UNASSIGNED: This research aims to explore how Puerariae Lobatae Radix regulates sebaceous gland secretion using network pharmacology, and validate its effects on important targets through animal studies.
UNASSIGNED: This study utilized UPLC-EQ-MS to analyze Puerariae Lobatae Radix extract and identify potential bioactive compounds. Predicted targets of these compounds were obtained from the Swiss Target Prediction database, while targets associated with sebaceous gland secretion were obtained from the GeneCards database. Common targets between the databases were identified and a protein-protein interaction (PPI) network was established using the STRING platform. The PPI network was further analyzed using Cytoscape software. Pathway enrichment analysis was performed using Reactome, and molecular docking experiments targeted pivotal pathway proteins. Animal experiments were then conducted to validate the regulatory effects of the primary active compounds of Puerariae Lobatae Radix on key pathway proteins.
UNASSIGNED: This research identified 17 active compounds in Puerariae Lobatae Radix and 163 potential targets associated with the regulation of sebum secretion. Pathway enrichment analysis indicates that these targets may modulate lipid metabolism pathways through involvement in peroxisome proliferator-activated receptor α, SREB, steroid metabolism, and arachidonic acid metabolism pathways. Molecular docking analysis demonstrates that puerarin and daidzein show favorable binding interactions with key targets in these pathways. Animal experiments demonstrated that the administration of Puerariae Lobatae Radix resulted in a significant reduction in the area of sebaceous gland patches compared to the control group. Histological analysis revealed notable alterations in the structure of sebaceous glands, including reductions in size, thickness, and density. Furthermore, the expression levels of TG, DHT, and IL-6 were significantly decreased in the Puerariae Lobatae Radix group (p < 0.05), and immunoblotting indicated a significant decrease in the expression of PPARG and ACC1 (p < 0.05).
UNASSIGNED: This study demonstrates that Puerariae Lobatae Radix can regulate skin lipid metabolism by targeting multiple pathways. The primary mechanism involves inhibiting sebaceous gland growth and reducing TG secretion by modulating the expression of PPARG and ACC1. Puerarin and Daidzein are identified as key bioactive compounds responsible for this regulatory effect. These findings highlight the therapeutic potential of Puerariae Lobatae Radix in addressing sebaceous gland-related conditions.

BACKGROUND: Steroid-induced osteonecrosis of femoral head (SONFH) is a severe health risk, and this study aims to identify immune-related biomarkers and pathways associated with the disease through bioinformatics analysis and animal experiments.
METHODS: Using SONFH-related datasets obtained from the GEO database, we performed differential expression analysis and weighted gene co-expression network analysis (WGCNA) to extract SONFH-related genes. A protein-protein interaction (PPI) network was then constructed, and core sub-network genes were identified. Immune cell infiltration and clustering analysis of SONFH samples were performed to assess differences in immune cell populations. WGCNA analysis was used to identify module genes associated with immune cells, and hub genes were identified using machine learning. Internal and external validation along with animal experiments were conducted to confirm the differential expression of hub genes and infiltration of immune cells in SONFH.
RESULTS: Differential expression analysis revealed 502 DEGs. WGCNA analysis identified a blue module closely related to SONFH, containing 1928 module genes. Intersection analysis between DEGs and blue module genes resulted in 453 intersecting genes. The PPI network and MCODE module identified 15 key targets enriched in various signaling pathways. Analysis of immune cell infiltration showed statistically significant differences in CD8 + t cells, monocytes, macrophages M2 and neutrophils between SONFH and control samples. Unsupervised clustering classified SONFH samples into two clusters (C1 and C2), which also exhibited significant differences in immune cell infiltration. The hub genes (ICAM1, NR3C1, and IKBKB) were further identified using WGCNA and machine learning analysis. Based on these hub genes, a clinical prediction model was constructed and validated internally and externally. Animal experiments confirmed the upregulation of hub genes in SONFH, with an associated increase in immune cell infiltration.
CONCLUSIONS: This study identified ICAM1, NR3C1, and IKBKB as potential immune-related biomarkers involved in immune cell infiltration of CD8 + t cells, monocytes, macrophages M2, neutrophils and other immune cells in the pathogenesis of SONFH. These biomarkers act through modulation of the chemokine signaling pathway, Toll-like receptor signaling pathway, and other pathways. These findings provide valuable insights into the disease mechanism of SONFH and may aid in future drug development efforts.

