A comprehensive review of Tripterygium wilfordii hook. f. in the treatment of rheumatic and autoimmune diseases: Bioactive compounds, mechanisms of action, and future directions.

Rheumatic and autoimmune diseases are a group of immune system-related disorders wherein the immune system mistakenly attacks and damages the body's tissues and organs. This excessive immune response leads to inflammation, tissue damage, and functional impairment. Therapeutic approaches typically involve medications that regulate immune responses, reduce inflammation, alleviate symptoms, and target specific damaged organs. Tripterygium wilfordii Hook. f., a traditional Chinese medicinal plant, has been widely studied in recent years for its application in the treatment of autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis. Numerous studies have shown that preparations of Tripterygium wilfordii have anti-inflammatory, immunomodulatory, and immunosuppressive effects, which effectively improve the symptoms and quality of life of patients with autoimmune diseases, whereas the active metabolites of T. wilfordii have been demonstrated to inhibit immune cell activation, regulate the production of inflammatory factors, and modulate the immune system. However, although these effects contribute to reductions in inflammatory responses and the suppression of autoimmune reactions, as well as minimize tissue and organ damage, the underlying mechanisms of action require further investigation. Moreover, despite the efficacy of T. wilfordii in the treatment of autoimmune diseases, its toxicity and side effects, including its potential hepatotoxicity and nephrotoxicity, warrant a thorough assessment. Furthermore, to maximize the therapeutic benefits of this plant in the treatment of autoimmune diseases and enable more patients to utilize these benefits, efforts should be made to strengthen the regulation and standardized use of T. wilfordii.

Rice bran oil supplementation protects swine weanlings against diarrhea and lipopolysaccharide challenge. / æ—¥ç²®æ·»åŠ ç±³ç³ æ²¹å¯å¢žå¼ºæ–­å¥¶ä»”çŒªæŠµæŠ—è ¹æ³»å’Œè„‚å¤šç³–åº”æ¿€.

Early weaned piglets suffer from oxidative stress and enteral infection, which usually results in gut microbial dysbiosis, serve diarrhea, and even death. Rice bran oil (RBO), a polyphenol-enriched by-product of rice processing, has been shown to have antioxidant and anti-inflammatory properties both in vivo and in vitro. Here, we ascertained the proper RBO supplementation level, and subsequently determined its effects on lipopolysaccharide (LPS)-induced intestinal dysfunction in weaned piglets. A total of 168 piglets were randomly allocated into four groups of seven replicates (42 piglets each group, (21±1) d of age, body weight (7.60±0.04) kg, and half males and half females) and were given basal diet (Ctrl) or basal diet supplemented with 0.01% (mass fraction) RBO (RBO1), 0.02% RBO (RBO2), or 0.03% RBO (RBO3) for 21 d. Then, seven piglets from the Ctrl and the RBO were treated with LPS (100 µg/kg body weight (BW)) as LPS group and RBO+LPS group, respectively. Meanwhile, seven piglets from the Ctrl were treated with the saline vehicle (Ctrl group). Four hours later, all treated piglets were sacrificed for taking samples of plasma, jejunum tissues, and feces. The results showed that 0.02% was the optimal dose of dietary RBO supplementation based on diarrhea, average daily gain, and average daily feed intake indices in early weaning piglets. Furthermore, RBO protected piglets against LPS-induced jejunal epithelium damage, which was indicated by the increases in villus height, villus height/crypt depth ratio, and Claudin-1 levels, as well as a decreased level of jejunal epithelium apoptosis. RBO also improved the antioxidant ability of LPS-challenged piglets, which was indicated by the elevated concentrations of catalase and superoxide dismutase, and increased total antioxidant capacity, as well as the decreased concentrations of diamine oxidase and malondialdehyde in plasma. Meanwhile, RBO improved the immune function of LPS-challenged weaned piglets, which was indicated by elevated immunoglobulin A (IgA), IgM, ß||-defensin-1, and lysozyme levels in the plasma. In addition, RBO supplementation improved the LPS challenge-induced dysbiosis of gut microbiota. Particularly, the indices of antioxidant capacity, intestinal damage, and immunity were significantly associated with the RBO-regulated gut microbiota. These findings suggested that 0.02% RBO is a suitable dose to protect against LPS-induced intestinal damage, oxidative stress, and jejunal microbiota dysbiosis in early weaned piglets.

Inhibition on XBP1s-driven lipogenesis by Qushi Huayu Decoction contributes to amelioration of hepatic steatosis induced by fructose.

