[Fuyu Decoction ameliorates myocardial fibrosis in rat model of heart failure by regulating Nrf2/GPX4-mediated ferroptosis].

This study aims to investigate the effect and mechanism of Fuyu Decoction(FYD) in the treatment of myocardial fibrosis in the rat model of heart failure(HF). Sixty Wistar rats were randomized into a modeling group(n=50) and a sham group(n=10). A post-myocardial infarction HF model was established by ligating the left anterior descending coronary artery in rats. The successfully modeled rats were assigned into model, low-dose(2.5 g·kg~(-1)) FYD(FYD-L), high-dose(5.0 g·kg~(-1)) FYD(FYD-H), and FYD+Nrf2 inhibitor(ML385, 30 mg·kg~(-1)) groups(n=10). FYD was administrated by gavage and ML385 by intraperitoneal injection. The rats in the sham and model groups were administrated with equal amounts of normal saline by gavage. After 8 weeks of intervention, the cardiac function indicators were measured, and the myocardial tissue morphology and collagen deposition were observed. The positive expression of collagens Ⅰ and Ⅲ, apoptosis, and oxidative stress were examined, and the levels of Fe~(2+) and reactive oxygen species(ROS) were determined. The protein levels of nuclear factor erythroid 2-related factor 2(Nrf2), solute carrier family 7 member 11(SLC7A11), glutathione peroxidase 4(GPX4), and acyl-coenzyme A synthase long chain family member 4(ACSL4) in the myocardial tissue were determined. Compared with sham group, the model group showed decreased left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS), increased left ventricular end internal dimension in systole(LVIDs), left ventricular internal diameter in diastole(LVIDd), and myocardial collagen deposition, positive expression of collagens Ⅰ and Ⅲ, elevated apoptosis rate and malondialdehyde(MDA), Fe~(2+), and ROS levels, lowered superoxide dismutase(SOD) and glutathione peroxidase(GSH) levels, down-regulated protein levels of Nrf2, SLC7A11, and GPX4, and up-regulated protein level of ACSL4. Compared with the model group, the above indicators were restored by FYD. Moreover, ML385 reversed the protective effect of FYD on myocardial fibrosis in HF rats. In conclusion, FYD can inhibit ferroptosis by activating the Nrf2/GPX4 pathway, thereby ameliorating myocardial fibrosis in HF rats.

Ginkgo biloba extract protects against depression-like behavior in mice through regulating gut microbial bile acid metabolism.

Depression is a mental disorder with high morbidity, disability and relapse rates. Ginkgo biloba extract (GBE), a traditional Chinese medicine, has a long history of clinical application in the treatment of cerebral and mental disorders, but the key mechanism remains incompletely understood. Here we showed that GEB exerted anti-depressant effect in mice through regulating gut microbial metabolism. GBE protected against unpredictable mild stress (UMS)-induced despair, anxiety-like and social avoidance behavior in mice without sufficient brain distribution. Fecal microbiome transplantation transmitted, while antibiotic cocktail abrogated the protective effect of GBE. Spatiotemporal bacterial profiling and metabolomics assay revealed a potential involvement of Parasutterella excrementihominis and the bile acid metabolite ursodeoxycholic acid (UDCA) in the effect of GBE. UDCA administration induced depression-like behavior in mice. Together, these findings suggest that GBE acts on gut microbiome-modulated bile acid metabolism to alleviate stress-induced depression.

Nanozyme: a rising star for cancer therapy.

In recent years, nanozymes have attracted enormous attention due to their effectiveness in promoting various catalytic reactions. To date, thousands of nanozymes have been discovered, including oxidase-like nanozymes, peroxidase-like nanozymes, and catalase-like nanozymes, covering noble metal, transition metal, and carbon nanomaterials. These nanozymes have been widely applied in various fields, including environmental protection, biosensing and nanomedicine. There are many reviews about this rising star being used in analytical chemistry. However, few works about nanozymes were related to cancer therapy. In this study, we comprehensively summarize the latest research advances on the strategies for cancer therapy based on different nanozymes. With traditional cancer treatment (including chemotherapy, radiotherapy, phototherapy), nanozyme catalytic therapy exhibited a synergistic effect for limiting the growth of tumors. Opportunities and trends for nanozymes in future cancer therapy are also discussed.

