Simiao pills alleviates renal injury associated with hyperuricemia: A multi-omics analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Simiao Pills, a classical traditional Chinese medicine prescription recorded in Cheng Fang Bian Du, has been traditionally used to treat hyperuricemia due to its heat-clearing and diuretic properties. Studies have shown that Simiao Pills effectively reduce uric acid levels. However, further research is needed to elucidate the precise composition of Simiao Pills for treating hyperuricemia and their potential pharmacological mechanism. AIM OF THE STUDY: This study aimed to investigate the therapeutic effects of Simiao Pills on hyperuricemia, with a particular focus on evaluating their protective role against hyperuricemia-induced renal injury and elucidating the underlying mechanism of action. MATERIALS AND METHODS: UPLC-MS/MS was used to identify the components of Simiao Pills. The hyperuricemia model mice were established by intraperitoneal injecting potassium oxonate (PO) and oral administrating hypoxanthine (HX). Network pharmacology, transcriptome, and metabolomics analyses were integrated to explore the mechanism of Simiao Pills in reducing uric acid and protecting the kidney. Mechanistic and functional studies were conducted to validate the potential mechanisms. RESULTS: Simiao Pills were found to contain 12 characteristic components. Treatment with Simiao Pills significantly reduced serum uric acid levels and ameliorated hyperuricemia-induced renal injury. Simiao Pills inhibited the enzymatic activities of XOD and XDH, and regulated the uric acid transporters in the kidney and ileum. Transcriptome and network pharmacology analyses highlighted quercetin, berberine, kaempferol, and baicalein as the principal active components of Simiao Pills acting on the kidney during hyperuricemia treatment, primarily impacting fibrosis, apoptosis, and inflammation-related signaling pathways. Metabolomic analysis unveiled 21 differential metabolites and 5 metabolic pathways associated with Simiao Pills against renal injury associated with hyperuricemia. Further experimental results validated that Simiao Pills reduced renal fibrosis, apoptotic renal cells, serum inflammation levels, and inhibited the NF-κB/NLRP3/IL-1ß signaling pathway. CONCLUSION: This study demonstrated that Simiao Pills significantly reduced serum uric acid levels and improved renal injury by regulating inflammation, apoptosis, and renal fibrosis. These findings have provided a robust scientific pharmacological basis for the use of Simiao Pills in treating hyperuricemia patients.

Frailty and psychiatric disorders: A bidirectional Mendelian randomization study.

BACKGROUND: The association between frailty and psychiatric disorders has been reported in observational studies. However, it is unclear whether frailty facilitates the appearance of psychiatric disorders or vice versa. Therefore, we conducted a bidirectional Mendelian randomization (MR) study to evaluate the causality. METHODS: Independent genetic variants associated with frailty index (FI) and psychiatric disorders were obtained from large genome-wide association studies (GWAS). The inverse variance weighted method was utilized as the primary method to estimate causal effects, followed by various sensitivity analyses. Multivariable analyses were performed to further adjust for potential confounders. RESULTS: The present MR study revealed that genetically predicted FI was significantly and positively associated with the risk of major depressive disorder (MDD) (odds ratio [OR] 1.79, 95 % confidence interval [CI] 1.48-2.15, P = 1.06 × 10-9), anxiety disorder (OR 1.61, 95 % CI 1.19-2.18, P = 0.002) and neuroticism (OR 1.38, 95 % CI 1.18-1.61, P = 3.73 × 10-5). In the reverse MR test, genetic liability to MDD (beta 0.232, 95 % CI 0.189-0.274, P = 1.00 × 10-26) and neuroticism (beta 0.128, 95 % CI 0.081-0.175, P = 8.61 × 10-8) were significantly associated with higher FI. Multivariable analyses results supported the causal association between FI and MDD and neuroticism. LIMITATIONS: Restriction to European populations, and sample selection bias. CONCLUSIONS: Our study suggested a bidirectional causal association between frailty and MDD neuroticism, and a positive correlation of genetically predicted frailty on the risk of anxiety disorder. Developing a deeper understanding of these associations is essential to effectively manage frailty and optimize mental health in older adults.

