The alleviating effect of Scutellaria amoena extract on the regulation of gut microbiota and its metabolites in NASH rats by inhibiting the NLRP3/ASC/caspase-1 axis.

Background: Scutellaria amoena (SA) is the root of S. amoena C.H. Wright of Labiatae, also known as Scutellaria southwestern. This is mainly distributed in Sichuan, Yunnan, and Guizhou in China. In southwest China, SA is used as an alternative method to genuine medicine for the treatment of allergy, diarrhea, inflammation, hepatitis, and bronchitis. Thus far, studies on the effects of SA on non-alcoholic steatohepatitis (NASH) are lacking. This paper investigated the effect of SA on the regulation of gut microbiota and its metabolites in NASH rats by inhibiting the NOD-like receptor 3 (NLRP3)/apoptosis-associated speck-like protein (ASC)/caspase-1 axis. Methods: A NASH rat model was induced by a high-fat diet (HFD) for 12 weeks, and rats were orally given different doses of SA extracts (150 and 300 mg/kg/d) for 6 weeks. Changes in histological parameters, body weight, organ indexes, cytokines, and biochemical parameters related to NLRP3 in NASH rats were checked. 16S rRNA gene sequencing and UPLC-MS/MS technology were used to analyze the changes in the gut microbiota composition and its metabolites in NASH rats. Results: SA significantly inhibited the HFD-induced increase in body weight, lipid levels, and inflammatory infiltration. SA notably inhibited the HFD-induced increase in the upper and lower factors of NLRP3, such as transforming growth factor (TGF)-ß, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-18, pro-IL-18, IL-1ß, pro-IL-1ß, NLRP3, ASC, and caspase-1. Additionally, mRNA expressions of caspase-1, NLRP3, and ASC were significantly downregulated after SA treatment. The results of the intestinal flora showed that SA could increase the diversity of flora and change its structure and composition in NASH rats by reducing Firmicutes/Bacteroidetes (F/B) ratio, Blautia (genus), Lachospiraceae (family), and Christensenellaceae R-7 group (genus), and increasing Muribaculaceae (family) and Bacteroides (genus). The metabolomics revealed that 24 metabolites were possibly the key metabolites for SA to regulate the metabolic balance of NASH rats, including chenodeoxycholic acid, xanthine, and 9-OxoODE. Nine metabolic pathways were identified, including primary bile acid biosynthesis, bile secretion, purine metabolism, and secondary bile acid biosynthesis. Conclusion: SA can regulate the intestinal microbial balance and metabolic disorder by inhibiting the NLRP3/ASC/caspase-1 axis to relieve NASH.

Effects of Tylophora yunnanensis Schltr on regulating the gut microbiota and its metabolites in non-alcoholic steatohepatitis rats by inhibiting the activation of NOD-like receptor protein 3.

ETHNOPHARMACOLOGICAL RELEVANCE: Tylophora yunnanensis Schltr (TYS) is widely distributed in Yunnan, Guizhou, and other places in China. It is commonly used by folks to treat hepatitis and other liver-related diseases; however, its mechanism of action is still unclear. AIM OF THE STUDY: This study aimed to determine the effects of TYS on regulating gut microbiota and its metabolites in non-alcoholic steatohepatitis (NASH) rats by inhibiting the activation of NOD-like receptor protein3 (NLRP3). MATERIAL AND METHODS: An HFD-induced rat model was established to investigate if the intragastric administration of TYS could mediate gut microbiota and their metabolites to ultimately improve the symptoms of NASH. The improving effects of TYS on NASH rats were assessed by measuring their body weight, lipid levels, histopathology, and inflammatory factor levels in the rat models. The regulatory effects of TYS on NLRP3 in the NASH rats were analyzed using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA), which determined the levels of NLRP3-related factors. The changes in the composition of the gut microbiota of NASH rats were analyzed using 16S rRNA gene sequencing technology. Meanwhile, the Ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used for the non-targeted analysis of metabolites in the cecum contents. RESULTS: The results showed that TYS could improve NASH by decreasing the body weight and levels of lipid, AST, ALT, LPS, FFA, VLDL, IL-1ß, IL-6, TNF-α, TGF-ß, NLRP3, ASC, and Caspase-1 in the NASH rats. The analysis of gut microbiota showed that TYS could improve the diversity and abundance of gut microbiota and alter their composition by decreasing the Firmicutes/Bacteroidetes (F/B) ratio and relative abundances of Lachnospiraceae, Christensenellaceae, Blautia, etc. while increasing those of Muribaculaceae, Rumiaococcus, Ruminococcaceae, etc. The analysis of metabolites in the cecum contents suggested that the arachidonic acid metabolism, bile secretion, serotonergic synapse, Fc epsilon RI signaling pathway, etc. were regulated by TYS. The metabolites enriched in these pathways mainly included chenodeoxycholic acid, prostaglandin D2, TXB2, 9-OxoODE, and 13(S)-HOTrE. CONCLUSIONS: These findings suggested that TYS could alleviate the NASH symptoms by decreasing the body weight, regulating the lipid levels, reducing the inflammatory response, and inhibiting the expression levels of NLRP3, ASC, and Caspase-1 in the NASH rats. The changes in the composition of gut microbiota and their metabolic disorder were closely related to the activation of NLRP3. TYS could significantly inhibit the activation of NLRP3 and regulate the composition of gut microbiota and the disorder of metabolites during NASH modeling.

