Serum AST Levels Research Articles

Silybin mitigated liver and brain damage after difenoconazole exposure: Crosstalk between oxidative stress, inflammation, ferroptosis and apoptosis

Long-term residue of difenoconazole (DFZ) in the environment caused multiple organ damage to aquatic organisms. Due to the potential hepatoprotective and neuroprotective properties of silybin (SIL), we hypothesized that SIL could alleviate growth inhibition, liver, and brain damage in carp induced by DFZ exposure. The in vivo experiments were divided into the Control group, the SIL group, the DFZ group and the DFZ + SIL group. The exposure concentration of DFZ was 0.39 mg/L, and the therapeutic dose of SIL was 400 mg/kg. The whole experiment lasted for 30 days. SIL was also found to reduce hepatic injury and lipid metabolism based on H&E staining, oil red O staining, and measurement of serum and liver tissue levels of ALT, AST, LDH, TG, and TC. Similarly, SIL reduced brain damage after DFZ exposure, according to H&E staining and detection transcription level of the ZO-1, ZO-2, occludin, and Claudin7 in carp brain. In terms of mechanism, the results showed that SIL inhibited the excessive production of ROS in liver and brain tissues, increased the activity of antioxidant enzymes (T-AOC, SOD, CAT) and resist oxidative stress. Also, SIL promoted the production of anti-inflammatory factors (TGF-β1 and IL-10) and inhibited the expression of pro-inflammatory factors (TNF-α and IL-6) to reduce the inflammatory response in liver and brain tissues caused by DFZ. ln terms of ferroptosis, by lowering iron levels, upregulating ferroptosis-related genes (GPX4, SIC7A11, GCLC), and downregulating the expression of NCOA4, STEAP3, COX2, and P53, SIL was able to inhibit ferroptosis of liver and brain tissues of carp. In addition, SIL restored the reduced mitochondrial membrane potential (MMP) level and inhibited apoptosis as measured by MMP level detection, TUNEL staining, and apoptosis gene transcript levels. In this study, we analyzed the interactions between genes and proteins associated with oxidative stress, inflammation, ferroptosis and apoptosis using the String database and ranked the nodes in the network using the Cytoscape plugin Cytohubba, and found that P53, Caspase3, TNF-α, IL-6 and Bcl-2 were the key hub genes. Our study not only revealed the multiple pharmacological activities of SIL, but also provided a reference for the prevention and reduction pesticide hazards to aquatic organisms.

Integrated transcriptomics and histopathology approach identifies a subset of rejected donor livers with potential suitability for transplantation

BackgroundLiver transplantation is an effective treatment for liver failure. There is a large unmet demand, even as not all donated livers are transplanted. The clinical selection criteria for donor livers based on histopathological evaluation and liver function tests are variable. We integrated transcriptomics and histopathology to characterize donor liver biopsies obtained at the time of organ recovery. We performed RNA sequencing as well as manual and artificial intelligence-based histopathology (10 accepted and 21 rejected for transplantation).ResultsWe identified two transcriptomically distinct rejected subsets (termed rejected-1 and rejected-2), where rejected-2 exhibited a near-complete transcriptomic overlap with the accepted livers, suggesting acceptability from a molecular standpoint. Liver metabolic functional genes were similarly upregulated, and extracellular matrix genes were similarly downregulated in the accepted and rejected-2 groups compared to rejected-1. The transcriptomic pattern of the rejected-2 subset was enriched for a gene expression signature of graft success post-transplantation. Serum AST, ALT, and total bilirubin levels showed similar overlapping patterns. Additional histopathological filtering identified cases with borderline scores and extensive molecular overlap with accepted donor livers.ConclusionsOur integrated approach identified a subset of rejected donor livers that are likely suitable for transplantation, demonstrating the potential to expand the pool of transplantable livers.