Causal effects of gut microbiota on sepsis: a two-sample Mendelian randomization study.

Background: Recent studies had provided evidence that the gut microbiota is associated with sepsis. However, the potential causal relationship remained unclear. Methods: The present study aimed to explore the causal effects between gut microbiota and sepsis by performing Mendelian randomization (MR) analysis utilizing publicly accessible genome-wide association study (GWAS) summary-level data. Gut microbiota GWAS (N = 18,340) were obtained from the MiBioGen study and GWAS-summary-level data for sepsis were gained from the UK Biobank (sepsis, 10,154 cases; 452,764 controls). Two strategies were used to select genetic variants, i.e., single nucleotide polymorphisms (SNPs) below the locus-wide significance level (1 × 10-5) and the genome-wide statistical significance threshold (5 × 10-8) were chosen as instrumental variables (IVs). The inverse variance weighted (IVW) was used as the primary method for MR study, supplemented by a series of other methods. Additionally, a set of sensitivity analysis methods, including the MR-Egger intercept test, Mendelian randomized polymorphism residual and outlier (MR-PRESSO) test, Cochran's Q test, and leave-one-out test, were carried out to assess the robustness of our findings. Results: Our study suggested that increased abundance of Deltaproteobacteria, Desulfovibrionales, Catenibacterium, and Hungatella were negatively associated with sepsis risk, while Clostridiaceae1, Alloprevotella, LachnospiraceaeND3007group, and Terrisporobacter were positively correlated with the risk of sepsis. Sensitivity analysis revealed no evidence of heterogeneity and pleiotropy. Conclusion: This study firstly found suggestive evidence of beneficial or detrimental causal associations of gut microbiota on sepsis risk by applying MR approach, which may provide valuable insights into the pathogenesis of microbiota-mediated sepsis and strategies for sepsis prevention and treatment.

Causal association of lipoprotein-associated phospholipids on the risk of sepsis: a Mendelian randomization study.

Background: Many previous studies have revealed a close relationship between lipoprotein metabolism and sepsis, but their causal relationship has, until now, remained unclear. Therefore, we performed a two-sample Mendelian randomization analysis to estimate the causal relationship of lipoprotein-associated phospholipids with the risk of sepsis. Materials and methods: A two-sample Mendelian randomization (MR) analysis was performed to investigate the causal relationship between lipoprotein-associated phospholipids and sepsis based on large-scale genome-wide association study (GWAS) summary statistics. MR analysis was performed using a variety of methods, including inverse variance weighted as the primary method, MR Egger, weighted median, simple mode, and weighted mode as complementary methods. Further sensitivity analyses were used to test the robustness of the data. Results: After Bonferroni correction, the results of the MR analysis showed that phospholipids in medium high-density lipoprotein (HDL; ORIVW = 0.82, 95% CI 0.71-0.95, P = 0.0075), large HDL (ORIVW = 0.92, 95% CI 0.85-0.98, P = 0.0148), and very large HDL (ORMR Egger = 0.83, 95% CI 0.72-0.95, P = 0.0134) had suggestive causal relationship associations with sepsis. Sensitivity testing confirmed the accuracy of these findings. There was no clear association between other lipoprotein-associated phospholipids and sepsis risk. Conclusions: Our MR analysis data suggestively showed a correlation between higher levels of HDL-associated phospholipids and reduced risk of sepsis. Further studies are required to determine the underlying mechanisms behind this relationship.

Identification of Interleukin-1-Beta Inhibitors in Gouty Arthritis Using an Integrated Approach Based on Network Pharmacology, Molecular Docking, and Cell Experiments.