Flavonoids from Scutellaria amoena C. H. Wright alleviate mitochondrial dysfunction and regulate oxidative stress via Keap1/Nrf2/HO-1 axis in rats with high-fat diet-induced nonalcoholic steatohepatitis.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is among the most common liver diseases in the world. Flavonoids from Scutellaria amoena (SAF) are used in the treatment of hepatopathy in China. However, the effect and mechanism against NASH remain unclear. We investigated the alleviating effect of SAF on NASH via regulating mitochondrial dysfunction and oxidative stress. METHODS: The effects of SAF on NASH were evaluated using in vitro and in vivo methods. L02 cells were induced by fat emulsion to establish an adipocytes model, followed by treatment with SAF for 24 h. NASH rat models were established by the administration of a high-fat diet for 12 weeks and were administered SAF for six weeks. Changes in body weight, organ indexes, lipid levels, inflammatory cytokines, mitochondrial indicators, and fatty acid metabolism were investigated. RESULTS: SAF significantly improved body weight, organ indexes, lipid levels, liver injury, and inflammatory infiltration in NASH rats. SAF notably regulated interleukin-6, tumor necrotic factor-alpha, superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), kelch-like ECH-associated protein 1 (Keap1), nuclear factor-erythroid factor 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1). Additionally, SAF improved mitochondrial dysfunction, increased the levels of GSH, SOD, ATP synthase, complex I and II, and decreased the level of MDA in liver mitochondria. SAF regulated the expression of ß-oxidation genes, including peroxisome proliferator-activated receptor -gamma coactivator-1alpha (PGC-1α), carnitine palmitoyltransferase-1 (CPT1) A, CPT1B, medium-chain acyl-CoA dehydrogenase, long-chain acyl-CoA dehydrogenase, very long-chain acyl-CoA dehydrogenase, and PPARα. CONCLUSION: SAF can alleviate NASH by regulating mitochondrial function and oxidative stress via the Keap1/Nrf2/HO-1 axis.

Two Novel Flavonoids with Lipid-Lowering Activity from Yi Medicine Shekaqi.

Yi medicine Shekaqi is the most attractive traditional ethnic medicine due to its significant and diverse pharmacological activities. Two novel flavonoids, including 5,2'-dihydroxy-6-methoxy-7-decyloxyflavone and tenaxin II-7-O-ß-D-glucuronopyranosyl acid butyl ester, along with six known flavonoids, were isolated from Yi medicine Shekaqi. Their structures were elucidated based on the analysis of their comprehensive spectral data. The in vitro lipid-lowering activities of the eight compounds showed that all the compounds significantly inhibited the lipopolysaccharide (LPS)-induced increase in the total cholesterol (TC) level, while compounds 1, 4, 6, 7, and 8 significantly inhibited the LPS-induced increase in the triglyceride (TG) level.

Efficacy and tolerability of combination therapy with alpha-blockers and phosphodiesterase-5 inhibitors compared with monotherapy for lower urinary tract symptoms: Protocol for a systematic review and network meta-analysis.