Efficacy and safety of Qiangli Dingxuan tablet combined with amlodipine besylate for essential hypertension: a randomized, double-blind, placebo-controlled, parallel-group, multicenter trial.

Background: Hypertension, a major cardiovascular risk factor, severely impacts patients' quality of life. Qiangli Dingxuan tablet (QDT) is a formally approved Chinese patent medicine, which has been widely used as an adjunctive treatment for hypertension. This study aimed to investigate the antihypertensive efficacy and safety of QDT combined with amlodipine besylate in patients with essential hypertension. Methods: In this randomized, double-blind, placebo-controlled, parallel-group, multicenter trial conducted in China, patients diagnosed with grade 1 to 2 essential hypertension were randomly assigned in a 1:1 to the treatment of QDT or placebo for 12 weeks, alongside their ongoing treatment with amlodipine besylate. The primary outcome was the change in office blood pressure (BP) from baseline to 12 weeks. In addition, safety analysis included the assessment of vital signs and laboratory values. Results: At baseline, 269 patients were randomly assigned to the QDT group (n = 133) or the placebo group (n = 136), and there were no significant differences in baseline characteristics between the two groups. The primary outcome based on the full analysis set from baseline to 12 weeks showed that the mean difference in the change of office systolic BP reduction between the two groups was 6.86 mmHg (95%CI, 4.84 to 8.88, p < 0.0001), for office diastolic BP, the mean difference in the change of office diastolic BP reduction between the two groups was 4.64 mmHg (95%CI, 3.10 to 6.18, p < 0.0001). In addition, traditional Chinese medicine symptom scores were significantly decreased in the QDT group compared with the placebo group. No severe adverse events attributable to QDT were reported. Conclusion: The combination of QDT and amlodipine besylate demonstrates superior efficacy compared to amlodipine besylate monotherapy in the management of essential hypertension. QDT shows potential as an adjunctive treatment for essential hypertension. However, further rigorous clinical trials are warranted to validate these findings. Clinical Trial Registration: [https://clinicaltrials.gov/study/NCT05521282?cond=NCT05521282&rank=1]; Identifier: [NCT05521282].

Fluorescence enhancement of flavonoids and its application in ingredient determination for some traditional Chinese medicines by CE-LIF.

Flavonoids are widely used in the treatment of various diseases due to their antioxidant, anti-inflammatory, anticancer and antiviral properties. Fluorescence detection is rarely applied for the determination of flavonoids because of their weak fluorescence. In this work, a method of fluorescence enhancement of flavonoids was firstly introduced by using sodium acetate for flavonoid derivatization. The study discovered that flavonoids, with a hydroxyl at the C3 position, had the ability to emit strong fluorescence after derivatization. Five flavonoids, kaempferide, galangin, isorhamnetin, kaempferol and quercetin, having a special structure, were selected, derivatized and analyzed by capillary electrophoresis with laser-induced fluorescence detection. Under the optimal conditions, the five flavonoids could be completely separated within 3 minutes. Good linear relationships were obtained for all analytes and the limits of detection for the five flavonoids were in the range of 1.18-4.67 × 10-7 mol L-1. Finally, the method was applied to the determination of flavonoids in five traditional Chinese medicines: aster, chamomile, galangal, tangerine peel and cacumen biotae. Flavonoids were successfully found in all these medicines by the developed method. The recoveries were in the range of 84.2-111%. The method developed in this study was fast, sensitive and reliable for the determination of flavonoids.

Circadian Genes MBOAT2/CDA/LPCAT2/B4GALT5 in the Metabolic Pathway Serve as New Biomarkers of PACA Prognosis and Immune Infiltration.

