Structurally Diverse Alkaloids with Anti-Renal-Fibrosis Activity from the Centipede Scolopendra subspinipes mutilans.

Twelve new alkaloids, scolopenolines A-L (1-7, 9-11, 13, 14), along with six known analogues, were isolated from Scolopendra subspinipes mutilans, identified by analysis of spectroscopic data and quantum chemical and computational methods. Scolopenoline A (1), a unique guanidyl-containing C14 quinoline alkaloid, features a 6/6/5 ring backbone. Scolopenoline B (2) is a novel sulfonyl-containing heterodimer comprising quinoline and tyramine moieties. Scolopenoline G (7) presents a rare C12 quinoline skeleton with a 6/6/5 ring system. Alkaloids 1, 8, 10, and 15-18 display anti-inflammatory activity, while 10 and 16-18 also exhibit anti-renal-fibrosis activity. Drug affinity responsive target stability and RNA-interference assays show that Lamp2 might be a potentially important target protein of 16 for anti-renal-fibrosis activity.

Acanthopanax senticosus cultures fermented by Lactobacillus rhamnosus enhanced immune response through improvement of antioxidant activity and inflammation in crucian carp (Carassius auratus).

Lactic acid bacteria (LAB) have been recognized as safe microorganism that improve micro-flora disturbances and enhance immune response. A well-know traditional herbal medicine, Acanthopanax senticosus (As) was extensively utilized in aquaculture to improve growth performance and disease resistance. Particularly, the septicemia, skin wound and gastroenteritis caused by Aeromonas hydrophila threaten the health of aquatic animals and human. However, the effects of probiotic fermented with A. senticosus product on the immune regulation and pathogen prevention in fish remain unclear. Here, the aim of the present study was to elucidate whether the A. senticosus fermentation by Lactobacillus rhamnosus improve immune barrier function. The crucian carp were fed with basal diet supplemented with L. rhamnosus fermented A. senticosus cultures at 2 %, 4 %, 6 % and 8 % bacterial inoculum for 8 weeks. After trials, the weight gain rate (WGR), specific growth rate (SGR) were significantly increased, especially in LGG-6 group. The results confirmed that the level of the CAT, GSH-PX, SOD, lysozyme, and MDA was enhanced in fish received with probiotic fermented product. Moreover, the L. rhamnosus fermented A. senticosus cultures could trigger innate and adaptive immunity, including the up-regulation of the C3, C4, and IgM concentration. The results of qRT-PCR revealed that stronger mRNA transcription of IL-1ß, IL-10, IFN-γ, TNF-α, and MyD88 genes in the liver, spleen, kidney, intestine and gills tissues of fish treated with probiotic fermented with A. senticosus product. After infected with A. hydrophila, the survival rate of the LGG-2 (40 %), LGG-4 (50 %), LGG-6 (60 %), LGG-8 (50 %) groups was higher than the control group. Meanwhile, the pathological damage of the liver, spleen, head-kidney, and intestine tissues of probiotic fermentation-fed fish could be alleviated after pathogen infection. Therefore, the present work indicated that L. rhamnosus fermented A. senticosus could be regard as a potential intestine-target therapy strategy to protecting fish from pathogenic bacteria infection.

Angiotensin II type-2 receptor signaling facilitates liver injury repair and regeneration via inactivation of Hippo pathway.

The angiotensin II type 2 receptor (AT2R) is a well-established component of the renin-angiotensin system and is known to counteract classical activation of this system and protect against organ damage. Pharmacological activation of the AT2R has significant therapeutic benefits, including vasodilation, natriuresis, anti-inflammatory activity, and improved insulin sensitivity. However, the precise biological functions of the AT2R in maintaining homeostasis in liver tissue remain largely unexplored. In this study, we found that the AT2R facilitates liver repair and regeneration following acute injury by deactivating Hippo signaling and that interleukin-6 transcriptionally upregulates expression of the AT2R in hepatocytes through STAT3 acting as a transcription activator binding to promoter regions of the AT2R. Subsequently, elevated AT2R levels activate downstream signaling via heterotrimeric G protein Gα12/13-coupled signals to induce Yap activity, thereby contributing to repair and regeneration processes in the liver. Conversely, a deficiency in the AT2R attenuates regeneration of the liver while increasing susceptibility to acetaminophen-induced liver injury. Administration of an AT2R agonist significantly enhances the repair and regeneration capacity of injured liver tissue. Our findings suggest that the AT2R acts as an upstream regulator in the Hippo pathway and is a potential target in the treatment of liver damage.

