International Journal of Immunopathology and Pharmacology最新文献

{"title":"Steroid initiation timing and outcome of coronavirus disease 2019 patients: A multicenter, retrospective, observational study.","authors":"Ryu Sugimoto, Tsuneaki Kenzaka, Ayako Mikami, Nobuaki Matsunaga, Takayuki Akiyama, Norio Ohmagari, Hogara Nishisaki","doi":"10.1177/03946320231216314","DOIUrl":"10.1177/03946320231216314","url":null,"abstract":"<p><p><b>Objectives</b>: Dexamethasone's (DEXA) beneficial effect on survival when administered to critically ill patients with coronavirus disease 2019 (COVID-19) has been documented in randomized trials and meta-analyses. Here, we conducted this study to clarify the association between time from COVID-19 onset to steroid initiation and mortality and to examine the factors underlying these results.<b>Methods</b>: This was a multicenter, retrospective, observational study of patients enrolled in the Japanese COVID-19 Registry from January 1, 2020, to April 30, 2021. Demographic and clinical factors were extracted from patient records. Patients diagnosed with COVID-19 using polymerase chain reaction, loop-mediated isothermal amplification, or antigen tests were included. Patients aged <18 years, pregnant, with a history of chronic obstructive pulmonary disease or steroid or immunosuppressive drug use, transferred to another hospital, or with an unknown symptom onset were excluded.<b>Results and Conclusion</b>: The analysis included 3692 patients (men, 64.1%; median age, 68 years). Unadjusted comparisons of mortality groups showed significant differences in demographic and clinical characteristics; patients with early dexamethasone initiation had more risk factors for severe disease and significantly higher mortality than did patients with delayed initiation (13.3% vs 7.9%, <i>p</i> < .001). No significant differences were found in intubation rates or duration, length of hospitalization, or time from intubation to death. Multivariate analyses showed significant differences from symptom onset to steroid administration, with an adjusted odds ratio of 0.7 (<i>p</i> = .05) for patients who received steroids for ≥8 days. Early steroid administration to COVID-19 patients was associated with increased mortality, suggesting a subset with early severe disease and high mortality and/or adverse effects of early steroid administration.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"37 ","pages":"3946320231216314"},"PeriodicalIF":3.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10656795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136399901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revolutionizing antiretroviral therapy for human immunodeficiency virus/AIDS: A computational approach using molecular docking, virtual screening, and 3D pharmacophore building to address therapeutic failure and propose highly effective candidates.","authors":"Azzeddine Annan,&nbsp;Noureddine Raiss,&nbsp;El Harti Elmir,&nbsp;Abdelkarim Filali-Maltouf,&nbsp;Leila Medraoui,&nbsp;Hicham Oumzil","doi":"10.1177/03946320231207514","DOIUrl":"10.1177/03946320231207514","url":null,"abstract":"<p><strong>Objectives: </strong>In the context of human immunodeficiency virus (HIV) treatment, the emergence of therapeutic failures with existing antiretroviral drugs presents a significant challenge. This study aims to employ advanced molecular modeling techniques to identify potential alternatives to current antiretroviral agents.</p><p><strong>Methods: </strong>The study focuses on three essential classes of antiretroviral drugs: nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs). Computational analyses were performed on a database of 3,343,652 chemical molecules to evaluate their binding affinities, pharmacokinetic properties, and interactions with viral reverse transcriptase and protease enzymes. Molecular docking, virtual screening, and 3D pharmacophore modeling were utilized to identify promising candidates.</p><p><strong>Results: </strong>Molecular docking revealed compounds with high binding energies and strong interactions at the active sites of target enzymes. Virtual screening narrowed down potential candidates with favorable pharmacological profiles. 3D pharmacophore modeling identified crucial structural features for effective binding. Overall, two molecules for class 1, 7 molecules for class 2, and 2 molecules for class 3 were selected. These compounds exhibited robust binding affinities, interactions with target enzymes, and improved pharmacokinetic properties, showing promise for more effective HIV treatments in cases of therapeutic failures.