Pancreatic cancer (PACA) is a highly malignant tumor with a poor prognosis. Recent studies have discovered substantial differences in the expression levels of several circadian genes in PACA samples compared to normal samples. The goal of this research was to find differentially expressed rhythm genes (DERGs) in PACA samples and determine their role in the development of PACA. A total of 299 DERGs were identified in PACA, including 134 downregulated genes and 165 upregulated genes. DERGs were significantly abundant in the metabolic pathway and immune response pathways, according to GO and KEGG analyses. Survival analyses showed that PACA patients who had higher expression levels of MBOAT2/CDA/LPCAT2/B4GALT5 had shorter overall survival times. Using cell assay verification, the mRNA levels of MBOAT2/CDA/LPCAT2/B4GALT5 in Patu-8988 and PNAC-1 cells were found to be significantly higher than those in HPDE6-C7 cells, which was in line with previous studies on PACA patient data. Through conducting univariate Cox analysis, it was determined that MBOAT2/CDA/LPCAT2/B4GALT5 expression, age and grade were all high-risk factors. The MBOAT2/CDA/LPCAT2/B4GALT5 genes were independently correlated with overall survival, according to the multivariate Cox analysis. The proportion of immune cells in PACA and normal samples significantly changed, according to the immune infiltration analysis. Furthermore, MBOAT2/CDA/LPCAT2/B4GALT5 expression levels were significantly related to the level of immune cell infiltration. The protein-protein interaction network of the MBOAT2/CDA/LPCAT2/B4GALT5 genes included 54 biological nodes and 368 interacting genes. In conclusion, the finding of these DERGs adds to the investigation of the molecular processes underlying the onset and progression of PACA. In the future, DERGs may serve as prognostic and diagnostic biomarkers as well as drug targets for chronotherapy in PACA patients.

Gastrodia elata Blume: A review of its mechanisms and functions on cardiovascular systems.

Gastrodia elata Blume (GEB), commonly called Tianma in Chinese, is a valuable and extensively used herbal Traditional Chinese Medicine with a wide range of clinical applications. It has been used to treat headaches, dizziness, stroke, epilepsy, amnesia, spasm, and other disorders since ancient times. Hundreds of compounds, including phenols, glycosides, polysaccharides, steroids, organic acids, and others, have been isolated and identified from this plant. Modern pharmacological studies have shown that its active ingredients possess many pharmacological effects, such as neuroprotective, analgesic, sedation and hypnosis, anti-anxiety, anti-depressant, anti-convulsant, anti-dizziness, blood pressure lowering, blood lipids lowering, liver protection, anti-tumor, and immunity enhancement effects. The present review discusses the pharmacological actions and mechanisms of various components of GEB in cardiovascular diseases to provide a reference for further study of GEB.

Structurally diverse glycosides with α-glucosidase inhibitory properties from water extract of the leaves of Cyclocarya paliurus.

In this work we investigated the chemical constituents of water extract of the leaves of Cyclocarya paliurus. Two new megastigmane glycosides (3 and 8), three aliphatic alcohol glycosides (9-11), and two aromatic glycosides (12 and 13), along with fourteen known compounds were isolated, and their in vitro inhibitory activity against α-glucosidase was evaluated. Compounds 13 and 15-18 displayed inhibitory activity with IC50 values varying from 27.05 to 96.58 µM, and the structure-activity relationship among isolated compounds was discussed.

