Frontiers in Pharmacology最新文献

{"title":"Modulation of ASC-derived extracellular vesicles containing cargo that specifically enhances wound healing.","authors":"Jodi P Gurney, John W Ludlow, Michael J Van Kanegan, Robin L Smith","doi":"10.3389/fphar.2025.1635151","DOIUrl":"10.3389/fphar.2025.1635151","url":null,"abstract":"<p><strong>Introduction: </strong>We have developed a bioreactor-based production system for manufacturing Human Adipose Stromal Cell (ASC) extracellular vesicles (EVs), which includes exosomes, using a highly controlled and tunable environment that can modify the cargo of these nanovesicles. The patented innovation focuses on engineering novel pro-healing EVs with therapeutic activity and using a topical formulation to treat diabetic ulcers.</p><p><strong>Methods: </strong>To evaluate biological activity of tuned ASC EVs, functional activity assays were performed using human primary dermal fibroblast and keratinocyte culture models. Molecular and biochemical assays were used to assess cytokine regulation, collagen production and cell migration. Rodent wound healing models were used to assess therapeutic potential of modified exosomes. A Human volunteer case study was carried out with a consenting individual suffering from chronic diabetic ulcers.</p><p><strong>Results: </strong>Herein we demonstrate that our proprietary engineered ASC EVs, eXo³ exosomes, contain a unique activity profile that reduces inflammatory cytokines, stimulates collagen production, as well as activates keratinocyte and fibroblast proliferation and migration. When formulated with an emollient and topically applied to an <i>in vivo</i> excisional wound model, tuned eXo³ exosomes demonstrated enhanced wound closure, increased keratinization, collagen deposition, and overall improved recover rate. In a clinical case study addressing non-healing diabetic foot ulcers, conducted under informed consent, topical treatment with tuned eXo³ exosomes formulated in a proprietary gel serum showed complete wound closure and dermal regeneration.</p><p><strong>Conclusion: </strong>Our current research efforts have developed an EV manufacturing system that can be directed to improve the healing capacity of ASC-derived EVs. We show enhanced wound healing and repair activity <i>in vitro</i> and <i>in vivo</i>. Our data supports the regenerative properties of exosomes and reinforces their strong therapeutic potential.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1635151"},"PeriodicalIF":4.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12477913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of structure and composition of cationic liposomes on the delivery of siRNA <i>in vitro</i> and <i>in vivo</i>.","authors":"Daniil V Gladkikh, Elena V Shmendel, Darya M Makarova, Mikhail A Maslov, Marina A Zenkova, Elena L Chernolovskaya","doi":"10.3389/fphar.2025.1656671","DOIUrl":"10.3389/fphar.2025.1656671","url":null,"abstract":"<p><p>This study explores the effects of the modifications of siRNA delivery systems based on cationic liposomes containing the polycationic amphiphile 2 × 3 and lipid-helper DOPE on their ability to deliver therapeutic siRNA <i>in vitro</i> and <i>in vivo</i>. We supplied the core liposome system with lipoconjugates differing in PEG length weights and conjugate structure, and additionally modified with a folate residue as an addressing moiety. The <i>in vitro</i> data revealed no direct correlations between PEG length, lipoconjugate structure and the transfection efficiency of siRNA lipoplexes. <i>In vivo</i> biodistribution studies highlighted the significant influence of tumor presence on siRNA accumulation and biodistribution, underscoring the importance of adaptive delivery systems. In healthy mice, the largest amount of siRNA accumulates in the liver, whereas in tumor-bearing mice, accumulation in the kidneys increases, with a noticeable amount of siRNA accumulating in the tumor. Despite the longer linear PEG increasing the circulation time of siRNA, diP800 showed the best tumor accumulation. Anti-TTR siRNA complexes with all liposomal formulations demonstrated significant suppression of the <i>Ttr</i> mRNA in the liver, complexes with diP2000 and 2 × 3 liposomes demonstrated the highest silencing efficiency. These results contribute to advancing nucleic acid therapeutics by offering a comprehensive understanding of liposomal delivery system optimization.