The Acetic Acid Produced by Lactobacillus Species Regulates Immune Function to Alleviate PEDV Infection in Piglets.

Porcine epidemic diarrhea virus (PEDV) infection results in significant mortality among newborn piglets, leading to substantial economic setbacks in the pig industry. Short-chain fatty acids (SCFA), the metabolites of intestinal probiotics, play pivotal roles in modulating intestinal function, enhancing the intestinal barrier, and bolstering immune responses through diverse mechanisms. The protective potential of Lactobacillus delbrueckii, Lactobacillus johnsonii, and Lactococcus lactis was first noted when administered to PEDV-infected piglets. Histological evaluations, combined with immunofluorescence studies, indicated that piglets receiving L. lactis displayed less intestinal damage, with diminished epithelial cell necrosis and milder injury levels. Differences in immunofluorescence intensity revealed a significant disparity in antigen content between the L. lactis and PEDV groups, suggesting that L. lactis might suppress PEDV replication, the intestine. We then assessed short-chain fatty acid content through targeted metabolomics, finding that acetate levels markedly varied from other groups. This protective impact was confirmed by administering acetate to PEDV-infected piglets. Data suggested that piglets receiving acetate exhibited resistance to PEDV. Flow cytometry analyses were conducted to evaluate the expression of innate and adaptive immune cells in piglets. Sodium acetate appeared to bolster innate immune defenses against PEDV, marked by elevated NK cell and macrophage counts in mesenteric lymph nodes, along with increased NK cells in the spleen and macrophages in the bloodstream. Acetic acid was also found to enhance the populations of CD8+ IFN-γ T cells in the blood, spleen, and mesenteric lymph, CD4+ IFN-γ T cells in mesenteric lymph nodes and spleen, and CD4+ IL-4+T cells in the bloodstream. Transcriptome analyses were carried out on the jejunal mucosa from piglets with PEDV-induced intestinal damage and from healthy counterparts with intact barriers. Through bioinformatics analysis, we pinpointed 189 significantly upregulated genes and 333 downregulated ones, with the PI3K-AKT, ECM-receptor interaction, and pancreatic secretion pathways being notably enriched. This transcriptomic evidence was further corroborated by western blot and qPCR. Short-chain fatty acids (SCFA) were found to modulate G protein-coupled receptor 41 (GPR41) and 43 (GPR43) in porcine intestinal epithelial cells (IPEC-J2). Post-acetic acid exposure, there was a notable upsurge in the ZO-1 barrier protein expression in IPEC-J2 compared to the unexposed control group (WT), while GPR43 knockdown inversely affected ZO-1 expression. Acetic acid amplified the concentrations of phosphorylated PI3K and AKT pivotal components of the PI3K/AKT pathway. Concurrently, the co-administration of AKT agonist SC79 and PI3K inhibitor LY294002 revealed acetic acid's role in augmenting ZO-1 expression via the P13K/AKT signaling pathway. This study demonstrates that acetic acid produced by Lactobacillus strains regulates intestinal barrier and immune functions to alleviate PEDV infection. These findings provide valuable insights for mitigating the impact of PEDV in the pig industry.

Equivalent radius of atmosphere aerosol in haze weather based on laser scattering.

