Clinical and Experimental Pharmacology and Physiology最新文献

{"title":"Activation of GPR39 Ameliorates Placental Dysfunction by Inhibiting Activation of NLRP1 Inflammasome in Gestational Diabetes Mellitus","authors":"Xiaohua Zhou,&nbsp;Hong Sun","doi":"10.1111/1440-1681.70074","DOIUrl":"10.1111/1440-1681.70074","url":null,"abstract":"<div>\u0000 \u0000 <p>Gestational diabetes mellitus (GDM) is a metabolic condition defined by glucose intolerance during pregnancy, which frequently results in placental malfunction, oxidative stress, and chronic inflammation, all of which are linked to the activation of the NLRP1 inflammasome. GPR39, a G protein-coupled receptor, has emerged as a possible therapeutic target, and its agonist, TC-G 1008, may provide protection against metabolic disorders. In this study, we investigated the expression of GPR39 in the murine placenta and its role in GDM-related placental dysfunction using a high-fat diet-induced GDM mouse model. Mice were treated with TC-G 1008 (7.5 and 15 mg/kg) from gestational day 0 to 18, and placental tissues were analysed via RT-PCR, Western blot, immunohistochemistry, ELISA, and biochemical assays. Our findings indicated that GPR39 expression was markedly reduced in GDM mice relative to wild-type controls. Administration of TC-G 1008 (7.5 and 15 mg/kg) enhanced fetal outcomes, including survival rate, weight, and crown-rump length, while also mitigating maternal metabolic disorders such as hyperglycaemia, insulin resistance, and dyslipidaemia. Moreover, the administration of TC-G 1008 mitigated placental oxidative stress by augmenting SOD activity and GSH levels, while inhibiting NLRP1 inflammasome activation, as shown by diminished expression of NLRP1, ASC, and Caspase-1, alongside lowered levels of IL-1β and IL-18. Furthermore, GPR39 activation suppressed the NF-κB and MAPK signalling pathways. These findings suggest that GPR39 activation by TC-G 1008 ameliorates placental dysfunction in GDM by mitigating oxidative stress and inflammation via suppression of the NLRP1 inflammasome, highlighting its potential as a therapeutic strategy for GDM-associated complications.</p>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 11","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091241","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":"Overexpression of miR-718 in Keratinocytes Affects the Psoriatic Inflammation via Targeting STAT1: In Vitro and In Vivo Evidence","authors":"Himani Rani,&nbsp;Neeru Saini","doi":"10.1111/1440-1681.70073","DOIUrl":"10.1111/1440-1681.70073","url":null,"abstract":"<div>\u0000 \u0000 <p>Psoriasis is a complex inflammatory autoimmune skin illness that causes epidermal keratinocyte hyperproliferation and dedifferentiation. In a previous study we did in the lab, we found that treating human keratinocytes (HaCaT) with PUVA increased the expression of hsa-miR-718 compared to control. In this study, an imiquimod (IMQ)-induced mouse model and HaCaT were used to look at how overexpressing miR-718 could help treat psoriasis and its causes. To gain more understanding, the in vivo study used the JAK1/3 inhibitor tofacitinib. We observed that miR-718 overexpression leads to the inhibition of JAK–STAT signalling, as evidenced by the reduced expression of STAT1, JAK proteins, and their phosphorylated forms, both in vitro and in vivo<i>.</i> Luciferase assay demonstrated the direct inhibition of STAT1 due to miR-718 overexpression. Additionally, in vitro experiments showed downregulation of STAT2 and STAT3. Inhibition of basal miR-718 in HaCaT overactivates JAK–STAT signalling proteins. In psoriatic mice, ectopic miR-718 reduces NF-kB, a key mediator of inflammation. IHC shows lower acanthosis and parakeratosis in IMQ-induced psoriatic mice. In the skin of mice that had been miR-718 transfected, there was less VEGF, MMP7 and MMP9. Understanding how miR-718 improves psoriasis not only provides new information but also inspires hope for its potential use as a psoriasis treatment.</p>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 11","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145084928","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":"Kaempferol Ameliorates Sepsis-Acute Lung Injury by Promoting Succinylation of SRPK1","authors":"Yuan Zhang,&nbsp;Huilin Liu,&nbsp;Yan Jin","doi":"10.1111/1440-1681.70077","DOIUrl":"10.1111/1440-1681.70077","url":null,"abstract":"<div>\u0000 \u0000 <p>Sepsis is the leading cause of acute lung injury (ALI), and kaempferol has a protective effect against ALI. However, the underlying mechanisms have not been fully elucidated. This study aimed to investigate the role of kaempferol in sepsis-induced ALI and its underlying molecular mechanism, particularly the involvement of succinylation. Human