Serum Transaminase Levels Research Articles

Protective Effect and Mechanism of L-Theanine on Acute Alcoholic Liver Injury in Mice.

Acute alcoholic liver injury (AALI), a global health concern, is exacerbated by excessive episodic drinking. L-theanine (LTA), a compound found in tea leaves, mitigates the AALI-induced liver oxidative stress and inflammation. However, its relationship with alcohol metabolism and its liver-protective mechanism remains unexplored. This study investigates the protective mechanisms of LTA against AALI in mice. The results demonstrate that LTA mitigates liver tissue damage and reduces the serum levels of aspartate aminotransferase and alanine aminotransferase, and liver levels of triglycerides, malondialdehyde, reactive oxygen species (ROS), tumor necrosis factor-α, interleukin-6, and interleukin-1β. However, LTA enhances the activity of ethanol-metabolizing enzymes and decreases ethanol and acetaldehyde serum levels. Mechanistically, LTA accelerates alcohol metabolism by upregulating the hepatic expression of ADH6, ALDH1B1, ALDH2, CAT, and ACSS1 mRNA and protein in AALI mice, LTA downregulates the expression of CYP2E1 mRNA and protein and promoting antioxidative activities thus reducing the accumulation of ROS. This attenuated inflammation by inhibiting the phosphorylation of nuclear factor-kappa B inhibitor alpha (IκBα) and downregulating the hepatic expression of NF-κB p65, TNF-α, IL-1β, IL-6 mRNA, and protein. LTA is a beneficial dietary supplement that protects against AALI by modulating alcohol metabolism and the TNF-α/NF-κB pathway.

Lipidomic profiling of serum and liver tissue reveals hepatoprotective mechanism of taxifolin in rats with CCl4-induced subacute hepatic injury based on LC-MS/MS

Currently, the hepatoprotective activity of taxifolin, a flavonoid isolated from Pseudotsuga taxifolia, has been reported in many animal models. However, whether the protective effect of taxifolin on the liver is related to its effect on lipidomics is unclear. Based on the significant therapeutic effect of taxifolin on CCl4 induced subacute hepatic injury, we observed the intervention of taxifolin by lipidomics. The results demonstrate that taxifolin can effectively reverse the damage caused by CCl4, which including hepatocyte vacuolization and necrosis. Lipomic profiling based on liquid chromatography-mass spectrometry showed that taxifolin was able to restore lipidomic changes caused by CCl4, including the levels of lysophosphatidylserine (LPS), phosphatidylcholine (PC), coenzyme (Co), phosphatidylglyceride (PG), phosphatidylserine (PS), dimethylphosphatidylethanolamine (dMePE), ceramide (Cer), sphingosine (So), triglycerides (TG), and monogalactosyl diacylglycerol (MGDG) in the rat liver, and phosphatidylcarbinol (PMe) and phosphatidylethanolamine (PE), plant sphingosine (phSM), glucose ceramide (CerG1), TG, and diglycerides (DG) in serum. Spearman's correlation analysis showed that CerG1, phSM, PE, and PMe in serum, and Cer, dMePE, PG, PS, So, TG, and MGDG in liver were positively correlated with serum levels of aspartate transaminase, alanine transaminase, and liver index; while TG, DG in serum, and Co, LPS, PC in liver were negatively correlated with the parameters. In total, 43 and 34 lipid molecules were altered by taxifolin treatment in the liver and serum, respectively, mainly including glycerophosphoglycerols, glycerophosphocholines, glycerophosphoethanolamines, and linoleic acids and derivatives. Our findings help to provide novel insights into the mechanism of the hepatoprotective effect of taxifolin from a lipidomics approach.

Trans-chalcone ameliorates CCl4-induced acute liver injury by suppressing endoplasmic reticulum stress, oxidative stress and inflammation