Phenotypic and Therapeutic Evaluation of Humanized C3 Transgenic Mice as a Model for C3 glomerulopathy-Like Autoimmune Disease

Abstract C3 glomerulopathy (C3G) encompasses a range of kidney disorders with autoimmune and genetic origins, where dysregulated alternative pathway (AP) complement activation stands as the underlying cause. This study develops a transgenic mouse strain that overexpresses human C3, thereby spontaneously generating a rapidly progressing and severe murine model of C3G. The C3G phenotype observed in humanized C3 transgenic mice may arise from a dysregulated interaction between human C3 protein and various mouse complement proteins, resulting in uncontrolled C3 activation via the AP. Male humanized C3 transgenic mice exhibit increased morbidity early in life. Proteinuria initiates at 4 weeks of age, accompanied by an elevation in the albumin/creatinine ratio. Significantly increased serum levels of ALT, AST, ALP, LDH, and CK in humanized C3 transgenic male mice compared to wild-type mice indicate liver and heart injuries. Moreover, serum T-CHOL and HDL levels are significantly reduced, suggesting anemia and malnutrition. Pathohistological analysis of the kidney reveals various renal lesions. Oral administration of Lnp023, a small-molecule inhibitor of complement factor B, effectively increases body weight and serum hC3 levels, improves anemia, and preserves liver, heart, and renal function. In conclusion, this novel model contributes significantly to unraveling the mechanisms underlying C3G and exploring potential therapeutic interventions.

Liensinine alleviates sepsis-induced acute liver injury by inhibiting the NF-κB and MAPK pathways in an Nrf2-dependent manner

Sepsis remains a serious public health issue that needs to be addressed globally. Severe liver injury caused by sepsis increases the risk of death in patients with sepsis. Liensinine (Lie) is one of the primary active components in Plumula nelumbinis and has anti-inflammatory and antioxidant effects. Nevertheless, the effects of Lie on septic liver injury are unclear. This research investigated the protective effect of Lie (10, 20 and 40 mg/kg) on liver damage via intraperitoneal administration of LPS (10 mg/kg) to C57BL/6 mice. Lie was given through intraperitoneal injection once a day for five days. Mice were treated with LPS intraperitoneally for 6 h at 1 h after Lie administration on the last day. The results suggested that Lie could decrease AST and ALT levels in serum, ameliorate histopathological changes and inhibit cell apoptosis in mice with LPS-induced septic liver injury. In addition, Lie inhibited increases in the mRNA levels of TNF-α, IL-1β, iNOS and IL-6. Lie also increased the mRNA level of IL-10. Lie reduced the content of MDA, a marker of lipid peroxidation, and increased the activity of the antioxidant enzymes GSH-Px, CAT and SOD. Our results also showed that Lie could suppress the LPS-activated MAPK and NF-κB pathways and trigger the Nrf2 signaling pathway both in vitro and in vivo. Additionally, an Nrf2 inhibitor (ML385) weakened the suppressive effect of Lie on the MAPK and NF-κB pathways. Our results demonstrated that the suppressive effect of Lie on the MAPK and NF-κB pathways was partially reliant on activation of the Nrf2 pathway. In summary, these results indicate that Lie can improve inflammation and oxidative stress by activating Nrf2, which is a prospective therapeutic drug for alleviating septic liver injury.

Noni enhances the anticancer activity of cyclophosphamide and suppresses myelotoxicity and hepatotoxicity in tumor-bearing mice

Background and aimMorinda citrifolia fruit juice (noni) is an herbal remedy documented to have antioxidant properties. It has been suggested that prevention of carcinogen-DNA adduct formation and the antioxidant activity of NJ may contribute to the cancer preventive effect. In the present study, the antitumor activity of noni was investigated in the presence of cyclophosphamide (CYL) in vitro and in vivo.MethodsIn vitro breast cancer cells (MDA-MB-468) were used to measure the percentage of inhibition and the IC50. The in vivo antitumor activity of noni was studied by monitoring the mean survival time (MST), percentage increase in life span (%ILS), viable and non-viable cell count, tumor volume, body weight, and hematological and serum biochemical parameters in mice. Treatment with noni and CYL exhibited dose- and time-dependent cytotoxicity toward breast cancer cells.ResultsIndividual treatment of noni and CYL exhibited dose- and time-dependent cytotoxicity on breast cancer cell lines, while in combination therapy of noni and CYL, noni enhances cytotoxic effect of CYL at 48 h than that at 24 h. Similar result was found in in vivo studies, the results of which revealed that alone treatment of CYL and noni suppressed tumor growth. However, combination treatment with CYL and noni presented better tumor inhibition than that of alone treatment of CYL and noni. On the contrary, CYL alone drastically attenuated hematological parameters, i.e., RBC, WBC, and Hb compared to normal and control groups, and this change was reversed and normalized by noni when given as combination therapy with CYL. Moreover, the levels of serum biochemical markers, i.e., AST, ALP, and ALT, were significantly increased in the control and CYL-treated groups than those in the normal group. In the combination treatment of noni and CYL, the above biochemical marker levels significantly decreased compared to CYL alone-treated group.ConclusionsThe present study suggested that CYL treatment can cause serious myelotoxicity and hepatic injury in cancer patients. In conclusion, the combined use of noni with CYL potentially enhances the antitumor activity of CYL and suppresses myelotoxicity and hepatotoxicity induced by CYL in tumor-bearing mice.