pulmonary microvascular endothelial cells were treated with lipopolysaccharide to induce injury. Cell apoptosis and inflammation were evaluated by flow cytometry and enzyme-linked immunosorbent assay. Succinylation was analysed using immunoblotting, co-immunoprecipitation and protein stability assay. The results showed that kaempferol inhibited apoptosis and inflammation response in LPS-treated HPMVECs and attenuated lung damage in septic mice. Moreover, kaempferol enhanced succinylation levels and reduced SIRT5 protein levels. SIRT5 suppressed the succinylation of SRPK1 at lysine (K) 588 site and facilitated SRPK1 degradation. Overexpression of SIRT5 or knockdown of SRPK1 reversed the inhibitory effects of kaempferol or SIRT5 knockdown on cellular biological behaviours, respectively. In conclusion, kaempferol attenuates sepsis-induced lung injury by inhibiting HPMVEC apoptosis and inflammation. Mechanistically, kaempferol suppresses SIRT5-mediated desuccinylation of SRPK1, thereby promoting SRPK1 protein stability. The findings suggest the important role of SRPK1 succinylation in ALI and kaempferol may be used for the treatment of the disease.</p>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 11","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074635","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":"Rufinamide Mitigates Seizures and Behavioural Deficits via BDNF/TrkB Modulation and Oxidative Stress Reduction in Pentylenetetrazole-Kindled Mice","authors":"Saima Abbas,&nbsp;Abida Parveen,&nbsp;Waseem Ashraf,&nbsp;Syed Muhammad Muneeb Anjum,&nbsp;Rana Muhammad Zahid Mushtaq,&nbsp;Faleh Alqahtani,&nbsp;Imran Imran","doi":"10.1111/1440-1681.70075","DOIUrl":"10.1111/1440-1681.70075","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Rufinamide (RUF) is a 3rd generation antiseizure medication (ASM) with a triazole ring that blocks voltage-gated sodium channels (VGSCs) and is most commonly used to treat Lennox–Gastaut syndrome. Thus, the present study examined the effect of RUF on EEG activity, behavioural testing, oxidative stress, and mRNA expression in PTZ-kindled mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Male BALB/c mice were administered rufinamide (30, 60, and 90 mg/kg) for 21 days along with 11 injections of PTZ (40 mg/kg) given every other day. EEG recordings were monitored and a series of behavioural tests after RUF treatment were done to assess the post-kindling associated anxiety and memory impairment. We also assessed the oxidative alterations, variation in real-time BDNF/TrkB mRNA expression as well as neuroinflammatory markers in isolated mice brains.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Analysis of results showed that RUF at the dose of 90 mg/kg maximally suppressed the progression of full-bloom seizures and decreased cortical epileptic spike discharge. Moreover, RUF showed significant anxiolytic action and prevented PTZ-induced cognitive decline in a dose-dependent manner. Because of its anti-inflammatory and antioxidant properties, RUF decreased lipid peroxidation, AChE activity, raised glutathione and superoxide dismutase levels in the mice brain. RUF suppressed the PTZ-induced upregulation of BDNF/TrkB signalling and significantly reduced pro-inflammatory cytokines.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>It is possible that the effects of RUF that have been seen are the consequence of decreased oxidative stress, BDNF/TrkB downregulation, and reduced expression of neuroinflammatory markers, which in turn reduce ictogenesis and improve the neuropsychiatric consequences associated with epilepsy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 11","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074620","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":"Effects of Genetic Polymorphisms of CYP450 Enzymes on Blood Hydroxychloroquine Levels and Clinical Response Among Patients With Cutaneous Lupus Erythematosus","authors":"Jatta Njundu,&nbsp;Qi E. Chia,&nbsp;Stanslas Johnson,&nbsp;Yong Audrey Chee Hui,&nbsp;Ho Wen Chung,&nbsp;Chua Eng Wee,&nbsp;Affandi Azura Mohd,&nbsp;Lee Sut Enn,&nbsp;Wong Siu Bee,&nbsp;How Kang Nien","doi":"10.1111/1440-1681.70076","DOIUrl":"10.1111/1440-1681.70076","url":null,"abstract":"<div>\u0000 \u0000 <p>Whole blood hydroxychloroquine (WBHCQ) levels were found to correlate with cutaneous lupus (CLE) disease severity. Studies have shown HCQ to be highly variable in blood concentrations and clinical response among patients; however, the exact cause of this variation is not well understood. Genetic polymorphism of CYP450 enzymes was suspected to be a possible contributing factor. This study aimed to determine the effects of genetic polymorphism of CYP450 enzymes on clinical response to