A major problem with current anti-depressant therapy is that it takes on average 6-7 weeks for remission. Since desensitization of serotonin (5-HT)1A receptor signaling contributes to the anti-depressive response, acceleration of the desensitization may reduce this delay in response to antidepressants. The purpose of the present study was to test the hypothesis that estradiol accelerates fluoxetine-induced desensitization of 5-HT1A receptor signaling in the paraventricular nucleus of the hypothalamus (PVN) of rats, via alterations in components of the 5-HT1A receptor signaling pathway. Ovariectomized rats were injected with estradiol and/or fluoxetine, then adrenocorticotropic hormone (ACTH) and oxytocin responses to a 5-HT1A receptor agonist (+)-8-hydroxy-2-dipropylaminotetralin (8-OH-DPAT) were examined to assess the function of 5-HT1A receptors in the PVN. Treatment with estradiol for either 2 or 7 days or fluoxetine for 2 days produced at most a partial desensitization of 5-HT1A receptor signaling, whereas 7 days of fluoxetine produced full desensitization. Combined treatment with estradiol and fluoxetine for 2 days produced nearly a full desensitization, demonstrating an accelerated response compared to either treatment alone. With two days of combined treatments, estradiol prevented the fluoxetine-induced increase in 5-HT1A receptor protein, which could contribute to the more rapid desensitization. Furthermore, EB treatment for 2 days decreased the abundance of the 35 kD Gαz protein which could contribute to the desensitization response. We found two isoforms of Gαz proteins with molecular mass of 35 and 33 kD, which differentially distributed in the detergent resistant microdomain (DRM) and in Triton X-100 soluble membrane region, respectively. The 35 kD Gαz proteins in the DRM can be sumoylated by SUMO1. Stimulation of 5-HT1A receptors with 8-OH-DPAT increases the sumoylation of Gαz proteins and reduces the 33 kD Gαz proteins, suggesting that these responses may be related to the desensitization of 5-HT1A receptors. Treatment with estradiol for 2 days also reduced the levels of the G-protein coupled estrogen receptor GPR30, possibly limiting to the ability of estradiol to produce only a partial desensitization response. These data provide evidence that estradiol may be effective as a short-term adjuvant to SSRIs to accelerate the onset of therapeutic effects.

Background: To investigate the association between sepsis and the vitamin D receptor (VDR) gene polymorphisms. Methods: Databases including PubMed, Cochrane Library, EMbase, CNKI, Wanfang Data, and VIP Data were systematically searched. The association was assessed using odds ratios (ORs), and 95% confidence intervals (CIs). The statistical tests were performed using Review Manager 5.4. Results: We identified a total of 5 studies. The relationship between VDR gene polymorphisms (Apa I, Bsm I, Taq I, and Fok I), and incidence of sepsis was investigated. The results of this meta-analysis showed that the allelic contrast model (F vs f, P = .03, OR = 0.65, 95% CI = 0.44–0.95), dominant genetic model (FF vs Ff + ff, P = .02, OR = 0.53, 95% CI = 0.30–0.91), and codominance genetic model (FF vs ff, P = .03, OR = 0.39, 95% CI = 0.16–0.91) of VDR Fok I locus increased the risk of sepsis, and the lack of association between the VDR Fok I gene polymorphism and the risk assessment of sepsis, based on the ethnic subgroup analysis, might be attributable to the small sample size. The risk of sepsis with Apa I, Bsm I, and Taq I did not appear to be correlated. Conclusion subsections: This meta-analysis revealed that the VDR Fok I polymorphism is closely associated with the susceptibility to sepsis, and patients with sepsis have lower 25-hydroxyvitamin D levels. VDR Fok I gene mutations may change the risk of sepsis.

Dendrobium officinale is a valuable medicinal and edible homologous health food. It has immunomodulatory, antioxidant, and metabolism-regulating properties. However, its adulteration is widespread, seriously compromising product quality and safety. Traditional adulteration detection methods are complex, costly, and time-consuming, making it urgent to establish a rapid and non-destructive detection approach. This study developed a rapid identification and quantification method for adulterated D. officinale. The method combined near-infrared (NIR) spectroscopy with data-driven soft independent modeling of class analogy (DD-SIMCA) and partial least squares regression (PLSR) models. PCA, PLS-DA, and OPLS-DA were first used to visualize sample clustering and group differences. DT, SVM, ANN, and NB were used for classification. DD-SIMCA and PLSR were used for one-class modeling and quantitative analysis. Raw spectral data were preprocessed using multiplicative scatter correction (MSC), the standard normal variate (SNV), the first derivative, and Savitzky–Golay smoothing. In the identification analysis, the DD-SIMCA model achieved 100% sensitivity and 100% specificity in the validation set. Its overall accuracy in the independent test set was 99.2%, demonstrating excellent discrimination performance. In addition, SVM combined with NIR also achieved good accuracy. In the quantitative analysis of adulteration, the PLSR model predicted different adulteration levels. Most calibration and validation sets showed R² values above 0.99 and RMSE values below 0.05, indicating excellent predictive performance. The results indicate that NIR combined with DD-SIMCA and PLSR can achieve rapid identification and accurate quantification of adulterated D. officinale samples. This approach provides strong support for quality control and regulatory supervision of high-value health foods.