Jian-Yan-Ling capsules ameliorate cognitive impairment in mice with D-galactose-induced senescence and inhibit the oxidation-induced apoptosis of HT22 hippocampal cells by regulating the Nrf2-HO1 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The Jian-Yan-Ling (JYL) capsule is a famous anti-aging Chinese patent medicine. It is applied mainly to delay senescence to improve cognition in aging individuals. However, the action mechanisms of JYL for improving cognition have not been determined. AIM OF THE STUDY: We will evaluate the effect of the JYL capsule at improving the cognition of aging mice by improving oxidative stress in the hippocampus and exploring its action mechanism. MATERIALS AND METHODS: A senescence mouse model was developed via intraperitoneal injection of D-galactose. The effect of the JYL capsule at improving the learning and memory abilities of mice was evaluated using the Morris water maze and novel object recognition tests. The apotosis of model mice hippocampus' were determined by TUNEL analysis. The antioxidant capacity of the JYL capsule was evaluated by determining the activities of antioxidant enzymes and expressions of oxidative products. The regulation of the Nrf2/HO-1 signaling pathway of the JYL capsule was evaluated by determining the expressions of related proteins via western blotting analysis. In vitro, H2O2-treated mouse hippocampal HT22 cells were used to evaluate the antioxidant capacity of JYL-containing rat serum by determining the cell viability, apoptotic level and expressions of related proteins. RESULTS: JYL capsules enhanced the learning and memory abilities of model mice according to behavioral tests. The results of TUNEL analysis showed that the JYL capsule ameliorated hippocampal apoptosis in model mice. JYL capsules also exerted significant antioxidant capacity by increasing the activities of antioxidant enzymes while decreasing the levels of oxidative products both in the hippocampus and serum. The regulation of Nrf2/HO-1 pathway might contribute to the antioxidant function. In vitro, JYL-containing rat serum protected HT22 cells from H2O2 induced oxidative stress. The apoptosis of HT22 cells was also attenuated by regulating the caspase and Nrf2/HO-1 signaling pathways. CONCLUSIONS: The amelioration of neuronal oxidative stress of hippocampus might contribute to the D-galactose-induced cognition impairment of senescence mice. These findings provide evidence for the application of JYL capsules to enhance cognition in aging individuals.

Effect of Ginkgo biloba extract on pharmacology and pharmacokinetics of atorvastatin in rats with hyperlipidaemia.

Ginkgo biloba extract (GBE) is a common dietary supplement used by people with dyslipidaemia worldwide to reduce the risk of cardiovascular disease. Many studies have found that GBE itself has a variety of pharmacological activities. However, the role of GBE as an adjunct to conventional therapy with chemical drugs remains controversial. Therefore, this study explored the additional benefits of GBE in the treatment of hyperlipidaemia with statins in terms of both pharmacodynamics and pharmacokinetics. A hyperlipidaemia model was established by feeding rats a high-fat diet for a long time. The animals were treated with atorvastatin only, GBE only, or a combination of atorvastatin and GBE. The results showed that statins combined with GBE could significantly improve the blood lipid parameters, reduce the liver fat content, and reduce the size of adipocytes in abdominal fat. The effect was superior to statin therapy alone. In addition, the combination has shown additional liver protection against possible pathological liver injury or statin-induced liver injury. A lipidomic study showed that GBE could regulate the abnormal lipid metabolism of the liver in hyperlipemia. When statins are combined with GBE, this callback effect introduced by GBE on endogenous metabolism has important implications for resistance to disease progression and statin resistance. Finally, in the presence of GBE, there was a significant increase in plasma statin exposure. These results all confirmed that GBE has incremental benefits as a dietary supplement of statin therapy for dyslipidaemia.

Highly efficient and reusable Mg-Fe layered double hydroxides anchored in attapulgite for uranium uptake from wastewater.

