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Exploring the therapeutic potential of natural products in modulating miRNA networks in prostate cancer.
IF 3.1 4区 医学
Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2025-02-20 DOI: 10.1007/s00210-025-03898-2
Osama A Mohammed
{"title":"Exploring the therapeutic potential of natural products in modulating miRNA networks in prostate cancer.","authors":"Osama A Mohammed","doi":"10.1007/s00210-025-03898-2","DOIUrl":"https://doi.org/10.1007/s00210-025-03898-2","url":null,"abstract":"<p><p>Prostate cancer (PC) is the most common cancer among men and the second leading cause of cancer-related deaths in the USA. It remains a significant health challenge, necessitating the exploration of novel therapeutic strategies. It primarily manifests as adenocarcinoma, which arises from glandular cells in the prostate gland, located below the bladder. While many men may not experience symptoms in the early stages, as the disease progresses, symptoms can include difficulty urinating, erectile dysfunction, and pelvic or back pain. MicroRNAs (miRNAs) are small, non-coding RNA molecules, typically consisting of 21 to 23 nucleotides, that play a vital role in regulating gene expression. miRNAs are found across a variety of organisms, including plants, animals, and some viruses. Their primary function is to modulate the expression of target genes, thereby influencing numerous biological processes such as development, differentiation, proliferation, and apoptosis. Natural compounds such as curcumin, ellagitannin, diindolylmethane, epigallocatechin-3-gallate (EGCG), resveratrol, genistein, luteolin, capsaicin, and berberine have been shown to modulate miRNA expression in PC, contributing to their anticancer effects. These compounds influence the expression of both tumor-suppressor and oncogenic miRNAs, thereby impacting critical pathways related to cell proliferation, apoptosis, and metastasis. Recent studies indicate that the deregulation of miRNA networks plays a critical role in cancer progression, and natural compounds have emerged as potential modulators of these pathways. Through a comprehensive literature survey, we identified various phytochemicals that exhibit anticancer properties by influencing miRNA expression. These natural agents can alter miRNA levels through direct binding, epigenetic modifications, or interaction with proteins involved in miRNA biogenesis. The findings underscore the potential of integrating natural agents into therapeutic approaches for PC, paving the way for innovative miRNA-targeted treatments. This review not only elucidates the molecular mechanisms underlying the health benefits of natural compounds but also highlights their promise in developing effective cancer therapies.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458713","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}
引用次数: 0
Obtusifolin improves cisplatin-induced hepatonephrotoxicity via the Nrf2/HO-1 signaling pathway.
IF 3.1 4区 医学
Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2025-02-20 DOI: 10.1007/s00210-025-03900-x
Selcan Cesur, Berrin Yalinbas-Kaya, Ali Tureyen, Fahriye Zemheri-Navruz, Hasan Huseyin Demirel, Sinan Ince
{"title":"Obtusifolin improves cisplatin-induced hepatonephrotoxicity via the Nrf2/HO-1 signaling pathway.","authors":"Selcan Cesur, Berrin Yalinbas-Kaya, Ali Tureyen, Fahriye Zemheri-Navruz, Hasan Huseyin Demirel, Sinan Ince","doi":"10.1007/s00210-025-03900-x","DOIUrl":"https://doi.org/10.1007/s00210-025-03900-x","url":null,"abstract":"<p><p>Cisplatin (CIS) is a highly effective chemotherapeutic drug, but one of its most serious side effects is hepatonephrotoxicity, which varies based on its dosage and duration of use. Previous studies have reported that obtusifolin (OBS) exhibits several pharmacological effects, including antioxidant and antidiabetic activities. In this study, we investigated the protective effects of OBS against CIS-induced hepatonephrotoxicity. OBS (0.5 and 1 mg/kg, i.p.) was administered to male mice for 10 days, while CIS (20 mg/kg, i.p.) was administered on day 7 to induce hepatonephrotoxicity. The results showed that OBS reduced the CIS-induced elevations in AST, ALT, ALP, BUN, and creatinine levels by approximately 14%, 11%, 9%, 18%, and 14%, respectively. OBS also decreased liver and kidney MDA levels by approximately 31% and 25%, while enhancing liver and kidney GSH, SOD, and CAT levels by 50-36%, 80-70%, and 95-55%, respectively. In association with oxidative stress and the apoptotic process, OBS reduced liver and kidney mRNA expression levels of Nrf2 (by approximately 1.7- and 1.6-fold, respectively), HO-1 (by 1.6- and 1.4-fold, respectively), and Bcl-2 (by 1.6- and 1.4-fold, respectively). Additionally, OBS suppressed the mRNA expression levels of NF-κB (by 0.7- and 0.7-fold), TNF-α (by 0.6- and 0.6-fold), Bax (by 0.8- and 0.7-fold), and Cas-3 (by 0.7- and 0.7-fold). Protein expression analysis revealed that OBS increased Nrf2 (showing a 1.7- to 1.2-fold) and Bcl-2 levels (by 1.3- to 1.8-fold), and reduced Bax (by 0.7- to 0.8-fold) and caspase-3 (by 0.7- and 0.7-fold) levels altered by CIS treatment. Histopathological examinations confirmed that OBS reduced liver and kidney damage caused by CIS. In conclusion, OBS significantly improved CIS-induced hepatonephrotoxicity by reducing oxidative stress, inflammation, and apoptosis via modulation of the Nrf2/HO-1 pathway. These findings suggest that OBS could be a potential therapeutic agent for mitigating the side effects of chemotherapeutics.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458646","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}
引用次数: 0
Gallic acid alleviates omeprazole-induced depressive behavior and memory impairment.
