ω-3 polyunsaturated fatty acid alleviates systemic lupus erythematosus by suppressing autoimmunity in a murine model.

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune inflammatory disease that damages multiple organs by the production of autoantibodies. Numerous research studies have demonstrated the anti-inflammatory effects of ω-3 polyunsaturated fatty acids (PUFAs). A diet rich in ω-3 PUFAs reduces chronic inflammatory and autoimmune conditions. Herein, we investigated the protective effect of ω-3 PUFAs against autoimmune injury in SLE. In a TMPD-induced mouse model of SLE, supplementation with eicosapentaenoic acid (EPA)-rich (97%) fish oil was found to alleviate systemic autoimmune phenotypes such as ascites, lipogranulomas and serum dsDNA levels. In addition, EPA also significantly improved renal manifestations, reducing proteinuria, glomerulonephritis, and immune complex deposition. Mechanistically, ω-3 PUFAs were shown to modulate the differentiation of B lymphocyte subsets of primary splenic lymphocytes in the spontaneous murine lupus model MRL/MpJ-Faslpr in vitro, specifically that both EPA and DHA suppressed the number of total B cells, B1B2 cells and plasma cells. Concurrently, they were also found to promote the secretion of the anti-inflammatory cytokine IL10, mainly produced by Breg and Treg cells. Thus, nutritional supplementation with ω-3 PUFAs can regulate B cell's differentiation and anti-inflammatory function and strongly prevent autoimmune responses and lupus nephritis. The diets balance between ω-6 and ω-3 PUFAs intake may represent a promising treatment strategy to prevent or delay the onset of SLE.

A general copper-catalysed enantioconvergent C(sp3)-S cross-coupling via biomimetic radical homolytic substitution.

Although α-chiral C(sp3)-S bonds are of enormous importance in organic synthesis and related areas, the transition-metal-catalysed enantioselective C(sp3)-S bond construction still represents an underdeveloped domain probably due to the difficult heterolytic metal-sulfur bond cleavage and notorious catalyst-poisoning capability of sulfur nucleophiles. Here we demonstrate the use of chiral tridentate anionic ligands in combination with Cu(I) catalysts to enable a biomimetic enantioconvergent radical C(sp3)-S cross-coupling reaction of both racemic secondary and tertiary alkyl halides with highly transformable sulfur nucleophiles. This protocol not only exhibits a broad substrate scope with high enantioselectivity but also provides universal access to a range of useful α-chiral alkyl organosulfur compounds with different sulfur oxidation states, thus providing a complementary approach to known asymmetric C(sp3)-S bond formation methods. Mechanistic results support a biomimetic radical homolytic substitution pathway for the critical C(sp3)-S bond formation step.

Clinical effect of acupoint application with turmeric blistering moxibustion plaster on post-stroke hemiplegic shoulder pain. / 姜黄天灸膏穴位贴敷治疗脑卒中偏瘫肩痛临床疗效观察.