The investigation of atmospheric aerosols holds paramount importance within the environmental realm. This significance arises from the intricate nature of aerosol distribution and size in real-life hazy weather conditions. In this work, we have employed the equivalent radius of the aerosols in haze weather obtained from the volume spectrum, and then the scattering characteristics of these aerosols are obtained using the equivalent radius. Pearson correlation coefficients have been used for revealing a strong correlation by comparing Aeronet website data and simulation results with a minimum value of 0.657.

Mechanistic insights into manganese oxide impacting the oxidation and transport of Cr(III) immobilized by nano-zero valent charged ion particles in water-saturated porous media.

The presence of manganese oxide (MnO2) could influence the stability of green-synthesized nano-zero valent iron (nZVI@GT) associated with trivalent chromium (Cr(III)) after its excess application in the in situ remediation of hexachromium (Cr(VI)) contaminated soil. The research findings revealed that the co-transport of the remaining nZVI@GT with Cr(III) was substantially inhibited by high δ-MnO2 concentrations due to the formation of hetero-aggregates between nZVI@GT and δ-MnO2, resulting in an increased irreversible attachment parameter at second-site in a two-site kinetic attachment model. Simultaneously, the Cr(III) complex immobilized on nZVI@GT could be oxidized leading to high levels of Cr(VI) leaching at high δ-MnO2 concentrations. During this process, Mn(IV) was converted to Mn(III)/Mn(II). Subsequently, leachate containing a partial amount of Cr(VI) preferentially adsorbed onto the nZVI@GT surface, enhancing the dispersion of the nZVI@GT and δ-MnO2 agglomerates. Thereafter, nZVI@GT transportability was enhanced with a decreased second-site attachment parameter and the flow content of dissolved Cr(VI) was increased to double, also increasing the potential risk of Cr(VI) being carried by nZVI@GT to underground water systems. This study provides theoretical support for preserving the long-term stability of nZVI@GT after the in situ remediation of heavy metal-contaminated sites in the presence of δ-MnO2.

Comprehensive analysis of zinc and ring finger 3 in prognostic value and pan-cancer immunity.

Zinc and ring finger 3 (ZNRF3) is a negative suppressor of Wnt signal and newly identified as an important regulator in tumorigenesis and development. However, the pan-cancer analysis of ZNRF3 has not been reported. We found that ZNRF3 was significantly decreased in six tumors including CESC, KIRP, KIRC, SKCM, OV, and ACC, but increased in twelve tumors, namely LGG, ESCA, STES, COAD, STAD, LUSC, LIHC, THCA, READ, PAAD, TGCT, and LAML. Clinical outcomes of cancer patients were closely related to ZNRF3 expression in ESCA, GBM, KIRC, LUAD, STAD, UCEC, LGG, and SARC. The highest genetic alteration frequency of ZNRF3 occurred in ACC. Abnormal expression of ZNRF3 could be attributed to the differences of copy number variation (CNV) and DNA methylation as well as ZNRF3-interacting proteins. Besides, ZNRF3 were strongly associated with tumor heterogeneity, tumor stemness, immune score, stromal score and ESTIMATE score in certain cancers. In terms of immune cell infiltration, ZNRF3 was positively correlated to infiltration of cancer-associated fibroblasts in CESC, HNSC, OV, PAAD, PRAD, and THYM, but negatively associated with infiltration of CD8 T cells in HNSC, KIRC, KIRP and THYM. Moreover, ZNRF3 expression was correlated with most immune checkpoint genes in SARC, LUSC, LUAD, PRAD, THCA, UVM, TGCT, and OV, and associated with overwhelming majority of immunoregulatory genes in almost all cancers. Most RNA modification genes were also remarkably related to ZNRF3 level in KIRP, LUAD, LUSC, THYM, UVM, PRAD, and UCEC, indicating that ZNRF3 might have an important effect on cancer epigenetic regulation. Finally, we verified the expression and role of ZNRF3 in clinical specimens and cell lines of renal cancer and liver cancer. This study provides a comprehensive pan-cancer analysis of ZNRF3 and reveals the complexity of its carcinogenic effect.

