Pharmacology最新文献

{"title":"Ginkgo Biloba extract improved Paraquat-induced pulmonary fibrosis via inhibiting p38 MAPK pathway.","authors":"Minxuan Peng, Genlin Liu, Ting Sun, Xiaoyan He, Yan Luo","doi":"10.1159/000545929","DOIUrl":"https://doi.org/10.1159/000545929","url":null,"abstract":"<p><p>Objective This study aims to reveal the potential mechanism of Ginkgo Biloba extract (GBE) in alleviating pulmonary fibrosis. Methods We examined cell viability, PINK1, Parkin and LC3 II/I ratio in PQ-stimulated rat alveolar epithelial type II cells (RLE-6TN) receiving GBE treatment. LC3 enrichment in mitochondria was detecting the immunofluorescence co-staining of LC3 and TOMM20. Then, epithelial mesenchymal transition (EMT) was evaluated by -SMA and E-cadherin using immunofluorescence. Also, p-p38 and p38 were measured to evaluate p38 MAPK pathway using western blot. SB203580 was used to inhibiting p38 in RLE-6TN cells. The changes in histopathological alteration, -SMA, E-cadherin, PINK1, Parkin, LC3 II/I ration and collagen deposition was also investigated in rats with PQ stimulation and GBE treatment. Results PQ caused the decrease in cell viability and E-cadherin, and the increase in LC3 enrichment, -SMA, PINK1, Parkin and LC3 II/I ratio (P<0.05). p-p38 was increased after PQ stimulation (P<0.05). In PQ-stimulated RLE-6TN cells, GBE elevated cell viability and E-cadherin and reduced LC3 enrichment, -SMA, PINK1, Parkin, LC3 II/I ratio and p-p38 (P<0.05). Both of GBE and SB203580 significantly reversed PQ-induced changes abovementioned in cells. Rats with PQ stimulation developed the increase in hydroxyproline activity, -SMA, p-p38, PINK1, Parkin LC3 II/I ratio and the decrease in E-cadherin (P<0.05). GBE significantly reversed PQ-induced changes abovementioned in rats. GBE mitigated inflammatory infiltrates, alveolar wall thickening and collagen deposition in rats undergoing PQ stimulation. Conclusion GBE significantly inhibited EMT and mitophagy in alveolar epithelial type II cells exposed to PQ via suppressing p38 MAPK pathway.</p>","PeriodicalId":20209,"journal":{"name":"Pharmacology","volume":" ","pages":"1-14"},"PeriodicalIF":2.9,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079869","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":"Retraction Statement.","authors":"","doi":"10.1159/000545109","DOIUrl":"https://doi.org/10.1159/000545109","url":null,"abstract":"","PeriodicalId":20209,"journal":{"name":"Pharmacology","volume":" ","pages":"1"},"PeriodicalIF":2.9,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144008830","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":"The effects and mechanisms of indole derivatives in improving doxorubicin-induced cardiomyopathy.","authors":"Jing Sun, Fangfang Qian, Fengmei Shi, Oushan Tang, Yinhong Cheng, Haoliang Zhou, Jiedong Zhou","doi":"10.1159/000546061","DOIUrl":"https://doi.org/10.1159/000546061","url":null,"abstract":"<p><strong>Significance: </strong>Doxorubicin is a first-line drug used in cancer chemotherapy, but its severe myocardial toxicity limits its widespread use. Indole derivatives, a large class of substances widely found in natural plants and metabolic products, exhibit a variety of biological effects.</p><p><strong>Recent advances: </strong>Previous studies have shown that indole compounds can protect against doxorubicin-induced myocardial damage through multiple mechanisms, including antioxidant activity, mitochondrial protection, anti-inflammatory effects, ferroptosis inhibition, apoptosis suppression, and endoplasmic reticulum stress attenuation.</p><p><strong>Critical issues: </strong>Understanding the pathogenesis of doxorubicin-induced cardiomyopathy and the molecular mechanisms by which indole compounds protect the myocardium is crucial for the development of novel drug molecules based on indole compounds in the future.</p><p><strong>Future directions: </strong>Focusing on the molecular characteristics of indole derivatives, investigating their pharmacodynamics and safety, and developing safe and effective antagonistic molecules to counteract doxorubicin toxicity, holds great potential and significance.