ETHNOPHARMACOLOGICAL RELEVANCE: Qushi Huayu Decoction (QHD) is a traditional Chinese medicine formula consisting of five herbs, which has been used for non-alcoholic fatty liver disease (NAFLD) treatment in clinic for decades in China and validated in several NAFLD animal models. The hepatic de novo lipogenesis (DNL) is enhanced greatly to contribute to steatosis in NAFLD. The spliced form of X-box binding protein 1 (XBP1s) initiates DNL independently of sterol regulatory element-binding protein (SREBP) and carbohydrate-responsive element-binding protein (ChREBP). AIM OF THE STUDY: To disclose the mechanism of inhibition on hepatic DNL by QHD and the responsible compounds. METHODS: The effects of QHD on hepatic DNL were evaluated in mice induced by high-fructose diet (HFru). The effects of the serum-absorbed compounds of QHD on XBP1s were evaluated in HepG2 cells induced by tunicamycin. Hepatic histology, triglyceride (TG) and nonesterified fatty acids were observed. Hepatic apolipoprotein B100 and very low-density lipoprotein were measured to reflect lipid out-transport. The mRNA expression of XBP1s and its target genes were detected by real-time polymerase chain reaction. The protein expression of TG synthetases and DNL enzymes, and inositol requirement enzyme 1 alpha (IRE1α), phosphorylated IRE1α and XBP1s were detected in liver tissue and HepG2 cells by western-blot. The binding activity of SREBP1, protein expression of ChREBP and XBP1s were detected in the nuclear extracts of liver tissue. RESULTS: Dynamical observing suggested feeding with HFru for 2 weeks was sufficient to induce hepatic lipogenesis and XBP1s. QHD ameliorated liver steatosis without enhancing out-transport of lipids, accompanied with more inhibitory effects on DNL enzymes than TG synthetases. QHD inhibits the nuclear XBP1s without affecting ChREBP and SREBP1. In QHD, chlorogenic acid, geniposide and polydatin inhibit lipogenesis initiated by XPB1s. CONCLUSION: QHD probably decreases hepatic DNL by inhibiting XBP1s independent of SREBP1 and ChREBP. Chlorogenic acid, geniposide and polydatin are the potential responsible compounds.

Taxifolin Alleviates DSS-Induced Ulcerative Colitis by Acting on Gut Microbiome to Produce Butyric Acid.

Taxifolin is a bioflavonoid which has been used to treat Inflammatory Bowel Disease. However, taxifolin on DSS-induced colitis and gut health is still unclear. Here, we studied the effect of taxifolin on DSS-induced intestinal mucositis in mice. We measured the degree of intestinal mucosal injury and inflammatory response in DSS treated mice with or without taxifolin administration and studied the changes of fecal metabolites and intestinal microflora using 16S rRNA. The mechanism was further explored by fecal microbiota transplantation. The results showed that the weight loss and diarrhea score of the mice treated with taxifolin decreased in DSS-induced mice and longer colon length was displayed after taxifolin supplementation. Meanwhile, the expression of GPR41 and GPR43 in the colon was significantly increased by taxifolin treatment. Moreover, the expression of TNF-α, IL-1ß, and IL-6 in colon tissue was inhibited by taxifolin treatment. The fecal metabolism pattern changed significantly after DSS treatment, which was reversed by taxifolin treatment. Importantly, taxifolin significantly increased the levels of butyric acid and isobutyric acid in the feces of DSS-treated mice. In terms of gut flora, taxifolin reversed the changes of Akkermansia, and further decreased uncultured_bacterium_f_Muribaculaceae. Fecal transplantation from taxifolin-treated mice showed a lower diarrhea score, reduced inflammatory response in the colon, and reduced intestinal mucosal damage, which may be related to the increased level of butyric acid in fecal metabolites. In conclusion, this study provides evidence that taxifolin can ameliorate DSS-induced colitis by altering gut microbiota to increase the production of SCFAs.

Dietary Quercetin Supplementation Attenuates Diarrhea and Intestinal Damage by Regulating Gut Microbiota in Weanling Piglets.

