Current pharmaceutical biotechnology最新文献

{"title":"Causal Relationships Between Specific Gut Microbiota Taxa, Plasma Metabolites, and Cerebral Small Vessel Disease Risk: A Mendelian Randomization Analysis.","authors":"Xuejiao Zhao, Yujie Li, Ting Lu, Huan Yan, Chao Xue, Juan Li","doi":"10.2174/0113892010373952250510105002","DOIUrl":"https://doi.org/10.2174/0113892010373952250510105002","url":null,"abstract":"<p><strong>Aims: </strong>This study investigates causal relationships between gut microbiota (GM), plasma metabolites, and cerebral small vessel disease (CSVD), with a focus on identifying GM taxa and metabolites that mediate disease risk.</p><p><strong>Methods: </strong>Summary data from genome-wide association studies on GM (MiBioGen), 1,400 plasma metabolites, and CSVD were analyzed using a two-step Mendelian randomization (MR) approach. The primary analysis utilized inverse-variance weighting, complemented by weighted median, weighted mode, and MR-Egger methods for robustness.</p><p><strong>Results: </strong>The MR analysis identified 12 GM taxa associated with CSVD risk, including 7 taxa linked to increased risk (Veillonellaceae, Hungatella, Ruminococcus2, Lachnospiraceae UCG010, Streptococcus, Cyanobacteria, Verrucomicrobia) and 5 taxa linked to decreased risk (Faecalibacterium, Alphaproteobacteria, Eubacterium nodatum group, Fusicatenibacter, Rhodospirillales). Additionally, 10 plasma metabolites were causally associated with CSVD risk, with sphingomyelin (d18:2/14:0, d18:1/14:1), nicotinamide, and 3-ethylcatechol sulfate (2) linked to increased risk, while phosphate-to-uridine ratio, adenosine 5'-diphosphate (ADP)-toflavin adenine dinucleotide (FAD) ratio, arginine, caffeine-to-theobromine ratio, N-succinylphenylalanine, sphingosine, and phenylpyruvate-to-4-hydroxyphenylpyruvate ratio were linked to decreased risk. Mediation analysis identified 8 causal pathways through which plasma metabolites connect GM taxa to CSVD.</p><p><strong>Conclusion: </strong>These findings underscore the substantial influence of GM and plasma metabolites on CSVD risk, highlighting potential therapeutic targets. Further investigation is needed to elucidate the biological mechanisms underlying these associations.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of the Mechanism of PGLP-1 Inhibiting Gluconeogenesis Based on Whole Transcriptome Sequencing.","authors":"Huashan Gao, Hao Yu, Weishuang Tong, Weiwei Fan, Yanqun Mai, Wenpo Feng, Yuanhao Qiu","doi":"10.2174/0113892010382822250516034835","DOIUrl":"https://doi.org/10.2174/0113892010382822250516034835","url":null,"abstract":"<p><strong>Objective: </strong>Through comprehensive transcriptome sequencing of liver RNA in mice induced with streptozotocin (STZ) to develop hyperglycemia, we uncovered crucial genes associated with hyperglycemic processes, shedding light on their respective functions. Furthermore, we delved deeply into a discussion surrounding the mechanism behind plasma glucagon-like peptide 1 (PGLP-1) and its role in inhibiting gluconeogenesis.</p><p><strong>Methods: </strong>Liver tissues from mice induced with STZ to develop hyperglycemia (M group), as well as those treated with PGLP-1 (P11 group) and Exendin-4 (E group), were collected. RNA extraction was performed for comprehensive transcriptome sequencing. Differentially expressed mRNA, microRNA (miRNA), and long-chain non-coding RNA (lncRNA) were identified and subjected to analysis of their respective GO and KEGG pathways. An association network involving mRNA-miRNA-lncRNA was constructed to pinpoint target molecules associated with gluconeogenesis. Furthermore, personalized analysis focused on eight gluconeogenesis-related signal pathways obtained from KEGG.</p><p><strong>Results: </strong>A total of 289 differentially expressed mRNA (dif-mRNA), 21 differentially expressed miRNA (dif-miRNA), and 463 differentially expressed lncRNA (dif-lncRNA) were screened from the M group and P11 group. 182 dif-mRNA, 239 dif-miRNA, and 384 dif-lncRNA were screened from the M group and E group. A total of 427 dif-mRNA, 261 dif-miRNA, and 525 diflncRNA were screened from the E group and the P11 group. Among them, mRNA was enriched to the PI3K-Akt signaling pathway, Type ll diabetes mellitus, the Insulin signaling pathway, and the PPAR signaling pathway, while lncRNA was mainly enriched in PI3K-Akt signaling pathway. Similar to the whole transcriptome sequencing, the results of gluconeogenesis personalized analysis showed that the PI3K-Akt signaling pathway was the key pathway, and Gck and Cyp7a1 were highly expressed after PGLP-1 was administered.