BackgroundAcute liver injury serves as a crucial marker for detecting liver damage due to toxic, viral, metabolic, and autoimmune exposures. Due to the response to adverse external stimuli and various cellular homeostasis, Endoplasmic reticulum stress (ERS), Oxidative stress, and Inflammation have great potential for treating liver injury. Trans-chalcones (TC) is a polyphenolic compound derived from a natural plant with anti-oxidative and anti-inflammatory abilities. Here, TC was aimed to attenuate liver injury by triggering ER stress, oxidative stress, inflammation, and apoptosis. A single dose of carbon tetrachloride (CCl4) 1 mL/kg was administered intraperitoneally into C57BL6 mice to construct an in vivo NAFLD model, whereas AML12 cells were treated with lipopolysaccharides (LPS) to construct an in vitro NAFLD model. The mice used in the experiment were randomly assigned to two groups: a 12-hour set and a 24-hour set. Forty-nine mice were randomly divided into seven groups, the control group (Group I), TC group (Group II) 10 mg/kg TC, negative control group (Group III) CCl4, TC + CCl4 groups (Groups IV−VI), mice were subcutaneously treated with (5, 10, and 20) mg/kg of TC for three consecutive days before the CCl4 injection and the positive control group (Group VII) received 10 mg/kg Silymarin. After the experiment, serum transaminase, liver histological pathology, hepatic expression levels ERS, oxidative stress, and inflammation-related markers were assessed. TC pre-treatment significantly alleviates the expression of ER stress, oxidative stress, inflammatory cytokines, and apoptosis in both in vivo and in vitro models of liver injury. TC treatment significantly reduced serum transaminase levels (ALT and AST), and improved liver histopathological scores. TC administration also led to a reduction in MDA levels and the suppression of ROS generated by CCl4 in hepatic tissue, which contributed to an increase in GSH levels. The protective effect of TC on the liver injury mouse model was achieved by inhibiting hepatocyte apoptosis. Moreover, TC pre-treatment dramatically decreased the protein levels of ER stress indicators such as CHOP, Bip, Ero-Lα, IRE1α, PERK, Calnexin, and PDI when compared to the CCl4-only treated group. TC exerts hepatoprotective effects against CCl4-induced acute liver injuries in mice by modulating ERS, oxidative stress, and inflammation. These results suggest that TC pre-treatment at a dose of (20 mg/kg BW) was as effective as silymarin (10 mg/kg) in preventing CCl4-induced acute liver injury. Further investigations are necessary to elucidate the precise molecular mechanisms underlying the hepatoprotective effects of TC and to explore its therapeutic potential in clinical trials.

Effects of licorice root (Glycyrrhiza glabra) extract on the livers of obese rats.

We have investigated anti-obesity effects of the extract of licorice (Glycyrrhiza glabra) root in rats with diet-induced obesity and hyperlipidemia by using histopathological and biochemical methods. Thirty-two Wistar albino rats were divided to four groups of eight: normal control (C), high fat diet (HFD), high fat Diet + Glycyrrhiza glabra (HFD+M), and normal diet with Glycyrrhiza glabra (M). The high fat diet contained 300 g/kg fat (4000 kcal/kg); the daily dosage of Glycyrrhiza glabra extract was 1g/kg body weight by orogastric gavage. Supplementation of Glycyrrhiza glabra extract dramatically reduced increases in body weight caused by the induction of obesity. A hepatoprotective effect of Glycyrrhiza glabra extract was supported by the almost normal histology in the livers of the HFD+M rats, in contrast to the degenerative changes in the HFD rats, which included macrovesicular and microvesicular fat deposits, hydropic degeneration, dilatation of sinusoids and coagulation necrosis of some hepatocytes. Serum levels of alanine transaminase (ALT), aspartic transaminase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), cholesterol (HDL and LDL) and triglycerides, were ameliorated by Glycyrrhiza glabra extract treatment. We conclude that Glycyrrhiza glabra extract given together with HFD could prevent obesity and reduce liver damage in rats.

Flaxseed Oil Alleviates PFOS-Induced Liver Injury by Regulating Hepatic Cholesterol Metabolism.

Perfluorooctanesulfonate (PFOS) is a widespread, persistent environmental pollutant that exerts apparent liver toxicity. Flaxseed oil (FO), a dietary oil rich in α-linolenic acid, has been demonstrated to possess a diverse array of health benefits. However, whether FO protects against PFOS-induced liver injury and its underlying mechanisms remain unclear. C57/BL6 mice were orally treated with different concentrations of FO alone or in combination with 10 mg/kg of PFOS for 28 consecutive days. Blood and liver tissues were collected for proteomic, histopathological, biochemical, immunohistochemical, and molecular examinations. Results demonstrated that FO supplementation reduced PFOS-induced liver injury, as evidenced by a decrease in histopathological changes, serum transaminase (ALT and AST) levels, levels of oxidative stress, and inflammatory cytokine (TNF-α, IL-1β, and IL-6) levels. Proteomic analyses showed that differentially expressed proteins were enriched in cholesterol metabolic pathways when comparing the PFOS group to the FO supplementation groups. The expression of cholesterol metabolism-related proteins was also subsequently measured, revealing that FO supplementation decreased the protein expressions of SREBP2, HMGCR, and LDLR while increasing the expression of CYP7A1. This study demonstrates that FO can alleviate PFOS-induced hepatotoxicity by regulating hepatic cholesterol metabolism, indicating that FO may serve as an effective dietary intervention for preventing liver injury caused by PFOS.

Prognosis of Acute HEV Infection in Patients With Liver Cirrhosis: A Retrospective Study of 628 Chinese Patients.