Experimental study on the inhibition of the NLRP3 signaling pathway with Shengsan Jiedu Huayu decoction to alleviate inflammatory injury in rats with acute-on-chronic liver failure

Objective: To observe the therapeutic effect of Shengsan Jiedu Huayu decoction in alleviating inflammatory liver injury in rats with acute-on-chronic liver failure (ACLF) and its effect on the activation intensity for the NLRP3 signaling pathway. Methods: 63 SD rats were randomly divided into a blank group, a model group, and low-, medium-, and high-dose groups of Shengsan Jiedu Huayu decoction (7.29 g/kg/d, 14.58 g/kg/d, and 29.16 g/kg/d). The ACLF rat model was replicated using carbon tetrachloride combined with d-galactosamine and lipopolysaccharide. Different dose gradients of the Shengsan Jiedu Huayu decoction were used for a five-day intervention treatment, and then rat serum and tissue samples were collected. A biochemical analyzer was used to detect the serum levels of ALT, AST, and TBIL in rats. ELISA was used to detect serum IL-18 and IL-1β content. HE staining was used to observe histomorphological changes in liver tissue. Immunohistochemistry was used to detect GSDMD expression in liver tissue. Western blot and PCR were used to detect NLRP3, Caspase1, ASC, TLR4, IL-1β, IL-18 protein, and mRNA expression levels.The groups were compared using analysis of variance and the rank-sum test. Results: Compared with the blank group, the model group's rat liver tissue was severely injured. Serum levels of ALT, AST, and TBIL, inflammatory factors IL-1β and IL-18, and the GSDMD protein expression level, NLRP3 expression level, TLR4, caspase 1, ASC, IL-1β, IL-18 protein, and mRNA (P<0.01) were all significantly increased in the model than the blank group (P<0.01). Additionally, compared with the model group, the low-, medium-, and high-dose groups of Shengsan Jiedu Huayu decoction had improved liver tissue injury in ACLF rats, while the serum levels of ALT, AST, TBIL, IL-1β, IL-18, liver tissue GSDMD protein, NLRP3, TLR4, caspase 1, and ASC expressions were all lower in the different dose gradients of the Shengsan Jiedu Huayu decoction than the model group, with the most evident reduction in the high-dose group (P<0.01). Conclusion: Shengsan Jiedu Huayu decoction can weaken the activation intensity of the NLRP3 signaling pathway, alleviate liver tissue pathological injury, reduce inflammatory factor release, and alleviate inflammatory liver injury in ACLF rats.

Study on the differential hepatotoxicity of raw polygonum multiflorum and polygonum multiflorum praeparata and its mechanism.

Polygonum multiflorum (PM), a widely used traditional Chinese medicine herb, is divided into two forms, namely raw polygonum multiflorum (RPM) and polygonum multiflorum praeparata (PMP), according to the processing procedure. Emerging data has revealed the differential hepatotoxicity of RPM and PMP, however, its potential mechanism is still unclear. In our study, we investigated the differential hepatotoxicity of RPM and PMP exerted in C57BL/6 mice. First, sera were collected for biochemical analysis and HE staining was applied to examine the morphological alternation of the liver. Then we treated L02 cells with 5mg / mL of RPM or PMP. The CCK8 and EdU assays were utilized to observe the viability and proliferation of L02 cells. RNA sequencing was performed to explore the expression profile of L02 cells. Western blotting was performed to detect the expression level of ferroptosis-related protein. Flow cytometry was used to evaluate ROS accumulation. In our study, a significant elevation in serum ALT, AST and TBIL levels was investigated in the RMP group, while no significant differences were observed in the PMP group, compared to that of the CON group. HE staining showed punctate necrosis, inflammatory cell infiltration and structural destruction can be observed in the RPM group, which can be significantly attenuated after processing. In addition, we also found RPM could decrease the viability and proliferation capacity of L02 cells, which can be reversed by ferroptosis inhibitor. RNA sequencing data revealed the adverse effect of PM exerted on the liver is closely associated with ferroptosis. Western blotting assay uncovered the protein level of GPX4, HO-1 and FTL was sharply decreased, while the ROS content was dramatically elevated in L02 cells treated with RPM, which can be partially restored after processing. The hepatotoxicity induced by RPM was significantly lower than the PMP, and its potential mechanism is associated with ferroptosis.