</p>","PeriodicalId":20209,"journal":{"name":"Pharmacology","volume":" ","pages":"1-16"},"PeriodicalIF":2.9,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144033406","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":"Retraction Statement.","authors":"","doi":"10.1159/000544828","DOIUrl":"https://doi.org/10.1159/000544828","url":null,"abstract":"","PeriodicalId":20209,"journal":{"name":"Pharmacology","volume":" ","pages":"1"},"PeriodicalIF":2.9,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144033405","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":"Inhibition of Interleukin-8/C-X-C Chemokine Receptor 2 Signaling Axis Prevents Tumor Growth and Metastasis in Triple-Negative Breast Cancer Cells.","authors":"Yisun Jeong, Sun Young Yoon, Seung Pil Jung, Seok Jin Nam, Jeong Eon Lee, Sangmin Kim","doi":"10.1159/000545659","DOIUrl":"10.1159/000545659","url":null,"abstract":"<p><strong>Introduction: </strong>Previously, we reported that interleukin-8 (IL-8) was associated with poor prognosis of basal-like breast cancer patients and has been identified as a pro-tumorigenic factor, facilitating cell invasion and migration. Here, we investigated the pharmacological impact of inhibitors targeting the chemokine receptors, C-X-C chemokine receptor 1 (CXCR1) and C-X-C chemokine receptor 2 (CXCR2), which are activated by IL-8.</p><p><strong>Methods: </strong>The survival rates of triple-negative breast cancer (TNBC) patients by IL-8 were analyzed by the Kaplan-Meier plotter. The levels of mRNA and protein expression were analyzed by real-time PCR and Western blotting. The alteration of apoptotic cell death-related proteins by SB225002 was analyzed by the Proteome Profiler Human Apoptosis Array. Cell growth was analyzed by MTT and colony-forming assay. Apoptosis and cell cycle were analyzed by fluorescence-activated cell sorting.</p><p><strong>Results: </strong>Aberrant IL-8 expression is involved with the prognosis of TNBC patients. Basal IL-8 levels are markedly elevated in TNBC cells compared to those in HER2+ and/or ER+ breast cancer cells. Furthermore, recombinant human IL-8 treatment enhanced cell invasiveness in TNBC cells. To counteract the tumor-promoting effects of IL-8, we assessed the therapeutic potential of CXCR1 and CXCR2 inhibitors. Notably, while reparixin, a CXCR1-specific inhibitor, exhibited no impact on cell viability, SB225002, a CXCR2-specific inhibitor, significantly reduced cell viability in a dose-dependent manner. There was a noticeable reduction in the levels of anti-apoptotic biomarkers, including Bcl-2, cIAP-1, cIAP-2, Survivin, XIAP, HIF-1α, and HO-1, following SB225002 treatment. Our findings indicate an increase in the apoptotic cell population with SB225002 treatment in TNBC cells. In xenograft models, SB225002 effectively diminished the metastatic potential of 4T1 cells, which are known to metastasize to the lung and liver.</p><p><strong>Conclusion: </strong>Our results underscore the significant role of the IL-8/CXCR2 signaling axis in the metastasis of TNBC and suggest that CXCR2 inhibitors such as SB225002 may be promising therapeutic agents for TNBC patients.</p>","PeriodicalId":20209,"journal":{"name":"Pharmacology","volume":" ","pages":"1-13"},"PeriodicalIF":2.9,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796174","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":"UBE2K Facilitates Erlotinib Resistance and Induces Epithelial Mesenchymal Transition in Osteosarcoma Cancer Stem-Like Cells via Activating the mTOR Signaling.","authors":"Tian Wang, Lian Zhang, Qi Liu, Dexing Wang, Ping Yang","doi":"10.1159/000545370","DOIUrl":"10.1159/000545370","url":null,"abstract":"<p><strong>Introduction: </strong>Osteosarcoma (OS) is an aggressive bone tumor, and EGFR inhibitors are commonly used as targeted drugs for OS treatment. Herein, roles of ubiquitin-conjugating enzyme E2K (UBE2K) in EGFR inhibitor resistance of OS were studied.</p><p><strong>Methods: </strong>CD133+ MG63 and CD133+ U2OS cells were isolated using sorting flow cytometry and defined as osteosarcoma stem cells (OSCs)-MG63 and OSCs-U2OS, respectively. The stemness in MG63 and U2OS cells was evaluated by sphere formation assay. Cell activity, apoptosis, and migration were appraised using CCK-8 assay, TUNEL staining, and wound healing assay. Western blotting was used to detect the expression of related proteins.</p><p><strong>Results: </strong>OSCs-MG63 and OSCs-U2OS cells showed erlotinib resistant and high expression of UBE2K. Knocking down UBE2K reversed the erlotinib resistance, declined migration rate, and inhibited mitochondrial biogenesis in OSCs-MG63 and OSCs-U2OS cells. Silencing UBE2K inhibited the stemness in MG63 and U2OS cells, accompanied by reduced CD133+ cell proportion and restrained sphere formation ability. Silencing UBE2K repressed the mTOR/4EBP1/Cyclin D1/p21 signaling pathway in OSCs-MG63 and OSCs-U2OS cells. Furthermore, the influence of UBE2K silencing on the stemness of MG63 cells and the epithelial-mesenchymal transition (EMT) progression in OSCs-MG63 cells was partially abolished by MHY1485, an agonist of mTOR signaling.