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1656671"},"PeriodicalIF":4.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12464033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ramucirumab plus paclitaxel as switch maintenance in patients with advanced HER2-negative gastric or gastro-oesophageal junction cancer: a cost-effectiveness analysis.","authors":"Jiefeng Luo, Zhengxiong Li, Qiong Du, Jiyong Liu","doi":"10.3389/fphar.2025.1616826","DOIUrl":"10.3389/fphar.2025.1616826","url":null,"abstract":"<p><strong>Objectives: </strong>The ARMANI trial demonstrated that ramucirumab plus paclitaxel (switch maintenance group) significantly prolonged progression-free survival (PFS) and overall survival in patients with advanced HER2-negative gastric cancer (GC) and gastroesophageal junction cancer (GEJC) compared to continued first-line oxaliplatin-based chemotherapy (control group). However, its cost-effectiveness remained unclear. This study aimed to evaluate its cost-effectiveness from the Chinese and United States (US) healthcare system perspective.</p><p><strong>Methods: </strong>A partitioned survival model was developed to compare the total costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) of switch maintenance group versus control group over a 10-year time horizon. Survival data were sourced from the ARMANI trial. Cost and utility were derived from open-access databases and published literature. The robustness of the results was verified through one-way sensitivity analysis and probabilistic sensitivity analysis (PSA). Additionally, subgroup analysis and scenario analysis were conducted.</p><p><strong>Results: </strong>The switch maintenance group yielded incremental gains of 0.15 QALYs in China and 0.16 QALYs in the US, with corresponding incremental costs of $56,738.32 and $185,250.55, resulting in ICERs of $373,219.84/QALY and $1,193,220.74/QALY, respectively. For the PD-L1 CPS ≥5 subgroup, incremental QALYs increased to 0.24 and 0.25, with incremental costs rising to $62,741.24 and $206,107.13, yielding ICERs of $266,259.94/QALY and $835,740.90/QALY, respectively. One-way sensitivity analysis revealed that the utility of PFS, the price of ramucirumab, and patient body weight were the most influential factors on the ICER, with consistent results observed from both Chinese and US perspectives. To be cost-effective in a 50% of chance, ramucirumab would need to reduce its price to 14.2% of the original price ($0.743 per mg) in China and 13.92% ($2.088 per mg) in the US, respectively.</p><p><strong>Conclusion: </strong>Ramucirumab plus paclitaxel is unlikely to be cost-effective compared to continuing oxaliplatin-based chemotherapy for patients with advanced HER2-negative GC or GEJC in China and US.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1616826"},"PeriodicalIF":4.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12463587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global burden and trends of adverse effects of medical treatment, 1990-2021: an analysis from the global burden of disease study 2021.","authors":"Keqing Zhang, Yuhai Gao, Yunfei Lu","doi":"10.3389/fphar.2025.1655864","DOIUrl":"10.3389/fphar.2025.1655864","url":null,"abstract":"<p><strong>Background: </strong>Adverse effects of medical treatment (AEMT) pose a significant global health concern, yet prior studies have mostly focused on specific adverse events or single countries, leaving the long-term global epidemiological patterns insufficiently characterized. As healthcare utilization grows, it is crucial to comprehensively quantify the global, regional, and national burden of AEMT and to forecast future trends for effective resource allocation and quality improvement.</p><p><strong>Methods: </strong>We utilized data from the Global Burden of Disease (GBD) study 2021. AEMT were defined based on GBD criteria, and incidence, prevalence, deaths, and disability-adjusted life years (DALYs) data were extracted. This study was stratified by age, gender, region and socio-demographic index (SDI), and estimated annual percentage change was used to assess the trends from 1990 to 2021. Based on SDI, we conducted health inequality analysis and used the Bayesian age-period-cohort model to predict the trend changes over the next 15 years.