[Effect of Zuogui Jiangtang Jieyu Formula on intestinal flora and short-chain fatty acid metabolism in rats with diabetes mellitus complicated with depression].

This study aimed to investigate the regulatory effects of Zuogui Jiangtang Jieyu Formula(ZJJ) on the intestinal flora, short chain fatty acids(SCFAs), and neuroinflammation in rats with diabetes mellitus complicated depression(DD). The DD model was established in rats and model rats were randomly divided into a model group, a positive drug(metformin + fluoxetine) group, a ZJJ low-dose group, and a ZJJ high-dose group, with eight rats in each group. Another eight rats were assigned to the blank group. Subsequently, depressive-like behavior test was conducted on the rats, and cerebrospinal fluid samples were collected to measure pro-inflammatory cytokines [interleukin-1ß(IL-1ß), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α)]. Blood serum samples were collected to measure proteins related to the hypothalamic-pituitary-adrenal axis(HPA axis), including corticotropin-releasing hormone(CRH), adrenocorticotropic hormone(ACTH), and cortisol(CORT), as well as glucose metabolism. Gut contents were collected from each group for 16S rRNA sequencing analysis of intestinal flora and SCFAs sequencing. The results indicated that ZJJ not only improved glucose metabolism in DD rats(P<0.01) but also alleviated depressive-like behavior(P<0.05) and HPA axis hyperactivity(P<0.05 or P<0.01). Besides, it also improved the neuroinflammatory response in the brain, as evidenced by a significant reduction in pro-inflammatory cytokines in cerebrospinal fluid(P<0.05 or P<0.01). Additionally, ZJJ improved the intestinal flora, causing the intestinal flora in DD rats to resemble that of the blank group, characterized by an increased Firmicutes abundance. ZJJ significantly increased the levels of SCFAs(acetic acid, butyric acid, valeric acid, and isovaleric acid)(P<0.01). Therefore, it is deduced that ZJJ can effectively ameliorate intestinal flora dysbiosis, regulate SCFAs, and thereby improve both glucose metabolism disturbances and depressive-like behavior in DD.

Vitamin E and Multiple Health Outcomes: An Umbrella Review of Meta-Analyses.

The relationship between vitamin E intake or circulating α-tocopherol and various health outcomes is still debatable and uncertain. We conducted an umbrella review to identify the relationships between vitamin E intake or circulating tocopherol and health outcomes by merging and recalculating earlier meta-analyses. The connections that were found to be statistically significant were then classified into different evidence levels based on p values, between-study heterogeneity, prediction intervals, and small study effects. We finally included 32 eligible meta-analyses with four vitamin E sources and 64 unique health outcomes. Only the association between circulating α-tocopherol and wheeze or asthma in children was substantiated by consistent evidence. Suggestive evidence was suggested for seven results on endothelial function (supplemental vitamin E): serum C-reactive protein (CRP) concentrations (supplemental vitamin E), cervical cancer (dietary vitamin E), esophageal cancer (dietary vitamin E), cervical intraepithelial neoplasia (CIN, dietary vitamin E), pancreatic cancer (total vitamin E intake), and colorectal cancer (circulating α-tocopherol levels); all of these showed a protective effect consistent with the vitamin E source. In conclusion, our work has indicated that vitamin E is protective for several particular health outcomes. Further prospective studies are required when other factors that may contribute to bias are considered.

The Chinese herbal prescription JieZe-1 inhibits caspase-1-dependent pyroptosis induced by herpes simplex virus-2 infection in vitro.