IF 3.1 4区 医学
Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2025-02-20 DOI: 10.1007/s00210-025-03812-w
Noreen Samad, Natasha Manzoor, Ali Irfan, Arslan Khalid, Umer Ejaz, Bakar Bin Khatab Abbas, Syed Aun Muhammad, Gamal A Shazly, Saima Khaliq, Yousef A Bin Jardan
{"title":"Gallic acid alleviates omeprazole-induced depressive behavior and memory impairment.","authors":"Noreen Samad, Natasha Manzoor, Ali Irfan, Arslan Khalid, Umer Ejaz, Bakar Bin Khatab Abbas, Syed Aun Muhammad, Gamal A Shazly, Saima Khaliq, Yousef A Bin Jardan","doi":"10.1007/s00210-025-03812-w","DOIUrl":"https://doi.org/10.1007/s00210-025-03812-w","url":null,"abstract":"<p><p>The study aims to evaluate the effect of various doses of gallic acid (GA) on omeprazole (OMZ)-induced depression, memory impairment, oxido-neuroinflammation, and altered serotonergic neurotransmission in the midbrain and cerebral cortex of rats. Forty-eight male rats were divided into six groups (n = 8): Veh (vehicle), Veh + GA (50 mg/kg/ml), Veh + GA (100 mg/kg/ml), OMZ (20 mg/kg/ml), OMZ + GA (50 mg/kg/ml), and OMZ + GA (100 mg/kg/ml). Animals received their respective treatment intraperitoneally, daily for 4 weeks. After that, behavioral analysis for depression and memory function was performed; then, animals were decapitated, and their brains were removed from skulls. Brain regions, i.e., midbrain and cerebral cortex, were isolated for various biochemical and neurochemical studies. Results showed that OMZ-induced depression-like behavior and memory impairment were attenuated by GA in a dose-dependent manner. OMZ instigated decreased antioxidant enzyme activity and serotonergic mechanism, and increased oxido-neuroinflammation and acetylcholinesterase (AChE) activity were normalized by dose-dependent GA administration in both regions. In silico study also showed that GA has a potent antioxidant effect on the brain. In conclusion, the present findings revealed that GA, as a potential agent that reduced PPIs, induced depression-like behavior and memory impairment. The supplementation of GA as a dietary constituent could provide relief against OMZ-induced negative effects.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458639","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}
引用次数: 0
Comparison of nebivolol, carvedilol, and bisoprolol for adverse clinical outcomes among patients with heart failure-a real-world nationwide investigation.