Acute hepatitis E virus infection is a serious global health problem, which a significant cause of morbidity and mortality. The aim of the present study was to characterise the clinical features and therapeutic response of patients with acute HEV infection and identify risk factors for poor prognosis. In a retrospective study from 01 January 2014 to 01 Januray 2022, we collected baseline data from all patients eligible for acute hepatitis E virus (HEV) infection and followed up with all patients via interviews and medical records. We explored the clinical feature of Chinese patients with acute HEV infection. The follow-up data of patients were used to identify risk factors for poor prognosis. In total, 628 acute hepatitis E (AHE) patients fulfilled the inclusion criteria and did not meet the exclusion criteria. Among them, 452 were males and 176 were females (M:F = 2.57:1). The median age at diagnosis was 57.0 years (interquartile range: 46-64 years). The median baseline serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) were elevated in this cohort (642.3 U/L, 216.2 U/L, 104.1 μmol/L, respectively). The median hospitalisation duration was 16 days. Compared with patients without other liver diseases, patients with liver cirrhosis show lower baseline ALT and AST level, poorer coagulation indices and higher MELD scores. According to multivariate analysis, liver cirrhosis, high MELD score, low albumin concentration was found to be independent predictors of poor prognosis in patients with AHE. Our study used a lager sample size to validate that some demographic and serological features were quite different between patients with/without CLDs. Liver cirrhosis was a significant independent predictor of poor prognosis in acute HEV hepatitis.

Evaluation of the therapeutic potential of novel nanoparticle formulations of glutathione and virgin coconut oil in an experimental model of carbon tetrachloride-induced liver failure.

Acute liver failure (ALF) is a critical condition characterized by rapid liver dysfunction, leading to high mortality rates. Current treatments are limited, primarily supportive, and often require liver transplantation. This study investigates the potential of a novel nanoparticle formulation of glutathione (GSH) and virgin coconut oil (VCO) alone and in combination to enhance therapeutic outcomes in a rat model of ALF induced by orogastric carbon tetrachloride (CCl4). The study employed adult male Albino rats divided into ten groups, with ALF induced via a single oral dose of CCl4. Various treatment regimens were administered over seven days, including conventional and nanoparticle forms of GSH and VCO and their combinations. The efficacy of treatments was evaluated through biochemical analysis of liver function markers, oxidative stress indicators, inflammatory biomarkers, and histopathological examinations. Nanoparticles were synthesized using established methods, and characterization techniques were employed to ensure their quality and properties. The nanoparticle formulations significantly improved liver function, as indicated by reduced serum levels of alanine aminotransferase and aspartate aminotransferase, alongside decreased oxidative stress markers such as malondialdehyde. Furthermore, they reduced tumor necrosis factor alpha and interleukin-1 beta inflammatory markers. Histological analysis revealed reduced hepatocellular necrosis and inflammation in treated groups compared to controls. Also, decreased nuclear factor-kappa B was detected by immunohistochemical analysis. The findings show that the nanoparticle mixture of GSH and VCO effectively reduces liver damage in ALF. This suggests a promising drug-based approach for improving liver regeneration and protection. This innovative strategy may pave the way for new therapeutic interventions in the management of ALF.

The Effect of Cinnamomum Burmanii Ethanol Extract on Isoniazid-induced Serum Levels of Serum Glutamate Piruvate Transaminase (SGPT) Wistar Strain Male Rats

Hepatotoxicity can be caused by excessive drug use, triggered by increased oxidative stress which is considered as the initial mechanism of Drug Induced Liver Injury (DILI). One of the causes of DILI is Isoniazid. One of the plants acting as a hepatoprotector in protecting liver cells is cinnamon (Cinamommum burmanii). This study aims to determine the effect of 96% ethanolic cinnamon extract as a hepatoprotector against an increase in Alanine Transaminase (ALT) levels induced by isoniazid. The parameters used to assess liver damage were rat plasma ALT. The sample used in this study was rat plasma, which was taken through the retro orbital sinus. This research is an experimental study with a sample of 25 experimental animals divided into five groups, namely negative control (K1), positive control l (K2), and experimental group with cinnamon ethanolic extract at a dose of 100 mg/kgbw (K3), 200 mg/kgbw(K4), and 400 mg/kgbw(K5). The research used a post-test-only control group design. The results were analyzed using the One-way ANOVA test followed by the post hoc Tukey test. The results proved that cinnamon ethanolic extract at doses of 100 mg/kgbw (P = 0.029), 200 mg/kgbw (P = 0.001), and 400 mg/kgbw (P = 0.000) was effective in reducing plasma SGPT levels in isoniazid-induced rats when compared with the positive control group (K2). The most effective dose was at 200 mg/kgbw (K4). Thus, this proves that all of the doses in experimental groups have a hepatoprotective effect against isoniazid-induced liver damage. Keywords: Alanine Transaminase (ALT), cinnamon ethanol extract, Drug Induced Liver Injury (DILI), isoniazid

E3 Ubiquitin Ligase Smurf1 Regulates the Inflammatory Response in Macrophages and Attenuates Hepatic Damage during Betacoronavirus Infection.