OBJECTIVES: To observe the effects of acupoint application with turmeric blistering moxibustion plaster on pain, shoulder range of motion (ROM) and upper limb motor function in the patients with post-stroke hemiplegic shoulder pain (PSHSP). METHODS: Eighty-two patients with PSHSP were randomly divided into an observation group (41 cases, 1 case was eliminated, 4 cases dropped out) and a control group (41 cases, 2 cases were eliminated and 2 cases dropped out). The routine treatment, nursing care and rehabilitation training were performed in the control group. On the basis of the intervention as the control group, in the observation group, the turmeric blistering moxibustion plaster was applied to bilateral ashi points, Jianyu (LI 15), Jianliao (TE 14), Binao (LI 14), Shousanli (LI 10) and Hegu (LI 4), once a day, remained for 6 hours each time. This moxibustion therapy was operated 5 times weekly, one course of treatment consisted of 2 weeks and 2 courses were required. Separately, before treatment and after 2 and 4 weeks of treatment, the score of visual analogue scale (VAS), shoulder ROM and the score of upper limbs in Fugl-Meyer assessment (U-FMA) were observed in the two groups. RESULTS: VAS scores were lower (P<0.05), ROM in shoulder flexion, abduction, internal rotation and external rotation was larger (P<0.05), and U-FMA scores were higher (P<0.05) after 2 and 4 weeks of treatment when compared with those before treatment in the two groups. After 4 weeks of treatment, VAS score decreased (P<0.05), and ROM in shoulder flexion, abduction, internal rotation, external rotation and U-FMA score increased (P<0.05) in comparison with those after 2 weeks of treatment in either group. In the observation group, VAS scores were dropped (P<0.05) after 2 and 4 weeks of treatment respectively, and ROM of shoulder flexion and abduction enlarged after 2 weeks of treatment (P<0.05) when compared with those in the control group. After 4 weeks of treatment, ROM in shoulder flexion, abduction, internal rotation and external rotation in the observation group was larger (P<0.05) and U-FMA score was higher (P<0.05) than those in the control group. CONCLUSIONS: Acupoint application with turmeric blistering moxibustion plaster may effectively reduce the degree of shoulder pain and improve the shoulder range of motion and the upper limb motor function in the patients with post-stroke hemiplegic shoulder pain.

Tea polyphenol EGCG ameliorates obesity-related complications by regulating lipidomic pathway in leptin receptor knockout rats.

Tea polyphenol epigallocatechin-3-gallate (EGCG) has been widely recognized for antiobesity effects. However, the molecular mechanism of lipidomic pathway related to lipid-lowering effect of EGCG is still not well understood. The aim of this study was to investigate the effects and mechanism of EGCG activated hepatic lipidomic pathways on ameliorating obesity-related complications by using newly developed leptin receptor knockout (Lepr KO) rats. Results showed that EGCG supplementation (100 mg/kg body weight) significantly decreased total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels both in the serum and liver, and significantly improved glucose intolerance. In addition, EGCG alleviated fatty liver development and restored the normal liver function in Lepr KO rats. Liver lipidomic analysis revealed that EGCG dramatically changes overall composition of lipid classes. Notably, EGCG significantly decreased an array of triglycerides (TGs) and diglycerides (DGs) levels. While EGCG increased 31 glycerophospholipid species and one sphingolipid species levels, such as phosphatidylcholines (PCs), phosphatidylethanolamines (PEs), phosphatidylserines (PSs) and phosphatidylinositols (PIs) levels in the liver of Lepr KO rats. Moreover, 14 diversely regulated lipid species were identified as potential lipid biomarkers. Mechanistic analysis revealed that EGCG significantly activated the SIRT6/AMPK/SREBP1/FAS pathway to decrease DGs and TGs levels and upregulated glycerophospholipids synthesis pathways to increase glycerophospholipid level in the liver of Lepr KO rats. These findings suggested that the regulation of glycerolipids and glycerophospholipid homeostasis might be the key pathways for EGCG in ameliorating obesity-related complications in Lepr KO rats.

Dietary choline increases brown adipose tissue activation markers and improves cholesterol metabolism in female APOE*3-Leiden.CETP mice.

OBJECTIVES: Studies in mice have recently linked increased dietary choline consumption to increased incidence of obesity-related metabolic diseases, while several clinical trials have reported an anti-obesity effect of high dietary choline intake. Since the underlying mechanisms by which choline affects obesity are incompletely understood, the aim of the present study was to investigate the role of dietary choline supplementation in adiposity. METHODS: Female APOE*3-Leiden.CETP mice, a well-established model for human-like lipoprotein metabolism and cardiometabolic diseases, were fed a Western-type diet supplemented with or without choline (1.2%, w/w) for up to 16 weeks. RESULTS: Dietary choline reduced body fat mass gain, prevented adipocyte enlargement, and attenuated adipose tissue inflammation. Besides, choline ameliorated liver steatosis and damage, associated with an upregulation of hepatic genes involved in fatty acid oxidation. Moreover, choline reduced plasma cholesterol, as explained by a reduction of plasma non-HDL cholesterol. Mechanistically, choline reduced hepatic VLDL-cholesterol secretion and enhanced the selective uptake of fatty acids from triglyceride-rich lipoprotein (TRL)-like particles by brown adipose tissue (BAT), consequently accelerating the clearance of the cholesterol-enriched TRL remnants by the liver. CONCLUSIONS: In APOE*3-Leiden.CETP mice, dietary choline reduces body fat by enhancing TRL-derived fatty acids by BAT, resulting in accelerated TRL turnover to improve hypercholesterolemia. These data provide a mechanistic basis for the observation in human intervention trials that high choline intake is linked with reduced body weight.