</p><p><strong>Results: </strong>Globally, there were 12,481,276 new cases of AEMT, with 122,330 deaths, resulting in 4,846,981 DALYs loss in 2021. The age-standardized incidence (ASIR) and prevalence rates (ASPR) worldwide were showing an upward trend, especially in high SDI regions. Both age-standardized mortality (ASMR) and DALYs rates (ASDR) showed a gradual decline during the study period, but they still carried a heavy burden in the low SDI regions (2021 ASDR: 3.71 [95% UI: 2.90 to 5.68] per 100,000 persons-year; 2021 ASR for DALYs: 150.37 [95% UI: 109.08 to 215.24] per 100,000 persons-year). Australasia demonstrated the highest ASIR and ASPR, while Western Sub-Saharan Africa showed the highest ASMR and ASDR. Health inequality analyses revealed that both absolute and relative inequalities of DALYs were narrowing. By 2036, it is forecast that ASIR will decrease to 72.33 (19.40-125.27) per 100,000 persons-year, and ASDR will decrease to 40.98 (21.52-60.43) per 100,000 persons-year.</p><p><strong>Conclusion: </strong>This study provided a comprehensive global, regional, and national assessment of the burden and inequality of AEMT over the past three decades, coupled with forecasts to 2036. The findings revealed distinct epidemiological patterns across SDI levels and regions, filling an important knowledge gap and offering evidence to guide healthcare safety strategies, medical education, and surveillance systems to further reduce the burden of AEMT worldwide.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1655864"},"PeriodicalIF":4.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12464418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Attitudes and use of complementary and alternative medicine: a cross-sectional comparison between medical and non-medical students.","authors":"Maryam Zakeri, Mahlagha Dehghan, Yaser Soltanmoradi, Shiva Monfared, Gulsah Kose, Hojjat Farahmandnia, Alaa Hamza Hermis, Xiao Xu, Mohammad Ali Zakeri","doi":"10.3389/fphar.2025.1529079","DOIUrl":"10.3389/fphar.2025.1529079","url":null,"abstract":"<p><p>Students are one of the groups in society that use complementary and alternative medicine (CAM). Given their role in promoting the use of CAM and the potential differences in attitudes due to their educational backgrounds, it is important to investigate their perspectives on CAM. This study aimed to compare the attitudes and use of CAM between medical and non-medical students. The study employed a cross-sectional design and was conducted among 525 medical and non-medical students in Iran. Data were collected using a descriptive information form, a CAM questionnaire, and the Holistic Complementary and Alternative Medicine Questionnaire (HCAMQ). The data were analyzed using SPSS version 25. The mean HCAMQ scores for medical and non-medical students were 33.10 ± 5.39 and 31.96 ± 5.48, respectively. A significant difference was found between medical and non-medical students in terms of their attitudes toward CAM, as measured by the HCAMQ subscale (p = 0.005). Additionally, 72.8% of medical students and 61.0% of non-medical students reported using at least one CAM method. A positive and statistically significant relationship was observed between medical and non-medical students in terms of their overall use of CAM (p = 0.005) and nutritional supplement methods (p = 0.025). Analysis of the reasons for using CAM revealed that only the use of medicinal herbs showed a significant difference between medical and non-medical students (p = 0.002). Finally, there was no statistically significant difference between the two groups in terms of consulting a physician before using CAM methods. Given the significant difference in attitudes toward CAM between medical and non-medical students, it is essential to address the distinct educational needs of these two groups. Developing effective and targeted educational programs could improve their knowledge and promote the safe and informed use of CAM.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1529079"},"PeriodicalIF":4.