Micro/nano interface adsorption is an effective strategy for separating uranium from aqueous solutions. However, their undesirable capture efficiency and poor cycling stability limit their practical application. In this study, we developed a clay-based micro-adsorbent constructed using attapulgite (ATP) and Mg-Fe layered double hydroxides (Mg-Fe LDHs) for uranium uptake from wastewater. The surface charge affinity between ATP and Mg-Fe LDHs contributed to the robust heterostructure of the ATP@Mg-Fe LDHs adsorbent, thereby enabling a uniform distribution of Mg-Fe LDHs on the ATP surface. Thus, the aggregation behavior of Mg-Fe LDHs was significantly reduced and stellated with an improved dispersion performance of this ATP@Mg-Fe LDHs micro-composite in an aqueous solution. The uranium adsorption capacity was 670.21 mg/g, which is the maximum among previously reported clay-based adsorbents. Notably, a satisfying performance was achieved for the adsorbent stability; the uranium adsorption efficiency remained as high as 97% after eight cycles of adsorption-desorption. The ATP@Mg-Fe LDHs adsorbent for separating UO22+ from water is a promising system that combines efficiency, capacity, selectivity, and reusability, and has potential for scaled-up applications.

Effect of Xuefu Zhuyu Capsule on Myocardial Infarction: Network Pharmacology and Experimental Verification.

Background: Myocardial infarction (MI) is the most severe manifestation of cardiovascular disease. Xuefu Zhuyu Capsule (XFC), a proprietary Chinese medicine, is widely used in various cardiovascular diseases. At present, the molecular mechanism of XFC remains unclear. Objective: To explore the mechanism of anti-MI effects of XFC by combining network pharmacology and experiments. Methods: TCMSP, GeneCards, and DisGeNET databases were used to find the target of XFC. PPI analysis was performed by the STRING database. KEGG and GO analyses were performed by Metascape Database. Molecular docking was performed by Autodock Vina. HE staining, echocardiography, immunofluorescence, and TUNEL were performed to verify the prediction results. Results: Network pharmacology showed that quercetin, kaempferol, ß-sitosterol, luteolin, and baicalein were the main active ingredients of XFC. TNF, IL6, TP53, VEGFA, JUN, CASP3, and SIRT1 were the main targets of XFC. KEGG results showed that key genes were mainly enriched in lipid and atherosclerosis, PI3K-Akt signaling pathway, MAPK signaling pathway, and NF-κB signaling pathway. HE staining showed that XFC could improve the morphology of myocardial tissue. Echocardiography showed that XFC could improve cardiac function. TUNEL showed that XFC could reduce cardiomyocyte apoptosis. Immunofluorescence showed that XFC could reduce the expression of α-smooth muscle actin (α-SMA) and increase the expression of CD31. In addition, we found that XFC may exert its therapeutic effects through SIRT1. Conclusion: This study demonstrated that SIRT1 may be the target of XFC in the treatment of MI. The active ingredients of XFC and SIRT1 can be stably bound. XFC could inhibit apoptosis, promote angiogenesis, and improve myocardial fibrosis through SIRT1.

Traditional Chinese medicine method of tonifying kidney for hypertension: Clinical evidence and molecular mechanisms.

Hypertension is the most common chronic disease. A large amount of evidence showed that traditional Chinese medicine (TCM) method of tonifying kidney (TK) combined with routine treatment is more effective and safer in the treatment of hypertension. This study integrated meta-analysis, data mining, and network pharmacology to explore the efficacy and potential mechanisms of TK in the treatment of hypertension. Meta-analysis was performed to explore the efficacy and safety of TK combined with routine treatment in the treatment of hypertension. Data mining was used to screen the core herbs of the TK. Network pharmacology was used to predict the antihypertensive mechanism of TK core herbs. A total of 18 studies with 2,024 patients were included in this study. Meta-analysis showed that TK combined with routine treatment was superior to routine treatment alone in lowering blood pressure (systolic and diastolic blood pressures), lowering blood lipids (total cholesterol, triglyceride, low-density lipoprotein cholesterol), improving vascular endothelial functions (nitric oxide, endothelin) and TCM symptoms (headache dizziness, soreness, and weakness of waist and knees). In addition, TK was safe and has no obvious adverse reactions. Data mining showed that the core herbs of TK were Eucommia ulmoides Oliv. (Duzhong), Vitex negundo L. (Huangjing), Taxillus chinensis (DC.) Danser (Sangjisheng), Ligustrum lucidum W.T.Aiton (Nuzhenzi), Astragalus mongholicus Bunge (Huangqi), Rehmannia glutinosa (Gaertn.) DC. (Shudihuang). Network pharmacology predicted that core herbs antihypertensive components were oleanolic acid, ursolic acid, and civetone, and the antihypertensive targets were NOS3, NOS2, MMP9, TNF, PTGS2, HMOX1. In addition, the antihypertensive targets were enriched in cGMP-PKG signaling pathway, calcium signaling pathway, aldosterone-regulated sodium reabsorption, HIF-1 signaling pathway. In conclusion, TK combined with routine treatment for hypertension is effective and safe. The mechanism of TK may be related to GMP-PKG signaling pathway, calcium signaling pathway, aldosterone-regulated sodium reabsorption. On the premise of syndrome differentiation and treatment, it is promising to treat hypertension with TK. Systematic review registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42022358276].