OBJECTIVE: JieZe-1 (JZ-1), a Chinese herbal prescription, has an obvious effect on genital herpes, which is mainly caused by herpes simplex virus type 2 (HSV-2). Our study aimed to address whether HSV-2 induces pyroptosis of VK2/E6E7 cells and to investigate the anti-HSV-2 activity of JZ-1 and the effect of JZ-1 on caspase-1-dependent pyroptosis. METHODS: HSV-2-infected VK2/E6E7 cells and culture supernate were harvested at different time points after the infection. Cells were co-treated with HSV-2 and penciclovir (0.078125 mg/mL) or caspase-1 inhibitor VX-765 (24 h pretreatment with 100 µmol/L) or JZ-1 (0.078125-50 mg/mL). Cell counting kit-8 assay and viral load analysis were used to evaluate the antiviral activity of JZ-1. Inflammasome activation and pyroptosis of VK2/E6E7 cells were analyzed using microscopy, Hoechst 33342/propidium iodide staining, lactate dehydrogenase release assay, gene and protein expression, co-immunoprecipitation, immunofluorescence, and enzyme-linked immunosorbent assay. RESULTS: HSV-2 induced pyroptosis of VK2/E6E7 cells, with the most significant increase observed 24 h after the infection. JZ-1 effectively inhibited HSV-2 (the 50% inhibitory concentration = 1.709 mg/mL), with the 6.25 mg/mL dose showing the highest efficacy (95.76%). JZ-1 (6.25 mg/mL) suppressed pyroptosis of VK2/E6E7 cells. It downregulated the inflammasome activation and pyroptosis via inhibiting the expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (P < 0.001) and interferon-γ-inducible protein 16 (P < 0.001), and their interactions with apoptosis-associated speck-like protein containing a caspase recruitment domain, and reducing cleaved caspase-1 p20 (P < 0.01), gasdermin D-N (P < 0.01), interleukin (IL)-1ß (P < 0.001), and IL-18 levels (P < 0.001). CONCLUSION: JZ-1 exerts an excellent anti-HSV-2 effect in VK2/E6E7 cells, and it inhibits caspase-1-dependent pyroptosis induced by HSV-2 infection. These data enrich our understanding of the pathologic basis of HSV-2 infection and provide experimental evidence for the anti-HSV-2 activity of JZ-1. Please cite this article as: Liu T, Shao QQ, Wang WJ, Liu TL, Jin XM, Xu LJ, Huang GY, Chen Z. The Chinese herbal prescription JieZe-1 inhibits caspase-1-dependent pyroptosis induced by herpes simplex virus-2 infection in vitro. J Integr Med. 2023; 21(3): 277-288.

Itaconate alleviates ß2-microglobulin-induced cognitive impairment by enhancing the hippocampal amino-ß-carboxymuconate-semialdehyde-decarboxylase/picolinic acid pathway.

ß2-microglobulin (B2M) has been established to impair cognitive function. However, no treatment is currently available for B2M-induced cognitive dysfunction. Itaconate is a tricarboxylic acid (TCA) cycle intermediate that exerts neuroprotective effects in several neurological diseases. The amino-ß-carboxymuconate-semialdehyde-decarboxylase (ACMSD)/picolinic acid (PIC) pathway is a crucial neuroprotective branch in the kynurenine pathway (KP). The present study sought to investigate whether Itaconate attenuates B2M-induced cognitive impairment and examine the mediatory role of the hippocampal ACMSD/PIC pathway. We demonstrated that 4-Octyl Itaconate (OI, an itaconate derivative) significantly alleviated B2M-induced cognitive dysfunction and hippocampal neurogenesis impairment. OI treatment also increased the expression of ACMSD, elevated the concentration of PIC, and decreased the level of 3-HAA in the hippocampus of B2M-exposed rats. Furthermore, inhibition of ACMSD by TES-991 significantly abolished the protections of Itaconate against B2M-induced cognitive impairment and neurogenesis deficits. Exogenous PIC supplementation in hippocampus also improved cognitive performance and hippocampal neurogenesis in B2M-exposed rats. These findings demonstrated that Itaconate alleviates B2M-induced cognitive impairment by upregulation of the hippocampal ACMSD/PIC pathway. This is the first study to document Itaconate as a promising therapeutic agent to ameliorate cognitive impairment. Moreover, the mechanistic insights into the ACMSD/PIC pathway improve our understanding of it as a potential therapeutic target for neurological diseases beyond B2M-associated neurocognitive disorders.

Lactiplantibacillus plantarum J-15 reduced calcium oxalate kidney stones by regulating intestinal microbiota, metabolism, and inflammation in rats.

