Antioxidant Effect via Bioconversion of Isoflavonoid in Astragalus membranaceus Fermented by Lactiplantibacillus plantarum MG5276 In Vitro and In Vivo

In this study, the antioxidant mechanism of Astragalus membranaceus fermented by Lactiplantibacillusplantarum MG5276 (MG5276F-AM) was evaluated in HepG2 cells and in an animal model. HPLC analysis was performed to confirm the bioconversion of the bioactive compounds in A. membranaceus by fermentation. Calycosin and formononetin, which were not detected before fermentation (NF-AM), were detected after fermentation (MG5276F-AM), and its glycoside was not observed in MG5276F-AM. In HepG2 cells, MG5276F-AM alleviated H2O2-induced oxidative stress by mediating lipid peroxidation and glutathione levels, and upregulated antioxidant enzymes including catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx). In the tBHP-injected mouse model, administration of MG5276F-AM reduced hepatic aspartate transaminase, alanine transaminase, and lipid peroxidation. MG5276F-AM also modulated antioxidant enzymes as well as HepG2 cells. Thus, fermentation of A. membranaceus with L. plantarum MG5276 elevated the isoflavonoid aglycone by hydrolysis of its glycosides, and this bioconversion enhanced antioxidant activity both in vitro and in vivo.

Protective effect of Rhus chinensis Mill. extract against liver cirrhosis in rats

Purpose: To study the effect of Rhus chinensis Mill. extract (RCME) on diethylnitrosamine (DEN)-induced liver cirrhosis in rats. Methods: RCME was obtained by extracting the dried Rhus chinensis Mill. in water. Liver cirrhosis rat model was prepared by injecting with DEN once a week for 8 weeks. After 8th-week of RCME treatment, biochemical index and oxidative stress were determined in DEN-induced liver cirrhosis in rats. Results: Compared with model group, plasma concentrations of alanine transaminase (ALT, 125.3 ± 4.1 U/L) and aspartate aminotransferase (AST, 152.4 ± 3.5 U/L) decreased significantly (p < 0.01) in the 8th week. Rhus chinensis Mill. extract (RCME) significantly decreased malondialdehyde (MDA, 0.18 ± 0.02 umol/L) and superoxide dismutase (SOD, 0.76 ± 0.05 U/mg protein) in DEN-induced liver cirrhosis in rats (p < 0.01) when compared with model group. Conclusion: RCME protects against diethylnitrosamine-induced liver cirrhosis in rats. However, further investigations are required to ascertain the plant extract’s suitability for the clinical management of liver cirrhosis.

Liposome-Mediated Delivery of MERS Antigen Induces Potent Humoral and Cell-Mediated Immune Response in Mice

The advancements in the field of nanotechnology have provided a great platform for the development of effective antiviral vaccines. Liposome-mediated delivery of antigens has been shown to induce the antigen-specific stimulation of the humoral and cell-mediated immune responses. Here, we prepared dried, reconstituted vesicles (DRVs) from DPPC liposomes and used them as the vaccine carrier system for the Middle East respiratory syndrome coronavirus papain-like protease (DRVs-MERS-CoV PLpro). MERS-CoV PLpro emulsified in the Incomplete Freund’s Adjuvant (IFA-MERS-CoV PLpro) was used as a control. Immunization of mice with DRVs-MERS-CoV PLpro did not induce any notable toxicity, as revealed by the levels of the serum alanine transaminase (ALT), aspartate transaminase (AST), blood urea nitrogen (BUN) and lactate dehydrogenase (LDH) in the blood of immunized mice. Immunization with DRVs-MERS-CoV PLpro induced greater antigen-specific antibody titer and switching of IgG1 isotyping to IgG2a as compared to immunization with IFA-MERS-CoV PLpro. Moreover, splenocytes from mice immunized with DRVs-MERS-CoV PLpro exhibited greater proliferation in response to antigen stimulation. Moreover, splenocytes from DRVs-MERS-CoV PLpro-immunized mice secreted significantly higher IFN-γ as compared to splenocytes from IFA-MERS-CoV PLpro mice. In summary, DRVs-MERS-CoV PLpro may prove to be an effective prophylactic formulation to prevent MERS-CoV infection.