IF 3.1 4区 医学
Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2025-02-19 DOI: 10.1007/s00210-025-03855-z
Wei-Syun Hu, Cheng-Li Lin
{"title":"Comparison of nebivolol, carvedilol, and bisoprolol for adverse clinical outcomes among patients with heart failure-a real-world nationwide investigation.","authors":"Wei-Syun Hu, Cheng-Li Lin","doi":"10.1007/s00210-025-03855-z","DOIUrl":"https://doi.org/10.1007/s00210-025-03855-z","url":null,"abstract":"<p><p>The authors report a retrospective cohort study based on a national dataset that explores the association between the prescription of three beta-blockers (BB) and a diagnosis of heart failure (HF) readmission, cardiovascular (CV) death, and all-cause death. Patients with HF who received nebivolol, carvedilol, and bisoprolol between 2016 and 2020 were identified. Univariate and multivariate Cox proportional hazard regression analyses were employed to assess and examine the crude and adjusted hazard ratio of the outcomes associated with the three BBs, demographics, comorbidities, and concomitant medications. We further performed Cox proportional hazards regression analyses for the three BBs stratified by age. A total of 109,466 BB patients including 85,166 bisoprolol patients, 19,741 carvedilol patients, 4559 nebivolol patients, and 109,466 non-BB patients were enrolled in our study. Both carvedilol and bisoprolol cohorts had a higher risk of readmission for HF than the non-BB cohort (carvedilol: adjusted HR = 1.13, 95% CI = 1.10-1.15; bisoprolol: adjusted HR = 1.17, 95% CI = 1.16-1.19). Nebivolol cohorts had a lower risk of readmission for HF than the non-BB cohort (adjusted HR = 0.78, 95% CI = 0.74-0.83). There were higher risks of CV (carvedilol: adjusted HR = 1.31, 95% CI = 1.26-1.36; bisoprolol: adjusted HR = 1.17, 95% CI = 1.14-1.2) and all-cause (carvedilol: adjusted HR = 1.26, 95% CI = 1.23-1.29; bisoprolol: adjusted HR = 1.18, 95% CI = 1.17-1.20) deaths in the carvedilol and bisoprolol cohorts in contrast to the non-BB nebivolol cohort. Nebivolol cohorts had a lower risk of CV deaths and all-cause deaths than the non-BB cohort (adjusted HR = 0.77, 95% CI = 0.69-0.85; adjusted HR = 0.78, 95% CI = 0.73-0.83). The authors concluded that the use of nebivolol was associated with better outcomes in patients with HF.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449510","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}
引用次数: 0
α-Hederin inhibited pancreatic cancer cell malignant progression by inhibiting LDHA-mediated glycolysis.
IF 3.1 4区 医学
Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2025-02-19 DOI: 10.1007/s00210-024-03621-7
Jingjing Li, Jiao Liu, Yue Wu, Yi Sun, Gang Huang, Mingming Jin
{"title":"α-Hederin inhibited pancreatic cancer cell malignant progression by inhibiting LDHA-mediated glycolysis.","authors":"Jingjing Li, Jiao Liu, Yue Wu, Yi Sun, Gang Huang, Mingming Jin","doi":"10.1007/s00210-024-03621-7","DOIUrl":"https://doi.org/10.1007/s00210-024-03621-7","url":null,"abstract":"<p><p>α-Hederin is a pentacyclic triterpenoid saponin extracted from Pulsatilla chinensis, which is known to suppress cancer cell proliferation. However, the role of this compound in pancreatic cancer cells remains unclear. The aim of this study was to reveal the docking molecular and the regulatory mechanism of α-hederin in pancreatic cancer. Here, we cultured Capan-1 and BxPC-3 cells and treated with different doses of α-hederin. Cell proliferation, migration, and apoptosis were detected using CCK8, EdU, Transwell, wound healing assay, and flow cytometer apoptosis assay. The in vivo experiment using subcutaneous tumor and caudal vein metastasis model to evaluate the inhibit effect of α-hederin Capan-1 cell tumor growth and metastasis. Proteomics were used to reveal the regulatory mechanism. The result shows that α-hederin treatment inhibits cell proliferation and invasion in concentration dependence way in both vivo and in vitro. The result shows that the IC50 for both Capan-1 and BxPC-3 were 32.5 Mµ and 15 Mµ, respectively. Flow cytometer apoptosis assay shows that α-hederin treatment promotion cell apoptosis in both Capan-1 and BxPC-3 cells. Proteomics and immunofluorescence detection confirmed that α-hederin treatment downregulated lactate dehydrogenase A (LDHA) expression and inhibited glycolysis. Molecular docking of α-hederin and LDHA proteins further confirmed that LDHA is a target of α-hederin. Taken together, this study confirms that α-hederin inhibits pancreatic cancer cell proliferation and invasion by inhibiting LDHA-mediated glycolysis. LDHA may be a direct target of α-hederin in pancreatic cancer.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449514","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}
引用次数: 0
Patient-derived tumor xenograft animal model of gastric cancer in precision chemotherapy.