</p><p><strong>Conclusions: </strong>According to our findings, we believe that PGLP-1 is a potential regulator of noncoding RNAs, including miRNAs and lncRNAs. Additionally, it modulates the PI3K-Akt signaling pathway, resulting in the upregulation of GcK and Cyp7a1. In this way, it effectively inhibits gluconeogenesis.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trojan Horses: A Secret Route for Nanomedicines.","authors":"Zoya Amin Khaskheli, Daniya Nadeem, Huzaifa Shakeel, Munsif Ali Jatoi, Rabail Baloch, Raahim Ali","doi":"10.2174/0113892010388510250515105129","DOIUrl":"https://doi.org/10.2174/0113892010388510250515105129","url":null,"abstract":"<p><p>The nanoparticles are widely used in various drug delivery applications due to their versatility to encapsulate, cargo loading, and transport of therapeutic agents. Numerous studies have explored the use of nanomedicine-based drug delivery systems for treating various diseases. This research provides a smart and precise review of one of the nanoparticles-based drug delivery approaches, i.e., the Trojan horse strategy which is employed for delivering the drug to the target efficiently and reliably. Furthermore, the applicability of nanomedicines to cancer treatment is discussed, with examples drawn from various systematic studies. The use of different nanomedicine platforms such as liposomes, nanoparticles, spherical nucleic acids, extracellular vesicles, and immune cells acting as Trojan horses is also explored in the context of cancer therapy. Finally, a precise conclusion and future recommendations are provided for future researchers in the field of applied nanotechnology for the pharmaceutical domain.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the Role and Mechanism of Mycoprotein for Reducing Cardiovascular Risk.","authors":"Akash Kumar, Yashna Bawa, Jhilam Pramanik, Kajol Batta, Bhupendra Prajapati, Rahul Mehra, Marija Menkinoska, Anka Trajkovska Petkoska","doi":"10.2174/0113892010347951250416140136","DOIUrl":"https://doi.org/10.2174/0113892010347951250416140136","url":null,"abstract":"<p><p>Cardiovascular diseases (CVDs) have the highest mortality rates worldwide. To reduce the risk of CVDs, dietary interventions are a potential approach. This review explores the potential of mycoprotein, a fungal-derived protein, as a dietary approach for maintaining cardiovascular health. A comprehensive literature search was conducted using various databases (Web of Science, Medline, Scopus, Google Scholar, EBSCO, PubMed) and government websites (WHO, CDC) to identify relevant studies. Mycoprotein provides essential amino acids with high bioavailability (0.996) while containing minimal saturated fat (1.5 grams) and high fiber (6 grams). Clinical studies have shown that mycoprotein consumption reduces cholesterol, improves lipid profiles, and potentially lowers blood pressure, possibly due to its impact on gut microbiota (GM) and short-chain fatty acids (SCFAs) production. The intestinal fermentation of mycoprotein fiber increases the abundance of beneficial gut bacteria, binds to Gprotein coupled receptors like GPR41 and 43 to promote vasodilation, inhibits the angiotensinconverting enzyme, and reduces hepatic cholesterol production. Chitin and beta-glucan, the primary fiber of mycoprotein, exhibit anti-inflammatory properties that may contribute to overall cardiovascular health. The study concludes that mycoprotein is a sustainable and nutritious alternative, and its consumption promotes cardiovascular health and reduces CVD risks.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimization of Hesperidin Nanoparticles as a Promising CYP2E1 and CYP3A11 Regulator in Paracetamol-Intoxicated Mice.","authors":"Mona M Mohamed, Mohammed A Hussein, Sahar M Elashmony, Eman R Saifeldeen, Tamer Roshdy, Azza M Metwaly","doi":"10.2174/0113892010336010250212060619","DOIUrl":"https://doi.org/10.2174/0113892010336010250212060619","url":null,"abstract":"<p><strong>Background: </strong>Hesperidin is a flavonoid found in citrus fruits, particularly in the peel and pulp of oranges and lemons. By encapsulating drugs or bioactive compounds within NPs, it's possible to enhance their stability, solubility, and bioavailability. The current investigation aims to optimize hesperidin nanoparticles (Hes-NPs) and evaluate their hepatoprotective and antioxidant effects in paracetamol-intoxicated mice.</p><p><strong>Methods: </strong>The characteristics of Hes-NPs were elucidated, including morphology, particle size, zeta potential, UV-vis, entrapment efficiency, and FT-IR spectra. Hes-NPs were also tested for their hepatoprotective and antioxidant effects in paracetamol-treated mice. Safety and toxicity assessments are crucial before pharmacological studies. In addition, liver enzymes, oxidative stress, inflammatory biomarkers, and gene expression of CYP2E1 and CYP3A11 were measured. Furthermore, the study examined the molecular docking of hesperidin with the CYP2E1 and CYP3A11 proteins.