Banxia baizhu tianma decoction, a Chinese herbal formula, for hypertension: Integrating meta-analysis and network pharmacology.

Hypertension is a major cardiovascular risk factor, which seriously affects the quality of life of patients. Banxia Baizhu Tianma Decoction (BXD) is a Chinese herbal formula that is widely used to treat hypertension in China. This study aimed to evaluate the efficacy and potential mechanism of BXD for hypertension by meta-analysis and network pharmacology. Meta-analysis was performed to explore the efficacy and safety of BXD combined with conventional treatment for hypertension. Network pharmacology was used to explore the molecular mechanism of BXD in antihypertension. A total of 23 studies involving 2,041 patients were included. Meta-analysis indicated that compared with conventional treatment, combined BXD treatment was beneficial to improve clinical efficacy rate, blood pressure, blood lipids, homocysteine, endothelial function, inflammation, and traditional Chinese medicine symptom score. In addition, meta-analysis indicated that BXD is safe and has no obvious adverse reactions. Network pharmacology showed that the antihypertensive targets of BXD may be AKT1, NOS3, ACE, and PPARG. The antihypertensive active ingredients of BXD may be naringenin, poricoic acid C, eburicoic acid, and licochalcone B. Due to the poor methodological quality of the Chinese studies and the small sample size of most, the analysis of this study may have been affected by bias. Therefore, the efficacy and safety of BXD for hypertension still need to be further verified by high-quality clinical studies. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022353666.

Chuanzhitongluo regulates microglia polarization and inflammatory response in acute ischemic stroke.

BACKGROUND AND PURPOSE: Chuanzhitongluo (CZTL), a traditional Chinese medicine mixture, is used in the recovery period of acute ischemic stroke (AIS), and effectively improves the prognosis of AIS patients. This study aims to evaluate whether CZTL regulates microglia polarization and inflammatory response to reduce brain damage in the acute phase of AIS. METHODS: A mouse model of AIS was prepared by the photochemical method. Cerebral infarct volume was detected by 2,3,5-Triphenyltetrazolium chloride (TTC) staining. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was used to assess neuronal apoptosis. Gene expression profile change was explored by Gene chip. Inflammatory factors were analyzed by Protein microarray. The Immunofluorescence double-labeling assay was executed to elucidate the effects of CD16+ / Iba-1+ and CD206+ / Iba-1+ in the peripheral area of cerebral ischemia. RESULTS: Results revealed that CZTL treatment alleviated the neurological impairment, reduced cerebral infarct volume, and inhibited neuronal apoptosis. CZTL altered gene expression profiles, which indicate that CZTL may be involved in regulating neuroinflammation. CZTL restrained inflammatory responses by down-regulated pro-inflammatory cytokines expression and enhanced anti-inflammatory cytokines level. Further experiments demonstrated that CZTL inhibited the activation of NLRP3 inflammasome, which decreasing the inflammatory response. In addition, CZTL promoted the transformation of microglia from M1 to M2 phenotype. CONCLUSIONS: These results indicate that CZTL alleviates neuroinflammation and brain damage after AIS in mice, which may be mediated by modulating microglia polarization.