OBJECTIVE: To explore the therapeutic mechanism of Euonymus alatus for diabetic kidney disease (DKD).
METHODS: TCMSP, PubChem and Swiss Target Prediction databases were used to obtain the active ingredients in Euonymus alatus and their targets. GEO database and R language were used to analyze the differentially expressed genes in DKD. The therapeutic targets of DKD were obtained using GeneCards, DisGeNet, OMIM and TTD databases. The protein-protein interaction network and the \"drug-component-target-disease\" network were constructed for analyzing the topological properties of the core targets, which were functionally annotated using GO and KEGG pathway enrichment analyses. Molecular docking was performed for the core targets and the main pharmacologically active components, and the results were verified in db/db mice.
RESULTS: Analysis of GSE96804, GSE30528 and GSE30529 datasets (including 60 DKD patients and 45 normal samples) identified 111 differentially expressed genes in DKD. Network pharmacology analysis obtained 161 intersecting genes between the target genes of Euonymus alatus and DKD, including the key core target genes SRC, EGFR, and AKT1. The core active ingredients of Euonymus alatus were quercetin, kaempferol, diosmetin, and naringenin, which were associated with responses to xenobiotic stimulionus and protein phosphorylation and regulated EGFR tyrosine kinase inhibitor resistance pathways. Molecular docking suggested good binding activities of the core active components of Euonymus alatus with the core targets. In db/db mouse models of DKD, treatment with Euonymus alatus obviously ameliorated kidney pathologies, significantly inhibited renal expressions of SRC, EGFR and AKT1, and delayed the progression of DKD.
CONCLUSIONS: Euonymus alatus contains multiple active ingredients such as quercetin, kakaferol, diosmetin, naringenin, which regulate the expressions of SRC, EGFR, and AKT1 to affect the EGFR tyrosine kinase inhibitor resistance signaling pathway to delay the progression of DKD.

UNASSIGNED: This study aims to assess the comprehensive and integrated modulatory effects of acupuncture and electroacupuncture on various ovarian dysfunctions.
UNASSIGNED: We systematically searched for articles on animal experiments related to polycystic ovary syndrome (PCOS), premature ovarian failure (POF), premature ovarian insufficiency (POI), and perimenopausal syndrome (PMS) across multiple databases, including PubMed, Web of Science, Cochrane Library, Embase, and four Chinese language databases. The search covered the period from inception to November 2023. We conducted a comparative analysis between the acupuncture group and the model group (untreated) based on eligible literature. Our primary outcomes encompassed serum sex hormones (Luteinizing hormone, Follicle-stimulating hormone, Testosterone, Estradiol, Progesterone, and Anti-Müllerian hormone) and ovarian weight. Dichotomous data were synthesized to establish the relative risk (RR) of notable post-treatment improvement, while continuous data were pooled to determine the standardized mean difference (SMD) in post-treatment scores between the groups. Statistical analyses, including sensitivity analysis, Egger\'s test, and the trim-and-fill method, were executed using Stata 15.0 software.
UNASSIGNED: The meta-analysis encompassed 29 articles involving a total of 623 rats. In comparison to rat models of PCOS, the experimental group exhibited a reduction in serum levels of LH, T and LH/FSH ratio. However, no statistically significant differences were observed in AMH, FSH, E2 levels, and ovarian weight between the two groups. In the ovarian hypoplasia model rats, both acupuncture and electroacupuncture interventions were associated with an increase in E2 levels. However, the levels of LH and FSH did not exhibit a significant difference between the two groups.
UNASSIGNED: Acupuncture or electroacupuncture facilitates the restoration of ovarian function primarily through the modulation of serum sex hormones, exerting regulatory effects across various types of ovarian dysfunction disorders.
UNASSIGNED: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022316279.

BACKGROUND: The first version of Animal Research: Reporting of in vivo Experiments (ARRIVE 1.0) guidelines was introduced to improve reporting of animal research but did not lead to major improvements in this respect. This applied also to animal studies on peritoneal dialysis (PD). Here, we examined the performance of the revised version of these guidelines (ARRIVE 2.0).
METHODS: Eighty-nine relevant articles published in 2018-2020 (ARRIVE 1.0 period) and 97 published in 2021-2023 (ARRIVE 2.0 period) were identified in PubMed® and analyzed for completeness and transparency of reporting.
RESULTS: In both periods, most studies were carried out in Asia, on rodents, and concerned the peritoneal pathophysiology. During ARRIVE 2.0, more studies were published in higher impact factor journals with the focus on pharmacology and immunology. Compared to ARRIVE 1.0, general aspects of study design and reporting improved during ARRIVE 2.0 period in studies generated in Europe and USA but did not change significantly in Asia. Detailed analysis showed no global improvement in completeness of reporting key information included in the ARRIVE 2.0 Essential 10 checklist. Articles from both periods were deficient in sample size calculations, use of blinding, recording adverse events and drop-outs, and specification of appropriate statistical methods. The level of reporting during ARRIVE 2.0 did not correspond to the journal impact factor and the presence of recommendations for the use of ARRIVE 2.0 in their instructions to authors.
CONCLUSIONS: So far, ARRIVE 2.0 has not produced significant improvements in the reporting of animal studies in PD.