</p><p><strong>Conclusion: </strong>UBE2K facilitated the erlotinib resistance and induced EMT in OSCs via regulating the mTOR signaling.</p>","PeriodicalId":20209,"journal":{"name":"Pharmacology","volume":" ","pages":"1-14"},"PeriodicalIF":2.9,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143754287","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":"Batryticatus bombyx Improved Atopic Dermatitis in NC/Nga Mice and Impact on Inflammation and Recovery of Skin Barrier via STAT1/P38/NF-κB Downregulation and HO-1/Nrf2 Activation in HaCaT Keratinocytes.","authors":"Gunhyuk Park, Yumi Jang, Byeong Cheol Moon, Hye-Sun Lim","doi":"10.1159/000543902","DOIUrl":"10.1159/000543902","url":null,"abstract":"<p><strong>Introduction: </strong>Batryticatus bombyx (BB) (Beauveria bassiana Vuill.) is used as a herbal medicine and food additive. Although BB has neuroprotective and antiapoptotic effects, its impacts on atopic dermatitis (AD) are unknown. We evaluated the effects of BB in an NC/Nga mouse model of house dust mite (HDM)-induced AD, in TNF-α- and IFN-γ (TI)-stimulated HaCaT keratinocytes, and in a 3D human skin model.</p><p><strong>Methods: </strong>NC/Nga mice were induced with HDM and treated with BB for 6 weeks. We assessed skin symptoms, serum levels of IgE, histamine, and IL-6, immune cell counts and performed histological analysis of dorsal skin tissue. Additionally, we induced inflammation in HaCaT cells and a 3D human skin model using TNF-α/IFN-γ. We measured inflammatory cytokine levels and skin hydration factors and delved into underlying mechanisms via ELISA, real-time PCR, and Western blot.</p><p><strong>Results: </strong>BB improved skin lesions, reduced thickness, and inflammatory cell infiltration in HDM-induced mice. It alleviated scratching, improved moisture retention, and reduced IgE, histamine, and IL-6 levels. In HaCaT cells, BB inhibited thymic stromal lymphopoietin and increased hyaluronan content. It also upregulated aquaporin-3, hyaluronan synthase-1/3, filaggrin, involucrin, and occludin, enhancing skin hydration and tight junction stability. BB decreased STAT1, p38 MAPK, and NF-κB p65 levels in HaCaT cells and exhibited antioxidant effects by increasing HO-1/Nrf2 expression.</p><p><strong>Conclusion: </strong>BB may serve as a therapeutic alternative for AD treatment by inhibiting skin inflammation.</p>","PeriodicalId":20209,"journal":{"name":"Pharmacology","volume":" ","pages":"1-15"},"PeriodicalIF":2.9,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143190236","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":"Pharmacological Characterization of GB1908, a Selective Galectin-1 Carbohydrate Binding Domain Inhibitor for the Treatment of Cancer.","authors":"Kimberly D Herman, Ian Holyer, Duncan C Humphries, James A Roper, Kristoffer Peterson, Fredrik R Zetterberg, Anders Pedersen, Alison C MacKinnon, Robert J Slack","doi":"10.1159/000543234","DOIUrl":"10.1159/000543234","url":null,"abstract":"<p><strong>Introduction: </strong>Galectin-1 (Gal-1) is a lectin that has been shown to be involved in a number of pro-tumorigenic mechanisms and has also been shown to be immune-suppressive. Therefore, pharmacological blockade of Gal-1 has the potential to be therapeutically beneficial in cancers that overexpress this lectin where it is hypothesized to be driving cancer progression.</p><p><strong>Methods: </strong>GB1908 is a novel, selective and high affinity inhibitor of the Gal-1 carbohydrate recognition domain and in this study, we have pharmacologically characterized this small molecule in a range of in vitro and in vivo systems in the context of cancer therapy. In addition, we used a data-driven approach to identify the cancer types which may benefit from Gal-1 inhibitor therapy.</p><p><strong>Results: </strong>The selectivity of GB1908 for Gal-1 compared with galectin-3 (Gal-3) was confirmed in biophysical and cellular assays. GB1908 attenuated Gal-1-induced T cell (Jurkat) apoptosis and reduced the production of immunosuppressive cytokines in a stromal non-small cell lung cancer tumor microenvironment model. Breast carcinoma and metastatic skin cutaneous melanoma were identified as cancers in which high Gal-1 expression correlated with poorer survival outcomes in patients. Treatment with GB1908 slowed tumor growth in syngeneic mouse models of these cancers.