The prevention role of Lactiplantibacillus plantarum against the formation of kidney stones has been increasingly recognized; its mechanism, however, has mainly been focused on inhibiting the inflammation in the colon in the gastrointestinal (GI) system, and the intestinal metabolites from microflora have not been revealed fully with regarding to the stone formation. In this study, we investigated the effect of L. plantarum J-15 on kidney stone formation in renal calcium oxalate (CaOx) rats induced by ethylene glycol and monitored the changes of intestinal microflora and their metabolites detected by 16S rRNA sequencing and widely targeted analysis, followed by the evaluation of the intestinal barrier function and inflammation levels in the colon, blood and kidney. The results showed that L. plantarum J-15 effectively reduced renal crystallization and urinary oxalic acid. Ten microbial genera, including anti-inflammatory and SCFAs-related Faecalibaculum, were enriched in the J-15 treatment group. There are 136 metabolites from 11 categories significantly different in the J-15 supplementation group compared with CaOx model rats, most of which were enriched in the amino acid metabolic and secondary bile acid pathways. The expression of intestinal tight junction protein Occludin and the concentration of pro-inflammatory cytokines and prostaglandin were decreased in the intestine, which further reduced the translocated lipopolysaccharide and inflammation levels in the blood upon J-15 treatment. Thus, the inflammation and injury in the kidney might be alleviated by downregulating TLR4/NF-κB/COX-2 signaling pathway. It suggested that L. plantarum J-15 might reduce kidney stone formation by restoring intestinal microflora and metabolic disorder, protecting intestinal barrier function, and alleviating inflammation. This finding provides new insights into the therapies for renal stones.

Shenlian (SL) Decoction, a Traditional Chinese Medicine Compound, May Ameliorate Blood Glucose via Mediating the Gut Microbiota in db/db Mice.

Shenlian (SL) decoction is a herbal formula composed of Coptis and ginseng, of which berberine and ginsenoside are the main constituents. Even though SL decoction is widely used in treating diabetes in China, the mechanism of its antidiabetes function still needs further study. Gut microbiota disorder is one of the important factors that cause diabetes. To explore the effect of SL decoction on intestinal microbiota, gut microbiota of mice was analyzed by sequencing the gut bacterial 16S rRNA V3+V4 region and metagenomics. In this study, results demonstrated that SL decoction had a better hypoglycemic effect and ß cell protection effect than either ginseng or Coptis chinensis. Alpha diversity analysis showed that all interventions with ginseng, Coptis, and SL decoction could reverse the increased diversity and richness of gut microbiota in db/db mice. PCoA analysis showed oral SL decoction significantly alters gut microbiota composition in db/db mice. 395 OTUs showed significant differences after SL treatment, of which 37 OTUs enriched by SL decoction showed a significant negative correlation with FBG, and 204 OTUs decreased by SL decoction showed a significant positive correlation with FBG. Results of KEGG analysis and metagenomic sequencing showed that SL decoction could reduce the Prevotellaceae, Rikenellaceae, and Helicobacteraceae, which were related to lipopolysaccharide biosynthesis, riboflavin metabolism, and peroxisome, respectively. It could also upregulate the abundance of Bacteroidaceae, which contributed to the metabolism of starch and sucrose as well as pentose-glucuronate interconversions. In the species level, SL decoction significantly upregulates the relative abundance of Bacteroides_acidifaciens which showed a significant negative correlation with FBG and was reported to be a potential agent for modulating metabolic disorders such as diabetes and obesity. In conclusion, SL decoction was effective in hypoglycemia and its mechanism may be related to regulating gut microbiota via upregulating Bacteroides_acidifaciens.

Effect of a community-based child health counselling intervention on health-seeking behaviours, complementary feeding and nutritional condition among children aged 6-23 months in rural China: A pre- and post-comparison study.

In China, the prevalence of undernutrition among children under 5 years of age has declined significantly during recent decades. However, noticeable gaps exist between rural and urban areas. Since 2012, a government-funded nutrition programme, Ying Yang Bao (YYB; soybean powder-based iron-rich supplement) programme, has been implemented in poor rural areas to decrease the risk of developing anaemia among children aged 6-23 months, but there are still inadequate health care awareness, feeding knowledge and skills among caregivers. From June 2018 to December 2020, a child health counselling intervention was delivered through a home visit based on the YYB programme in Liangshan. Child health messages were given by trained village child health assistants while distributing YYB. Surveys were conducted before and after the intervention to analyse changes in child health check-up frequency, complementary feeding practice and prevalence of undernutrition. After the intervention, the proportion of children who had regular health check-ups, who were vaccinated and who met the minimum YYB consumption significantly increased from 26.0%, 81.6%, and 67.8% to 59.7%, 95.0%, and 79.2%. Increased rates of IYCF indicators (introduction of solid, semisolid, or soft foods, minimum dietary diversity and consumption of iron-rich or iron-fortified foods) were observed after the intervention. The prevalence of stunting, underweight, wasting, and anaemia significantly decreased from 26.3% to 10.8%, 13.4% to 8.7%, 14.0% to 10.5%, and 52.1% to 43.9%. This intervention can be well integrated into the YYB programme with less additional resources. Children in resource-limited areas will benefit more from a comprehensive nutritional package, including food supplements and child health education.