The E3 ubiquitin ligase Smurf1 catalyzes the ubiquitination and proteasomal degradation of several protein substrates related to inflammatory responses and antiviral signaling. This study investigated the role of Smurf1 in modulating inflammation induced by Betacoronavirus infection. Bone marrow-derived macrophages (BMDMs) from C57BL/6 (wild-type) or Smurf1-deficient (Smurf1-/-) mice were infected with MHV-A59 to evaluate the inflammatory response in vitro. Smurf1 was found to be required to downregulate the macrophage production of pro-inflammatory mediators, including TNF, and CXCL1; to control viral release from infected cells; and to increase cell viability. To assess the impact of Smurf 1 in vivo, we evaluated the infection of mice with MHV-A59 through the intranasal route. Smurf1-/- mice infected with a lethal inoculum of MHV-A59 succumbed earlier to infection. Intranasal inoculation with a 10-fold lower dose of MHV-A59 resulted in hematological parameter alterations in Smurf1-/- mice suggestive of exacerbated systemic inflammation. In the lung parenchyma, Smurf1 expression was essential to promote viral clearance, downregulating IFN-β mRNA and controlling the inflammatory profile of macrophages and neutrophils. Conversely, Smurf1 did not affect IFN-β mRNA regulation in the liver, but it was required to increase TNF and iNOS expression in neutrophils and decrease TNF expression in macrophages. In addition, Smurf1-/- mice exhibited augmented liver injuries, accompanied by high serum levels of alanine aminotransferase (ALT). These findings suggest that Smurf1 plays a critical role in regulating the inflammatory response in macrophages and attenuating systemic inflammation during Betacoronavirus infection.

Quercetin Promotes the M1-to-M2 Macrophage Phenotypic Switch During Liver Fibrosis Treatment by Modulating the JAK2/STAT3 Signaling Pathway.

To investigate the underlying mechanism by which quercetin (Que) regulates macrophage polarization and its subsequent therapeutic effect on liver fibrosis, an important pathological precondition for hepatocellular carcinoma (HCC). In vitro experiments were performed on the RAW264.7 mouse macrophage line. After the induction of M1-type macrophages with LPS, the effects of Que on cell morphology, M1/M2 surface marker expression, cytokine expression, and JAK2/STAT3 expression were analyzed. In vivo, male SD rats were used as a model of CCL4-induced hepatic fibrosis, and the effects of Que on serum aminotransferase levels, the histopathological structure of liver tissues, and macrophage-associated protein expression in liver tissues were analyzed. In vitro experiments revealed that Que can suppress the activation of the JAK2/STAT3 signaling pathway, leading to decreases in the expression of M1 macrophage surface markers and cytokines. Additionally, Que was found to increase the expression of M2 macrophage surface markers and cytokines. In vivo, assays demonstrated that Que significantly ameliorated the development of inflammation and fibrosis in a rat liver fibrosis model. Que can inhibit hepatic fibrosis by promoting M1 to M2 macrophage polarization, which could be associated with its ability to suppress the JAK2/STAT3 signaling pathway in macrophages.

Hepatocyte activation and liver injury following cerebral ischemia promote HMGB1-mediated hepcidin upregulation in hepatocytes and regulation of systemic iron levels.

We previously reported that high mobility group box 1 (HMGB1), a danger-associated molecular pattern (DAMP), increases intracellular iron levels in the postischemic brain by upregulating hepcidin, a key regulator of iron homeostasis, triggering ferroptosis. Since hepatocytes are the primary cells that produce hepcidin and control systemic iron levels, we investigated whether cerebral ischemia induces hepcidin upregulation in hepatocytes. Following middle cerebral artery occlusion (MCAO) in a rodent model, significant liver injury was observed. This injury was evidenced by significantly elevated Eckhoff's scores and increased serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Additionally, total iron levels were significantly elevated in the liver, with intracellular iron accumulation detected in hepatocytes. Hepcidin expression in the liver, which is primarily localized in hepatocytes, increased significantly starting at 3 h after MCAO and continued to increase rapidly, reaching a peak at 24 h. Interestingly, HMGB1 levels in the liver were also significantly elevated after MCAO, with the disulfide form of HMGB1 being the major subtype. In vitro experiments using AML12 hepatocytes showed that recombinant disulfide HMGB1 significantly upregulated hepcidin expression in a Toll-like receptor 4 (TLR4)- and RAGE-dependent manner. Furthermore, treatment with a ROS scavenger and a peptide HMGB1 antagonist revealed that both ROS generation and HMGB1 induction contributed to hepatocyte activation and liver damage following MCAO-reperfusion. In conclusion, this study revealed that cerebral ischemia triggers hepatocyte activation and liver injury. HMGB1 potently induces hepcidin not only in the brain but also in the liver, thereby influencing systemic iron homeostasis following ischemic stroke.