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12464550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects and safety of Salvia miltiorrhiza on the improvement of renal function, inflammatory factors, and vascular endothelium in patients with diabetic kidney disease: a meta-analysis and systematic review.","authors":"Shuyu Zheng, Meng Zhang, Wenkuan Wang, Qian Zhang, Ning Zhang","doi":"10.3389/fphar.2025.1556368","DOIUrl":"10.3389/fphar.2025.1556368","url":null,"abstract":"<p><strong>Objective: </strong>To elucidate the efficacy and safety of Radix et rhizoma Salvia miltiorrhiza (SM) in the treatment of Diabetic Kidney Disease (DKD), and to provide a rationale and scientific reference for the use of SM preparations in the treatment of DKD. This study is the first systematic evaluation and Meta-analysis focusing exclusively on the use of SM as a single agent in the treatment of DKD.</p><p><strong>Methods: </strong>A comprehensive search was conducted in PubMed, Web of Science, Cochrane Library, Elsevier Science Direct, CNKI, Wanfang, and VIP databases, covering the timeframe from the inception of the journals to May 2025. The search was restricted to randomized controlled trials conducted within the past decade that investigated the use of SM/SM preparations as a treatment for DKD. The control group received conventional interventions, while the intervention group received SM/SM preparations. Endnote 20 and Excel were employed for literature management and data organization, and Revman 5.3 and Stata 18 software were used for the analyses.</p><p><strong>Results: </strong>This study involved 21 RCTs with 1970 participants. The results demonstrated that SM preparations led to reductions in serum creatinine (Scr), blood urea nitrogen (BUN), urinary albumin excretion rate (UAER), 24-h urinary total protein (24 h-utp), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and endothelin-1 (ET-1) levels among patients with DKD (<i>P</i> < 0.05). Moreover, these preparations elevated flow-mediated vasodilation (FDM), showcasing their clinical effectiveness over the control group (<i>P</i> < 0.05). Notably, the safety profile remained sound, with no significant differences in adverse event rates between the two groups (<i>P</i> > 0.05).</p><p><strong>Conclusion: </strong>These results indicate that SM preparations could considerably improve renal and vascular endothelial function while simultaneously decreasing harmful inflammatory markers in patients with DKD, which allow it serve as a safe and effective therapeutic option.</p><p><strong>Systematic review registration: </strong>https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier CRD42024623452.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1556368"},"PeriodicalIF":4.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12464425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Icaritin inhibits osteoclast differentiation and reduces bone loss by targeting ESR1 to inhibit miR503/RANK pathway.","authors":"Baoping Xie, Xiaofei Liao, Liuyan Xin, Zhen Xie, Qi Jin, An Li, Hongliang Li, Jinping Li","doi":"10.3389/fphar.2025.1603333","DOIUrl":"10.3389/fphar.2025.1603333","url":null,"abstract":"<p><strong>Background: </strong>Postmenopausal osteoporosis (PMOP) is a prevalent metabolic disorder characterized by pathogenic mechanisms associated with the dysfunction of osteoclasts (OC) and osteoblasts (OB). Icaritin (ICT) is a flavonoid derived from icariin and epimedium, which is a natural product, and has demonstrated promising anti-osteoporosis properties. Nevertheless, the targets and mechanisms of ICT in osteoclast differentiation and PMOP remain unclear.</p><p><strong>Methods: </strong>we developed a bilateral ovariectomy-induced osteoporosis model in animals and receptor activator of nuclear factor kappa-B ligand (RANKL) induced RAW264.7 to differentiate into osteoclasts with or without MPP dihydrochloride (MPP) and antagomir-503-5p. Micro-CT, tartrate-resistant acid phosphatase (TRAP) staining, enzyme-linked immunosorbent assay (ELISA), Western blot and qRT-PCR were used to detect bone resorption function, bone metabolism parameters, osteoclast differentiation rate and the expression of related genes, as well as the expression of ESR1, miR-503 and RANK. Molecular docking, cell thermal shift assay (CETSA) and drug affinity responsive target stability (DARTs) experiments were used to confirmed that ESR1 is the direct target of ICT, and binding site of ICT with ESR1.