PURPOSE: This study aimed to compare the efficacy and safety of combination therapy consisting of α-blockers and different phosphodiesterase type 5 inhibitors for lower urinary tract symptoms (LUTS) by performing a network meta-analysis. METHOD: Relevant articles were retrieved from the Cochrane Library, PubMed, and EMBASE databases. Bayesian network meta-analyses were performed with a random-effect model to compare the efficacy and safety of combination therapy with α-blockers and phosphodiesterase-5 inhibitors for LUTS. The odds ratio (OR), mean difference (MD) and surface under the cumulative ranking curve (SUCRA) were calculated with the GeMTC R package. RESULTS: Twenty randomized trials with 4131 patients were included in this network meta-analysis. Based on the SUCRA values, vardenafil (10 mg) combined with α-blockers ranked first, first and sixth; sildenafil (25 mg) combined with α-blockers ranked second, third and first; and tadalafil (20 mg) combined with α-blockers ranked third, second and fourth in IPSS, post void residual, and maximum flow rate, respectively. CONCLUSIONS: Combination therapy with α-blockers and phosphodiesterase-5 inhibitors was effective and well tolerated for LUTS. For men who prioritize high efficacy, vardenafil (10 mg) combined with α-blockers seems to be the treatment of choice. For men wishing to optimize minimally invasive treatment, sildenafil (25 mg) and tadalafil (20 mg) combined with α-blockers appears to have a possible advantage in terms of avoiding adverse effects.

Enhanced thermoelectric properties of Bi2S3 polycrystals through an electroless nickel plating process.

Bi2S3 is an eco-friendly alternative compound for thermoelectric devices. However, the low electrical conductivity of the pristine Bi2S3 hinders the improvement of its ZT value, which further restricts its application in the field of thermoelectricity. In this work, we report the first attempt to optimize the thermoelectric properties of Bi2S3 by electroless nickel plating. A nickel plated Bi2S3 powder sample was synthesized by electroless nickel plating on the precursor Bi2S3 powder prepared by mechanical alloying. Then, the powder was sintered to a bulk material by spark plasma sintering. The relationships between the composition, microstructure and thermoelectric properties of the bulk samples were investigated. The XRD results showed a AgBi3S5 second phase which was formed by the reaction of Ag residues with the Bi2S3 substrate during the sintering process. The nickel element and AgBi3S5 second phase introduced in the nickel plating process directly affect the electronic conductivity and Seebeck coefficient of the nickel plating sample, resulting in the relatively high power factor of 244 µW m-1 K-2 at 628 K. What's more, the thermal conductivity of the sample was also reduced moderately, obtaining a low value of 0.40 µW m-1 K-1 at 628 K. Therefore, a maximum ZT value of 0.38 was obtained at 628 K for the nickel plated sample, which is three times higher than that (0.12 at 628 K) of pristine Bi2S3 materials.

The treatment of non-musle-invasive cancer by narrow band imaging or white light imaging: a review and meta-analysis / 中华泌尿外科杂志

Objective The purpose of this work was to compare the efficacy of narrow band imaging-assisted transurethral resection of bladder tumour (TURB) with conventional white light imagingassisted TURB in primary non-muscle-invasive bladder cancer.Methods Several databases were searched,including Cochrance Libarary,PubMed,Embase,Wanfang,VIP,CNKI and CBM.The endpoints were biochemical failure in 3 months,1 year and 2 years.We performed a meta-analysis of the published data.The results are expressed as risk ratio (RR),with the corresponding 95％ confidence interval (CI).Results The final analysis included seven trials comprising 1889 patients.Biochemical failure in 3months (RR0.73,95％ CI 0.55-0.96;P =0.02),1 year(RR 0.69,95％ CI 0.58-0.80;P ＜ 0.01) and 2 years (RR 0.58,95％ CI 0.41-0.82;P =0.002) were fewer in patients who received narrow band imagingassisted TURB.The recurrence rates of 3 months,1 year and 2 years were 14.44％,29.35％ and 30％ in white light imaging group.The recurrence rates of 3 months,1 year and 2 years were 3.61％,9.35％ and 12.59％ lower in narrow band imaging group compared with white light imaging group.Conclusions Narrow band imaging-assisted TURB was superior to conventional white light imaging-assisted TURB in primary non-muscle-invasive bladder cancer in 2 years.

Effect of Yupingfeng granules on HA and Foxp3(+) Treg expression in patients with nasopharyngeal carcinoma.

OBJECTIVE: To investigate the effect of Yupingfeng on hyaluronic acid (HA) and Foxp3(+) Treg in patients with nasopharyngeal carcinoma. METHODS: A total of 58 cases of nasopharyngeal carcinoma were divided into two groups, 30 cases in the treatment group, 28 cases in the control group. Patients in two groups were treated with synchronous radiotherapy and chemotherapy treatment, the treatment group was treated with the Yupingfeng granules through oral administration, 10 g/time, tid for 2 courses. The serum Foxp3(+) Treg markers of each group were detected by flow cytometry assay before treatment and after treatment, and the level of HA in serum was detected by radio immunoassay. RESULTS: After radiotherapy and chemotherapy, the contents of Foxp3(+) Treg and HA were significantly decreased in two groups (P < 0.05), and the decrease of treatment group was more significantly (P < 0.01). Correlation analysis showed positive correlation between Foxp3(+) Treg and HA (P < 0.05). After treatment, the incidence of side effects in two groups was significantly decreased. And there was significant difference between two groups (P < 0.05). CONCLUSIONS: Combined chemotherapy and radiotherapy with Yupingfeng treatment can decrease the levels of Foxp3(+) Treg and HA in nasopharyngeal carcinoma patients. Yupingfeng can also effectively reduce the side effect due to radiation and chemotherapy.