Choline and butyrate beneficially modulate the gut microbiome without affecting atherosclerosis in APOE*3-Leiden.CETP mice.

BACKGROUND AND AIMS: Choline has been shown to exert atherogenic effects in Apoe-/- and Ldlr-/- mice, related to its conversion by gut bacteria into trimethylamine (TMA) that is converted by the liver into the proinflammatory metabolite trimethylamine-N-oxide (TMAO). Since butyrate beneficially modulates the gut microbiota and has anti-inflammatory and antiatherogenic properties, the aim of the present study was to investigate whether butyrate can alleviate choline-induced atherosclerosis. To this end, we used APOE*3-Leiden.CETP mice, a well-established atherosclerosis-prone model with human-like lipoprotein metabolism. METHODS: Female APOE*3-Leiden.CETP mice were fed an atherogenic diet alone or supplemented with choline, butyrate or their combination for 16 weeks. RESULTS: Interestingly, choline protected against fat mass gain, increased the abundance of anti-inflammatory gut microbes, and increased the expression of gut microbial genes involved in TMA and TMAO degradation. Butyrate similarly attenuated fat mass gain and beneficially modulated the gut microbiome, as shown by increased abundance of anti-inflammatory and short chain fatty acid-producing microbes, and inhibited expression of gut microbial genes involved in lipopolysaccharide synthesis. Both choline and butyrate upregulated hepatic expression of flavin-containing monooxygenases, and their combination resulted in highest circulating TMAO levels. Nonetheless, choline, butyrate and their combination did not influence atherosclerosis development, and TMAO levels were not associated with atherosclerotic lesion size. CONCLUSIONS: While choline and butyrate have been reported to oppositely modulate atherosclerosis development in Apoe-/- and Ldlr-/- mice as related to changes in the gut microbiota, both dietary constituents did not affect atherosclerosis development while beneficially modulating the gut microbiome in APOE*3-Leiden.CETP mice.

Polyphenol-Rich Liupao Tea Extract Prevents High-Fat Diet-Induced MAFLD by Modulating the Gut Microbiota.

The modulation of gut microbiota dysbiosis might regulate the progression of metabolic-associated fatty liver disease (MAFLD). Here, we found that polyphenol-rich Liupao tea extract (PLE) prevents high-fat diet (HFD)-induced MAFLD in ApoE-/- male mice accompanied by protection of the intestinal barrier and downregulation of lipopolysaccharide (LPS)-related Toll-like receptor 4 (TLR4)-myeloid differentiation primary response 88 (MyD88) signaling in the liver. Fecal microbiome transplantation (FMT) from PLE-and-HFD-treated mice delayed MAFLD development significantly compared with FMT from HFD-treated mice. In this case, 16S rRNA gene sequencing revealed that Rikenellaceae and Odoribacter were significantly enriched and that Helicobacter was significantly decreased in not only the HFD+PLE group but also the HFD+PLE-FMT group. Furthermore, the level of 3-sulfodeoxycholic acid was significantly decreased in the HFD+PLE-FMT group compared with the HFD-FMT group. In conclusion, our data demonstrate that PLE could modulate the MAFLD phenotype in mice and that this effect is partly mediated through modulation of the gut microbiota.

[Research progress on antitumor effect and molecular mechanism of capsaicin].