Short-Chain Fatty Acids Reduced Renal Calcium Oxalate Stones by Regulating the Expression of Intestinal Oxalate Transporter SLC26A6.

Renal calcium oxalate (CaOx) stone is a common urologic disease with a high prevalence and recurrence rate. However, short-chain fatty acids (SCFAs) are less often reported in the prevention of urolithiasis. This study aimed to explore the effect of SCFAs on the renal CaOx stone formation and the underlying mechanisms. Ethylene glycol was used to induce renal CaOx crystals in rats. SCFAs (acetate, propionate, or butyrate) were added as supplements to the drinking water with or without antibiotics. Because intestinal oxalate transporters SLC26A6 and SLC26A3 regulate the excretion and absorption of oxalate in the intestine, we injected adeno-associated virus 9 (AAV9)-SLC26A6-shRNA (short hairpin RNA) and AAV9-SLC26A3 into the tail vein of rats to suppress SLC26A6 and overexpress SLC26A3 expression in the intestine, respectively, to explore the role of SLC26A3 and SLC26A6 (SLC26A3/6) in the reduction of renal CaOx crystals induced by SCFAs. Results showed that SCFAs reduced renal CaOx crystals and urinary oxalate levels but, however, increased the abundance of SCFA-producing bacteria and cecum SCFA levels. SCFA supplements still reduced renal crystals and urinary oxalate after gut microbiota depletion. Propionate and butyrate downregulated intestinal oxalate transporter SLC26A3 expression, while acetate and propionate upregulated SLC26A6 expression, both in vivo and in vitro. AAV9-SLC26A3 exerted a protective effect against renal crystals, while AAV9-SLC26A6-shRNA contributed to the renal crystal formation even though the SCFAs were supplemented. In conclusion, SCFAs could reduce urinary oxalate and renal CaOx stones through the oxalate transporter SLC26A6 in the intestine. SCFAs may be new supplements for preventing the formation of renal CaOx stones. IMPORTANCE Some studies found that the relative abundances of short-chain-fatty-acid (SCFA)-producing bacteria were lower in the gut microbiota of renal stone patients than healthy controls. Our previous study demonstrated that SCFAs could reduce the formation of renal calcium oxalate (CaOx) stones, but the mechanism is still unknown. In this study, we found that SCFAs (acetate, propionate, and butyrate) reduced the formation of renal calcium oxalate (CaOx) crystals and the level of urinary oxalate. Depleting gut microbiota increased the amount of renal crystals in model rats, and SCFA supplements reduced renal crystals and urinary oxalate after gut microbiota depletion. Intestinal oxalate transporter SLC26A6 was a direct target of SCFAs. Our findings suggested that SCFAs could reduce urinary oxalate and renal CaOx stones through the oxalate transporter SLC26A6 in the intestine. SCFAs may be new supplements for preventing the formation of renal CaOx stones.

Lactiplantibacillus plantarum Reduced Renal Calcium Oxalate Stones by Regulating Arginine Metabolism in Gut Microbiota.

Renal calcium oxalate (CaOx) stones are a common kidney disease. There are few methods for reducing the formation of these stones. However, the potential of probiotics for reducing renal stones has received increasing interest. We previously isolated a strain of Lactiplantibacillus plantarum N-1 from traditional cheese in China. This study aimed to investigate the effects of N-1 on renal CaOx crystal deposition. Thirty rats were randomly allocated to three groups: control group (ddH2O by gavage), model group [ddH2O by gavage and 1% ethylene glycol (EG) in drinking water], and Lactiplantibacillus group (N-1 by gavage and 1% EG in drinking water). After 4 weeks, compared with the model group, the group treated with N-1 exhibited significantly reduced renal crystals (P < 0.05). In the ileum and caecum, the relative abundances of Lactobacillus and Eubacterium ventriosum were higher in the control group, and those of Ruminococcaceae UCG 007 and Rikenellaceae RC9 were higher in the N-1-supplemented group. In contrast, the relative abundances of Staphylococcus, Corynebacterium 1, Jeotgalicoccus, Psychrobacter, and Aerococcus were higher in the model group. We also predicted that the arginase level would be higher in the ileal microbiota of the model group than in the N-1-supplemented group with PICRUSt2. The arginase activity was higher, while the level of arginine was lower in the ileal contents of the model group than in the N-1-supplemented group. The arginine level in the blood was also higher in the N-1-supplemented group than in the model group. In vitro studies showed that exposure to arginine could reduce CaOx crystal adhesion to renal epithelial HK-2 cells. Our findings highlighted the important role of N-1 in reducing renal CaOx crystals by regulating arginine metabolism in the gut microbiota. Probiotics containing L. plantarum N-1 may be potential therapies for preventing renal CaOx stones.