Effect of Yupingfeng granules on HA and Foxp3(+) Treg expression in patients with nasopharyngeal carcinoma

OBJECTIVE@#To investigate the effect of Yupingfeng on hyaluronic acid (HA) and Foxp3(+) Treg in patients with nasopharyngeal carcinoma.@*METHODS@#A total of 58 cases of nasopharyngeal carcinoma were divided into two groups, 30 cases in the treatment group, 28 cases in the control group. Patients in two groups were treated with synchronous radiotherapy and chemotherapy treatment, the treatment group was treated with the Yupingfeng granules through oral administration, 10 g/time, tid for 2 courses. The serum Foxp3(+) Treg markers of each group were detected by flow cytometry assay before treatment and after treatment, and the level of HA in serum was detected by radio immunoassay.@*RESULTS@#After radiotherapy and chemotherapy, the contents of Foxp3(+) Treg and HA were significantly decreased in two groups (P < 0.05), and the decrease of treatment group was more significantly (P < 0.01). Correlation analysis showed positive correlation between Foxp3(+) Treg and HA (P < 0.05). After treatment, the incidence of side effects in two groups was significantly decreased. And there was significant difference between two groups (P < 0.05).@*CONCLUSIONS@#Combined chemotherapy and radiotherapy with Yupingfeng treatment can decrease the levels of Foxp3(+) Treg and HA in nasopharyngeal carcinoma patients. Yupingfeng can also effectively reduce the side effect due to radiation and chemotherapy.

Effect of Yupingfeng granules on HA and Foxp3+ Treg expression in patients with nasopharyngeal carcinoma

Objective: To investigate the effect of Yupingfeng on hyaluronic acid (HA) and Foxp3+ Treg in patients with nasopharyngeal carcinoma. Methods: A total of 58 cases of nasopharyngeal carcinoma were divided into two groups, 30 cases in the treatment group, 28 cases in the control group. Patients in two groups were treated with synchronous radiotherapy and chemotherapy treatment, the treatment group was treated with the Yupingfeng granules through oral administration, 10 g/time, tid for 2 courses. The serum Foxp3+ Treg markers of each group were detected by flow cytometry assay before treatment and after treatment, and the level of HA in serum was detected by radio immunoassay. Results: After radiotherapy and chemotherapy, the contents of Foxp3+ Treg and HA were significantly decreased in two groups (P + Treg and HA (P + Treg and HA in nasopharyngeal carcinoma patients. Yupingfeng can also effectively reduce the side effect due to radiation and chemotherapy.

[Reconstruction of orbital floor defect with polylacticglycolide acid/recombinant human bone morphogenetic protein 2 compound implanted material in sheep].

OBJECTIVE: To study the effect and safety of polylacticglycolide acid copolymer (PLGA) and recombinant human bone morphogenetic protein 2 (rhBMP-2) as implanted biomaterials for reconstruction orbital floor defects in sheep and find the relationship between implant materials degradation and orbital floor defects restoration. METHODS: Nine sheep (eighteen eyes) with orbital floor defect were divided into three groups randomly. Group A was the control without treatment. Group B was treated with PLGA and group C was received PLGA/rhBMP-2. Cosmetic appearances and complications were observed after surgery. CT scan, 3D reconstruction, defect area measurement and histological examination were performed on a week, three months and six months after operation. RESULTS: No complication was observed. The CT examinations showed that orbital floor defect in group C was almost disappeared by six months, however in group A and group B only partially orbital floor defect was repaired. Histological examinations showed that all materials were absorbed on six months. The orbit defects in group A were replaced by fiber tissue. The defect areas in group B were consisted of bone tissue in the peripheral and fiber tissue in the center. In group C the reconstructed areas were replaced by bone tissue, loose connective tissue and mucosal epithelia layers. CONCLUSION: The thick of 0.5 mm PLGA/rhBMP-2 sheet is a good substitute material of bone graft and may be used for orbital fracture defect reconstruction in clinic in the future.