Psychiatric Comorbidities and Liver Injury Are Associated With Unbalanced Plasma Bile Acid Profile During Methamphetamine Withdrawal

BackgroundThe pathogenesis of methamphetamine usedisorders (MUDs) remains largely unknown; however, bile acids may play arole as potential mediators of liver injury and psychiatric comorbidities.The aim of this study was to characterize bile acid (BA) profiles in plasmaof patients with MUDs undergoing withdrawal.MethodsLiver functions and psychiatric symptoms wereevaluated in a retrospective cohort (30 MUDs versus 30 control subjects) andan exploratory cohort (30 MUDs including 10 subjects each at the 7-day,3-month, and 12-month withdrawal stages versus 10 control subjects). BAcompositions in plasma samples from MUD patients in the exploratory cohortwere determined by gas-liquid chromatography.ResultsBoth psychiatric comorbidities andmethamphetamine-induced liver injury were observed in patients in both MUDcohorts. The plasma concentrations of the total BA, cholic acid (CA), andchenodeoxycholic acid (CDCA) were lower in MUD patients relative tocontrols. The maximum decline was observed at the 3-month stage, withgradual recovery at the 12-month stage. Notably, the ratios of deoxycholicacid (DCA)/CA and lithocholic acid (LCA)/CDCA were statistically significantat the 3-month stage comparing with controls. Significant correlations werefound between the LCA/CDCA and taurolithocholic acid (TLCA)/CDCA ratios andthe levels of alanine transaminase and aspartate aminotransferase, andbetween the LCA/CDCA ratio and the HAM-A score.ConclusionBA profile during METH withdrawal weremarkedly altered, with these unbalanced BAs being associated with liverinjury. The associations between BA profiles and psychiatric symptomssuggest an association between specific BAs and disease progression,possibly through the liver-brain axis.

Elevated De Ritis Ratio Is Associated With Poor Prognosis in COVID-19: A Systematic Review and Meta-Analysis

Objective: This meta-analysis aims to assess whether elevated De Ritis ratio is associated with poor prognosis in patients with coronavirus 2019 (COVID-19).Methods: A systematic literature search was performed using PubMed, Embase, and EuropePMC databases up until September 17, 2021. De Ritis ratio is also known as Aspartate aminotransferase/alanine transaminase (AST/ALT) ratio. The main outcome was poor prognosis, a composite of mortality, severity, the need for ICU care, and intubation. The effect measure was odds ratios (ORs) and mean differences. We generated sensitivity and specificity, negative and positive likelihood ratio (NLR and PLR), diagnostic odds ratio (DOR), and area under curve (AUC).Results: There were eight studies with 4,606 patients. De Ritis ratio was elevated in 44% of the patients. Patients with poor prognosis have higher De Ritis ratio [mean difference 0.41 (0.31, 0.50), p &lt; 0.001; I2: 81.0%] and subgroup analysis showed that non-survivors also have higher De Ritis Ratio [mean difference 0.47 (0.46, 0.48), p &lt; 0.001; I2: 0%]. Elevated De Ritis ratio was associated with poor prognosis [OR 3.28 (2.39, 4.52), p &lt; 0.001; I2: 35.8%]. It has a sensitivity of 55% (36–73), specificity of 71% (52–85), PLR 1.9, NLR.63, DOR of 3 (2–4), and AUC of.67 (0.63–0.71). The posterior probability of poor prognosis was 38% if De Ritis is elevated, while 17% if De Ritis is not elevated.Conclusion: Elevated De Ritis ratio is associated with poor prognosis in patients with COVID-19.Systematic Review Registration: PROSPERO ID: CRD42020216634.

Fifteen-minute update: International normalised ratio as the treatment end point in children with acute paracetamol poisoning

Paracetamol is one of the most frequent reasons for poisonings across the UK with an estimated 90,000 patients and 150 deaths annually. International normalised ratio (INR) may be elevated due to hepatocellular damage and is frequently used to monitor progress on N-acetyl cysteine. N-acetyl cysteine is associated with reduced activity of vitamin K dependent clotting factors leading to a benign elevation of INR. In asymptomatic children with normal aspartate transaminase/alanine transaminase, isolated borderline elevation of INR following paracetamol overdose should be reviewed for possible N-acetyl cysteine induced elevation of INR. Due to these factors, in those with borderline persistent elevation of INR, N-acetyl cysteine can be safety stopped if INR is falling on two or more consecutive tests and is <3.0.