Capsaicin is a lipid-soluble vanillin alkaloid extracted from Capsicum plants in the Solanaceae family, which is the main active ingredient in capsicum, with multiple functions such as anti-inflammation, analgesia, cardiovascular expansion, and gastric mucosa protection. Recently, capsaicin has been confirmed as a potential antitumor compound. It can induce cell cycle arrest, inhibit cancer cell proliferation, metastasis, invasion, and angiogenesis, and promote apoptosis or autophagy in malignancy cell models and animal models of lung cancer, breast cancer, gastric cancer, and liver cancer. Meanwhile, capsaicin shows a synergistic antitumor effect when combined with other antitumor drugs such as sorafenib. Based on the recent literature on the antitumor effect of capsaicin, the present study analyzed the molecular mechanism of capsaicin in resisting tumors by inducing apoptosis and reviewed the effects of capsaicin in inducing tumor cell cycle arrest, inhibiting tumor cell proliferation, metastasis, and angiogenesis, and combating tumors with other drugs, thereby providing a theoretical basis for further research of capsaicin and its rational development and utilization.

Comparative efficacy of 6 traditional Chinese patent medicines combined with lifestyle modification in patients with prediabetes: A network meta-analysis.

OBJECTIVE: To evaluate the efficacy of 6 Traditional Chinese patent medicines combined with lifestyle modification in the treatment of prediabetes with network meta-analysis. METHOD: The randomized controlled trials (RCTs) of Shen qi jiang tang capsule/granule (Shenqi), Tian mai xiao ke tablet (Tianmai), Tian qi capsule (Tianqi), Jin qi jiang tang tablet (Jinqi), Jin li da granule (Jinlida), Tang mai kang granule (Tangmaikang) in the treatment of prediabetes in PubMed, Web of Science, The Cochrane Library, EMbase, China Knowledge Network (CNKI), WanFang and Weipu databases were searched. Three reviewers independently conducted the screening, extracted the data and assessed methodological quality. Data analysis was performed using Rev Man 5.3 and STATA 15.0 software. RESULTS: A total of 50 RCTs, including 4594 patients, were included. The addition of Shenqi (OR 0.19 [95 %CI: 0.07, 0.52]) and Jinqi (OR 0.32 [95 %CI: 0.15, 0.71]) to existing lifestyle modification resulted in significant lower incidence rate of DM compared with none/placebo added to lifestyle modification. The addition of Jinlida (SMD -0.41% [95 %CI:-0.81, -0.01]) and Tangmaikang (SMD -0.83%[95 %CI: -1.46,-0.20]) resulted in significant additional HbA1c reductions compared with none/placebo added to lifestyle modification. The addition of all CTPMs except Tianqi resulted in significant additional FBG reductions and the addition of Shenqi (SMD -1.96[95 %CI: -3.64, -0.28]) resulted in significant additional PBG reductions. CONCLUSION: For patients with prediabetes, Shenqi + LM was among the most effective in reducing the incidence of diabetes for patients with prediabetes, while Jinlida + LM was among the least effective. Jinqi + LM and Tianqi + LM might be among the most effective, while western oral drugs + LM, Tianmai + LM, Tangmaikang + LM and Placebo + LM might be among the least effective. In addition, Tangmaikang + LM and Jinlida + LM might be among the most effective in reducing HbA1c, while Tianmai + LM, Tangmaikang + LM, Shenqi + LM, Jinlida + LM and Jinqi + LM might be among the most effective in reducing FPG for patients with prediabetes. Yet direct comparison and further investigation to explore mechanisms are warranted.