</p><p><strong>Results: </strong>The synthesized Hes-NPs were uniform, spherically shaped, and well dispersed, with no aggregation noted, with a size range of 155.12 ± 14.13 nm. The measured zeta potential value of Hes-NPs was -21.57 ± 0.8 mV with a polydispersity index (PDI) of 0.49. Also, the UV spectra of hesperidin are at 220 and 279 nm, and Hes-NPs have strong absorption at 225 and 280 nm. Also, the LD50 of Hes-NPs was 1137.5 mg/kg b.w. Moreover, administering paracetamol-intoxicated mice with Hes-NPs resulted in improved plasma lipid profile &amp;#40;TC, TG, and HDL-C&amp;#41; and liver enzymes (ALT, AST, ALP, and LDH) as well as oxidative stress (GSH, SOD, CAT, Pr-SHs, and MDA) and inflammatory (TNF-α) biomarker levels, as well as attenuated CYP2E1, and CYP3A11 gene expression. In-silicon results proved that hesperidin showed a stronger estimated binding affinity with a ∆G of -8.6 and -10.5 kcal/mol. towards CYP2E1, and CYP3A11 activity, respectively. Our results showed that hesperidin forms hydrogen bonds with amino acid residues through the 9 and 12 bonds of CYP2E1 and CYP3A11, respectively.</p><p><strong>Conclusion: </strong>Hes-NPs could offer several advantages. It can be designed to specifically target liver cells, minimizing off-target effects, enhancing bioavailability, and shielding hesperidin from degradation in the body. The current results suggest that Hes-NPs may enhance antioxidant defenses and protect against oxidative stress in paracetamol-intoxicated mice.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circ-LRP6 Inhibits the Development and Progression of AAA Via miR-29a-3p/HIF-1α Axis.","authors":"Fang Wang, Zhijian Sun, Wenke Yan, Haiqing Wang","doi":"10.2174/0113892010327133250424073216","DOIUrl":"https://doi.org/10.2174/0113892010327133250424073216","url":null,"abstract":"<p><strong>Background: </strong>At present, the research on the potential molecular mechanism of abdominal aortic aneurysm (AAA) is limited, which hinders the treatment of aneurysm and the development of drugs. CircRNA has been identified as a potential therapeutic target for diagnostic biomarkers in a variety of diseases. The purpose of this study was to explore the molecular mechanism of circLRP6 in AAA and to provide a theoretical basis for further clinical optimization of treatment.</p><p><strong>Methods: </strong>The animal model and cell model of AAA were constructed, and the circLRP6 expression was verified by in situ hybridization and qRT-PCR. The effect of circLRP6 on cell viability was determined using CCK-8 and BrdU. The effects of circLRP6 on the cell cycle and apoptosis were determined by flow cytometry. In addition, the interaction of circLRP6 with miR-29a-3p and HIF-1α was verified by the luciferase reporter gene and RIP. HIF-1α or caspase 3 expression was detected by immunofluorescence or western blot analysis.</p><p><strong>Results: </strong>Our previous results showed that the circLRP6 had reduced expression in AAA, and its overexpression significantly inhibited AngII-induced hAoSMC cell viability. In addition, bioinformatics prediction showed that there was a binding site between miR-29a-3p and circLRP6, showing a negative regulatory relationship in hAoSMC. In addition, the results of the luciferase reporter gene and RIP showed that the circLRP6 interacted with HIF-1α, and achieved effective treatment of AAA by inhibiting the miR-29a-3p/HIF-1α.</p><p><strong>Conclusion: </strong>CircLRP6 effectively inhibited the development of AAA by inhibiting the miR- 29a-3p/HIF-1α, providing a theoretical basis for further clinical optimization of treatment.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antifungal Resistance in Vaginal Candidiasis Among Reproductive-age Women: A Review.","authors":"Utkalika Mallick, Binay Krushna Sahu, Rashmi Hegde, Prativa Jena, Jyotirmayee Turuk, Mahesh Chandra Sahu, Sujogya Kumar Panda","doi":"10.2174/0113892010368329250503175104","DOIUrl":"https://doi.org/10.2174/0113892010368329250503175104","url":null,"abstract":"<p><p>Candida is a type of fungus that can cause infections in humans. Sometimes, these infections become tough to treat because the Candida fungus resists antifungal drugs. This resistance depends on both the specific type of Candida and how it interacts with the human body. For instance, Candida can change its genetic makeup or produce proteins that pump out the drugs, making them less effective. Additionally, Candida can form a protective layer called