HCQ among Malaysians with CLE and its association with blood [HCQ], [DHCQ] or [HCQ]: [DHCQ] ratio. This study was a multicentre cohort study targeting CLE subjects on HCQ, recruited from five main hospitals in Malaysia. A total of 33 subjects were recruited from 1 September 2021 to 30 November 2023. Blood [HCQ], [DHCQ] or its concentration ratio and clinical response to HCQ were the outcome variables determined. Statistical Analysis showed that CYP2D6*10 was significantly associated with blood [HCQ] (<i>p</i> &lt; 0.05), while CYP3A5*3 was shown to be significantly associated with [DHCQ]: [HCQ] ratio (<i>p</i> &lt; 0.05). However, a statistically significant association was not observed between identified SNPs and clinical response to HCQ (OR: 4.444, CI: 0.770, 25.654, <i>p</i> = 0.095). These findings are aligned with those reported previously on blood HCQ and CYP polymorphism; however, clinical response to HCQ and CYP polymorphism is still debatable, as we did not observe any significant association. CYP450 genetic polymorphism significantly affects levels of HCQ in patients. Thus, individual genotypes of CYP450 enzymes may be considered for the optimum use of HCQ among CLE subjects.</p>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 11","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074632","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":"Early and Stable Mouse Model of Amphotericin B-Induced Acute Kidney Injury: Application of Continuous Non-Invasive GFR Monitoring","authors":"Lifeng Shen,&nbsp;Yuchen Song,&nbsp;Yu Xiao,&nbsp;Yu Xin,&nbsp;Yanqi Liu,&nbsp;Yuxi Liu,&nbsp;Yinghao Luo,&nbsp;Qianqian Zhang,&nbsp;Xinran Wang,&nbsp;Kaijiang Yu,&nbsp;Changsong Wang","doi":"10.1111/1440-1681.70071","DOIUrl":"https://doi.org/10.1111/1440-1681.70071","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Amphotericin B (AmB) remains a cornerstone in antifungal therapy, but its clinical use is limited by dose-dependent nephrotoxicity. Lipid-based formulations such as amphotericin B cholesterol sulfate complex dispersion (ABCD) were developed to mitigate renal injury, though their comparative renal safety profiles remain incompletely defined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to establish a pharmacologically relevant mouse model to characterise the nephrotoxicity of conventional AmB (AmB-D) and ABCD formulations, using continuous non-invasive glomerular filtration rate (GFR) monitoring and renal injury biomarkers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Male C57BL/6 mice received a single intravenous dose of AmB-D or ABCD at low or high doses. Renal function was assessed via real-time GFR monitoring, serum creatinine (SCr), blood urea nitrogen (BUN) and mRNA expression of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL). Histopathological injury was evaluated at defined time points.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>High-dose AmB-D (2 mg/kg) and ABCD (20 mg/kg) induced rapid GFR decline within 2 h, preceding significant increases in SCr, BUN, and injury biomarkers. ABCD demonstrated 6–10-fold lower nephrotoxic potency compared to AmB-D. Low-dose groups exhibited mild, reversible changes in GFR and minimal tubular injury.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Continuous GFR monitoring enables sensitive detection of early renal dysfunction and reveals distinct nephrotoxic profiles between AmB-D and ABCD. This pharmacologically relevant model provides a powerful tool for preclinical nephrotoxicity assessment and for quantitatively comparing the renal safety of different drug formulations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 10","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144929801","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":"Glycyrrhizic Acid Ameliorates LPS-Induced WI-38 Cell Inflammation, Oxidative Stress, and Ferroptosis via Targeting METTL14 in Infantile Pneumonia","authors":"Xiaofei Xie,&nbsp;Caiwen Wang,&nbsp;Yingying Sun,&nbsp;Ting Sun,&nbsp;Yongfu Song,&nbsp;Na Wang,&nbsp;Zhuang Wang,&nbsp;Yongji Wang","doi":"10.1111/1440-1681.70068","DOIUrl":"https://doi.org/10.1111/1440-1681.70068","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Infantile pneumonia is a common and significant health concern in the world, with elevated morbidity and mortality rates among affected children. This research is designed to demonstrate the therapeutic action of glycyrrhizic acid (GA) on infantile pneumonia and unravel the underlying mechanisms involved.