Pharmacology最新文献

{"title":"Inhibition of IL-8/CXCR2 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":"https://doi.org/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, CXCR1 and CXCR2, which are activated by IL-8.</p><p><strong>Methods: </strong>The survival rates of 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 FACS.</p><p><strong>Results: </strong>Aberrant IL-8 expression is involved with the prognosis of triple-negative breast cancer (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":"1-17"},"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":"https://doi.org/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 EMT progression in OSCs-MG63 cells was partially abolished by MHY1485, an agonist of mTOR signaling.</p><p><strong>Conclusions: </strong>UBE2K facilitated the erlotinib resistance and induced EMT in OSCs via regulating the mTOR signaling.</p>","PeriodicalId":20209,"journal":{"name":"Pharmacology","volume":" ","pages":"1-18"},"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}

{"title":"Nephroprotective Effects of Curcumin in Murine Models of Focal and Segmental Glomerulosclerosis.","authors":"Sufia Husain, Nervana Mustafa Kamal Bayoumy, Fatima Noor, Hanan Hagar","doi":"10.1159/000543293","DOIUrl":"10.1159/000543293","url":null,"abstract":"<p><strong>Introduction: </strong>This study aims to explore the reno-protective effect of curcumin in focal and segmental glomerulosclerosis (FSGS) in murine models, a common chronic glomerulopathy that leads to end-stage renal disease.</p><p><strong>Methods: </strong>Adult Wistar rats were used in this experiment. One group was treated with intravenous Adriamycin (ADR) injection to induce FSGS similar to that seen in humans and a second group was co-administered ADR and curcumin (ADR-CUR). Saline-treated rats served as controls. Renal injury was assessed by measuring the levels of serum creatinine, blood urea nitrogen (BUN), triglyceride, and urinary protein. The homogenates of renal cortex were used to estimate the renal content of the inflammatory marker tumor necrosis factor-a (TNF-a); oxidative stress marker malonaldehyde (MDA); and two antioxidants superoxide dismutase (SOD) and reduced glutathione (GSH). In addition, the rat kidneys were harvested by ends of week 8 and week 12 and examined for histological abnormalities.</p><p><strong>Results: </strong>The ADR-treated rats showed biochemical and histological evidence of FSGS, in the form of proteinuria, elevated serum creatinine, BUN, and triglycerides, elevated renal TNF-a and MDA, and segmental glomerulosclerosis. The ADR-CUR-treated rats showed significant correction of all these variables. Co-administration with curcumin resulted in improvement of the proteinuria, serum creatinine, BUN, and triglyceride. The renal tissue levels of antioxidants SOD and GSH increased and that of TNF-a and MDA decreased and the histology revealed reduction in the extent of segmental glomerulosclerosis. The FSGS-associated renal damage was notably antagonized by curcumin treatment.</p><p><strong>Conclusion: </strong>Our findings confirm the reno-protective effects of curcumin as a potential therapeutic agent in protection against the progression of FSGS and indicate that it is mitigated by inhibition of oxidant injury and inflammation and also by promotion of antioxidants. Curcumin ameliorated the ADR-induced FSGS in murine models. It may be a promising compound in the treatment of FSGS in human subjects. More human studies are needed to further elucidate its effects in FSGS.</p>","PeriodicalId":20209,"journal":{"name":"Pharmacology","volume":" ","pages":"1-10"},"PeriodicalIF":2.9,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142953662","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":"Drug-Drug Interactions in Hospitalized Urological Patients: A Retrospective Cohort Study.","authors":"Ivan R Milovanovic, Ana V Pejcic","doi":"10.1159/000540427","DOIUrl":"10.1159/000540427","url":null,"abstract":"<p><strong>Introduction: </strong>Exposure to potential drug-drug interactions (pDDIs) can be a notable source of avoidable drug-related harm that requires adequate management to prevent medical errors. We aimed to evaluate pDDIs and associated factors in hospitalized urological patients on admission, during hospitalization, and on discharge.</p><p><strong>Methods: </strong>A retrospective cohort study was conducted at the Clinic of Urology of the University Clinical Centre Kragujevac, Serbia. To detect pDDIs, we used Lexicomp, which categorizes pDDIs as follows: X (avoid combination), D (consider therapy modification), C (monitor therapy), B (no action needed), and A (no known interaction). Multiple linear regression analysis was used to identify factors associated with the number of pDDIs.