Coffee Consumption and Prostate Cancer Risk: Results from National Health and Nutrition Examination Survey 1999-2010 and Mendelian Randomization Analyses.

The aim of this study was to examine the association between coffee and prostate cancer. Firstly, we conducted an observational study using data from National Health and Nutrition Examination Survey (NHANES) 1999-2010. Coffee intake was derived from 24 h dietary recalls. Weighted multivariable-adjusted logistic regression was applied to evaluate the association. Then, we performed Mendelian randomization (MR) to explore the possible causal effect of coffee on prostate cancer risk. Primary and secondary genetic instruments were obtained from genome-wide association studies among 375,833 and 91,462 individuals separately. Prostate cancer summary statistics were extracted from Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome (PRACTICAL) (79,194 cases and 61,112 controls) and FinnGen project (4754 cases and 63,465 controls). Inverse variance weighted (IVW) was the primary analytical method. Through selection, we enrolled 8336 individuals (weighted number = 58,796,070) for our observational study in NHANES. Results suggested that there was no association between coffee and prostate cancer. MR analyses with primary genetic instruments also did not support a causal association between coffee intake and prostate cancer risk, whether using summary data from PRACTICAL (IVW: OR 1.001, 95% CI 0.997-1.005) or FinnGen (IVW: OR 1.005, 95% CI 0.998-1.012). Similar results were observed when using secondary genetic instruments. Therefore, our study did not support a causal association between coffee intake and prostate cancer risk. Further studies with a larger sample size are needed to examine if an association exists by different coffee bean types, roasting procedures, and brewing methods.

First Report of Alternaria tenuissima Causing Brown Spot Disease of Angelica dahurica in China.

Angelica dahurica (Fisch. ex Hoffm.) is an abundantly cultivated Chinese herbal medicine plant in China with about 4000 hectares grown, the annual production is up to 24,000 tons. The medicinal part of A. dahurica is its root, and mainly function for treat cold, headache, toothache, rhinitis, diabetes, etc. Besides, A. dahurica is also used as a spice in Asia. In September 2018, brown spot was observed on the leaves of A. dahurica in fields of Anguo City, Hebei Province, China. In the field investigated, the incidence of brown spot disease reached 15%. The infected leaves showed brown spots surrounded with pale yellow edge, resulting in withered of the whole leaf. It seriously endangers the growth of A. dahurica, reducing the yield and quality of medicinal materials, even leading to the death of plants. We isolated the pathogen from 10 leaves with same lesions, the small square leaf pieces of approximately 3 to 5 mm were obtained with the sterile scissors from the junction of infected and healthy tissues, sterilized with sodium hypochlorite (10%) for 1 min followed by washing in sterile water for 3 times, then incubated on potato dextrose agar (PDA) plates at 25°C for 4 days. The culture was transferred to new PDA plates and was cultivated in dark at 25°C for 10 days. A total of 3 species of fungi were isolated, and only one fungus species has been found to be able to cause the original pathological characteristics of A. dahurica leaves through the back-grafting experiment. The mycelium was black and began to sporulate after 8 days on PDA media by single spore separation. Multiple spores joined together to form spores chain. The spores were spindle-shaped, yellow to yellow brown, and size ranged from 45 to 55 × 15 to 20 µm (n=50), with zero to three longitudinal septa and one to five transverse septa. For pathogenicity tests, the spore suspension (3.5×105 spores/mL) were inoculated to healthy plants grown in experimental field, the test was repeated four times, and 10 leaves were inoculated in each repetition, and the sterile water was inoculated as the blank control. Inoculated leaves were covered with transparent plastic bags for 24 h to keep humidity. Nine days later, it was found that there were lesions on the leaves inoculated with the pathogen, and the traits were the same as those in the field, while the controls are healthy. The fungus was consistently isolated from the inoculated leaves. The similar isolates were re-isolated from the inoculated and infected leaves and identified as Alternaria tenuissima by DNA sequencing, fulfilling Koch's postulates. Fungal genomic DNA was extracted from 7-day-old culture. PCR amplifications were performed using primers ITS1 / ITS4 and TEFF / TEFR respectively (Takahashi et al. 2006, Du 2008). The nucleotide sequence of PCR products, which have been deposited in Genebank under the accession numbers MN153514 and MN735428, showed 99.8%-100% identity with the corresponding sequences of A. tenuissima (MW194297 and MK415954). In order to further identify the pathogen species, we constructed a phylogenetic tree by combining TEF sequence and ITS sequence to distinguish the relationship between the pathogen and other minor species in the genus Alternaria, the isolate was clustered in the Alternaria clade. Therefore, the pathogen was identified as A. tenuissima based on the morphological characteristics and molecular identification. To our knowledge, this is the first report of A. tenuissima causing leaf spot on A. dahurica in China.