Background: This study aimed to investigate the molecular mechanism of Tongfengding capsule (TFDC) in treating immune-inflammatory diseases of gouty arthritis (GA) and interleukin-1-beta (IL-1ß) inhibitors by using network pharmacology, molecular docking, and cell experiments. Methods: In this study, the compounds of TFDC and the potential inflammatory targets of GA were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Online Mendelian Inheritance in Man (OMIM), and GeneCards databases. The TFDC-GA-potential targets interaction network was accomplished by the STRING database. The TFDC-active compound-potential target-GA network was constructed using Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used to further explore the GA mechanism and therapeutic effects of TFDC. Quantitative real-time PCR (qPCR) was used to verify whether the TFDC inhibited IL-1ß in GA. Molecular docking technology was used to analyze the optimal effective compounds from the TFDC for docking with IL-1ß. Result: 133 active compounds and 242 targets were screened from the TFDC, and 25 of the targets intersected with GA inflammatory targets, which were considered as potential therapeutic targets. Network pharmacological analysis showed that the TFDC active compounds such as quercetin, stigmasterol, betavulgarin, rutaecarpine, naringenin, dihydrochelerythrine, and dihydrosanguinarine had better correlation with GA inflammatory targets such as PTGS2, PTGS1, NOS2, SLC6A3, HTR3A, PPARG, MAPK14, RELA, MMP9, and MMP2. The immune-inflammatory signaling pathways of the active compounds for treating GA are IL-17 signaling pathway, TNF signaling pathway, NOD-like receptor signaling pathway, NF-kappa B signaling pathway, Toll-like receptor signaling pathway, HIF-1 signaling pathway, etc. The TFDC reduced IL-1ß mRNA expression in GA by qPCR. Molecular docking results suggested that rutaecarpine was the most appropriate natural IL-1ß inhibitor. Conclusion: Our findings provide an essential role and bases for further immune-inflammatory studies on the molecular mechanisms of TFDC and IL-1ß inhibitors development in GA.

The role of microbiota in autism spectrum disorder: A bibliometric analysis based on original articles.

Background: Gastrointestinal (GI) symptoms can be observed in autism spectrum disorder (ASD) children. It is suggested that the gut microbiota and its metabolites are associated, not only with GI symptoms, but also with behaviors of ASD. The aim of this study was to explore the development context, research hotspots and frontiers of gut microbiota and ASD from January 1, 1980 to April 1, 2022 by bibliometric analysis. Materials and methods: Publications of ASD and gut microbiota research from 1 January 1980 to 1 April 2022 were retrieved from the Web of Science Core Collection (WoSCC). Publications and citations trends were analyzed by Excel 2010. CiteSpace was used to analyze countries/regions, authors, institutes, references, and keywords and to visualize the knowledge map. Results: A total of 1027 studies were retrieved, and 266 original articles were included after screening. The most published countries and institutes were the United States and King Saud University. Afaf El-Aansary published the most articles, while Finegold SM had the highest co-citations. Hotspots and emerging trends in this area may be indicated by co-cited references and keywords and their clusters, including "gut-brain axis," "behavior," "chain fatty acid," "brain," "feces," "propionic acid," "clostridium perfringens," and "species clostridium innocuum." Conclusion: The United States dominants the research in this field, which focuses on the alterations of gut microbiota composition and its metabolites, among which the roles of the genus Clostridium and metabolites of short-chain fatty acids, especially propionic acid, are priorities. Fecal microbiota transplantation (FMT) is a promising complementary therapy. In general, research in this area is sparse, but it still has great research prospects.

Mechanism of Peitu Shengjin Formula Shenlingbaizhu Powder in Treating Bronchial Asthma and Allergic Colitis through Different Diseases with Simultaneous Treatment Based on Network Pharmacology and Molecular Docking.