IF 3.1 4区 医学
Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2025-02-19 DOI: 10.1007/s00210-025-03903-8
Yiyin Zhang, Yongming Yang, Jiayi Zhou, Qianqian Yu, Lixia Chen, Lili Zhao, Yongsheng Meng, Jing Wang, Lei Yan, Ziyang Huang, Shuchen Song, Wenqi Bai, Ruifang Sun, Xihua Yang
{"title":"Patient-derived tumor xenograft animal model of gastric cancer in precision chemotherapy.","authors":"Yiyin Zhang, Yongming Yang, Jiayi Zhou, Qianqian Yu, Lixia Chen, Lili Zhao, Yongsheng Meng, Jing Wang, Lei Yan, Ziyang Huang, Shuchen Song, Wenqi Bai, Ruifang Sun, Xihua Yang","doi":"10.1007/s00210-025-03903-8","DOIUrl":"https://doi.org/10.1007/s00210-025-03903-8","url":null,"abstract":"<p><p>This study aims to establish a patient-derived tumor xenograft (PDX) model for gastric cancer and apply it in pharmacodynamic studies for chemotherapeutic agents. So as to provide guidance for personalized treatment in gastric cancer patients. Fresh gastric cancer tissues were collected from surgical patients and transplanted into NOG mice to establish PDX model. Human source markers were identified by immunofluorescence and immunohistochemistry methods. Exon sequencing was used to verify the retention of humanized features in the PDX model. The efficacy of six chemotherapeutic drugs (oxaliplatin, cisplatin, paclitaxel, fluorouracil, Tegafur, capecitabine) and optimal dose of capecitabine were evaluated by the PDX model. The study has successfully established the PDX model of gastric cancer with transplantation success rates of P0 to P1 (45%), P1 to P2 (88.89%), and P2 to P3 (87.5%). Importantly, original tumor features were effectively preserved till P3. Drug screening results revealed notable antitumor effect of capecitabine in the PDX model of gastric cancer. The study has successfully established a gastric cancer PDX model, highlighting its potential for chemotherapy drug screening and personalized treatment. The transplantation success rates and preservation of original tumor features underscore the model's reliability and relevance for future studies. Findings from drug screening, especially capecitabine's effectiveness, suggest a promising avenue for precision treatment strategies in gastric cancer patients.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449512","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}
引用次数: 0
TFAP2A facilitates the metastasis and radioresistance of esophageal cancer by promoting EGFR transcription.
IF 3.1 4区 医学
Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2025-02-18 DOI: 10.1007/s00210-025-03848-y
Jinjin Yuan, Junqi Liu, Ruitai Fai, Zongwen Liu
{"title":"TFAP2A facilitates the metastasis and radioresistance of esophageal cancer by promoting EGFR transcription.","authors":"Jinjin Yuan, Junqi Liu, Ruitai Fai, Zongwen Liu","doi":"10.1007/s00210-025-03848-y","DOIUrl":"https://doi.org/10.1007/s00210-025-03848-y","url":null,"abstract":"<p><p>Epidermal growth factor receptor (EGFR) is considered to play tumor-promoting role in esophageal cancer (EC). However, the underlying molecular mechanisms of EGFR-mediated EC progression and radioresistance still need to be further revealed. The mRNA and protein levels of EGFR and transcription factor AP-2 alpha (TFAP2A) in EC tissues and cells were tested by qRT-PCR and western blot. Cell migration, invasion, apoptosis, and radiosensitivity were detected by transwell assay, flow cytometry, and colony formation assay. The protein level of γH2AX and the number of γH2AX-foci were examined using western blot and immunofluorescence staining. The interaction between TFAP2A and EGFR promoter was evaluated using ChIP assay and dual-luciferase reporter assay. The ratio of p-ERK1/2/ERK1/2 was assessed by western blot. Animal study was performed to measure the effect of TFAP2A knockdown on EC tumor growth and radiosensitivity. EGFR had increased expression in EC tissues and cells. EGFR knockdown suppressed EC cell migration and invasion, while promoted apoptosis and radiosensitivity. TFAP2A was upregulated in EC, and it could bind to EGFR promoter region to activate EGFR transcription. Silencing of TFAP2A restrained EC cell metastasis, enhanced apoptosis, and radiosensitivity, while these effects were abolished by EGFR overexpression. TFAP2A promoted EGFR expression to activate ERK1/2 pathway. Also, interference of TFAP2A reduced EC tumorigenesis and enhanced radiosensitivity in mice models by decreasing EGFR expression. TFAP2A-activated EGFR promoted EC cell metastasis and radioresistance via regulating ERK1/2 pathway, providing a new idea for EC treatment.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441383","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}
引用次数: 0
NMDA glutamatergic receptor-signalling in the ventrolateral columns of the periaqueductal grey matter mediates riparin A-induced antinociception to noxious heat stimulation.