3D printing incorporating gold nanozymes with mesenchymal stem cell-derived hepatic spheroids for acute liver failure treatment

Acute liver failure (ALF) is a highly fatal disease, necessitating the advancement and optimization of alternative therapeutic strategies to benefit patients awaiting liver transplantation. In this study, we innovatively established the antioxidant nanozyme-hepatocyte-like cells (HLCs) microtissue sheets (HS/N–Au@composite) for ALF therapy. We first prepared a 3D-printed hyaluronic acid/gelatin/sodium alginate scaffold with N-acetylcysteine (NAC)-capped gold nanoclusters (NAC-Au NCs), forming the N–Au@hydrogel. For the encapsulation of HLC spheroids, we used a biocompatible hybrid hydrogel composed of decellularized extracellular matrix (dECM), thrombin, and fibrinogen, resulting in the HS@dECM hydrogel. Utilizing 3D printing technology, we integrated the N–Au@hydrogel with the HS@dECM hydrogel to create the HS/N–Au@composite for in situ transplantation to treat ALF. Our results demonstrated that NAC-Au NCs effectively mitigated reactive oxygen species (ROS)-induced liver necrosis in ALF. Additionally, the N–Au@hydrogel provided mechanical support, ensuring the proper landing and effective functioning of the transplanted HLC spheroids. The HS/N–Au@composite synergistically decreased serum transaminase levels, reduced the accumulation of pro-inflammatory cytokines, accelerated liver function recovery, and promoted liver regeneration in ALF treatment. This combination of HLC spheroids and NAC-Au NCs nanozymes via 3D-printed composite scaffolds represents a promising strategy for enhancing hepatocyte transplantation and advancing stem cell regenerative medicine in ALF therapy.

Effect of Incorporating Soursop (Annona muricata) Leaves Powder on Reproductive Performance of Japanese Quail (Coturnix coturnix japonica)

Introduction: Soursop leaves are rich in various molecules, including total phenols, terpenes, and steroids, which possess a range of pharmacological properties that can be utilized in animal production to enhance both growth and reproduction of animals. The present study aimed to evaluate the effect of incorporating soursop (Annona muricata; A. muricata) leaves powder into feed on the reproductive performance of Japanese quail. Materials and methods: A total of 80 Japanese quails (64 females and 16 males) aged two weeks were randomly divided into four experimental groups, labeled T0, T1, T2, and T3, and received feed additives with 0 mg/kg body weight (bw), 250 mg/kg bw, 500 mg/kg bw, and 750 mg/kg bw of powdered soursop leaves, respectively. Additionally, water was provided ad libitum, and the quails' weights were measured every 7 days for a period of 75 days. At the end of the period, 12 female quails from each group were sacrificed after 24 hours fasting period. Blood was collected for hematological (Leukocyte, Erythrocyte, and Platelet indices) and serum biochemical (total serum cholesterol, total proteins, albumin, and globulin, Aspartate aminotransferase, Alanine aminotransferase, Urea, and Creatinine) analysis. The males were also sacrificed to evaluate the spermatozoa characteristics (mobility, concentration, and viability). Results: No statistical significant changes in growth characteristics or hematological parameters were observed. However, biochemical parameters increased significantly with the inclusion of Soursop (A. muricate) in quail feed, including increased total cholesterol, total protein, and globulin levels, and decreased malondialdehyde levels. This effect was most significant at dosage of 500 mg/kg bw. Serum levels of urea, Alanine aminotransferase, and Aspartate aminotransferase were not significantly affected by A. muricata whatever the concentration considered. A significant increase in fast progressive spermatozoa, along with a decrease in immotile spermatozoa, was observed with A. muricate at dosage of 500 mg/kg bw compared to the control. Sperm viability also increased significantly, particularly in live at dosage of 500 mg/kg bw. Significant increase was observed in fertility parameters, including increased fertility rate, hatchability rate of fertile eggs, total hatchability rate, and chick weight, along with decreased embryonic mortality at 500 mg/kg bw treatment compared to the control. Conclusion: In conclusion, the findings indicated that incorporating A. muricata leaf powder at 500 mg/kg bw into quail feed positively influences reproductive cells and boosts fertility growth promoters.

Pentagalloylglucose alleviates acetaminophen-induced acute liver injury by modulating inflammation via cGAS-STING pathway

BackgroundThe cGAS-STING pathway is an important component of the innate immune system and plays significant role in acetaminophen-induced liver injury (AILI). Pentagalloylglucose (PGG) is a natural polyphenolic compound with various beneficial effects, including anti-cancer, antioxidant, anti-inflammatory, and liver-protective properties; however, whether it can be used for the treatment of AILI and the specific mechanism remain unclear.Materials and methodsA cell culture model was created to study the effect of PGG on cGAS-STING pathway activation using various techniques including western blotting (WB), real-time quantitative polymerase chain reaction (RT-qPCR), immunofluorescence (IF), and immunoprecipitation (IP). The effect of PGG was investigated in vivo by establishing a dimethylxanthenone acetic acid (DMXAA)-mediated activation model. An AILI model was used to evaluate the hepatoprotective and therapeutic effects of PGG by detecting liver function indicators, liver histopathology, and cGAS-STING pathway-related indicators in mice with AILI.ResultsPGG blocked cGAS-STING pathway activation in bone marrow-derived macrophages (BMDMs), THP-1 cells, and peripheral blood mononuclear cells (PBMCs) in vitro. Furthermore, PGG inhibited the generation of type I interferons (IFN-I) and the secretion of inflammatory factors in DMXAA-induced in vivo experiments. In addition, PGG also reduced serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP), improved liver tissue damage and apoptosis, and inhibited the cGAS-STING pathway activation caused by acetaminophen. In terms of the mechanism, PGG disrupted the connection between STING and TBK1.ConclusionsPGG exerts a protective effect against AILI by blocking the cGAS-STING pathway, offering a promising treatment strategy.