Design of a single-center, phase II trial to explore the efficacy and safety of 'R-ISV-RO' treatment in advanced tumors.

Background: The authors' preclinical study has confirmed that RO adjuvant (composed of TLR 7 agonists [imiquimod/R837] and OX40 agonists) injected into local lesions induces the regression of both primary tumor and distant metastasis. The authors propose to realize local control and exert abscopal effect through an 'R-ISV-RO' in situ strategy plus anti-PD-1 monoclonal antibody in advanced tumors. Methods: This study is a single-center, exploratory, phase II trial to evaluate the efficacy and safety of R-ISV-RO plus anti-PD-1 monoclonal antibody in advanced tumors. 30 patients with one or more measurable extracerebral lesions that are accessible for radiation or injection will be enrolled. The primary endpoint is the objective response rate of target lesions. Discussion/Conclusion: The efficacy and safety of the novel strategy will be further validated through this clinical trial. Clinical trial registration: ChiCTR2100053870 (www.chictr.org.cn/).

HERC5-catalyzed ISGylation potentiates cGAS-mediated innate immunity.

The cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS) is essential to elicit type I interferon cascade response; thus, the activity of cGAS must be strictly regulated to boost the antiviral innate immunity. Here, we report that cGAS is responsible for the DNA-induced ISG15 conjugation system. The E3 HERC5 catalyzes the ISGylation of cytoplasmic cGAS at lysine 21, 187, 219, and 458, whereas Ubl carboxy-terminal hydrolase 18 removes the ISGylation of cGAS. The interaction of cGAS and HERC5 depends on the cGAS C-terminal domain and the RRC1-4 and RRC1-5 domains of HERC5. Mechanically, HERC5-catalyzed ISGylation promotes DNA-induced cGAS oligomerization and enhances cGAS enzymatic activity. Deficiency of ISGylation attenuates the downstream inflammatory gene expression induced by the cGAS-STING axis and the antiviral ability in mouse and human cells. Mice deficient in Isg15 or Herc6 are more vulnerable to herpes simplex virus 1 infection. Collectively, our study shows a positive feedback regulation of the cGAS-mediated innate immune pathway by ISGylation.

Restricted internal diffusion weakens transpiration-photosynthesis coupling during heatwaves: Evidence from leaf carbonyl sulphide exchange.

Increasingly frequent and intense heatwaves threaten ecosystem health in a warming climate. However, plant responses to heatwaves are poorly understood. A key uncertainty concerns the intensification of transpiration when heatwaves suppress photosynthesis, known as transpiration-photosynthesis decoupling. Field observations of such decoupling are scarce, and the underlying physiological mechanisms remain elusive. Here, we use carbonyl sulphide (COS) as a leaf gas exchange tracer to examine potential mechanisms leading to transpiration-photosynthesis decoupling on a coast live oak in a southern California woodland in spring 2013. We found that heatwaves suppressed both photosynthesis and leaf COS uptake but increased transpiration or sustained it at non-heatwave levels throughout the day. Despite statistically significant decoupling between transpiration and photosynthesis, stomatal sensitivity to environmental factors did not change during heatwaves. Instead, midday photosynthesis during heatwaves was restricted by internal diffusion, as indicated by the lower internal conductance to COS. Thus, increased evaporative demand and nonstomatal limitation to photosynthesis act jointly to decouple transpiration from photosynthesis without altering stomatal sensitivity. Decoupling offered limited potential cooling benefits, questioning its effectiveness for leaf thermoregulation in xeric ecosystems. We suggest that adding COS to leaf and ecosystem flux measurements helps elucidate diverse physiological mechanisms underlying transpiration-photosynthesis decoupling.

Gut microbiota-derived LCA mediates the protective effect of PEDV infection in piglets.