Cytotoxic compound triacremoniate from Marine Fungus Acremonium citrinum. MMF4.

Two new compounds, triacremoniate (1) and dietziamide C (2) along with known compounds ß-Adenosine (3) and acrepyrone A (4) were obtained from the mangrove-derived fungus Acremonium citrinum. MMF4. Their structures were unambiguously determined by extensive spectroscopic methods, including UV, IR, HRESIMS and NMR. Triacremoniate (1) can promote apoptosis of HeLa cells by increasing the PARP cleavage and the phosphorylation of JNK and p38.

Achieving enhanced biological nitrogen removal via 2450 MHz electromagnetic wave loading on returned sludge in anaerobic-anoxic-oxic process.

To evaluate the enhancing of the biological nitrogen removal effectiveness by electromagnetic wave loading on returned sludge in the A/A/O reactor, some experiments were completed with the returned sludge loaded by 2,450 MHz electromagnetic wave. The excess sludge yield and pollutant removal effect of the system were evaluated. Results showed that stronger denitrification effect and less sludge yield were achieved. When 30% of the returned sludge was loaded by electromagnetic wave, the actual denitrification efficiency increased by 7% without dosage. The dissolution of carbon, nitrogen and phosphorus from loaded returned sludge was detected, thus providing the system with a supplemental carbon source of 4.6 g/d SCOD. The specific oxygen uptake rate of the oxic activated sludge increased by 14%, and the denitrification rate of the anoxic activated sludge increased by 29%. Illumina MiSeq analysis showed that the microbial richness increased obviously, and denitrifying bacteria (i.e. Dechloromonas, Zoogloea and Azospira, etc.) were accumulated.

Auranofin mitigates systemic iron overload and induces ferroptosis via distinct mechanisms.

Iron homeostasis is essential for health; moreover, hepcidin-deficiency results in iron overload in both hereditary hemochromatosis and iron-loading anemia. Here, we identified iron modulators by functionally screening hepcidin agonists using a library of 640 FDA-approved drugs in human hepatic Huh7 cells. We validated the results in C57BL/6J mice and a mouse model of hemochromatosis (Hfe-/- mice). Our screen revealed that the anti-rheumatoid arthritis drug auranofin (AUR) potently upregulates hepcidin expression. Interestingly, we found that canonical signaling pathways that regulate iron, including the Bmp/Smad and IL-6/Jak2/Stat3 pathways, play indispensable roles in mediating AUR's effects. In addition, AUR induces IL-6 via the NF-κB pathway. In C57BL/6J mice, acute treatment with 5 mg/kg AUR activated hepatic IL-6/hepcidin signaling and decreased serum iron and transferrin saturation. Whereas chronically treating male Hfe-/- mice with 5 mg/kg AUR activated hepatic IL-6/hepcidin signaling, decreasing systemic iron overload, but less effective in females. Further analyses revealed that estrogen reduced the ability of AUR to induce IL-6/hepcidin signaling in Huh7 cells, providing a mechanistic explanation for ineffectiveness of AUR in female Hfe-/- mice. Notably, high-dose AUR (25 mg/kg) induces ferroptosis and causes lipid peroxidation through inhibition of thioredoxin reductase (TXNRD) activity. We demonstrate the ferroptosis inhibitor ferrostatin significantly protects liver toxicity induced by high-dose AUR without comprising its beneficial effect on iron metabolism. In conclusion, our findings provide compelling evidence that TXNRD is a key regulator of ferroptosis, and AUR is a novel activator of hepcidin and ferroptosis via distinct mechanisms, suggesting a promising approach for treating hemochromatosis and hepcidin-deficiency related disorders.