a biofilm, which shields it from the drugs. Candida can cause a variety of diseases, and vaginal candidiasis is among the most troublesome. Nearly every woman experiences this infection at least once in her lifetime. Higher rates of treatment failures and recurrent infections result from the developing issue of antifungal resistance, underscoring the need for a more thorough understanding of resistance mechanisms. Changes in hormonal levels and immune responses can significantly influence the effectiveness of antifungal treatments. Hormonal fluctuations can alter vaginal pH and immune functions, which in turn affects Candida colonization and persistence. Moreover, an imbalance in the vaginal microbiome can lead to an overgrowth of Candida and lead to the drug resistance candidiasis. This review delves into the molecular pathways that contribute to the resistance of vaginal candidiasis to antifungal treatments, focusing on both acquired and intrinsic resistance mechanisms. Acquired resistance develops due to genetic alterations following antifungal exposure, including mutations in genes encoding drug targets, overexpression of efflux pumps, and increased biofilm formation. In contrast, intrinsic resistance refers to the innate traits of the Candida species that inherently reduce the efficacy of antifungal agents. These characteristics include changes in membrane sterols, genetic mutations in target enzymes, and the presence of efflux pumps that remove antifungal medications. Understanding these complex mechanisms can inform future therapeutic strategies and improve clinical outcomes.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimization and Characterization of Khellin Loaded Nanogel for the Potential Use in Psoriasis Management.","authors":"Sehernaz Topuzoğlu, Evren Algın Yapar, Lüceyn Abdo, İmren Esentürk-Güzel, Aslı Gürbüz Yurtsever, Selin Gümrükçü, Meryem Sedef Erdal, Rakesh K Sindhu","doi":"10.2174/0113892010375509250429052937","DOIUrl":"https://doi.org/10.2174/0113892010375509250429052937","url":null,"abstract":"<p><strong>Background: </strong>Psoriasis is a chronic skin disease that affects patients' quality of life. Treating psoriasis remains a significant challenge due to various factors, including individual response variability, drug resistance, and the range of side effects associated with currently available medications. Nowadays, numerous research efforts are being made aiming at overcoming the obstacles of the available psoriasis treatments are still taking place.</p><p><strong>Objective: </strong>This research aims to develop and evaluate a nanogel formulation loaded with khellin for the effective treatment of psoriasis.</p><p><strong>Methods: </strong>Khellin nanogel was prepared using the self-assembly method with a synthesized gelatin- pluronic copolymer. The novel formulation was characterized via size, size distribution, encapsulation efficiency, in vitro release, and ex vivo skin deposition.</p><p><strong>Results: </strong>The final nanogel formulation had an average size of 119.6 nm, a polydispersity index of 0.248 and an excellent encapsulation efficiency of 88%. In vitro drug release study demonstrated that nanogels showed a great accelerated drug release profile by releasing khellin within 2 hours, which is suitable for photochemotherapy applications. In addition, khellin-loaded nanogel formulation had 1.7 times better skin deposition potential than the control gel formulation.</p><p><strong>Conclusion: </strong>The prepared nanogel formulation provides a high potential to be an ideal drug delivery system of khellin in combination with phototherapy for more efficient psoriasis treatment.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the Role of Immune Cells and Plasma Metabolites in Breast Cancer Risk: A Mendelian Randomization and Mediation Analysis.","authors":"Yiran Li, Yinfu Zhu, Kunxiang Gong, Yi Wang, Yinger Huang, Wenbo Hao","doi":"10.2174/0113892010360983250417112456","DOIUrl":"https://doi.org/10.2174/0113892010360983250417112456","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Breast cancer (BC) is the most common cancer worldwide, yet identifying effective therapeutic targets continues to pose challenges. To understand the biological mechanisms driving BC and uncover potential therapeutic strategies, we performed a comprehensive Mendelian randomization (MR) analysis. The objective of this study is to investigate the causal relationships between immune cell phenotypes and BC risk, with a focus on identifying intermediary metabolites involved in these processes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We conducted MR analysis using genome-wide association study (GWAS) data from publicly available databases, focusing on 731 immune cell traits (n = 3757), 1400 plasma metabolites (n = 8299), and breast cancer (n case = 6188, n control = 182,678). We used a two-step MR approach to examine the potential intermediary role of plasma metabolites in the immune cell-BC relationship. The research employs the inverse variance weighting (IVW) method as its primary approach. To assess potential sources of bias, such as horizontal pleiotropy and heterogeneity, we employed the MR Egger intercept test and the Cochran's Q test, respectively. These rigorous analytical approaches ensured the robustness of our findings. Furthermore, Bayesian colocalization was employed to enhance the accuracy of causal inference and reduce false positives.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The IVW method of reverse MR analysis revealed a causal relationship between 20 immune cell traits and BC. Notably, our analysis identified three plasma metabolites as potential mediators in the causal link between immune cells and BC. In particular, vanillic acid glycine partially mediated the relationship between CD28+ CD45RA- CD8dim %CD8dim cells and BC. This suggests that vanillic acid glycine may act as a molecular link, modulating immune cell functions that contribute to BC. Additionally, the pyruvate to N-acetylneuraminate ratio exhibited negative mediation effects involving IgD- CD38dim AC, HLA DR on DC, CD8dim NKT %T cells, and CCR2 on monocytes. The negative mediation implies that this metabolite might inhibit certain immune cell behaviors that would otherwise promote cancer progression. Furthermore, cysteinylglycine disulfide partially mediated the relationship between CD8 on TD CD8br cells and BC, suggesting its involvement in the modulation of CD8 +T cell responses in BC. Key immune cell phenotypes, such as CCR2 on monocytes (odds ratio, ORIVW = 0.969; 95% CI: 0.943-0.996; p = 0.027), IgD- CD38dim AC cells (ORIVW = 1.100; 95% CI: 1.023-1.183; p = 0.009), were highlighted for their significant roles in BC progression.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This study shows that vanillic acid glycine levels, the pyruvate to N-acetylneuraminate ratio, and cysteinylglycine disulfide levels can act as mediators in reducing breast cancer risk. These findings support the idea that metabolic pathways and metabolites are crucial in cancer progression","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network Pharmacology Analysis and Experimental Verification of Weinaian Capsule for Treating Gastric Cancer.","authors":"Qisheng Cheng, Xinghua Li, Lujun Shen, Ting Yang","doi":"10.2174/0113892010365834250418065923","DOIUrl":"https://doi.org/10.2174/0113892010365834250418065923","url":null,"abstract":"<p><strong>Background: </strong>Traditional Chinese medicine has been widely used to treat gastric cancer, but the effect of the Weinaian capsule on gastric cancer is still unclear.</p><p><strong>Objective: </strong>This study aimed to find the potential therapeutic targets and pharmacological mechanisms of Weinaian capsule in gastric cancer.</p><p><strong>Methods: </strong>We employed the network pharmacological analysis to find the therapeutic targets. Firstly, we searched the bioactive components of Weinaian capsule in TCMSP and the Swiss database. We downloaded disease gastric cancer targets from the GeneCards database and used the Venn diagram to identify common targets for disease and drugs. Then, we performed GO and KEGG pathway enrichment analyses, used the Cytoscape software to screen core targets and components, and constructed a drug-disease-target network. In addition, visual molecular docking and molecular dynamics simulation of targets and components with strong affinity were performed. Finally, we verified the effect of the drug on cell proliferation and metastasis using CCK8, clonal formation, and wound healing assays, and investigated the molecular mechanism by qRT-PCR.</p><p><strong>Results: </strong>A total of 33 bioactive components were procured; 128 common targets for gastric cancer and drugs were screened. The GO and KEGG pathway enrichment analyses showed the PI3K-AKT pathway to be at the top. The core target AKT1 and the core component isorhamnetin exhibited the strongest molecular binding force and good binding stability. Compared to the control group, Weinaian capsule group inhibited gastric cancer cell proliferation and migration by down-regulating the expressions of PI3K and AKT.</p><p><strong>Conclusion: </strong>Weinaian capsule inhibited cell proliferation and metastasis by affecting the PI3K-AKT pathway in gastric cancer.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}