Antioxidant polyphenols from plants are potential dietary supplementation to alleviate early weaning-induced intestinal disorders in piglets. Recent evidences showed polyphenol quercetin could reshape gut microbiota when it functioned as anti-inflammation or antioxidation agents in rodent models. However, the effect of dietary quercetin supplementation on intestinal disorders and gut microbiota of weanling piglets, along with the role of gut microbiota in this effect, both remain unclear. Here, we determined the quercetin's effect on attenuating diarrhea, intestinal damage, and redox imbalance, as well as the role of gut microbiota by transferring the quercetin-treated fecal microbiota to the recipient piglets. The results showed that dietary quercetin supplementation decreased piglets' fecal scores improved intestinal damage by increasing tight junction protein occludin, villus height, and villus height/crypt depth ratio but decreased crypt depth and intestinal epithelial apoptosis (TUNEL staining). Quercetin also increased antioxidant capacity indices, including total antioxidant capacity, catalase, and glutathione/oxidized glutathione disulfide but decreased oxidative metabolite malondialdehyde in the jejunum tissue. Fecal microbiota transplantation (FMT) from quercetin-treated piglets had comparable effects on improving intestinal damage and antioxidative capacity than dietary quercetin supplementation. Further analysis of gut microbiota using 16S rDNA sequencing showed that dietary quercetin supplementation or FMT shifted the structure and increased the diversity of gut microbiota. Especially, anaerobic trait and carbohydrate metabolism functions of gut microbiota were enriched after dietary quercetin supplementation and FMT, which may owe to the increased antioxidative capacity of intestine. Quercetin increased the relative abundances of Fibrobacteres, Akkermansia muciniphila, Clostridium butyricum, Clostridium celatum, and Prevotella copri but decreased the relative abundances of Proteobacteria, Lactobacillus coleohominis, and Ruminococcus bromii. Besides, quercetin-shifted bacteria and carbohydrate metabolites short chain fatty acids were significantly related to the indices of antioxidant capacity and intestinal integrity. Overall, dietary quercetin supplementation attenuated diarrhea and intestinal damage by enhancing the antioxidant capacity and regulating gut microbial structure and metabolism in piglets.

A novel approach of synchronously recovering phosphorus as vivianite and volatile fatty acids during waste activated sludge and food waste co-fermentation: Performance and mechanisms.

This research proposed an innovative approach to synchronously enhance the recovery of phosphorus (P) as vivianite and volatile fatty acids (VFAs) during waste activated sludge (WAS) and food waste (FW) co-fermentation. A high performance was achieved under 30% FW addition and pH uncontrolled, which gained 83.09% of TP recovery as high-purity vivianite (93.90%), together with efficient VFAs production (7671 mg COD/L). The FW supplement could enhance VFAs production and subsequently lower pH to contribute to the release of Fe2+ and PO43-. Also, it could dampen disrupting effects of strong acidic pH on microbial cells (lowering LDH release). Moreover, the flexible pH variation caused by biological acidification could maintain relatively higher microbial activities (increasing enzymes' activities), which was advantageous to the biological effects involved in Fe2+ and PO43 release and VFAs generation. Therefore, this research provide a promising and economic alternative to dispose of WAS and FW simultaneously for valuable resource recovery.

Enhanced volatile fatty acids production from waste activated sludge with synchronous phosphorus fixation and pathogens inactivation by calcium hypochlorite stimulation.

An efficient approach for synchronous volatile fatty acids (VFAs) promotion, phosphorus fixation and pathogens inactivation during waste activated sludge (WAS) anaerobic fermentation was achieved with optimal calcium hypochlorite (Ca(ClO)2) stimulation. The maximal VFAs were 3.6 folds of control in reactors with 0.01 g Ca(ClO)2/g TSS addition. The low dosage of Ca(ClO)2 enhanced WAS solubilization and hydrolysis by disrupting the extracellular polymeric substance (EPS) effectively. Sufficient substrates for fermentative bacteria were thereby provided with the maintenance of acceptable microbial activity and viability. However, high dosage of Ca(ClO)2 deteriorated the performance of anaerobic fermentation due to its strong oxidative ability, resulting in cell lysis greatly. Moreover, the largely released phosphorus during WAS fermentation was effectively precipitated and removed by the combination of Ca2+ at 0.01 g Ca(ClO)2/g TSS dosage. In addition, Ca(ClO)2 had distinguished effects on pathogens inactivation. The simultaneous phosphorus fixation and pathogens reduction during VFAs production increased the utilization value of fermentation liquid and benefitted the further disposal of fermented sludge.

Glottis motion effects on the particle transport and deposition in a subject-specific mouth-to-trachea model: A CFPD study.