BACKGROUND: The gut microbiota is a critical factor in the regulation of host health, but the relationship between the differential resistance of hosts to pathogens and the interaction of gut microbes is not yet clear. Herein, we investigated the potential correlation between the gut microbiota of piglets and their disease resistance using single-cell transcriptomics, 16S amplicon sequencing, metagenomics, and untargeted metabolomics. RESULTS: Porcine epidemic diarrhea virus (PEDV) infection leads to significant changes in the gut microbiota of piglets. Notably, Landrace pigs lose their resistance quickly after being infected with PEDV, but transplanting the fecal microbiota of Min pigs to Landrace pigs alleviated the infection status. Macrogenomic and animal protection models identified Lactobacillus reuteri and Lactobacillus amylovorus in the gut microbiota as playing an anti-infective role. Moreover, metabolomic screening of the secondary bile acids' deoxycholic acid (DCA) and lithocholic acid (LCA) correlated significantly with Lactobacillus reuteri and Lactobacillus amylovorus, but only LCA exerted a protective function in the animal model. In addition, LCA supplementation altered the distribution of intestinal T-cell populations and resulted in significantly enriched CD8+ CTLs, and in vivo and in vitro experiments showed that LCA increased SLA-I expression in porcine intestinal epithelial cells via FXR receptors, thereby recruiting CD8+ CTLs to exert antiviral effects. CONCLUSIONS: Overall, our findings indicate that the diversity of gut microbiota influences the development of the disease, and manipulating Lactobacillus reuteri and Lactobacillus amylovorus, as well as LCA, represents a promising strategy to improve PEDV infection in piglets. Video Abstract.

The association of systemic inflammatory biomarkers with non-alcoholic fatty liver disease: a large population-based cross-sectional study.

Purpose: The aim of this study was to explore the relationship between non-alcoholic fatty liver disease (NAFLD) and the two blood inflammatory markers including the systemic immune-inflammation (SII) index, and the system inflammation response index (SIRI). Methods: The National Health and Nutrition Examination Survey data between the year of 2017-2018 was used for this cross-sectional study. In order to analyze the association of SII index, and SIRI and risk of NAFLD, we used multivariable logistic regression models, restricted cubic spline (RCS) plot, and subgroup analysis to analyze the data. Results: In total, there were 1,199 individuals who participated in the survey. As shown by the RCS plot, SII index, and SIRI were linked with NAFLD risk in a U-shaped pattern. With regard to known confounding variables, when comparing the lowest quartile, the odds ratio with 95 % confidence interval for prevalence of NAFLD across the quartiles of SII index and SIRI were (0.89 (0.57, 1.41), 0.56 (0.35, 0.89) and 1.01 (0.64, 1.59)), and (0.77 (0.48, 1.23), 0.79 (0.50, 1.24) and 0.94 (0.60, 1.47)), respectively. Additionally, SII index, and SIRI and NAFLD risk also were U-curve correlated among the participants in age ≥60 years, female, without hypertension, and BMI of ≥30 kg/m2. Conclusions: There was a U-shaped association of SII index and SIRI with prevalence of NAFLD, indicating that SII index and SIRI should be monitored dynamically.

Microbial enhanced oil recovery (MEOR): recent development and future perspectives.

After conventional oil recovery operations, more than half of the crude oil still remains in a form, which is difficult to extract. Therefore, exploring and developing new enhanced oil recovery (EOR) technologies have always been priority research in oilfield development. Microbial enhanced oil recovery (MEOR) is a promising tertiary oil recovery technology that has received widespread attention from the global oil industry in recent years due to its environmental friendliness, simplicity of operation, and cost-effectiveness. This review presents the: principle, characteristics, classification, recent development, and applications of MEOR technology. Based on hundreds of field trials conducted worldwide, the microbial strains, nutrient systems, and actual effects used in these technologies are summarized, with an emphasis on the achievements made in the development and application of MEOR in China in recent years. These technical classifications involve: microbial huff and puff recovery (MHPR), microbial flooding recovery (MFR), microbial selective plugging recovery (MSPR), and microbial wax removal and control (MWRC). Most of them have achieved good results, with a success rate of approximately 80%. These successful cases have accumulated into rich experiential indications for the popularization and application of MEOR technology, but there are still important yet uncertain factors that hinder the industrialization of this technology. Finally, based on the extensive research and development of MEOR by the authors, especially in both laboratory and industrial large scales, the main challenges and future perspectives of the industrial application for MEOR are presented.