Percutaneous tibial nerve stimulation for overactive bladder syndrome: a systematic review and meta-analysis.

INTRODUCTION AND HYPOTHESIS: This systematic review and meta-analysis aimed to evaluate the efficacy and safety of percutaneous tibial nerve stimulation (PTNS) for the treatment of overactive bladder (OAB) syndrome. METHODS: PubMed, Embase, Web of Science and Cochrane Library were searched systematically to identify all the relevant studies. Void frequency per day, nocturia frequency per day, urgency episodes per day, incontinence episodes per day, urodynamic values, success rate and side effects, etc., were extracted from the included studies and analyzed. RESULTS: Twenty-eight studies with 2461 patients in total were included. Results showed that there was a significant clinical effect on the voiding frequency per day (MD = -2.48; 95% CI -3.19, -1.76; P < 0.001), nocturia frequency per day (MD = -1.57; 95% CI -2.16, -0.99; P < 0.001), urgency episodes per day (MD = -2.20; 95% CI -3.77, -0.62; P = 0.006), incontinence episodes per day (MD = -1.37; 95% CI -1.71, -1.02; P < 0.001), maximum cystometric capacity (MD = 63.76; 95% CI 31.90, 95.61; P < 0.001) and compliance (MD = 7.62; 95% CI 0.61, 14.63; P = 0.033). The pooled success rate was 0.68 (95% CI 0.59, 0.78). The major complication was the pain at the puncture site, but the incidence was low. CONCLUSIONS: PTNS is effective and safe in treating OAB symptoms.

Effects of Dazomet Fumigation on Soil Phosphorus and the Composition of phoD-Harboring Microbial Communities.

The soil phosphorus (P) cycle and P transformation are largely driven by the soil bacterial microbial community. However, little is known about the effects of dazomet (DZ) soil fumigation on soil P and soil microbial communities associated with P transformation. This research investigated P released from three farm soils as a result of DZ fumigation and changes in enzyme activity, gene abundance, and the encoding alkaline phosphatase PhoD microbial community. After DZ fumigation, we observed a briefly significant increase in the available P and the active P fractionation. The soil ALP activity, 16s rRNA abundance, and the phoD gene decreased significantly after DZ fumigation. The abundance and diversity of phoD-harboring microbes also decreased shortly after fumigation, increased significantly 14-28 days later, and then decreased again toward the end of the experimental period of 86 days. The shared OTUs between treatments became fewer with increasing time after fumigation. The changes in available P and the active P fractionation after DZ fumigation were significantly correlated with the abundance of the dominant phoD-harboring microbes. DZ fumigation promoted P mineralization in these farm soils and changed the composition of phoD-harboring microbial communities, which will benefit crops able to absorb and use P.

Tripterygium and its extracts for diabetic nephropathy: Efficacy and pharmacological mechanisms.

Diabetic nephropathy (DN) is a common but intractable diabetic microvascular complication. Tripterygium, a Chinses herb, has been proven to be effective for DN treatment. In this review, the efficacy and pharmacological mechanism of tripterygium and its extracts on DN is elucidated. Tripterygium and its extracts could effectively reduce urine protein and protect renal function. Its pharmacological mechanism involves anti-inflammation, anti-oxidation, anti-glomerulosclerosis and anti-fibrosis, which is achieved by balancing the Th1/Th2 cells, regulating macrophage infiltration, and regulating the following pathways: p38 MAPK, NF-κB, TGF-ß, Wnt/ß-catenin, Akt and Notch1. Although tripterygium and its extracts may result in some adverse effects, including liver-function damage, gastrointestinal reaction, menstrual disorders, and reproductive problems, they are considered good alternative medicines for DN if used with caution and in the proper manner.

Effect of Astragali Radix Membranaceus in Promoting Blood Circulation and Its Modern Pharmacology Research / 中国实验方剂学杂志