Effect of RG (Coptis root and ginseng) formula in patients with type 2 diabetes mellitus: a study protocol for a randomized controlled and double-blinding trial.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a common metabolic disease with significant health, social, and economic consequences. Traditional Chinese medicine (TCM) could effectively regulate blood sugar and influence gut microbiota in T2DM patients. Preliminary studies showed that the Coptis root and ginseng (RG) formula could relieve insulin resistance and prevent the progression of diabetes in mice. OBJECTIVES: The purpose of this study is to explore the efficacy and safety of RG formula in the treatment of adult patients with T2DM, as well as observing its effects on gut microbiota. METHODS AND ANALYSIS: This trial is a randomized, double-blind, placebo-controlled study. A total of 60 participants will be randomized in a 1:1 ratio into an experiment group (RG formula) and a control group (placebo). Patients in both groups will be given diabetes education and basic blood glucose control. Glucose-lowering drugs with significant influence on gut microbiota will be avoided. This trial will last 25 weeks including 1-week run-in, 12-week intervention, and 12-week follow-up visit. The primary outcome is the change in the HbA1c. The secondary outcomes comprise the change in the fasting blood glucose (FBG), postprandial blood glucose (PBG), fasting insulin (FIL), fasting C-peptide(C-P), insulin resistance index (IRI), inflammatory factors, and species abundance of gut microbiota between the two groups. Safety of medication will also be evaluated. The correlation analysis will be explored between the glycemic indicators, inflammatory factors, and abundance of gut microbiota. DISCUSSION: This study will provide the clinical evidence for the efficacy of RG formula in regulating blood sugar and influencing gut microbiota, which will be beneficial to form the integrated therapeutic regimen in T2DM with TCM. TRIAL REGISTRATION: "Clinical Study on the Intervention of Coptis Root and Ginseng," Chinese Clinical Trials Registry ChiCTR 2100042126 . Registered on 14 January 2021.

A Strategy for Screening the Lipid-Lowering Components in Alismatis Rhizoma Decoction Based on Spectrum-Effect Analysis.

Alismatis Rhizoma decoction (ARD), comprised of Alisma plantago-aquatica subsp. orientale (Sam.) Sam and Atractylodes macrocephala Koidz. at a ratio of 5 : 2, is a classic traditional Chinese medicine (TCM) formula with successful clinical hypolipidemic effect. This paper aimed to explore the major bioactive compounds and potential mechanism of ARD in the treatment of hyperlipidemia on the basis of spectrum-effect analysis and molecular docking. Nine ARD samples with varying ratios of the constituent herbs were prepared and analyzed by UPLC-Q-TOF/MS to obtain the chemical spectra. Then, the lipid-lowering ability of the nine samples was tested in an oleic acid-induced lipid accumulation model in human hepatoma cells (HepG2). Grey relational analysis and partial least squares regression analysis were then performed to determine the correlation between the chemical spectrums and lipid-lowering efficacies of ARD. The potential mechanisms of the effective compounds were investigated by docking with the farnesoid X receptor (FXR) protein. The results indicated that alisol B 23-acetate, alisol C 23-acetate, and alisol B appeared to be the core effective components on hyperlipidemia in ARD. Molecular docking further demonstrated that all three compounds could bind to FXR and were potential FXR agonists for the treatment of hyperlipidemia. This study elucidated the effective components and potential molecular mechanism of action of ARD for treating hyperlipidemia from a perspective of different compatibility, providing a new and feasible reference for the research of TCM formulas such as ARD.

Qingre Yiqi Method along with Oral Hypoglycemic Drugs in Treating Adults with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the efficacy of the Qingre Yiqi method in the treatment of type 2 diabetes mellitus (T2DM) with meta-analysis. METHOD: The randomized controlled trials (RCTs) of the Qingre Yiqi method in the treatment of T2DM in the PubMed, Medline, EMBase, Cochrane Library, Web of Science, Weipu Journal, China Knowledge Network (CNKI), and Wanfang database were conducted. Three reviewers independently conducted the screening, extracted the data, and assessed methodological quality. Data analysis was performed using Rev Man 5.3 software for statistical analysis. RESULTS: A total of 15 RCTs, including 1440 patients, were included. The results showed that compared with oral hypoglycemic drugs alone, the add-on treatment of the Qingre Yiqi method could significantly improve Chinese medicine syndrome (OR (95%CI) = 3.66 [2.47,5.42], P < 0.00001) and lower the level of HbA1c (MD (95%CI) = -0.68 [0.91, -0.45], P < 0.00001), triglyceride (TG) (MD (95%CI) = -0.38 [-0.58,-0.17], P=0.0004), low-density lipoprotein cholesterol (LDL-C) (MD (95%CI) = -0.25 [-0.37, -0.13], P < 0.0001), and total cholesterol(TC) (MD(95%CI) = -0.40[-0.67, -0.13], P=0.003). In terms of fasting blood glucose (FBG) and postprandial blood sugar (PBG), subgroup analysis showed that the baseline of FBG and the number of combined oral hypoglycemic drugs of PBG were the major sources of heterogeneity. CONCLUSION: Compared with the standard treatment, the Qingre Yiqi method along with oral hypoglycemic drugs showed the more beneficial effects for T2DM on improving TCM syndromes and reducing the blood glucose and partial lipid parameter.