The contribution of small heterodimer partner to the occurrence and progression of cholestatic liver injury.

Small heterodimer partner (SHP, encoded by NR0B2) plays an important role in maintaining bile acid homeostasis. The loss of the hepatic farnesoid X receptor (FXR)/SHP signal can cause severe cholestatic liver injury (CLI). FXR and SHP have overlapping and nonoverlapping functions in bile acid homeostasis. However, the key role played by SHP in CLI is unclear. In this study, an alpha-naphthylisothiocyanate (ANIT)-induced cholestasis mouse model was established. The effect of SHP knockout (SHP-KO) on liver and ileal pathology was evaluated. 16S rRNA gene sequencing analysis combined with untargeted metabolomics was applied to reveal the involvement of SHP in the pathogenesis of CLI. The results showed that ANIT (75mg/kg) induced cholestasis in WT mice. No significant morphological changes were found in the liver and ileal tissue of SHP-KO mice. However, the serum metabolism and intestinal flora characteristics were significantly changed. Moreover, compared with the WT+ANIT group, the serum levels of ALT and AST in the SHP-KO+ANIT group were significantly increased, and punctate necrosis in the liver tissue was more obvious. The ileum villi showed obvious shedding, thinning, and shortening. In addition, SHP-KO-associated differential intestinal flora and differential biomarkers were significantly associated. In this study, we elucidated the serum metabolic characteristics and intestinal flora changes related to the aggravation of CLI in SHP-KO mice induced by ANIT.

Ursodeoxycholic acid loaded dual-modified graphene oxide nanocomposite alleviates cholestatic liver injury through inhibiting hepatocyte apoptosis

Ursodeoxycholic acid (UDCA) is the preferred treatment for various types of cholestasis, however, its effectiveness is limited because of its insolubility in water. We used polyethylene glycol (PEG) and cationic polymer polyethylenimine (PEI) to double-modify graphite oxide (PPG) as a drug delivery system. UDCA was successfully loaded onto PPG through intermolecular interactions to form UDCA-PPG nanoparticles. UDCA-PPG nanoparticles not only improve the solubility and dispersibility of UDCA, but also have good biocompatibility and stability, which significantly improve the delivery rate of UDCA. The results indicated that UDCA-PPG significantly reduced ROS levels, promoted cell proliferation, protected mitochondrial membrane potential, reduced DNA damage and reduced apoptosis in the DCA-induced cell model. In a mouse cholestasis model established by bile duct ligation (BDL), UDCA-PPG improved liver necrosis, fibrosis, and mitochondrial damage and reduced serum ALT and AST levels, which were superior to those in the UDCA-treated group. UDCA-PPG reduced the expression of the apoptosis-related proteins, Caspase-3 and Bax, increased the expression of Bcl-2, and reduced the expression of the oxidative stress-related proteins, NQO and HO-1, as well as the autophagy-related proteins LC3, p62 and p-p62. Therefore, UDCA-PPG can enhance the therapeutic effect of UDCA in cholestasis, by significantly improving drug dispersibility and stability, extending circulation time in vivo, promoting absorption, decreasing ROS levels, enhancing autophagy flow and inhibiting apoptosis via the Bcl-2/Bax signaling pathway.

Turmeric Extract-loaded Selenium Nanoparticles Counter Doxorubicin-induced Hepatotoxicity in Mice via Repressing Oxidative Stress, Inflammatory Cytokines, and Cell Apoptosis.