</p><p><strong>Conclusion: </strong>The inhibition of both tumor growth and immune-suppressive cytokines, in cancers in which high Gal-1 is associated with poorer survival outcomes, suggests a potential therapeutic benefit for Gal-1 inhibitors such as GB1908.</p>","PeriodicalId":20209,"journal":{"name":"Pharmacology","volume":" ","pages":"1-14"},"PeriodicalIF":2.9,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123420","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":"Estrogen Receptors and Platelet-Activating Acetylhydrolase Activity in the Pathogenesis of Systemic Lupus Erythematosus.","authors":"Akira Sato, Yuta Ogawa, Ayano Yabuki, Genta Sato, Hina Nemoto, Makoto Ohira","doi":"10.1159/000543797","DOIUrl":"10.1159/000543797","url":null,"abstract":"<p><strong>Introduction: </strong>Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that affects various body systems, including the skin and facial features. Estrogen promotes lupus in human and mouse models of SLE. In this study, we conducted an in vivo study to investigate the relationship between two estrogen receptors (ERα and ERβ) and platelet-activating factor acetylhydrolase (PAF-AH) on the symptoms of SLE.</p><p><strong>Methods: </strong>Skin and facial features, serum PAF-AH activity, tumor-necrosis factor-alpha (TNF-α), and anti-double stranded DNA (anti-dsDNA) antibody titer, all of which are central to the classification and pathogenesis of SLE, were measured in SLE model mice injected with various ER antagonists.</p><p><strong>Results: </strong>In SLE mice, the injection of an ERβ antagonist 4-[2-phenyl-5,7-bis(trifluoromethyl)pyrazolo[1,5-α]pyrimidine-3-yl]-phenol induced the expression of facial erythema (especially around a cheek). The injection of an ERα/β antagonist tamoxifen induced hair-loss on the head and the neck. The injection of an ERα antagonist methylpiperidino pyrazole or tamoxifen increased PAF-AH activity and decreased TNF-α levels and anti-dsDNA antibody in mouse serum.</p><p><strong>Conclusions: </strong>The activation of ERα and inactivation of ERβ can cause inflammatory and cutaneous symptoms of SLE, respectively, implying that ERα antagonists and/or ERβ agonists can be useful for the prevention and treatment of SLE.</p>","PeriodicalId":20209,"journal":{"name":"Pharmacology","volume":" ","pages":"1-6"},"PeriodicalIF":2.9,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143053310","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":"Safety, Tolerability, Pharmacokinetics, and Effects of Gene Polymorphisms on Furaprevir (TG-2349), a Novel Hepatitis C Inhibitor: A Randomized Phase I Study.","authors":"Su-Mei Xu, Ying-Jun Zhang, Li-Wen Chang, Cheng-Yuan Tsai, Dai Li, Ping-Sheng Xu","doi":"10.1159/000543416","DOIUrl":"10.1159/000543416","url":null,"abstract":"<p><strong>Introduction: </strong>The purpose of our study was to evaluate the safety, tolerability, and pharmacokinetics of furaprevir, a new highly selective hepatitis C virus NS3/4A protease inhibitor.</p><p><strong>Methods: </strong>The study was divided into 2 parts: part A (single ascending dose study [SAD]) and part B (multiple ascending dose study [MAD]). A total of 62 healthy subjects were enrolled in the studies. DNA samples were extracted from all subjects, and genotypes of CYP3A5*3, CYP3A4*1 G, and POR*28 were analyzed by ligase detection reaction.</p><p><strong>Results: </strong>We used nonlinear mixed-effects model (NONMEM) to construct furaprevir population pharmacokinetics model. (1) In SAD, Cmax and area under the curve (AUC) were greater than dose increased ratio in the dose rang of 100-400 mg; (2) In MAD, Cmax and AUC increased in an approximately dose-proportional manner in the dose range of 200-600 mg; (3) A one-compartment model with transit absorption described the plasma concentrations of furaprevir. The apparent clearance was estimated at 33.4 L/h. The distribution volume of compartment (V2) was 219.0 L. No serious adverse event occurred in the studies. But other screening gene mutations had no statistically significant effects on the pharmacokinetics of furaprevir.</p><p><strong>Conclusion: </strong>Food significantly impacts the bioavailability of furaprevir. Furaprevir does not accumulate in vivo after multiple rising doses and has demonstrated safety and tolerability in healthy subjects, supporting its further investigation in patients with hepatitis C.</p>","PeriodicalId":20209,"journal":{"name":"Pharmacology","volume":" ","pages":"1-14"},"PeriodicalIF":2.9,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010234","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}