Beneficial effects of extravascular lung water index-guided volum management in patients with cardiogenic shock

Objective: To evaluate the role of volume management guided by extravascular lung water index(EVLWI) in improving the clinical outcomes and cardiac function for patients with cardiogenic shock. Methods: This study was a single-center, prospective cohort study. Patients with cardiogenic shock admitted to the Department of Cardiovascular Medicine, Shanghai East Hospital from July 2022 to December 2023 were enrolled. Patients were matched 1∶1 by propensity score and divided into EVLWI group and control group. In the control group, the volume management strategy was determined by the attending physician based mainly on conventional factors, including clinical features, biochemical assessments, and certain blood pressure measurements. In EVLWI group, the volume management plan was formulated by integrating conventional factors with EVLWI derived from pulse index continuous cardiac output (PiCCO) monitoring. Baseline clinical data, in-hospital treatment, and hemodynamic data were collected. Major adverse cardiovascular events and cardiac function related parameters were compared at 30 d after treatment between the two groups. Baseline EVLWI levels were compared between the non-survivors and the survivors in the EVLWI group. The receiver operating characteristic curve was plotted to assess the accuracy of baseline EVLWI and central venous pressure in predicting all-cause mortality at 30 d after treatment in patients with cardiogenic shock, and subgroup analysis was performed according to ischemic/non-ischemic etiology and with/without use of inotropic drugs. Kaplan-Meier curve was used for survival analysis, with log-rank tests comparing all-cause mortality, cardiac death, and readmission rate for heart failure at 30 d after treatment. Results: A total of 200 patients with cardiogenic shock were enrolled, aged (71.35±12.82) years, 144(72%) males, EVLWI group and control group 100 patients each. Compared with the control group, EVLWI group had lower all-cause mortality (16%(16/100) vs. 42%(42/100), log-rank P<0.01), cardiac death (14%(14/100) vs. 34%(34/100), log-rank P<0.01), and readmission rate for heart failure (4%(4/100) vs. 12%(12/100), log-rank P=0.03) at 30 d after treatment. Subgroup analysis showed that EVLWI-guided volume management was associated with lower all-cause mortality at 30 d after treatment in patients with cardiogenic shock of ischemic or non-ischemic etiology and with or without inotropic drugs (all P<0.05). In EVLWI group, baseline EVLWI levels were higher in non-survivors than those in survivors [(15.99±6.47) ml/kg vs.(9.75±2.55) ml/kg, P<0.01]. The baseline EVLWI could predicting all-cause mortality at 30 d after treatment in patients with cardiogenic shock, with an area under the receiver operating characteristic curve of 0.84 (95%CI: 0.75-0.94, P<0.01), while the baseline central venous pressure had no predicting value (AUC=0.54, 95%CI: 0.40-0.69, P=0.60). The optimal cutoff value of EVLWI in pridicting all-cause mortality at 30 d after treatment in patients with cardiogenic shock was >10.3 ml/kg. With the optimization of hemodynamic parameters, left ventricular ejection fraction was improved in EVLWI group, and serum levels of N-terminal pro-brain natriuretic peptide, creatinine, alanine aminotransferase and lactic acid were decreased (all P<0.05). Conclusion: EVLWI-guided volume management exerts a beneficial effect on therapeutic decision-making and improves clinical outcomes and cardiac function in patients with cardiogenic shock.

Phase Preparation of Xiao-chai-hu Decoction and its Pharmacodynamics of Acute Liver Injury.