Network Pharmacology and Molecular Docking Analysis on the Pharmacological Mechanisms of Modified Sanmiaosan in Treating Ulcerative Colitis.

Background: Modified Sanmiaosan is an effective cure in the treatment of ulcerative colitis, but its mechanisms of action remain unclear. This study revealed the pharmacological mechanisms of Modified Sanmiaosan acting on ulcerative colitis through a pharmacology approach. Materials and Methods: The active compounds and the targets of Modified Sanmiaosan were selected from the Traditional Chinese Medicine Systems Pharmacology database according to the absorption and metabolism. The UC-related therapeutic targets were collected from the PharmGKB database, the GeneCards database, the GADA database, and the OMIM database. The networks of "drug-component-target-disease" and "herbal-component-target" were constructed by the Cytoscape software. Protein-protein interaction network was generated by the STRING database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed by the R software. Molecular docking technology was used to identify the affinity and activity between active compounds and targets. Results: The 80 effective ingredients of MSM were collected. A total of 5180 UC-related genes and the 153 key targets of MSM and UC-related were obtained. JUN, Akt1, and MAPK1 were identified as the "hub targets" involved in the effects of Modified Sanmiaosan on ulcerative colitis. Hub targets were mainly involved in inflammatory response and oxidative stress. As the results of GO analysis, biological processes such as DNA-binding transcription and RNA polymerization may participate in the treatment process; KEGG pathway analysis showed that hub targets were mainly involved in IL-17 signal pathway and TNF signal pathway of ulcerative colitis. The high affinity and activity of the active compounds and targets were verified through molecular docking. Conclusion: These findings demonstrate the active ingredients in Modified Sanmiaosan reduce inflammatory response by TNF and IL-17 signaling pathways to treat ulcerative colitis. Anti-inflammation and immune regulation may be the main mechanism of Modified Sanmiaosan in the treatment of ulcerative colitis. This study not only provide new insights into the development of a natural therapy for the prevention and treatment of ulcerative colitis but also proves a feasible method for discovering potential activated compounds from Chinese herbs.

Effects and Prognostic Values of Circadian Genes CSNK1E/GNA11/KLF9/THRAP3 in Kidney Renal Clear Cell Carcinoma via a Comprehensive Analysis.

Kidney renal clear cell carcinoma (KIRC) is one of the most prevalent and deadly types of renal cancer in adults. Recent research has identified circadian genes as being involved in the development and progression of KIRC by altering their expression. This study aimed to identify circadian genes that are differentially expressed in KIRC and assess their role in KIRC progression. In KIRC, there were 553 differentially expressed rhythm genes (DERGs), with 300 up-regulated and 253 down-regulated DERGs. Functional enrichment analyses showed that DERGs were greatly enriched in the circadian rhythm and immune response pathways. Survival analyses indicated that higher expression levels of CSNK1E were related to shorter overall survival of KIRC patients, whereas lower expression levels of GNA11, KLF9, and THRAP3 were associated with shorter overall survival of KIRC patients. Through cell assay verification, the mRNA level of CSNK1E was significantly up-regulated, whereas the mRNA levels of GNA11, KLF9, and THRAP3 were dramatically down-regulated in KIRC cells, which were consistent with the bioinformatics analysis of KIRC patient samples. Age, grade, stage, TM classification, and CSNK1E expression were all shown to be high-risk variables, whereas GNA11, KLF9, and THRAP3 expression were found to be low-risk factors in univariate Cox analyses. Multivariate Cox analyses showed that CSNK1E and KLF9 were also independently related to overall survival. Immune infiltration analysis indicated that the proportion of immune cells varied greatly between KIRC tissues and normal tissue, whereas CSNK1E, GNA11, KLF9, and THRAP3 expression levels were substantially linked with the infiltration abundance of immune cells and immunological biomarkers. Moreover, interaction networks between CSNK1E/GNA11/KLF9/THRAP3 and immune genes were constructed to explore the stream connections. The findings could help us better understand the molecular mechanisms of KIRC progression, and CSNK1E/GNA11/KLF9/THRAP3 might be used as molecular targets for chronotherapy in KIRC patients in the near future.