</p><p><strong>Results: </strong>More than half of the 220 included patients had at least one pDDI on admission and discharge (57.3% and 63.6%, respectively), whereas 95.0% had at least one pDDI during hospitalization. The total number and number of X, D, C, and B categories of pDDIs were the highest during hospitalization and the lowest on admission. Duration of hospitalization, arrhythmias, dementia, renal failure, cancer, surgery during hospitalization, number of prescribed drugs, and various pharmacological drug classes were risk factors for a higher number of pDDIs, while age, ischemic heart disease, hypertension, and development of infection during hospitalization were protective factors in at least one of the stages. The impact of renal colic depended on the stage and category of pDDI.</p><p><strong>Conclusion: </strong>More than half of the urological patients were exposed to at least one pDDIs at all stages. Medical professionals should regularly screen for pDDIs, particularly in patients with risk factors.</p>","PeriodicalId":20209,"journal":{"name":"Pharmacology","volume":" ","pages":"15-25"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141856287","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":"Population Pharmacokinetic of Vancomycin Administered by Continuous Infusion in Critically Ill Patients.","authors":"Haifa Ben Romdhane, Jean Baptiste Woillard, Najah Ben Fadhel, Zohra Chadli, Amel Chaabane, Naceur Boughattas, Nadia Ben Fredj, Karim Aouam","doi":"10.1159/000539866","DOIUrl":"10.1159/000539866","url":null,"abstract":"<p><strong>Introduction: </strong>Administration of vancomycin dose by continuous infusion (CI) according to population pharmacokinetic (Pop Pk) models is highly recommended in critically ill patients who exhibit pathophysiological changes.</p><p><strong>Objective: </strong>The objective of this study was to develop and validate a Pop Pk model of vancomycin administered by CI in critically ill patients with normal and impaired renal functions.</p><p><strong>Methods: </strong>The Pop Pk study was performed using a nonparametric approach (Pmetrics*). The influence of covariates (gender, age, weight, height, and creatinine clearance [Cr-Cl]) was tested on the model's Pk parameters. The performance of the final model was assessed using an external dataset.</p><p><strong>Results: </strong>A one-compartment model (volume of distribution [Vd], elimination from compartment [Ke]) was found to show a good prediction performance. The influence of covariates has shown that age and Cr-Cl affected significantly Vd and Ke, respectively. The distribution of simulated vancomycin clearance (CLv) according to different renal function levels showed a negative correlation between CLv and the severity of the renal impairment. The internal validation of the final model showed that the plot of individual-predicted concentration versus observed concentration resulted in r2 = 0.86 in the final model. The external validation of the final model showed an acceptable predictive performance.</p><p><strong>Conclusion: </strong>We developed a Pop Pk model for vancomycin administered by CI in critically ill patients. A significant impact of Cr-Cl and different stages of renal failure on CLv has been demonstrated. The establishment of an individualized proposal dose based on this model may be helpful to achieve the target range which is critical in optimizing the efficacy and safety of this antibiotic.</p>","PeriodicalId":20209,"journal":{"name":"Pharmacology","volume":" ","pages":"65-76"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000564","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":"Non-Coding RNA Networks in Pulmonary Arterial Hypertension.","authors":"Bing Chen, Yu Xia, Yanjiao Jiang, Zengxian Sun, Yanyan Zhang, Yun Liu","doi":"10.1159/000541060","DOIUrl":"10.1159/000541060","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary artery hypertension (PAH) is a severe cardiovascular disease marked by a persistent increase in pulmonary artery resistance and pressure, leading to right ventricular strain, hypertrophy, and eventually right heart failure and death. Despite numerous available targeted therapies, the clinical needs for treating PAH remain unmet. Current treatments primarily aim to dilate pulmonary vessels rather than reverse pulmonary vascular remodeling, failing to offer a fundamental solution for PAH. Therefore, developing new therapies for this condition is urgently required.</p><p><strong>Summary: </strong>Recent research has highlighted the crucial role of non-coding RNAs (ncRNAs) in the occurrence and development of PAH. NcRNAs, such as long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), microRNAs (miRNAs), and PIWI-interacting RNAs (piRNAs), are a class of transcripts that do not translate proteins but affect various diseases at different levels, including chromatin modification, transcription regulation, post-translational processes.</p><p><strong>Key message: </strong>The current study delves into recent advancements in understanding how lncRNAs, circRNAs, miRNAs, and piRNAs contribute to the pathogenesis of PAH. This review addresses the existing research challenges and explores the potential of ncRNAs as both biomarkers and therapeutic targets, suggesting that ncRNAs may serve as valuable indicators and treatment options for the disease.</p>","PeriodicalId":20209,"journal":{"name":"Pharmacology","volume":" ","pages":"110-121"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352535","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}