Mouse Organ-Specific Proteins and Functions

Organ-specific proteins (OSPs) possess great medical potential both in clinics and in biomedical research. Applications of them—such as alanine transaminase, aspartate transaminase, and troponins—in clinics have raised certain concerns of their organ specificity. The dynamics and diversity of protein expression in heterogeneous human populations are well known, yet their effects on OSPs are less addressed. Here, we used mice as a model and implemented a breadth study to examine the panorgan proteome for potential variations in organ specificity in different genetic backgrounds. Using reasonable resources, we generated panorgan proteomes of four in-bred mouse strains. The results revealed a large diversity that was more profound among OSPs than among proteomes overall. We defined a robustness score to quantify such variation and derived three sets of OSPs with different stringencies. In the meantime, we found that the enriched biological functions of OSPs are also organ-specific and are sensitive and useful to assess the quality of OSPs. We hope our breadth study can open doors to explore the molecular diversity and dynamics of organ specificity at the protein level.

A Randomized, Double-Blind, Placebo-Controlled Parallel Study on the Efficacy and Safety of Centella asiatica L. Extract for Reducing Alanine Transaminase (ALT) Level in Subjects with Elevated ALT

The liver is an important organ that detoxifies various metabolites, synthesizes proteins, and produces biochemicals necessary for life. There are many medications on the market to treat liver diseases, but these can be a strain on the liver due to the need for a detoxification process in the organ. Herbal medicines are replacing synthetic drugs. In the present study, we aimed to evaluate the efficacy and safety of Centella aisatica L. extract for reducing alanine transaminase (ALT) levels using a randomized, double-blind, placebo-controlled parallel study. Investigators performed a clinical trial in which an herbal treatment was administered every morning for 12 weeks to 80 patients in two groups. The study protocol number was SYN/RM/CA-008. The results demonstrated improved ALT levels with a positive change in the investigational product (IP) group (−19.9) compared to the placebo group (1.8) (p < 0.0001). In addition, IP treatment was safe and non-toxic. The current data indicate that CA-HE50 exhibits clinically significant changes for all hepatoprotective efficacy parameters, suggesting potential for development and applicability as a hepatoprotective substance.

Elevated Serum Alanine Transaminase (ALT) in Patients of Type 2 Diabetes Mellitus

Objective: The objective of this study was to determine the prevalence of raised serum alanine transaminase level in patients of type 2 diabetes mellitus. Design: cross-sectional study Study Settings: This study was conducted at Department of Internal Medicine Abbas Institute of Medical Sciences Muzaffarabad from November 2020 to April 2021. Material and Methods: Total 144 patients were included in the study having age from 18 to 60 of both genders with Type 2 DM. It was labeled as elevated if it was ≥50 IU/L. A written informed consent was taken from each patient. Results: Patient’s age ranged from 36 to 70 years having mean value of 44.4±8.3 y. BMI ranged from 21.2 Kg/m2 to 34.7 Kg/m2 with a mean of 27.2±3.7 Kg/m2. Disease duration was from 2 to 14 years with a mean of 7.1±3.8 years. Elevated serum ALT was noted in 38 (26.4%) patients with type-II diabetes. Conclusion: Elevated serum ALT was noted in a substantial proportion of patients with type-II diabetes and was significantly more frequent in patients with poor glycemic control which warrants good glycemic control to prevent and routine screening of such patients in future practice to timely identify and manage this complication to improve the outcome. Keywords: Type 2 Diabetes Mellitus, Serum Alanine Transaminase, Prevalence

Mouse Organ Specific Proteins and Functions

Organ specific proteins (OSPs) possess great medical potentials both in clinics and in biomedical research. Applications of them - such as alanine transaminase, aspartate transaminase, and troponins - in clinics have raised certain concerns of their organ specificity. The dynamics and diversity of protein expression in heterogeneous human population are well known, yet their effects on OSPs are less addressed. Here we use mouse as a model and implemented a scheme of breadth study to examine the pan-organ proteome for potential variations of organ specificity in different genetic backgrounds. Using reasonable resources, we generated pan-organ proteomes of four in-bred mouse strains. The results revealed a large diversity that is more profound among OSPs than the overall proteomes. We defined a robustness score to quantify such variation and derived three sets of OSPs with different stringencies. In the meantime, we found that the enriched biological functions of OSPs are also organ specific that are sensitive and useful to assess the quality of OSPs. We hope our breadth study can open doors to explore the molecular diversity and dynamics of organ specificity at the protein level.