Doxorubicin (DOX) is an antitumor anthracycline used to treat a variety of malignancies; however, its clinical use is associated with noticeable hepatotoxicity. Therefore, the current study was designed to delineate if biosynthesized SeNPs with turmeric extract (Tur-SeNPs) could alleviate DOX-induced hepatic adverse effects. Mice were orally post-treated with Tur extract, Tur-SeNPs, or N-acetyl cysteine after the intraperitoneal injection of DOX. Our findings have unveiled a remarkable liver attenuating effect in DOX-injected mice post-treated with Tur-SeNPs. High serum levels of ALT, AST, ALP, and total bilirubin induced by DOX were significantly decreased by Tur-SeNPs therapy. Furthermore, Tur-SeNPs counteracted DOX-caused hepatic oxidative stress, indicated by decreased MDA and NO levels along with elevated levels of SOD, CAT, GPx, GR, GSH, and mRNA expression levels of Nrf-2. Noteworthily, decreased hepatic IL-1β, TNF-α, and NF-κB p65 levels in addition to downregulated iNOS gene expression in Tur-SeNPs-treated mice have indicated their potent antiinflammatory impact. Post-treatment with Tur-SeNPs also mitigated the hepatic apoptosis evoked by DOX injection. A liver histological examination confirmed the biochemical and molecular findings. In brief, the outcomes have demonstrated Tur loaded with nanoselenium to successfully mitigate the liver damage induced by DOX via blocking oxidative stress, and inflammatory and apoptotic signaling.

CsHscB Derived from a Liver Fluke Clonorchis sinensis Ameliorates Cholestatic Hepatic Fibrosis in a Mouse Model of Sclerosing Cholangitis.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by inflammatory fibrosis usually involving the whole biliary tree. However, there are very limited treatment options to treat this disease. Our previous study found a lipid-protein rCsHscB from a liver fluke - Clonorchis sinensis, which had full capacities of immune regulation. Therefore, we investigated the role of rCsHscB in a mouse model of sclerosing cholangitis induced by xenobiotic 3,5- diethoxycarbonyl-1,4-dihydrocollidine (DDC) to explore whether this protein had potential therapeutic value for PSC. Mice were fed 0.1% DDC for 4 weeks and treated with CsHscB (30 μg/mouse, intraperitoneal injection, once every 3 days); the control group was given an equal amount of PBS or CsHscB under normal diet conditions. All the mice were sacrificed at 4 weeks for the evaluation of biliary proliferation, fibrosis, and inflammation. rCsHscB treatment attenuated DDC-induced liver congestion and enlargement and significantly decreased the upregulation of serum AST and ALT levels. The administration of rCsHscB to DDC-fed mice significantly decreased cholangiocyte proliferation and pro-inflammatory cytokine production compared to mice fed with DDC alone. Also, rCsHscB treatment showed a decreased expression of α-SMA in the liver and other markers of liver fibrosis (Masson staining, Hydroxyproline content, and collagen deposit). More interestingly, DDC-fed mice treated with rCsHscB showed a significant up-regulation of PPAR-γ expression, which was similar to control mice, indicating the involvement of PPAR-γ signaling in the protective action of rCsHscB. Overall, our data show that rCsHscB attenuates the progression of cholestatic fibrosis induced by DDC and supports the potential for manipulating the parasite-derived molecule to treat certain immune-mediated disorders.

A single-chain antibody construct with specificity of a natural IgM antibody reduces hepatic ischemia reperfusion injury in mice.

Natural immunoglobulin M (IgM) antibodies have been shown to recognize post-ischemic neoepitopes following reperfusion of tissues and to activate complement. Specifically, IgM antibodies and complement have been shown to drive hepatic ischemia reperfusion injury (IRI). Herein, we investigate the therapeutic effect of C2 scFv (single-chain antibody construct with specificity of a natural IgM antibody) on hepatic IRI in C57BL/6 mice. Compared with PBS-treated mice, C2 scFv-treated mice displayed almost no necrotic areas, significant reduction in serum ALT, AST and LDH levels, and significantly reduced in the number of TUNEL positive cells. Moreover, C2 scFv-treated mice exhibited a notable reduction in inflammatory cells after hepatic IRI than PBS-treated mice. The serum IL-6, IL-1β, TNF-α and MPC-1 levels were also severely suppressed by C2 scFv. Interestingly, C2 scFv reconstituted hepatic inflammation and IRI in Rag1-/- mice. We found that C2 scFv promoted hepatic cell death and increased inflammatory cytokines and infiltration of inflammatory cells after hepatic IRI in Rag1-/- mice. In addition, IgM and complement 3d (C3d) were deposited in WT mice and in Rag1-/- mice reconstituted with C2 scFv, indicating that C2 scFv can affect IgM binding and complement activation and reconstitute hepatic IRI. C3d expression was significantly lower in C57BL/6 mice treated with C2 scFv compared to PBS, indicating that excessive exogenous C2 scFv inhibited complement activation. These data suggest that C2 scFv alleviates hepatic IRI by blocking complement activation, and treatment with C2 scFv may be a promising therapy for hepatic IRI.