Deep eutectic solvent-homogenate based microwave-assisted hydrodistillation of essential oil from Litsea cubeba (Lour.) Pers. fruits and its chemical composition and biological activity.

As an important natural product, the sufficient separation of plant essential oil (EO) is helpful to improve its utilization value. In this work, deep eutectic solvent-homogenate based microwave-assisted hydrodistillation (DES-HMAHD) was developed and applied to isolate EO from the fruits of Litsea cubeba (Lour.) Pers. Different types of DES were investigated in terms of the EO kinetics and composition, among which oxalic acid/choline chloride (OA/ChCl) had obvious advantages. Following, molar ratio of OA and ChCl (1:1), water content (50%), liquid-solid ratio (12.5:1 mL/g), homogenate time (2 min), and microwave power (700 W) were found to be the optimum conditions. Gas chromatography-mass spectrometer (GC-MS) analysis showed that the EO isolated from DES-HMAHD contained a large proportion of m-cymene and trans-linalool oxide, which were quite different from the conventionally reported L. cubeba EO. In addition, the proposed DES-HMAHD resulted in higher separation efficiency and economic value, as well as lower environmental impact, as compared with other techniques. Afterwards, the EO isolated by different methods was evaluated from the perspective of biological activity. The EO obtained by DES-HMAHD showed higher antioxidant activity (DPPH and ABTS) but lower antifungal activity, which was related to its chemical composition. In general, DES-HMAHD produced a kind of L. cubeba EO with different components, which provided a scientific foundation for the sufficient isolation of plant EO and its application in the natural products.

Androgen is responsible for enhanced susceptibility of melatonin against traumatic brain injury in females.

BACKGROUND: Numerous publications have demonstrated that melatonin administration is associated with mortality reduction and improvement in neurological outcomes after traumatic brain injury (TBI). However, there are significant sex differences in several diseases associated with melatonin. We aimed to determine whether androgen was responsible for enhanced susceptibility of melatonin against TBI in females, as well as potential molecular mechanisms. METHODS: Weight-drop was used to establish a rodent model of TBI. Melatonin (10 mg/kg) and testosterone (1 mg/kg) were administered three times every day for three days after TBI using subcutaneous injection, respectively. Seven days after TBI, an open field assay was used to evaluate locomotor and exploratory activities. Neuronal amount, neuronal apoptosis, and expression of phosphorylated extracellularly regulated protein kinases 1/2 (ERK1/2), c-jun N-terminal kinase 1/2 (JNK1/2), and p38 mitogen-activated protein kinase (p38MAPK) in neurons were assessed using immunofluorescence assay seven days after TBI. The expression of caspase-3, Bax, and Bcl-2 in the frontal cortex was detected using western blot. RESULTS: Compared with female rats, melatonin administration exhibited more neuroprotective effects (including improved locomotor and exploratory activities, elevated neuronal amount, and reduced neuronal apoptosis) in male rats exposed to TBI. Moreover, testosterone significantly improved locomotor and exploratory activities, elevated neuronal amount, decreased neuronal apoptosis, downregulated phosphorylation of JNK1/2- and p38MAPK-positive neurons, but upregulated phosphorylation of ERK1/2-positive neurons in the frontal cortex, and reduced the expressions of cleaved caspase-3, Bax, but increased Bcl-2 expressions in female rats exposed to TBI. CONCLUSIONS: Androgen was responsible for the enhanced susceptibility to TBI under melatonin supplementation in females through a mechanism that may be associated with MAPK pathway regulation.