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The models in vitro and in vivo were created to analyse the action of GA in infantile pneumonia. Human embryonic lung WI-38 cells were treated with lipopolysaccharide (LPS), and mice were administered LPS to mimic infantile pneumonia. Cell viability was tested via cell counting kit-8 (CCK8). The lactate dehydrogenase (LDH) content was examined using the LDH Cytotoxicity Assay Kit. Flow cytometry was performed to analyse cell apoptosis. The pro-inflammatory cytokine (tumour necrosis factor-alpha [TNF-a], interleukin [IL]-6 and IL-1β) levels were detected using TNF-a, IL-6 and IL-1β ELISA assay kits. The levels of ferrous ion (Fe²⁺), antioxidant glutathione (GSH), malondialdehyde (MDA) and reactive oxygen species (ROS) were analysed using corresponding assay kits. The potential target genes of GA in infantile pneumonia were predicted using molecular docking. The m6A level of mRNA was tested using the m6A RNA Methylation Assay Kit. Lung tissue pathology was analysed using haematoxylin and eosin staining.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>GA abolished LPS-induced inhibition of WI-38 cell viability and promotion of cell apoptosis, while reducing production of LDH, TNF-a, IL-6 and IL-1β. Besides, GA suppressed the levels of Fe²⁺, MDA and ROS and facilitated the GSH, solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) levels. The molecular docking predicted that the methyltransferase-like 14 (METTL14) was a potential target of GA and had good bonding ability. Interestingly, METTL14 expression was promoted in LPS-stimulated WI-38 cells and the serum of patients with infantile pneumonia. GA repressed cell apoptosis, levels of LDH, TNF-a, IL-6, IL-1β, Fe²⁺, MDA and ROS, and facilitated the GSH, SLC7A11 and GPX4 levels of LPS-induced WI-38 cells by METTL14 silence. GA abrogated lung injury of LPS-induced mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>GA alleviates LPS-induced WI-38 cell cytotoxicity, inflammation, oxidative stress and ferroptosis by METTL14 knockdown. Our findings suggest that GA may pave the way for the treatment of infantile pneumonia.</p>\u0000 </section>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 10","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144910086","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":"Clinical Analysis of Pulmonary Nontuberculous Mycobacterial Infection in Patients With Pre-Existing Stage II–IV Lung Cancer","authors":"Juan Li,&nbsp;Junsheng Fan,&nbsp;Zhili Tan,&nbsp;Anqi Li,&nbsp;Siyuan He,&nbsp;Yaping Jia,&nbsp;Rong Li,&nbsp;Yani Lin,&nbsp;Zihao Liu,&nbsp;Haiqing Chu,&nbsp;Zhemin Zhang","doi":"10.1111/1440-1681.70060","DOIUrl":"https://doi.org/10.1111/1440-1681.70060","url":null,"abstract":"<div>\u0000 \u0000 <p>Immune checkpoint inhibitors (ICIs) targeting programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) have improved cancer outcomes but can induce immune-related adverse events, including mycobacterial infections. This study retrospectively analysed pulmonary nontuberculous mycobacteria (NTM) infection in 91 patients with pre-existing stage II–IV lung cancer at Shanghai Pulmonary Hospital between June 2015 and June 2024. Among these patients, 78.0% [71/91] were male, and 16.5% [15/91] were receiving ICIs monotherapy at the time of initial pulmonary NTM infection diagnosis (ICIs group). Compared with the non-ICIs group, ICIs-treated patients developed pulmonary NTM infection earlier (median time: 12 months [IQR, 6–18] vs. 21.5 months [IQR, 13–30]; <i>p</i> = 0.004), and had a higher proportion of rapid-growing NTM isolates (73.3% [11/15] vs. 30.3% [23/76]; <i>p</i> = 0.003), predominantly <i>Mycobacterium abscessus</i> complex (40.0% [6/15]). In contrast, <i>Mycobacterium avium</i> complex was the predominant NTM species in the non-ICIs group (71.1% [54/76]). During 12 months of anti-NTM therapy, the ICIs group showed a lower cumulative sputum culture conversion rate (36.4% [4/11] vs. 59.6% [31/52]; <i>p</i> = 0.19) and a longer median time to initial sputum culture conversion (12 months vs. 6 months; <i>p</i> = 0.13), though these differences were not statistically significant. The most commonly administered ICIs drugs were tislelizumab (40.0% [6/15]) and sintilimab (26.7% [4/15]). These findings suggest that ICIs may be associated with earlier development of pulmonary NTM infection in lung cancer patients. Future prospective studies with larger sample sizes are needed to validate this conclusion.