Astragali Radix membranaceus is first recorded in Shennong Bencaojing, which has the effect in replenishing Qi and rising Yang, strengthening the body surface resistance, inducing diuresis to alleviate edema, and supporting for detoxication and tissue generation. As an essential medicine for invigorating Qi and invigorating the spleen, it is often used in diseases, such as Qi deficiency and fatigue, spleen deficiency diarrhea and so on, and has been well known by doctors. In recent years, scholars have a comprehensive understanding of the mechanisms in replenishing Qi, invigorating spleen and promoting water. However, Tao Hongjing first recorded that Astragali Radix membranaceus can " clear the evil blood between the five organs" . In Bencaojing Jizhu, this herbal medicine has the effect in promoting blood circulation at the same time. At present, traditional Chinese medicine often explains the mechanism of this herbal medicine in promoting blood circulation based on the theory of " replenishing Qi and activating blood circulation" and " blood circulation due to Qi circulation" , which however is not equivalent to the fact that this herbal medicine has no blood circulation effect. By summarizing the records of Astragali Radix membranaceus in the herbal literatures of the previous dynasties, it was found that its promoting blood circulation effect was widely used. In summary of the applications of traditional prescriptions and modern prescriptions in promoting blood circulation, Astragali Radix membranaceus can remove obstruction and activate blood circulation, activate blood and promote diuresis, activate blood circulation and strengthen the body resistance, which can best reflect the effect in activating blood circulation of this medicine. Modern pharmacology shows that Astragali Radix membranaceus has a good regulatory effect on the molecular mechanism of blood stasis pathological indexes by activating blood circulation. Due to no in-depth research, there is still room for study. Therefore, this paper thoroughly explores the mechanism of action of Astragali Radix membranaceus in promoting blood circulation by summarizing the effects of Astragali Radix membranaceus in literatures of previous dynasties and modern pharmacological studies, in order to expand the clinical application of Astragali Radix membranaceus and provide theoretical guidance for clinical treatment.

[Expert consensus statement on treatment of type 2 diabetes with Xiaoke Pills in clinical practice].

Xiaoke Pills are Chinese and Western medicine compound preparations with effects of nourishing kidney and Yin,and supplementing Qi and promoting fluid. It is widely used in clinical treatment of type 2 diabetes( Qi and Yin deficiency syndrome),and continuously included in 2010,2013 and 2017 editions of Chinese prevention guide for type 2 diabetes. For the purpose of accurate positioning and rational use in clinic,it is necessary to further define the curative effect,indications,medication precautions and contraindications of Xiaoke Pills,in order to improve medication safety. This consensus was reached by reference of international clinical guidelines and expert consensus approach based on clinical evidence-based evidence,expert experience and standard specification. The evidence-based evaluation was oriented to clinical problems summarized by no less than 200 front-line clinical physicians in two rounds.GRADE system was adopted for quality classification and evaluation of the evidences,and then the nominal group method was used to form consensus recommendations or suggestions. This consensus defined the curative effect advantages,target users,dosage,administration method,contraindications and precautions of Xiaoke Pills,and provided valuable reference for the clinical use of the drug. Thisconsensus still needs to be updated and revised based on new clinical problems and evidence-based evidence in practical application in the future.

Effects of adjuvant chemotherapy in T1N0M0 triple-negative breast cancer.

OBJECTIVES: Patients with T1N0M0 breast cancers are considered to have an excellent prognosis, even in triple-negative breast cancer (TNBC), which is often associated with diminished recurrence-free survival (RFS) and overall survival. Chemotherapy remains the only adjuvant treatment for TNBC, but evidence that adjuvant chemotherapy is beneficial for stage T1N0M0 TNBC patients is limited. In this study, we aimed to evaluate the effect of adjuvant chemotherapy and the benefit of taxanes in T1N0M0 TNBC patients. MATERIAL AND METHODS: A cohort of 354 consecutive patients with newly diagnosed T1N0M0 TNBC between January 2008 and December 2015 were included from the Fudan University Shanghai Cancer Center. Univariate and multivariate survival analyses were performed to compare patients treated with adjuvant chemotherapy with/without taxane addition. RESULTS: Median follow-up was 45 months. Chemotherapy was used in 92.4% of patients. The 5-year estimated RFS rates of patients with and without adjuvant chemotherapy were 94.5% and 83.6%, respectively. In multivariate analysis, adjuvant chemotherapy and a lack of lymphovascular invasion were associated with a significant benefit for RFS. A significant RFS benefit from adjuvant chemotherapy was observed in T1c (hazard ratio, HR = 0.24, 95% CI [0.08-0.76], P = 0.014) but not in T1b (HR = 0.32, 95% CI [0.03-3.18], P = 0.330) subgroups. Addition of taxane to an anthracycline-based regimen was not significantly associated with improved RFS in T1N0M0 TNBC patients. CONCLUSION: Adjuvant chemotherapy improves recurrence-free survival in T1c TNBC patients but not in T1b. Anthracycline-based taxane-free regimens might be sufficient to achieve RFS benefits in T1N0M0 TNBC patients.