Discovery of Piperidol Derivatives for Combinational Treatment of Azole-Resistant Candidiasis.

Effective strategies are needed to deal with invasive fungal infections caused by drug-resistant fungi. Previously, we designed a series of antifungal benzocyclane derivatives based on the drug repurposing of haloperidol. Herein, further structural optimization and antifungal mechanism studies were performed, leading to the discovery of new piperidol derivative B2 with improved synergistic antifungal potency, selectivity, and water solubility. In particular, the combination of compound B2 and fluconazole showed potent in vitro and in vivo antifungal activity against azole-resistant Candida albicans. Compound B2 inhibited important virulence factors by regulating virulence-associated genes and improved the efficacy of fluconazole by down-regulating the CYP51-coding gene and efflux pump gene. Taken together, the piperidol derivative B2 represents a promising lead compound for the combinational treatment of azole-resistant candidiasis.

Efficacy of thermotherapy for herpes zoster and postherpetic neuralgia: A protocol for systemic review and meta-analysis.

BACKGROUND: Herpes zoster (HZ), is a painful skin rash disease with cutaneous symptoms and acute zoster-associated pain (ZAP). Postherpetic neuralgia (PHN), as the most frequent sequela of HZ, can persist a long time. Both HZ and PHN may significantly impact the quality of life and made great economical afford to affected patients. Its optimal treatment on HZ and PHN is still an urgent problem. In China, thermotherapy, including moxibustion and fire needle, is widely used because they can quickly promote the recovery of shingles and reduce the occurrence of PHN. Thermotherapy can also reduce pain intensity, relieve anxiety, and improve quality of life of PHN. Based on the current literatures, the effect and safety of thermotherapy will be systematically evaluated to provide appropriate complementary therapies for HZ and PHN. METHODS: Studies search for eligible randomized controlled trials (RCTs) that use thermotherapy including fire needle and moxibustion for HZ or PHN from the following databases: PubMed, EMBASE, Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), China Biology Medicine Database (CBM), Technology Periodical database (VIP), and Wanfang database. Language restrictions for retrieving literature are English and Chinese. Their data extraction will be done by 2 researchers. Mean difference (MD) or relative risk (RR) with fixed or random effect model in terms of 95% confidence interval (CI) will be adopted for the data synthesis. To evaluate the risk of bias, the Cochrane's risk of bias assessment tool will be utilized. The sensitivity or subgroup analysis will also be conducted when meeting high heterogeneity (I2 > 50%). RESULTS: This meta-analysis will provide an authentic synthesis of the thermotherapy's effect on HZ and PHN, including incidence of postherpetic neuralgia and adverse events. DISCUSSION: The findings of the review offer updated evidence and identify whether thermotherapy can be an effective treatment for HZ and PHN for clinicians. REGISTRATION NUMBER: INPLASY2020110009.

Identification of the bioactive components of Banxia Xiexin Decoction that protect against CPT-11-induced intestinal toxicity via UPLC-based spectrum-effect relationship analyses.