A Comparative Study of Growth Performance, Blood Biochemistry, Rumen Fermentation, and Ruminal and Fecal Bacterial Structure between Yaks and Cattle Raised under High Concentrate Feeding Conditions.

This study compared the growth performance, serum biochemical indicators, rumen fermentation parameters, rumen bacterial structure, and fecal bacterial structure of cattle and yaks fed for two months and given a feed containing concentrate of a roughage ratio of 7:3 on a dry matter basis. Compared with cattle, yak showed better growth performance. The serum biochemical results showed that the albumin/globulin ratio in yak serum was significantly higher than that in cattle. Aspartate aminotransferase, indirect bilirubin, creatine kinase, lactate dehydrogenase, and total cholesterol were significantly lower in yaks than in cattle. The rumen pH, acetate to propionate ratio, and acetate were lower in yaks than in cattle, whereas the lactate in yaks was higher than in cattle. There were significant differences in the structure of ruminal as well as fecal bacteria between cattle and yaks. The prediction of rumen bacterial function showed that there was a metabolic difference between cattle and yaks. In general, the metabolic pathway of cattle was mainly riched in a de novo synthesis of nucleotides, whereas that of yaks was mainly riched in the metabolic utilization of nutrients. This study provides a basis for understanding a rumen ecology under the condition of a high concentrate diet.

Identification of the Porcine Vascular Endothelial Cell-Specific Promoter ESAM1.0 Using Transcriptome Analysis.

The vascular endothelium of xenografted pig organs represents the initial site of rejection after exposure to recipient immune cells. In this study, we aimed to develop a promoter specific to porcine vascular endothelial cells as a step toward overcoming xenograft rejection. Transcriptome analysis was performed on porcine aortic endothelial cells (PAECs), ear skin fibroblasts isolated from GGTA knockout (GTKO) pigs, and the porcine renal epithelial cell line pk-15. RNA sequencing confirmed 243 differentially expressed genes with expression changes of more than 10-fold among the three cell types. Employing the Human Protein Atlas database as a reference, we identified 34 genes exclusive to GTKO PAECs. The endothelial cell-specific adhesion molecule (ESAM) was selected via qPCR validation and showed high endothelial cell specificity and stable expression across tissues. We selected 1.0 kb upstream sequences of the translation start site of the gene as the promoter ESAM1.0. A luciferase assay revealed that ESAM1.0 promoter transcriptional activity was significant in PAECs, leading to a 2.8-fold higher level of expression than that of the porcine intercellular adhesion molecule 2 (ICAM2) promoter, which is frequently used to target endothelial cells in transgenic pigs. Consequently, ESAM1.0 will enable the generation of genetically modified pigs with endothelium-specific target genes to reduce xenograft rejection.

[Salvianolic acid A contributes to cartilage endplate cell restoration by regulating miR-940 and miR-576-5p].