Selenium-rich Lactobacillus plantarum alleviates salinity stress in Cyprinus carpio: Growth performance, oxidative stress, and immune and inflammatory responses

Salinity is an important environmental factor that affects the health of aquatic animals, when salinity level above the tolerance threshold can pose a significant threat to the survival of aquatic animals. As a trace element necessary for animal growth, selenium participates in the body’s antioxidant reaction, and protect aquatic animals from oxidative stress damage. Biological methods for synthesizing selenium nanoparticles (bio-Se-NPs) from bacteria are safe, inexpensive, and accessible. Therefore, we synthesized selenium nanoparticles using Lactobacillus plantarum (probiotic) to study the growth, immune, antioxidant, and inflammatory responses of selenium-rich Lactobacillus plantarum (SL, a type of bio-Se-NPs) fed Cyprinus carpio under low-salinity (5 g/L salinity) and high-salinity (10 g/L salinity) stresses. Analyses revealed that the addition of SL at a concentration of 1 mg/kg significantly alleviated the growth inhibition caused by high-salinity stress. SL significantly alleviated salinity-induced liver tissue injury (numerous cytoplasmic vacuolations the accumulation, inflammatory cell infiltration, nuclear lysis, and some blood congestion). SL significantly alleviated the abnormal levels of serum ALT, AST, GGT and LDH caused by salinity stress, and improved lipid metabolism (TG, TC, LDL-C, HDL-C). SL can also regulates cytokines and antioxidant genes (TNF-α, iL-1β, iL-10, TGFβ-1, SOD, CAT, GPx1, and HO-1) through the NF-κB and Nrf-2 signaling pathways and thereby reduce the inflammatory response and increase the antioxidant level, and these effects attenuate salinity-mediated oxidative damage. In conclusion, our findings indicate that SL can significantly promote the growth and development of fish and alleviate the adverse effects of high-salinity stress and thus, SL can be a potential feed additive for alleviating oxidative stress and inflammatory responses.

Effects of Nano Selenium on Some Metabolic and Rumen Parameters in Dorper Sheep

The aim of the study was to investigate the effects of nano selenium (N-Se) supplementation on some metabolik parameters and rumen fermentation in sheep. In the study, twenty female Dorper sheep, average 60.1±0.44 kg of body weight were used and blood samples and rumen fluid were taken at the end of trial. The animals were randomly divided into two trial groups (n=10). The control animals received the basal ration without Se supplementation, containing a native Se content of 0.06 mg/kg DM. The other sheep were fed the same basal ration supplemented with 3 g/head/day N-Se. Trial were 66 days with 10 days of adaptation to feed and 56 days of feeding period. Serum total protein (p=0.514) and albumin (p=0.126) levels did not change by feeding N-Se. Serum T-cholesterol, triglycerides, AST (p=0.001) and ALT (p=0.030) levels were decreased in the N-Se-treated group when compared with the control. Supplementation of N-Se did not effect ruminal pH values (p=0.792), the molar concentration of acetic acid (p=0.133) and butyric acid (p=0.089), but the ammonia concentration (p=0.001) was decreased, and total VFA concentration (p=0.003) was increased. The ratio of acetate to propionate decreased due to the increasing of propionate concentration (p=0.034). The obtained results indicated that N-Se supplementation positively improved ruminal fermentation and metabolic status. It was concluded that N-Se can be used as an alternatively available selenium source in sheep.

Evaluation of hematoprotective, hepatoprotective, and anti-inflammatory potentials of chia seed (Salvia hispanica L.) extract in rats