Background: Shenlingbaizhu powder (SLBZP), one of the classic Earth-cultivating and gold-generating prescriptions of traditional Chinese medicine, is widely used to treat various diseases. However, the pharmacological mechanisms of SLBZP on bronchial asthma (BA) and allergic colitis (AC) remain to be elucidated. Methods: Network pharmacology and molecular docking technology were used to explore the potential mechanism of SLBZP in treating BA and AC with the simultaneous treatment of different diseases. The potential active compounds of SLBZP and their corresponding targets were obtained from BATMAN-TCM, ETCM, SymMap TCM@TAIWAN, and TCMSP databases. BA and AC disease targets were collected through DisGeNET, TTD, GeneCards, PharmGKB, OMIM, NCBI, The Human Phenotype Ontology, and DrugBank databases. Common targets for drugs and diseases were screened by using the bioinformatics and evolutionary genomics platform. The analyses and visualizations of Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of common targets were carried out by R software. The key targets were screened by using the plug-in "cytoHubba" of Cytoscape software, and the "active compound-key target" network was constructed. Molecular docking analysis was performed using AutoDock software. The miRTarBase database was used to predict microRNAs (miRNAs) targeting key targets, and the key target-miRNA network was constructed. Result: Through screening, 246 active compounds and 281 corresponding targets were obtained. Common targets were mainly enriched in 2933 biological processes and 182 signal pathways to play the role of treating BA and AC. There were 131 active compounds related to key targets. The results of molecular docking showed that the important active compounds in SLBZP had good binding ability with the key targets. The key target-miRNA network showed that 94 miRNAs were predicted. Conclusion: SLBZP has played the role of treating different diseases with the same treatment on BA and AC through the characteristics of multicompound, multitarget, and multipathway of traditional Chinese medicine, which provides a theoretical basis for explaining the mechanism and clinical application of SLBZP treating different diseases with the same treatment in BA and AC.

Superior ZSM-5@γ-Al2O3 Composite Catalyst for Methanol and Ethanol Coconversion to Light Olefins.

This paper proposes a ZSM-5@γ-Al2O3 composite with a core-shell structure for the high-efficiency cocatalytic conversion of a methanol-ethanol system to light olefins. Using ZSM-5 and γ-Al2O3 as sole catalysts for comparison, the effects of physical blending, impregnation, and liquid-phase precipitation coating strategies on the catalytic performance and physicochemical properties of the composite catalysts were systematically investigated. The results indicated that the ZSM-5@γ-Al2O3 composite catalyst prepared by a liquid-phase precipitation coating exhibited excellent catalytic performance. When the ethanol content was 25 wt % and the reaction occurred at 350 °C, the conversion rates of methanol and ethanol were 96.1 and 99.9%, respectively; the selectivity and yield of light olefins reached 92.3 and 89.9%, respectively. The introduction of ethanol into methanol enhanced the selectivity of light olefins as target products. The interfacial composite phase formed by in situ nucleation growth of pseudoboehmite produced distinct Brønsted-Lewis acid synergistic active centers. It also increased the mesopore/micropore ratio in the composite catalyst.

Qiweibaizhu Decoction Treats Diarrheal Juvenile Rats by Modulating the Gut Microbiota, Short-Chain Fatty Acids, and the Mucus Barrier.

BACKGROUND: Qiweibaizhu decoction (QBD), a classic Chinese herbal formula, has been widely used for treating diarrhea in infants and children with spleen deficiency syndrome for centuries, but its mechanism of action remains unclear. The gut microbiota, short-chain fatty acids (SCFAs), and intestinal mucus are closely associated with diarrhea. METHODS: In this study, the composition of the gut microbiota in diarrheal rats was analyzed by 16S rDNA amplicon sequencing. The concentrations of colon SCFAs were determined using gas chromatography-mass spectrometry (GC-MS). The expression of mucin 2 (MUC2) in the colon was detected by immunofluorescence. RESULTS: Diarrhea significantly changed the diversity and structure of the gut microbiota and disrupted the mucus barrier in juvenile rats. QBD did not significantly change the diversity and structure of the intestinal flora, but it enhanced the increasing tendencies of Verrucomicrobia and Akkermansia and decreased the abundance of Turicibacter (P=0.037) and Flavonifractor (P=0.043). QBD tends to repair the mucus layer and promote MUC2 expression in juvenile rats with diarrhea. Moreover, S. boulardii significantly increased the abundance of Parasutterella (P=0.043). In addition, QBD treatment tends to increase the propionic acid concentration during diarrhea, but its levels of acetic acid, propionic acid, butyric acid, and total SCFAs were lower than those in the S. boulardii group. CONCLUSION: S. boulardii significantly increased the abundance of Parasutterella, leading to increased production of acetic acid, propionic acid, and butyric acid, consequently leading to alleviation of diarrhea. In comparison, QBD affected diarrhea via regulation of the intestinal flora, especially by increasing the abundance of Verrucomicrobia and Akkermansia, resulting in mucus barrier repair, protection of the intestines, and treatment of diarrhea.