IF 3.1 4区 医学
Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2025-02-18 DOI: 10.1007/s00210-025-03877-7
Raphaela Gonçalves Barros, Luiz Luciano Falconi-Sobrinho, Marcelo Lourenço da Silva, Norberto Cysne Coimbra, Rene Oliveira Beleboni
{"title":"NMDA glutamatergic receptor-signalling in the ventrolateral columns of the periaqueductal grey matter mediates riparin A-induced antinociception to noxious heat stimulation.","authors":"Raphaela Gonçalves Barros, Luiz Luciano Falconi-Sobrinho, Marcelo Lourenço da Silva, Norberto Cysne Coimbra, Rene Oliveira Beleboni","doi":"10.1007/s00210-025-03877-7","DOIUrl":"https://doi.org/10.1007/s00210-025-03877-7","url":null,"abstract":"<p><p>Riparin A, a synthetic form of natural riparins, has been shown to produce antinociception. However, little is known regarding the neural mechanisms and structures that mediate its pain-supressing effects. Glutamatergic neurons in the ventrolateral columns of the periaqueductal grey matter (vlPAG) are implicated in modulating spinally projecting pain inhibitory pathways. The aim of this work was to examine the antinociceptive effect of systemic treatment with riparin A at increasing doses and then investigate whether riparin A-induced antinociception is mediated by vlPAG glutamatergic NMDA receptors. Male Wistar Hannover rats were intraperitoneally treated with riparin A at different doses (5, 10 or 20 mg/kg), and after 60 min, they were submitted to either tail-flick or Hargreaves' plantar tests. After the specification of the most effective dose of riparin A (20 mg/kg), independent groups of animals were pretreated with the NMDA receptor selective antagonist LY235959 (0.1 nmol/0.2 μL) in vlPAG. Ten minutes later, these animals received intraperitoneal injections of riparin A, and after 60 min, they were subjected to the same nociceptive tests. Intraperitoneal injections of riparin A caused antinociception in all laboratory rats. In contrast, previous intra-vlPAG microinjections of the LY235959 decreased the analgesic effect produced by riparin A. Our findings suggest that NMDA receptor-signalling in the vlPAG is critical for the antinociceptive effect produced by riparin A.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441272","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}
引用次数: 0
Molecular characterization of metallo-beta-lactamase producers among carbapenem-resistant Pseudomonas aeruginosa from clinical samples in a tertiary care hospital, Lucknow, India.
IF 3.1 4区 医学
Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2025-02-18 DOI: 10.1007/s00210-025-03913-6
Nadeem Ahmad, Areena Hoda Siddiqui, Amita Arya, Mohd Shahid Khan
{"title":"Molecular characterization of metallo-beta-lactamase producers among carbapenem-resistant Pseudomonas aeruginosa from clinical samples in a tertiary care hospital, Lucknow, India.","authors":"Nadeem Ahmad, Areena Hoda Siddiqui, Amita Arya, Mohd Shahid Khan","doi":"10.1007/s00210-025-03913-6","DOIUrl":"https://doi.org/10.1007/s00210-025-03913-6","url":null,"abstract":"<p><p>Pseudomonas aeruginosa is a significant opportunistic pathogen in healthcare-associated infections. Its intrinsic resistance and ability to acquire resistance genes pose therapeutic challenges, particularly with the emergence of multidrug-resistant (MDR), extensively drug-resistant (XDR), and pan-drug-resistant (PDR) strains. This study aimed to assess the prevalence, antimicrobial susceptibility, and metallo-β-lactamase (MBL) resistance genes (blaNDM, blaOXA48) in P. aeruginosa isolates from clinical samples over 14 months. A total of 4410 clinical samples were processed, yielding 241 non-duplicate P. aeruginosa isolates. Antimicrobial susceptibility testing (AST) identified MDR, XDR, and PDR isolates. Carbapenemase production was detected using the eCIM test, and blaNDM and blaOXA48 genes were identified via PCR. Among the 241 isolates, 128 (53.1%) were from female patients and 113 (46.9%) from males. The most common sample sources were pus 111 (46.1%), sputum 36 (14.9%), and urine 