This study was conducted to evaluate the effects of chia seed extract on CCl4-induced hepatotoxicity, hematological profile, and carrageenan-induced inflammation in rats. Water-ethanol-acetone extract of chia seeds at the doses of 200 and 400 mg/kg body weight/day were applied to evaluate the comparative protective roles. Hematological profile and serum biochemical parameters were measured to evaluate the hematoprotective, and hepatoprotective effects of chia seed extract. Paw thickness and motility level were assessed at 0, 1, 3, 5, and 7 h after sub-planter injection of carrageenan to evaluate the anti-inflammatory potential. Tissue histopathology was performed in both cases. Chia seed extract reduced the elevated level of serum AST and ALT significantly in a dose-dependent manner following intra-peritoneal injection of CCl4. Histopathological study of the liver tissue exhibited acute impairment of the hepatocytes and liver parenchyma following CCl4 exposure, which was markedly regenerated by the chia seed extract treatment. Protective effects of the extracts were also evidenced by the RBC count, Hb (%), PCV (%), ESR, and neutrophil count. Chia seed extract was found to inhibit the carrageenan-induced paw edema and increase motility level in a dose-oriented fashion. Histological examination of the paw tissue revealed severe inflammation characterized by massive infiltration of inflammatory cells in the carrageenan group, which was significantly reduced by chia seed extract treatment. The higher dose of chia seed extract showed significant increases in bodyweight gain and feed efficiency ratio but decrease in visceral fat deposition. These results suggest that chia seeds possess potentials for hematoprotective, hepatoprotective, and anti-inflammatory activities.

A study on the treatment effects of Crataegus pinnatifida polysaccharide on non-alcoholic fatty liver in mice by modulating gut microbiota.

The objective of this study was to investigate the protective effect of Crataegus pinnatifida polysaccharide (CPP) on non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet (HFD) in mice. The findings demonstrated that CPP improved free fatty acid (FFA)-induced lipid accumulation in HepG2 cells and effectively reduced liver steatosis and epididymal fat weight in NAFLD mice, as well as decreased serum levels of TG, TC, AST, ALT, and LDL-C. Furthermore, CPP exhibited inhibitory effects on the expression of fatty acid synthesis genes FASN and ACC while activating the expression of fatty acid oxidation genes CPT1A and PPARα. Additionally, CPP reversed disturbances in intestinal microbiota composition caused by HFD consumption. CPP decreased the firmicutes/Bacteroidetes ratio, increased Akkermansia abundance, and elevated levels of total short-chain fatty acid (SCFA) content specifically butyric acid and acetic acid. Our results concluded that CPP may intervene in the development of NAFLD by regulating of intes-tinal microbiota imbalance and SCFAs production. Our study highlights that CPP has a potential to modulate lipid-related pathways via alterations to gut microbiome composition thereby ex-erting inhibitory effects on obesity and NAFLD development.

GSDMD induces hepatocyte pyroptosis to trigger alcoholic hepatitis through modulating mitochondrial dysfunction

BackgroundMechanisms and consequences of Gasdermin D (GSDMD) activation in alcoholic hepatitis (AH) are unclear. In the present study, we investigated whether GSDMD induces hepatocyte pyroptosis by regulating mitochondrial dysfunction in AH.ResultsLiver damage in AH mice was assessed by HE staining, serum levels of AST, ALT, TC, and TG. The levels of IL-1β, IL-18, LDH, inflammasome-associated proteins and hepatocyte death were assessed to determine pyroptosis. Mitochondrial dysfunction was assessed through various parameters including mitochondrial DNA (mtDNA) levels, ROS generation, mitochondrial membrane potential, ATP contents, levels of mitochondrial function-related proteins and morphological changes of mitochondria. AH induced gasdermin D (GSDMD) activation, leading to increased protein expression of N-terminal GSDMD (GSDMD-N), NLRP3, and Caspase 11 in liver tissues. Downregulation of GSDMD alleviated alcohol-induced hepatocyte pyroptosis. Alcohol also causes mitochondrial dysfunction in hepatocytes in AH, which was improved by inhibiting GSDMD. Furthermore, enhancing mitochondrial function suppressed alcohol-induced hepatocyte pyroptosis. Further, knockdown of GSDMD or dynamin-related protein 1 (Drp1) improved AH-induced liver injury, accompanied by a decrease in hepatocyte pyroptosis.ConclusionGSDMD induces hepatocyte pyroptosis by modulating mitochondrial dysfunction during AH-induced inflammation and liver injury. These findings may pave the way to develop new therapeutic treatments for AH.