To explore the molecular mechanism of Simiao Decoction (SMD) intervening atherosclerosis (AS). The main components and potential mechanisms of SMD remain unknown. This study aims to initially clarify the potential mechanism of SMD in the treatment of AS based on network pharmacology and molecular docking techniques. The principal components and corresponding protein targets of SMD were searched on Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and the compound-target network was constructed by Cytoscape3.9.1. AS targets were searched on DrugBank, OMIM, and TTD databases. The intersection of compound target and disease target was obtained and the coincidence target was imported into STRING database to construct a protein–protein interaction network. We further performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis on the targets. The molecular docking method was used to verify the interaction between core components of SMD and targets. We created the active compounds-targets network and the active compounds-AS-targets network based on the network database containing Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, DrugBank, OMIM, and TTD. We discovered that the therapy of AS with SMD involves 3 key substances—quercetin, kaempferol, and luteolin—as well as 5 crucial targets—ALB, AKT1, TNF, IL6, and TP53. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that the shared targets involved a number of signaling pathways, including the advanced glycosylation end product-receptor of AGE signaling pathway in diabetic complications, Hepatitis B, Lipid and atherosclerosis, Chemical Carcinogenesis-Receptor Activation, and Pathways in Cancer. The molecular docking demonstrated that the binding energies of quercetin, kaempferol, and luteolin with 5 important targets were favorable. This study reveals the active ingredients and potential molecular mechanism of SMD in the treatment of AS, and provides a reference for subsequent basic research.

This study investigates the mechanism by which bis(2-ethylhexyl) phthalate (DEHP) induces premature ovarian failure (POF) using network toxicology analysis and molecular docking methods. The potential toxic targets of DEHP were identified using databases such as STITCH and SwissTargetPrediction. Disease-related targets associated with POF were retrieved from the GeneCards and OMIM databases. The overlapping targets related to DEHP-induced POF were identified by intersecting the 2 datasets. Furthermore, the protein–protein interaction network was constructed using the STRING database and visualized through Cytoscape software to identify key targets. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed on the overlapping targets using the DAVID database. Finally, molecular docking simulations were performed using AutoDock Vina to validate the findings. A total of 116 intersection targets associated with DEHP-induced POF were identified. Among these, 6 key core targets were screened: caspase 3, b-cell lymphoma 2 (BCL2), matrix metalloproteinase 9, peroxisome proliferator-activated receptor gamma, BCL2L1, and cyclin D1. Gene ontology analysis revealed that these targets are primarily involved in response to xenobiotic stimulus, assembly of cyclin-dependent protein kinase holoenzyme complex, and BH domain binding. Kyoto Encyclopedia of Genes and Genomes analysis indicated that these targets are predominantly associated with critical signaling pathways, including the p53 signaling pathway and apoptosis pathways. Additionally, molecular docking studies demonstrated low binding energies between DEHP and the core target proteins, supporting their potential role in the pathophysiology of DEHP-induced POF. This study indicates that caspase 3, BCL2, matrix metalloproteinase 9, peroxisome proliferator-activated receptor gamma, BCL2L1, and cyclin D1 might be potential toxic targets of DEHP-induced POF. It reveals the potential molecular mechanisms underlying DEHP-induced POF, emphasizing the synergistic roles of the p53 signaling pathway and apoptosis in its pathogenesis. These insights provide a novel theoretical framework and identify potential therapeutic targets for the prevention and management of POF.

The diagnosis and monitoring of malignant respiratory diseases are heavily reliant on imaging techniques and tissue biopsies. Confocal laser endomicroscopy (CLE) is an advanced real-time imaging modality with high resolution, capable of visualizing the morphology and structure of pulmonary tissue in conjunction with conventional bronchoscopy. Within the realm of malignant respiratory diseases, it enables differentiation between normal and abnormal regions in the central airways, lung parenchyma, mediastinal lymph nodes, and pleura. Although CLE has not yet been integrated into routine clinical practice, it has the potential to guide biopsies, thereby enhancing diagnostic yield while mitigating the occurrence of associated complications. Moreover, this technology holds significant potential for elucidating disease pathogenesis, facilitating intraoperative assessment, and monitoring therapeutic efficacy. Looking towards the future, the integration of CLE with artificial intelligence represents a promising direction for the development of this technology. This review encapsulates the latest advancements of CLE in the context of malignant respiratory diseases, with a particular emphasis on its application in the diagnosis and treatment of lung cancer.