Self-emulsifying nano-phase of traditional Chinese medicine are a research hotspot. Xiao-Chai-Hu decoction is a commonly used compound decoction in clinical practice, which is of great research significance. The aim of this study was to isolate and characterize the self-emulsifying nano-phase and other phases of Xiao-Chai-Hu decoction, and to study the effects of each phase on acute liver injury. The liquid medicine was prepared employing centrifugation followed by dialysis. Single- factor investigation methodology was utilized to optimize the preparation parameters for both phases. Characterization of the formulated phase involved analyses such as surface morphology assessment, measurement of nanoparticle size and Zeta potential using an analyzer, observation of the Tyndall effect, conducting diffusion and dilution tests, examination under a microscope, and structural visualization via transmission electron microscopy (TEM). Furthermore, an acute liver injury model was established in rats through intraperitoneal injection of D-Galactosamine (D-Gal- N). To assess hepatic function and oxidative stress status, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), superoxide dismutase (SOD) activity, and malondialdehyde (MDA) content in liver tissue were quantified. The liver coefficients for each group were calculated as an additional parameter. For histopathological evaluation, liver tissue sections from the experimental group were stained with Hematoxylin and Eosin (H&E) and examined microscopically under light conditions. These revisions aim to enhance clarity, correct minor grammatical errors (such as capitalization of "HE" to "H&E"), and ensure a smoother flow of information without altering the scientific content of your original text. Successful establishment and separation of four distinct phases were achieved, including the self-emulsifying nano-phase, precipitation phase, suspension phase, and true solution phase. The self-emulsifying nano-phase was characterized as spherical particles with an average diameter of approximately 100 nm. Pharmacodynamic assessments revealed that both Xiao-Chai-Hu decoction and its self-emulsifying nano-phase significantly reduced liver coefficients and alanine aminotransferase (ALT) levels compared to controls (P<0.05). However, no statistically significant differences were observed in regards to aspartate aminotransferase (AST) concentrations, malondialdehyde (MDA) content, or superoxide dismutase (SOD) activity between the treatment groups and control (P>0.05). These findings indicate that both Xiao-Chai-Hu decoction and its self-emulsifying nano-formulation ameliorated D-GalN-induced acute liver injury, albeit without statistically distinguishable efficacy between them (P>0.05). The presence of a self-emulsifying nano-phase within Xiao-Chai-Hu decoction is confirmed, and this nano-phase emerges as a therapeutically efficacious component in mitigating acute liver injury.

Corynoline alleviates hepatic ischemia-reperfusion injury by inhibiting NLRP3 inflammasome activation through enhancing Nrf2/HO-1 signaling.

Corynoline has displayed pharmacological effects in reducing oxidative stress and inflammatory responses in many disorders. However, its effects on hepatic ischemia-reperfusion (I/R) injury remain unclear. This study aimed to investigate the protective effects of corynoline against hepatic I/R injury and the underlying mechanisms. Rat models with hepatic I/R injury and BRL-3A cell models with hypoxia/reoxygenation (H/R) insult were constructed. Models were pretreated with corynoline and/or other inhibitors for functional and mechanistic examination. Corynoline pretreatment effectively mitigated hepatic I/R injury verified by reduced serum transaminase levels, improved histological damage scores, and decreased apoptosis rates. Additionally, corynoline pretreatment significantly inhibited I/R-triggered oxidative stress and inflammatory responses, as indicated by enhanced mitochondrial function, reduced levels of ROS and MDA, reduced neutrophil infiltration and suppressed proinflammatory cytokine release. In vitro experiments further showed that corynoline pretreatment increased cellular viability, decreased LDH activity, reduced cellular apoptosis, and inhibited oxidative stress and inflammatory injury in H/R-induced BRL-3A cells. Mechanistically, corynoline significantly increased Nrf2 nuclear translocation and expression levels of its target gene, HO-1. It also blocked NLRP3 inflammasome activation both in vivo and in vitro. Furthermore, pretreatment with Nrf2 inhibitor ML-385 counteracted the protective effect of corynoline on hepatic I/R injury. Ultimately, in vitro studies revealed that the NLRP3 activator nigericin could also nullified the protective effects of corynoline in BRL-3A cells, but had minimal impact on Nrf2 nuclear translocation. Corynoline can exert protective effects against hepatic I/R injury by inhibiting oxidative stress, inflammatory responses, and apoptosis. These effects may be associated with inhibiting ROS-induced NLRP3 inflammasome activation by enhancing Nrf2/HO-1 signaling. These data provide new understanding about the mechanism of corynoline action, suggesting it is a potential drug applied for the treatment and prevention of hepatic I/R injury.

Dual-factor model of sleep and diet: a new approach to understanding central fatigue.

Numerous studies have recently examined the impact of dietary factors such as high-fat diets on fatigue. Our study aims to investigate whether high-fat diet (HFD) alone or combined with alternate-day fasting (ADF) can lead to the central fatigue symptoms and to investigate the potential integration of dietary and sleep variables in the development of central fatigue models. Seventy-five male Wistar rats were divided into five groups: control, HFD, HFD + ADF, modified multiple platform method (MMPM), and MMPM+HFD + ADF. Each group underwent a 21-day modeling period according to their respective protocol. Their behavioral characteristics, fatigue biochemical markers, hippocampal pathological changes, mitochondrial ultrastructure, and oxidative stress damage were analyzed. Our findings demonstrate that using only HFD did not cause central fatigue, but combining it with ADF did. This combination led to reduced exercise endurance, decreased locomotor activity, impaired learning and memory abilities, along with alterations in serum levels of alanine aminotransferase (ALT), creatine kinase (CK), and lactate (LAC), as well as hippocampal pathological damage and other central fatigue symptoms. Moreover, the MMPM+HFD + ADF method led to the most obvious central fatigue symptoms in rats, including a variety of behavioral changes, alterations in fatigue-related biochemical metabolic markers, prominent pathological changes in hippocampal tissue, severe damage to the ultrastructure of mitochondria in hippocampal regions, changes in neurotransmitters, and evident oxidative stress damage. Additionally, it was observed that rats subjected to HFD + ADF, MMPM, and MMPM+HFD + ADF modeling method exhibited significant brain oxidative stress damage. We have demonstrated the promotive role of dietary factors in the development of central fatigue and have successfully established a more stable and clinically relevant animal model of central fatigue by integrating dietary and sleep factors.