</p><p><strong>Results: </strong>ICT significantly inhibited OC differentiation and the expression of related genes (<i>Trap</i>, <i>Mmp9</i>, and <i>Nfatc1</i>), reduced bone loss, and improved osteoporosis and bone trabecular structure, and inhibited the levels of TRAP and RANKL in the serum and increase the level of osteoprotegerin (OPG). ICT significantly enhanced the expression of ESR1, ESR2 and miR-503, while inhibiting RANK expression, and ESR1 is the direct target of ICT, and Asparagine at 455 is the direct binding site of ICT with ESR1. Moreover, blocking ESR1 significantly reduced the regulatory effect of ICT on OC differentiation and related gens expression by MPP, especially the expression of miR-503 and RANK, as well as weakened the regulatory effect of ICT on inhibiting bone loss. Antagomir-503-5p significantly reduced the regulatory effect of ICT on OC differentiation, as well as the expression of genes related to OC differentiation.</p><p><strong>Conclusion: </strong>Taken together, our study confirmed that ESR1 is the direct target of ICT, and Asparagine at 455 is the direct binding site of ICT, and ICT inhibits OC differentiation and reduces bone loss by targeting ESR1 to upregulate miR503 level and weaken miR503/RANK pathway.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1603333"},"PeriodicalIF":4.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12464588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Petroselinum sativum</i> (Parsley) extract suppresses oxidative stress and inflammatory responses in human keratinocytes and reduces atopic dermatitis symptoms in mouse skin.","authors":"Juan Wang, Xiaoqian Wu, Huihao Tang, Zhiwei Liu, Yun Ding, Minyi Feng, Shasha Wang, Jiaqi Zuo, Qi Zhao, Yaozhao Li, Chuntao Zhai, Zhenlin Hu, Xiaolei Ding, Nan Liu","doi":"10.3389/fphar.2025.1646822","DOIUrl":"10.3389/fphar.2025.1646822","url":null,"abstract":"<p><p><i>Petroselinum crispum</i> (Mill.) Fuss (parsley), a traditional botanical drug used for treating skin conditions including atopic dermatitis (AD), has unclear effects on epidermal keratinocytes. This study investigated the antioxidant and anti-inflammatory properties of parsley extracts in human keratinocytes and evaluated their therapeutic potential in an experimental AD model. The aqueous, ethanolic, and hydro-ethanolic (HE) extracts of parsley were evaluated for total polyphenol and flavonoid metabolites (TPC, TFC) and antioxidant activity using DPPH and FRAP assays. <i>In vitro</i>, HaCaT cells were treated with tert-butyl hydroperoxide (t-BHP) and TNF-α/IFN-γ to induce oxidative stress and inflammation. Therapeutic efficacy was further evaluated in 2,4-dinitrofluorobenzene (DNFB)-induced AD-like mouse model. The results showed that HE extracts of parsley (HEP) contained the highest TPC and TFC and exhibited the strongest antioxidant activity, significantly improving cell viability and reducing ROS levels in t-BHP-treated cells. Mechanistically, HEP alleviated oxidative stress by activating Nrf2 pathway and enhancing the expression of antioxidant enzymes, such as superoxide dismutase (SOD) and catalase (CAT). In addition, HEP suppressed inflammatory cytokines IL-33, IL-6, and IL-8 expression by inhibiting JAK1/STAT1 and NF-κB signaling, and simultaneously increased the expression of skin barrier proteins, including filaggrin and claudin-1 in TNF-α/IFN-γ-stimulated HaCaT cells. Moreover, HEP application could alleviate AD-like symptoms in DNFB-induced mouse model, including reduced skin hyperplasia and decreased immune cells infiltration. These findings suggest that HEP modulates oxidative stress and inflammation through multiple signaling pathways, offering promising natural therapeutic agent for AD management.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1646822"},"PeriodicalIF":4.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12463907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of intraperitoneal instillation of drugs on postoperative analgesia after laparoscopic cholecystectomy: a network meta-analysis.","authors":"Dongmei Zhang, Xiaojiao Wang, Xiaoli Yang, Dajian Xia","doi":"10.3389/fphar.2025.1646917","DOIUrl":"10.3389/fphar.2025.1646917","url":null,"abstract":"<p><strong>Background: </strong>Postoperative pain is a critical factor contributing to delayed discharge and postoperative recovery after laparoscopic cholecystectomy (LC). Intraperitoneal instillation of analgesic agents has been proposed as a means to alleviate pain in patients undergoing LC. This study aimed to evaluate the efficacy of various drugs administered via intraperitoneal instillation for postoperative analgesia after LC using a network meta-analysis approach.