An enhanced cardio-protective effect of nanoparticles loaded with active components from Polygonum orientale L. against isoproterenol-induced myocardial ischemia in rats

In this study, nanoparticles loaded with active components from Polygonum orientale L. (PO), a traditional Chinese herb known for its anti-myocardial ischemic properties, were investigated for cardio-protective properties. Specifically, OVQ-Nanoparticles (OVQ-NPs) with Orientin (Ori), Vitexin (Vit), and Quercetin (Que) was obtained by double emulsion-solvent evaporation method. The OVQ-NPs exhibited a spherical shape, with a uniform size distribution of 136.77 ± 3.88 nm and a stable ζ-potential of −13.40 ± 2.24 mV. Notably, these nanoparticles exhibited a favorable sustained-release characteristic, resulting in an extended circulation time within the living organism. Consequently, the administration of these nanoparticles resulted in significant improvements in electrocardiograms and heart mass index of myocardial ischemic rats induced by isoproterenol, as well as decreased serum levels of CK, LDH, and AST. Furthermore, the results of histopathological examination, such as H&E staining and TUNEL staining, confirmed a reduced level of cardiac tissue pathology and apoptosis. Moreover, the quantification of biochemical indicators (SOD, MDA, GSH, NO, TNF-α, and IL-6) demonstrated that OVQ-NPs effectively mitigated myocardial ischemia by regulating oxidative stress and inflammatory pathways. In conclusion, OVQ-NPs demonstrate promising therapeutic potential as an intervention for myocardial ischemia, providing a new perspective on traditional Chinese medicine treatment in this area.

Isolation and purification of polysaccharides from Bupleurum marginatum Wall.ex DC and their anti-liver fibrosis activities.

Bupleurum marginatum Wall.ex DC [Apiaceae] (BM)is widely grown in southwestern China, and the whole plant is used as Traditional Chinese Medicine (TCM). Polysaccharides are main natural products in lots of TCM and have been studied for their effects of reducing oxidative stress, anti-inflammation and immune regulation. Herein, we investigated the extraction techniques of Bupleurum marginatum Wall.ex DC polysaccharides (BMP), the identification of their key components, and their ability to inhibit liver fibrosis in both cellular and animal models. Component identification indicated that monosaccharides in BMP mainly consisted of glucose, galactose, mannose, rhamnose, arabinose, and xylose. In vivo analysis revealed that BMP provided significant protective effects on N-Nitroso dimethylamine (NDMA)-induced liver fibrosis rats through reducing hepatomegaly, reducing tissue inflammation, and reducing collagen deposition. BMP also improved the hepatobiliary system and liver metabolism in accord to reduce the serum levels of ALT, AST, ALP, r-GT, and TBIL. In addition, BMP could reduce the level of inflammation and fibrosis through inhibition of IL-1β and TGF-β1. Cellular studies showed that the BMP could provide therapeutic effects on lipopolysaccharide (LPS)-induced cellular fibrosis model, and could reduce the level of inflammation and fibrosis by decreasing the level of TGF-β1, IL-1β, and TNF-α. Our study demonstrated that BMP may provide a new therapy strategy of liver injury and liver fibrosis.

Bioefficacy of dietary inclusion of Nannochloropsis oculata on Eimeria spp. challenged chicks: clinical approaches, meat quality, and molecular docking

ABSTRACT Although anticoccidial drugs have been used to treat avian coccidiosis for nearly a century, resistance, bird harm, and food residues have caused health concerns. Thus, Nannochloropsis oculata was investigated as a possible coccidiosis treatment for broilers. A total of 150 1-day-old male Cobb broiler chicks were treated as follows: G1-Ng: fed a basal diet; G2-Ps: challenged with Eimeria spp. oocysts and fed basal diet; G3-Clo: challenged and fed basal diet with clopidol; G4-NOa: challenged and fed 0.1% N. oculata in diet, and G5-NOb: challenged and fed 0.2% N. oculata. Compared to G2-Ps, N. oculata in the diet significantly (P < 0.05) decreased dropping scores, lesion scores, and oocyst shedding. Without affecting breast meat colour metrics, N. oculata improved meat quality characters. At 28 days of age, birds received 0.2% N. oculata had significantly (P < 0.05) higher serum levels of MDA, T-SOD, HDL, and LDL cholesterol compared to G2-Ps. Serum AST, ALT, and urea levels were all decreased when N. oculata (0.2%) was used as opposed to G2-Ps. Histopathological alterations and the number of developmental and degenerative stages of Eimeria spp. in the intestinal epithelium were dramatically reduced by 0.2% N. oculata compared to G2-Ps. Molecular docking revealed a higher binding affinity of N. oculata for E. tenella aldolase, EtAMA1, and EtMIC3, which hindered glucose metabolism, host cell adhesion, and invasion of Eimeria. Finally, N. oculata (0.2%) can be used in broiler diets to mitigate the deleterious effects of coccidiosis.