Study on the mechanism of Shenling Baizhu powder on the pathogenesis of pregnancy complicated with non-alcoholic fatty liver, based on PI3K/AKT/mTOR signal pathway.

This study investigates the effectiveness of Shenlin Baizhu powder in managing non-alcoholic fatty liver disease (NAFLD) during pregnancy and its mechanism through the PI3K/AKT/mTOR signaling pathway. Eight healthy male and 24 female Sprague-Dawley rats were used. After acclimatization, 6 female rats were fed normal chow, and 18 female rats were fed high-fat chow to induce NAFLD. After 8 weeks, female rats were mated with males to create a pregnant NAFLD model. The rats were divided into four groups: normal feeding, high-fat diet with saline, high-fat diet with 1.6 g/kg Shenlin Baizhu powder, and high-fat diet with 4.8 g/kg Shenlin Baizhu powder. Maternal body weight, serum and liver levels of aspartate aminotransferase (AST), alanine transaminase (ALT), triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), related inflammatory indexes interleukin-1 β (IL-1 β), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were measured. Liver tissue was examined using hematoxylin and oil red O staining, and protein expression related to the PI3K/AKT/mTOR pathway was assessed via Western blotting, immunohistochemistry and RT-PCR. Results showed significant weight gain and increases in ALT, AST, TG, TC, LDL-C, IL-1β, TNF-α, and IL-6, along with decreased HDL-C in NAFLD rats compared to controls. The high and low-dose Shenlin Baizhu powder groups exhibited improvements in body weight, liver histopathology, and reductions in serum TG, TC, LDL-C, ALT, AST, IL-1β, TNF-α, and IL-6, with increased HDL-C levels. Notably, the high-dose group showed greater efficacy in reducing hepatic fat accumulation, liver function markers, blood lipids, and inflammatory indexes, and decreased expression of hepatic PPARγ mRNA, SREBP1 mRNA, AKT mRNA, and related proteins. Shenlin Baizhu powder demonstrates potential in ameliorating high-fat diet-induced NAFLD in pregnant rats, likely through modulation of the PI3K/AKT/mTOR pathway, suggesting its therapeutic potential for gestational NAFLD.

Saffron (Crocus Sativus Linnaeus) based protection against Aflatoxin B1 induced organ damage in rats

Saffron is well-known for its anti-apoptotic, anti-inflammatory, and antioxidant properties. Saffron's nutritional and medicinal properties support its numerous uses as a flavouring and herbal remedy. This study investigated the protective efficacy of saffron administration against aflatoxin B1 (AFB1)-induced toxicity in adult male Wistar albino rats during an experimental period of 21 days. Aflatoxin B1 (AFB1) is a common mycotoxin of soils and foodstuffs. Thirty-two rats were divided into four groups (Control group, AFB1 group, Saffron group, and AFB1+ Saffron group), and their body weights were measured on days 1, 7, 14, and 21. Blood samples were collected on the 21st day for haematological and biochemical studies (testosterone, kidney and liver function tests, and oxidative stress markers). Tissue samples from testes, liver, and kidney were subjected to histological examinations. The results depicted a significant decrease in the body weights after 7, 14, and 21 days of Saffron, AFB1, and AFB1+ Saffron treatments in comparison to control. Haematological investigations showed that basophils, platelets, monocytes, lymphocytes, and eosinophils greatly increased compared to the control group, whereas neutrophils and eosinophils dramatically decreased. There was a significant rise in the serum levels of uric acid, creatinine, aspartate transaminase, alkaline phosphatase, nitric oxide, and malondialdehyde. Contrarily, testosterone levels notably reduced in AFB1-administered rats as compared to controls. AFB1 group exhibited several histological modifications in testes, liver, and kidney tissues. Oxidative stress biomarkers, testosterone, kidney and liver functions, and haematological parameters of the AFB1+ Saffron group remained similar to the control group. Kidney and liver tissues of Saffron-treated rats also displayed normal structure similar to the control group, which confirmed its protective efficacy against AFB1-induced toxicity. Saffron's bioactive components and antioxidant and pharmacological properties might have contributed to its promising anti-AFB1-toxicity potential.