Synergistic simultaneous endogenous partial denitrification/anammox (EPDA) and denitrifying dephosphatation for advanced nitrogen and phosphorus removal in a complete biofilm system.

To achieve simultaneous biological nitrogen and phosphorus removal from municipal wastewater, the endogenous partial denitrification/anammox (EPDA) was combined with denitrifying dephosphatation in a complete biofilm reactor. Advanced nitrogen and phosphorus removal were achieved with effluent total nitrogen (TN) and PO43--P concentrations of 7.77 ± 0.33 mg/L and 0.35 ± 0.10 mg/L, respectively. Anammox took a major role in the system, accounting for 76 ± 7% of nitrogen removal. 16S rRNA high-throughput sequencing results showed that the anammox bacteria co-existed with the denitrifying glycogen accumulating organisms (DGAOs) and the denitrifying phosphorus accumulating organisms (DPAOs). Anammox bacteria were mainly distributed in the inner layer, while DGAOs and DPAOs existed in the outer layer of EPDA biofilms. Furthermore, based on the EPDA biofilm system, a promising advanced nitrogen and phosphorus removal process was suggested to achieve lower requirements for energy and reagent consumption.

Scutellarin enhances anti-tumor immune responses by reducing TNFR2-expressing CD4+Foxp3+ regulatory T cells.

One characteristic of tumor-associated CD4+Foxp3+ regulatory T cells (Tregs) is the high expression of tumor necrosis factor receptor type II (TNFR2), a receptor that mediates the decisive effect of tumor necrosis factor (TNF) in the activation and expansion of Tregs. There is increasing evidence that inhibition of TNFR2 can enhance anti-tumor immune responses. Therefore, we screened Chinese herbal extracts for their capacity to block TNF-TNFR2 interaction. The results showed that the treatment with a Chinese herb extract could inhibit TNFR2-induced biological responses in vitro, including the proliferation of TNFR2+ Tregs. Our subsequent study led to the identification of flavonoid compound scutellarin was responsible for the activity. Our results showed that scutellarin is able to disrupt the interaction of TNF-TNFR2 and inhibited the phosphorylation of p38 MAPK, a down-stream signaling component of TNFR2. Importantly, in vivo scutellarin treatment markedly enhanced the efficacy of tumor immunotherapy with CpG oligodeoxynucleotide in mouse CT26 colon cancer model. This effect of scutellarin was associated with the reduction of the number of tumor-infiltrating TNFR2-expressing Tregs and increased tumor infiltration of interferon-γ-producing CD8+ T cells. Our result also suggests that scutellarin or its analogs may be used as an adjuvant to enhance the anti-tumor effect of immunotherapeutic agent by eliminating TNFR2+ Treg activity.

Reduction of selenite to selenium nanospheres by Se(IV)-resistant Lactobacillus paralimentarius JZ07.

Elemental selenium nanosphere is considered to exhibit high bioavailability compared to its salts. In this study, a Se(IV)-resistant Lactobacillus paralimentarius strain JZ07 with great selenium biotransformation ability was screened and the red elemental selenium biosynthesized by it was characterized. The results indicated that Se(0) occurred as major accumulated species and the S atom content of the cells increased significantly in the presence of selenite. The reduced amorphous selenium nanospheres (150 to 300 nm in diameter) deposited in the extracellular space of JZ07 and the cells exhibited altered morphology under selenium stress. The macromolecules containing carboxylate bands and amide groups played an important role in Se(IV) bioaccumulation. The findings of present study indicate that JZ07 can be a promising SeNPs producing probiotic LAB and has the potential to be explored as an alternative source of Se supplements for human or animal consumption.