OBJECTIVE: To investigate whether Salvianolic acid A (SAA) can restore cartilage endplate cell degeneration of intervertebral discs and to identify the mechanism via regulation of micro-RNA. METHODS: Cartilage endplate cells were isolated from lumbar intervertebral disc surgical samples and were treated with serum containing a series of concentrations of SAA (2, 5, and 10 ?M) for 24, 48, and 72 h to identify a proper dose and treatment time of SAA. The effect SAA on interlenkin-1ß (IL-1ß)-induced extracellular matrix degradation of cartilage endplate cells were analyzed by Alcian blue staining and assessment of the expression levels of ADAMTS-5, MMP3 and Col2a1. Further, the potential target miRNAs were preliminarily screened by micro-RNA sequencing combining qRT-PCR and Western blot, and then, the miRNAs mimics and inhibitors were used to verify the regulatory effect of SAA on potential target miRNAs. RESULTS: The 10 µM SAA treatment for 48 h significantly enhanced the viability of cartilage endplate cells, and increased Col2a1 expression and glycosaminoglycan accumulation that were repressed by IL-1ß, and reduced the effect of IL-1ß on ADAMTS-5, and MMP3. Screening analysis based on micro-RNA sequencing and Venny analysis identified the downstream micro-RNAs, including miR-940 and miR-576-5p. Then, the miR-940-mimic or miR-576-5p-mimic were transfected into CEPCs. Compared with the SAA group, the expression of ADAMTS-5 and MMP3 increased significantly and the expression of COL2A1 obviously decreased after overexpression of miR-940 or miR-576-5p in CEPCs. CONCLUSION: Salvianolic acid A attenuated the IL-1ß-induced extracellular matrix degradation of cartilage endplate cells by targeting regulate the miR-940 and the miR-576-5p.

Dextran sulfate sodium-induced gut microbiota dysbiosis aggravates liver injury in mice with S100-induced autoimmune hepatitis.

Recently, the incidence of autoimmune hepatitis (AIH) has gradually increased, and the disease can eventually develop into cirrhosis or even hepatoma if left untreated. AIH patients are often characterized by gut microbiota dysbiosis, but whether gut microbiota dysbiosis contributes to the progression of AIH remains unclear. In this study, we investigate the role of gut microbiota dysbiosis in the occurrence and development of AIH in mice with dextran sulfate sodium salt (DSS) induced colitis. C57BL/6J mice were randomly divided into normal group, S100-induced AIH group, and DSS+S100 group (1 % DSS in the drinking water), and the experimental cycle lasted for four weeks. We demonstrate that DSS administration aggravates hepatic inflammation and disruption of the intestinal barrier, and significantly changes the composition of gut microbiota in S100-induced AIH mice, which are mainly characterized by increased abundance of pathogenic bacteria and decreased abundance of beneficial bacteria. These results suggest that DSS administration aggravates liver injury of S100-induced AIH, which may be due to DSS induced gut microbiota dysbiosis, leading to disruption of the intestinal barrier, and then, the microbiota translocate to the liver, aggravating hepatic inflammation.

Traditional Chinese Medicine formula Bu-Shen-Huo-Xue-Fang (BSHXF) protects nucleus pulposus cells against the inflammatory and oxidative stress-induced degenerative changes.

Degeneration of the intervertebral disc is primarily caused by the loss of nucleus pulposus cells (NPCs) and extracellular matrix (ECM) (IDD). Bu-Shen-Huo-Xue-Fang (BSHXF), a traditional Chinese medicine decoction, has been used to treat IDD in clinical; nevertheless, the active components and underlying molecular mechanisms remain unknown. BSHXF improved IL-1ß and H2O2 stimulation-induced injuries on NPCs by promoting cell viability, increasing ECM deposition, inhibiting cell senescence, and decreasing the levels of inflammatory factors. The active ingredients in BSHXF were identified by LC-MS/MS analysis; three active ingredients from the principal drugs, Aucubin, Tanshinol, and Tanshinone II A promoted NPC viability; and Aucubin and Tanshinol promoted NPC viability more. Aucubin and Tanshinol, respectively, improved H2O2 stimulation-induced injuries on NPCs by promoting cell viability, increasing ECM deposition, inhibiting cell senescence, and decreasing the levels of inflammatory factors. The activator of NF-κB and Wnt signaling pathways attenuated Aucubin and Tanshinol's protective effects by promoting ECM degradation and NPC senescence. Aucubin, Tanshinol, and Tanshinone II A were identified as the most potent compounds in BSHXF protection against degenerative changes in NPCs. The NF-κB and Wnt signaling pathways might be involved in the protective effects of Aucubin and Tanshinol against H2O2-induced degenerative changes.