35 (14.5%). The highest prevalence was observed in the Medicine department (45, 18.7%) and TB & Chest (42, 17.4%). Inpatients contributed 126 (52.3%) isolates, while 115 (47.7%) were from outpatients. AST showed the highest sensitivity to piperacillin/tazobactam (70.2%), piperacillin (67.2%), and tobramycin (67.6%), while imipenem (47.7%) and ceftazidime (33.6%) exhibited the lowest sensitivity. MDR was identified in 88 (36.5%) isolates, XDR in 29 (12.0%), and PDR in 9 (3.7%). MDR isolates were most common in pus (33, 13.6%), while XDR and PDR were frequently found in bronchoalveolar lavage (6, 2.4%) and urine (3, 1.2%), respectively. Among 20 eCIM-positive isolates, all carried the blaNDM gene, and 17 (85.0%) harbored blaOXA48. Males accounted for 70.0% of blaNDM and 70.6% of blaOXA48 cases. The highest prevalence of blaNDM (35.0%) was in the 41-60 age group, while blaOXA48 was equally distributed between the 20-40 and 41-60 age groups (35.3% each). Sputum (25.0% blaNDM, 23.5% blaOXA48) and urine (20.0% each) were the most common specimen sources. This study demonstrates the presence of antimicrobial resistance in P. aeruginosa isolates, including MDR, XDR, and PDR strains. The detection of carbapenemase-producing isolates carrying blaNDM and blaOXA-48 genes emphasizes the importance of effective infection control measures, antimicrobial stewardship, and ongoing surveillance to monitor and manage resistance trends.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441351","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}
引用次数: 0
Enhancer zeste homolog 2 (EZH2) targeting by small interfering RNA (siRNA); recent advances and prospect.
IF 3.1 4区 医学
Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2025-02-17 DOI: 10.1007/s00210-025-03883-9
Chou-Yi Hsu, Abdulsalam Najm Mohammed, Ahmed Hjazi, Subasini Uthirapathy, Jyothi S Renuka, Abhayveer Singh, Thyagarajan, Subhashree Ray, Hanen Mahmod Hulail
{"title":"Enhancer zeste homolog 2 (EZH2) targeting by small interfering RNA (siRNA); recent advances and prospect.","authors":"Chou-Yi Hsu, Abdulsalam Najm Mohammed, Ahmed Hjazi, Subasini Uthirapathy, Jyothi S Renuka, Abhayveer Singh, Thyagarajan, Subhashree Ray, Hanen Mahmod Hulail","doi":"10.1007/s00210-025-03883-9","DOIUrl":"https://doi.org/10.1007/s00210-025-03883-9","url":null,"abstract":"<p><p>Enhancer of zeste homolog 2 (EZH2) serves as the enzymatic catalytic subunit of the polycomb repressive complex 2 (PRC2), which is capable of modifying the expression of downstream target genes through the trimethylation of Lys-27 on histone 3 (H3K27me3). In addition to its role in H3K27me3 modification, EZH2 may influence gene expression through alternative mechanisms. The involvement of EZH2 in cellular processes such as proliferation, apoptosis, and senescence has been established. Its significant contributions to the pathophysiology of cancer have garnered considerable attention. Consequently, pursuing EZH2 as a target for cancer therapy has become a prominent area of research, leading to the development of various EZH2 inhibitors. A growing number of efforts are being made to investigate the possible application of small interfering RNA (siRNA) in medical applications after the practical application of this technique to decrease gene expression in various research models. Pharmacological inhibition of EZH2 induces apoptosis in cancer cells, while siRNA-mediated downregulation of EZH2 suppresses cancer cell growth. The cell cycle is modulated by siRNA-induced suppression of EZH2, yet its precise cause is unclear. Furthermore, inadequate research has been done on the signaling route affecting cancer cells' cell cycle following EZH2 suppression with siRNA. Investigating the molecular basis of EZH2 siRNA's anticancer activity will aid in developing fresh methods for identifying, managing, and preventing cancer.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441230","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}
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