, cars, and offices, marketed to create a clean and pleasant indoor atmosphere. However, many air fresheners contain volatile organic compounds (VOCs), which can have harmful effects on human health. This study evaluated the effects of exposure to a gel air freshener on hepatic enzymes and hematological parameters in albino rats. Thirty (30) albino rats, weighing 200-260g, were divided into three groups of ten rats each, and acclimatized for two weeks under 12-hour light/dark cycles with free access to food and water. Group I (Control) was not exposed to the air freshener, Group II was exposed to the air freshener for 4 hours daily for 28 days, and Group III for 8 hours daily for 28 days. After the treatment, the rats fasted overnight, were anesthetized with chloroform, and blood samples were collected via cardiac puncture. AST and ALT were assayed using enzymatic methods, and hematological parameters were measured with the Sysmex XP-300 Automated Haematology Analyzer (5-part). Results showed a significant increase (p&lt;0.05) in AST, ALT, hematocrit, hemoglobin, red blood cells, and platelet levels in Group III compared to Groups I and II. No significant difference was found between Groups I and II. This suggests that 8-hour daily exposure to air freshener for 28 days induces hepatocellular damage and alters hematological parameters in albino rats, with the extent of damage increasing with longer exposure. However, further studies on humans are recommended.

Microwave ablation followed by cTACE in 5-cm HCC lesions: does a single-session approach affect liver function?

PurposeMicrowave ablation (MWA) and conventional transarterial chemoembolization (cTACE) are locoregional treatments commonly performed in very early, early and intermediate stages of hepatocellular carcinoma (HCC). Despite combined locoregional approaches have shown encouraging results in obtaining complete tumor necrosis, their application in a single session is poorly described.Our aim was to evaluate the safety and efficacy of single-session MWA and cTACE treatment in 5-cm HCCs and its influence on liver function.Materials and methodsAll 5-cm HCCs treated by MWA and cTACE performed in a single-session in our Interventional Radiology unit between January 2020 and December 2022 were retrospectively recorded and analyzed. Patients with poor or missing pre- and post-treatment imaging were excluded. Technical success, clinical success, and complications rate were examined as primary endpoints. Pre- and post-treatment liver function laboratory parameters were also evaluated.ResultsA total of 15 lesions (mean lesion diameter, 5.0 ± 1.4 cm) in 15 patients (11 men; mean age, 67.1 ± 8.9 years) were retrospectively evaluated. Technical and clinical success were 100% and 73%, respectively. Four (27%) cases of partial response and no cases of progressive or stable disease were recorded. AST and ALT values have found to be significantly higher in post-treatment laboratory tests. No other significant differences between pre- and post-treatment laboratory values were registered. AST and ALT pre- and post-treatment higher differences (ΔAST and ΔALT) were significantly associated with a lower clinical success rate.ConclusionMWA and cTACE single-session approach is safe and effective for 5-cm HCCs, without significant liver function impairment. A post-treatment increase in AST and ALT values may be a predictor for clinical failure.