</p>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 10","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144894354","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":"Chlorogenic Acid Improves Salicylic Acid-Induced Cochlear Injury by Reducing Oxidative Stress and Inflammatory Response Through TLR4/NF-κB Signalling Pathway","authors":"Yi Lin,&nbsp;Lili Li,&nbsp;Jianbin Cheng","doi":"10.1111/1440-1681.70067","DOIUrl":"https://doi.org/10.1111/1440-1681.70067","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Sodium salicylate (SS) causes hearing damage and tinnitus in humans and animals. Chlorogenic acid (CGA) has strong antioxidant and anti-apoptotic effects, but whether it can protect the cochlea is unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>SS was used to induce cochlear injury in rats, followed by 150, 300 and 600 mg/kg CGA treatment. The changes of tinnitus behaviour in each group were detected by auditory brainstem response (ABR), behavioural test, beam balance, Preyer reflex and auditory startle test. The levels of oxidative stress and inflammation were detected by kit. The pathological damage of cochlea was detected by HE staining, immunofluorescence staining, succinate dehydrogenase staining, and toluidine blue staining. The apoptosis of outer hair cell and spiral ganglion cell and TLR4/NF-κB pathway were detected by TUNEL staining, immunohistochemistry, immunofluorescence and Western blot.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>After SS induction, the ABR threshold, EP score and beam balance score of the rats increased significantly, and the AA score, Preyer reflex and auditory startle response decreased significantly; that is, the cochlear injury model was successfully constructed. Together, the levels of oxidative indexes (ROS, MDA) and inflammatory indexes (TNF-α, IL-1β) in rats after cochlear injury were significantly increased, and the spiral ganglion, organ of Corti, outer hair cells and nerve fibres of cochlear tissue were severely damaged. The outer hair cell and spiral ganglion cell were significantly apoptotic, and the number of TLR4 positive cells, NF-κB p65 fluorescence intensity and protein level in the cochlea of rats were significantly increased. However, after CGA treatment, the above indicators were significantly improved.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>CGA can reduce SS-induced oxidative stress and inflammatory response in the cochlea through restraining the TLR4/NF-κB pathway, improve the pathological damage of the cochlea and reduce ototoxicity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 10","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144897404","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":"Mapping Nutrition and Tuberculosis Research: Insights From Bibliometric Perspective","authors":"Chenqi Li,&nbsp;Biao Gao,&nbsp;Hongmei Xiao,&nbsp;Wenjing Shi,&nbsp;Hongtao Lu,&nbsp;Gen Miao,&nbsp;Xiaohua Tu,&nbsp;Yuxiao Tang,&nbsp;Hui Shen","doi":"10.1111/1440-1681.70069","DOIUrl":"https://doi.org/10.1111/1440-1681.70069","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Malnutrition and tuberculosis form a mutually reinforcing vicious cycle. While nutritional interventions are crucial for TB management, the knowledge structure and research frontiers remain insufficiently characterised.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To systematically analyse the structure, trajectory and frontiers of research in the nutrition-tuberculosis field using bibliometric methods.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Relevant literature published since 2007 was retrieved from the Web of Science Core Collection database. CiteSpace was employed to perform multidimensional analyses, including co-occurrence, cluster timeline visualisation and burst detection for keywords, citations and authors, thereby constructing knowledge maps and identifying key nodes through network centrality metrics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 4502 bibliographic records were analysed. Key findings include: (1) Vitamin D occupies a central position (frequency 326, centrality 70), bridging basic immune mechanisms and clinical applications; (2) research paradigms evolved from molecular mechanism exploration (2007–2012), through clinical translation validation (2011–2019), to systems biology integration (2019–2025); (3) gut microbiota (burst strength 11.73) and (fatty) acids emerged as frontiers; (4) diabetes–tuberculosis comorbidity revealed the complexity of metabolic-immune interaction networks and (5) high citation frequency of WHO reports indicates a pressing need for translating research into policy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Nutrition–tuberculosis research is shifting from single-nutrient studies towards integrated ‘nutrition–microbiome–metabolism–immunity’ networks. Vitamin D remains central, but future priorities should focus on precision interventions, multi-omics integration and translation from mechanism to practice, especially for high-risk groups.</p>\u0000 </section>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 10","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144894233","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}