BACKGROUND: Computational Fluid-Particle Dynamics (CFPD) models have been employed to predict lung aerosol dynamics for decades, estimating the delivery efficiency of inhaled drugs into the tracheobronchial tree. However, existing CFPD models assume the glottis is static during the breathing cycle. Failing to capture the dynamic motion of the glottis may introduce significant errors in drug deposition estimations. METHODS: A novel CFPD model was developed with the capability of modeling the glottis motion using the dynamic mesh method. To explore the causal relationships between the glottis motion and the inhaled drug particle dynamics, simulations were performed to compare static and different dynamic glottis models in a subject-specific mouth-to-trachea geometry under idealized sinusoidal and realistic breathing waveforms. By defining the movement of each node in the glottis region using a generalized glottis motion function (GGMF) validated with clinical data, the abduction and adduction of the glottis were accurately described. Transient transport characteristics of inhaled particle-laden airflows were investigated and analyzed, including the glottis motion effect on the inhaled particles with the aerodynamic diameters from 0.1 to 10 µm. RESULTS: Numerical results indicate that the static glottis assumption deviates the total deposition fraction predictions by more than 8% in relative differences. Compared with the CFPD models with the static glottis assumption, the dynamic glottis model can more realistically predict the complexity of the secondary flows near the vocal fold and the resultant particle depositions. Inter-subject variabilities of the glottis motion patterns were observed, and their influences on particle transport dynamics are not uniform. Parametric analyses also demonstrate that the maximum deformation ratio of the glottis is a key feature to describe whether the glottis motion can enhance or reduce particle depositions in the mouth-to-trachea region, over the static glottis model. CONCLUSIONS: The glottis motion shows a significant influence on the accuracy of predicting inhaled particle dynamics, and it should be integrated into CFPD simulations validated by subject-specific glottis motion data from clinical studies in the future. Furthermore, the proposed dynamic glottis model has been demonstrated to be a computationally effective method to recover the physiologically realistic motions of the glottis, and ready to be added into the next-generation holistic virtual lung modeling approach.

Phosphorus recovery as vivianite from waste activated sludge via optimizing iron source and pH value during anaerobic fermentation.

This study presented an innovative method for phosphorus (P) recovery as vivianite from waste activated sludge (WAS) via optimizing iron dosing and pH value during anaerobic fermentation (AF). The optimal conditions for vivianite formation were in the pH range of 6.0-9.0 with initial PO43- >5 mg/L and Fe/P molar ratio of 1.5. Notably, FeCl3 showed advantages over ZVI for the simultaneous release of Fe2+ and PO43- during WAS fermentation, especially in acidic conditions. The FeCl3 dosing at pH 3.0 could contribute to 78.81% Fe2+ release and 85.69% of total PO43- release from WAS. They were ultimately recovered in the form of high-purity vivianite (93.67%). Clostridiaceae (40.25%) was the predominant bacteria in FeCl3-pH3 reactors, which played key roles in inducing dissimilatory iron reduction for Fe2+ formation. Therefore, P recovery as vivianite from WAS fermentation might be a promising and highly valuable approach to relieve the P crisis.

Traditional Chinese medicine syndromes of chronic hepatitis B with precore mutant.

AIM: This study aims at exploring the distribution of TCM syndromes in CHB patients with HBV pre-core mutation (1896) and the relationship between pre-core mutation and T lymphocytes subgroup, through which to provide objective data on clinical syndrome differentiation of TCM, and further to suggest the therapeutic principle and guide clinical treatment. METHODS: One hundred and forty CHB patients were evenly divided into two study groups, HBV pre-core mutant group and HBV pre-core wild-type group. Besides, 30 healthy blood donors were selected as a healthy control group. HBV-labeled compound, T lymphocytes subgroup, and HBV-DNA pre-core mutant were tested in the study groups. T lymphocytes subgroup were also tested in the control group. All the patients were both diagnosed by syndrome differentiation of TCM and western medicine. RESULTS: The most common syndrome in mutant group was damp-heat combined with blood stasis, and the most common syndrome in the wild-type group was damp-heat stasis in the middle-jiao. There were more cases of medium and severe hepatitis in mutant group than that in wild-type group. The content of CD4+ lymphocytes and CD4+/CD8+ ratio were decreased gradually (healthy control group>wild-type group>mutant group). In the wild-type group, severe and medium CHB patients had considerably lower level of them than mild CHB patients. However, in the mutant group, the opposite result appeared. Meanwhile, the content of HBV-DNA in mutant group was higher than that in wild-type group. CONCLUSION: Damp, heat, toxin and blood stasis were the basic pathogens of CHB, whether pre-core mutant or not. CHB with precore mutant may lead to more severe hepatitis. The decreased content of CD4+ lymphocytes and ratio of CD4+/CD8+ may be taken as one of the indices in confirming the deficiency syndrome of CHB patients with pre-core mutation.