ETHNOPHARMACOLOGICAL RELEVANCE: Irinotecan (CPT-11) is a valuable chemotherapeutic compound, but its use is associated with severe diarrhea in some patients. The CPT-11 prodrug is converted into the active 7-ethyl-10-hydroxycamptothecin (SN-38) metabolite, which can then be retained for extended periods in the intestine, leading to the onset of diarrhea and related symptoms. Banxia Xiexin Decoction (BXD) is commonly employed for the treatment of gastroenteritis in traditional Chinese medicine (TCM), and in clinical settings, it is used to prevent diarrhea in patients undergoing CPT-11 treatment. To date, however, there have been no studies specifically examining which components of BXD can alleviate the gastrointestinal symptoms associated with CPT-11 administration. AIM: This study aimed to identify the main herbal components of BXD associated with protection against CPT-11-induced intestinal toxicity in a murine model system. MATERIALS AND METHODS: SN-38 levels were measured by UPLC-ESI-MS/MS in samples collected from mice subjected to CPT-11-induced diarrhea that had been administered BXD or different components thereof. Pearson correlation and Grey relational analyses were then used to explore spectrum-effect relationships between reductions in intestinal SN-38 levels and specific chemical fingerprints in samples from mice administered particular combinations of BXD component herbs. RESULTS: We found that different herbal combinations were associated with significant differences in intestinal SN-38 reductions in treated mice. Our spectrum-effect analysis revealed that BXD components including chrysin 6-C-arabinoside-8-C-glucoside, coptisine, hydroxyl oroxylin A 7-O-glucuronide (hydroxyl wogonoside), baicalin, an isomer of 5,6,7-trihydroxyl-flavanone-7-O-glucuronide, berberine, palmatine, and chrysin-7-O-glucuronide were all directly linked with reductions in intestinal SN-38 levels. We therefore speculate that these compounds are the primary bioactive components of BXD, suggesting that they offer protection against CPT-11-induced diarrhea. CONCLUSION: By utilizing UPLC to analyze SN-38 levels in mice treated with a variety of herbal combinations, we were able to effectively explore BXD spectrum-effect relationships and to thereby establish the components of this medicinal preparation that were bioactive and capable of preventing CPT-11-induced diarrhea in mice. This and similar spectrum-effect studies represent a robust means of exploring the mechanistic basis for the pharmacological activity of TCM preparations.

The MADS-box transcription factor GlMADS1 regulates secondary metabolism in Ganoderma lucidum.

MADS-box transcription factors play crucial roles in regulating development processes and biosynthesis of secondary metabolites in eukaryotes. However, the role of MADS-box transcription factors vary among fungal species, and their function remains unclear in the medicinally and economically important fungus Ganoderma lucidum. In this study, we characterized a MADS-box gene, GlMADS1, in G. lucidum. Analyses using quantitative real-time polymerase chain reaction (qRT-PCR) showed that GlMADS1 expression levels were up-regulated from the mycelia to the primordia stage. In order to further evaluate the effect of MADS-box transcription factors on secondary metabolism, we utilized RNA interference (RNAi) to silence GlMADS1 in G. lucidum. Ganoderic acid (GA) and flavonoid contents were enhanced in GlMADS1-silenced strains, suggesting that GlMADS1 negatively regulates GA and flavonoid accumulation.

Cystine transporter SLC7A11/xCT in cancer: ferroptosis, nutrient dependency, and cancer therapy

The cystine/glutamate antiporter SLC7A11 (also commonly known as xCT) functions to import cystine for glutathione biosynthesis and antioxidant defense and is overexpressed in multiple human cancers. Recent studies revealed that SLC7A11 overexpression promotes tumor growth partly through suppressing ferroptosis, a form of regulated cell death induced by excessive lipid peroxidation. However, cancer cells with high expression of SLC7A11 (SLC7A11

Moxibustion for post-stroke urinary incontinence in adults: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND PURPOSE: Urinary incontinence (UI) is a frequently identified complication among stroke survivors. Moxibustion is commonly used to treat post-stroke UI in Asian countries. This study aimed to synthesize the evidence of using moxibustion for post-stroke UI management. METHODS: Twelve databases were searched to identify randomized controlled trials (RCTs) using moxibustion to improve post-stroke UI management. Four Chinese journals were also manually screened for potentially eligible articles. RESULTS: Ten studies with a total of 719 participants and one completed trial without published results were included. Compared with "routine methods of treatment and/or care," the meta-analyses revealed that moxibustion had superior effects in improving UI symptoms and alleviating the severity of UI. CONCLUSION: This systematic review identified preliminary research evidence that moxibustion may be effective in managing the symptoms of post-stroke UI. More rigorously designed, large-scale RCTs are warranted to provide more robust evidence in this area.