</p><p><strong>Methods: </strong>A comprehensive search was conducted in PubMed, EMbase, Web of Science and Cochrane Library databases from inception to August, 2025. Randomized controlled trials (RCTs) investigating the effects of intraperitoneal instillation on post-LC analgesia were included. Two independent reviewers screened studies, extracted data, and assessed the risk of bias. A frequentist network meta-analysis was performed to estimate standardized mean differences (SMDs) and 95% confidence intervals (CIs). The surface under the cumulative ranking curve (SUCRA) was used to rank the interventions for each outcome.</p><p><strong>Results: </strong>Eleven RCTs comprising 667 patients were included. According to SUCRA values, bicarbonate (96.5%) ranked highest in reducing VAS scores at 24 h post-surgery. Acetazolamide (85.9%) was most effective at 12 h, MgSO₄ (98.4%) at 6 h, and ondansetron (96.4%) at 2 h. Dexamethasone was associated with the lowest analgesic consumption (SUCRA: 95.3%) and the longest time to first analgesic request (81.5%).</p><p><strong>Conclusion: </strong>Intraperitoneal instillation of bicarbonate, acetazolamide, MgSO₄, and ondansetron provides differential analgesic benefits at various time points after LC. Dexamethasone appears to be a promising adjunctive agent for reducing analgesic requirements and prolonging the duration of analgesia.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1646917"},"PeriodicalIF":4.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12463911/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploration of the renoprotective effect of Yi-Shen-Hua-Shi granules on db/db mice and the mechanism of podocyte apoptosis based on the GRP78/CHOP signaling pathway.","authors":"Yanmo Cai, Yunhua Liu, Sitong Wang, Ge Jin, Kaidong Zhou, Xin Zhou, Xinxue Zhang, Min Zhang, Zongjiang Zhao","doi":"10.3389/fphar.2025.1586333","DOIUrl":"10.3389/fphar.2025.1586333","url":null,"abstract":"<p><strong>Objective: </strong>Yi-Shen-Hua-Shi (YSHS) granules are a widely utilized Chinese medicine formula for treating diabetic kidney disease (DKD). Although their effectiveness in treating DKD is established, the precise regulatory mechanism remains unclear. We aimed to explore the potential targets and mechanisms of action of YSHS in delaying DKD progression through network pharmacology and experimental validation.</p><p><strong>Methods: </strong>Network pharmacology was employed to identify the potential targets and signaling pathways of YSHS in treating DKD, which was hypothesized to be associated with endoplasmic reticulum stress and apoptosis, and these predictions were validated through animal and cellular experiments. Following a 12-week YSHS intervention in db/db mice, assessments were conducted on blood glucose, lipid levels, renal function indices (24-h urinary protein, blood glucose, serum creatinine, blood urea, and urinary albumin-to-creatinine ratio), and kidney pathology. Apoptosis in mouse podocyte clone-5 (MPC-5) cells was assessed using TUNEL labeling. The expression levels of GRP78, PERK, p-PERK, CHOP, Bcl-2, Bax, and Nephrin proteins and mRNAs in mouse kidney tissues and MPC-5 cells were evaluated by immunohistochemistry, Western blotting, and real-time PCR.</p><p><strong>Results: </strong>YSHS significantly improved the general status of db/db mice, with a significant reduction in body mass, renal function indices, total cholesterol, triglycerides, and low-density lipoprotein. Pathological staining showed reduced renal tissue damage in mice, and electron microscopy revealed reduced pedunculopontine fusion and basement membrane thickening. YSHS decreased GRP78, PERK, p-PERK, CHOP, and Bax proteins and mRNA levels in renal tissues and MPC-5 cells (<i>p</i> < 0.05 and <i>p</i> < 0.01) while increasing the expression level of Nephrin protein and Bcl-2 mRNA (<i>p</i> < 0.05 and <i>p</i> < 0.01).</p><p><strong>Conclusion: </strong>YSHS inhibited podocyte apoptosis, protected the glomerular filtration barrier, attenuated proteinuria, and improved renal function indices by activating the GRP78/CHOP signaling pathway in the kidneys and the <i>in vitro</i> cultured podocytes of db/db mice.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1586333"},"PeriodicalIF":4.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12464004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}