Foxf2 and Smad6 co-regulation of collagen 5A2 transcription is involved in the pathogenesis of intrauterine adhesion.

The replacement of normal endometrial epithelium by fibrotic tissue is the pathological feature of intrauterine adhesion (IUA), which is caused by trauma to the basal layer of the endometrium. COL5A2 is a molecular subtype of collagen V that regulates collagen production in fibrotic tissue. Here, we investigated the roles of Foxf2 and Smad6 in regulating the transcription of COL5A2 and their involvement in the pathogenesis of IUA. Small interference-mediated Foxf2 (si-Foxf2) silencing and pcDNA3.1-mediated Smad6 (pcDNA3.1-Smad6) up-regulation were performed in a TGF-ß1-induced human endometrial stromal cell line (HESC) fibrosis model. Assessment of collagen expression by Western blotting, immunofluorescence and qRT-PCR showed that COL5A2, COL1A1 and FN were significantly down-regulated in response to si-Foxf2 and pcDNA3.1-Smad6. Transfection of lentivirus vector-Foxf2 (LV-Foxf2) and pcDNA3.1-Smad6 into HESCs and qRT-PCR showed that Foxf2 promoted COL5A2 expression and Smad6 inhibited Foxf2-induced COL5A2 expression. Co-immunoprecipitation, chromatin immunoprecipitation and dual-luciferase reporter assays to detect the interaction between Foxf2 and Smad6 and their role in COL5A2 transcription showed that Foxf2 interacted with Smad6 and bond the same promoter region of COL5A2. In a rat IUA model, injection of ADV2-Foxf2-1810 and ADV4-Smad6 into the uterine wall showed that Foxf2 down-regulation and Smad6 up-regulation decreased fibrosis and the expression of COL5A2 and COL1A1, as detected by haematoxylin/eosin, Masson trichrome staining and immunohistochemistry. Taken together, these results suggested that Foxf2 interacted with Smad6 and co-regulated COL5A2 transcription in the pathogenesis of IUA, whereas they played opposite roles in fibrosis.

Pd-catalyzed desulfitative arylation for the synthesis of 2,5-diarylated oxazole-4-carboxylates using dioxygen as the terminal oxidant.

A desulfitative arylation of 2-aryloxazole-4-carboxylate with sodium arylsulfinates under an oxygen (O2) atmosphere to afford 2,5-diarylated oxazole-4-carboxylates is described. This transformation provides a novel approach for the utilization of sodium arylsulfinates as the aryl source and O2 as the sole oxidant.

[Determination of apparent oil-water partition coefficient of andrographolide and dehydroandrographolide and effect of pH on them].

OBJECTIVE: To determine the apparent n-octanol-water/buffer partition coefficient of andrographolide and dehydroandrographolide. METHODS: The apparent n-octanol-water/buffer partition coefficients of andrographolide and dehydroandrographolide were measured by shaking flask method. The concentrations of andrographolide and dehydroandrographolide were analyzed by HPLC method. RESULTS: The Papp of andrographolide and dehydroandrographolide were 3.90 (log Papp = 0.59) and 19.75 (log Papp = 1. 30) in water at 37 degrees C, respectively. CONCLUSIONS: The apparent n-octanol-buffer partition coefficients of andrographolide and dehydroandrographolide are influenced by pH, and the higher pH may decrease the apparent n-octanol-buffer partition coefficients of them. Andrographolide has the highest partition coefficient in pH6, and dehydroandrogapholide in pH5.