</p><p><strong>Conclusion: </strong>The combination of molecular docking, virtual screening, and 3D pharmacophore modeling yielded lead compounds that hold potential for addressing HIV therapeutic failures. Further experimental investigations are essential to validate the efficacy and safety of these compounds, with the ultimate goal of advancing toward clinical applications in HIV management.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"37 ","pages":"3946320231207514"},"PeriodicalIF":3.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/96/60/10.1177_03946320231207514.PMC10585989.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41239939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes in serum hypoxia-inducible factor-1α and erythropoietin in allergic rhinitis patients: Correlation with the Th inflammatory profile and disease comorbidities.","authors":"Abdullah N Al-Rasheedi,&nbsp;Abdulrahman H Almaeen,&nbsp;Abdullah D Alotaibi,&nbsp;Abdulaziz S D Alruwaili,&nbsp;Sultan H H Alruwaili,&nbsp;Wadad M A Alruwaili,&nbsp;Aljoharah S Alsakhry,&nbsp;Ghuyudh M Alruwaili,&nbsp;Hala M ALkuwaykibi,&nbsp;Noof N Alrawili,&nbsp;Rahaf Z Alabdullah,&nbsp;Reem S Alatwi,&nbsp;Ibrahim Taher,&nbsp;Tarek H El-Metwally","doi":"10.1177/03946320231196745","DOIUrl":"10.1177/03946320231196745","url":null,"abstract":"<p><strong>Objectives: </strong>The balance between proinflammatory IFN-γ Th1 vs. the anti-inflammatory allergy-mediating IL-4-heralded Th2 reactions is pivotal in IgE-mediated allergic rhinitis (AR). Hypoxia-Inducible Factor (HIF)-1α is inducible by hypoxia and various cytokines. HIF-1α activates different anti-pathogen and allergic immune cells. This cross-sectional study assessed the changes in serum HIF-1α and its dependent erythropoietin (EPO) levels among hospital-characterized AR patients. Type of the immune reaction, Th1 vs. Th2, was stratified based on the calculated IL-4/IFN-γ direct ratio, after being measured using specific ELISA assays.</p><p><strong>Methods: </strong>147 AR patients (83 males/64 females), and age-, BMI-, and gender-matched 24 healthy controls (13 males/11 females) were sequentially enrolled at ENT Unit, Prince Muteb General Hospital, Sakaka, Saudi Arabia. Measurement of serum parameters was carried out using specific ELISA assays.</p><p><strong>Results: </strong>Contrary to the majority of previous publications, all controls and the majority of patients (<i>n</i> = 137/147) exhibited naive Th0 immune response. IFN-γ and HIF-1α levels were greater in controls than in patients (168.9 ± 173.9 vs 108 ± 94.5 pg/mL; <i>p</i><.012) and controls had a lower IL-4/IFN-ratio (2.439 ± 0.897 vs 3.33 ± 1.19; <i>p</i><.001) than patients. The HIF-1α results disagree with earlier studies. Due to the wide inter-individual variations, serum IL-4 and EPO levels in controls were non-significantly higher than patients. Lower IL-4 levels (267.3 ± 79.95 vs 353.4 ± 320.6 pg/mL; <i>p</i> < .01) and the ratio (2.814 ± 1.335 vs 3.431 ± 1.137; <i>p</i> < .05) were associated with obstructive sleep apnea. Lower ratio was also associated with inferior turbinate hypertrophy (3.051 ± 1.026 vs 3.787 ± 1.310; <i>p</i> < .001). EPO and IL-4 levels were lower in patients with deviated nasal septum (66.69 ± 26.81 vs 84.24 ± 61.5 pg/mL; <i>p</i> < .021; and 299.5 ± 137.3 vs 391.1 ± 52.780 pg/mL; <i>p</i> < .001, respectively). Significant correlations were found between the recorded levels and AR comorbidities.</p><p><strong>Conclusion: </strong>These results confirmed a pathogenic implication for HIF-1α and IFN-γ in AR that warranted future bigger and longitudinal studies.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"37 ","pages":"3946320231196745"},"PeriodicalIF":3.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c3/06/10.1177_03946320231196745.PMC10440105.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10047571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of the regulation of mesenchymal stem cells on macrophages in sepsis.","authors":"Jie Xing,&nbsp;Rui Wang,&nbsp;Fengqi Cui,&nbsp;Linlin Song,&nbsp;Quanlin Ma,&nbsp;Huiyun Xu","doi":"10.1177/03946320221150722","DOIUrl":"https://doi.org/10.1177/03946320221150722","url":null,"abstract":"<p><p>Sepsis is a common clinical critical disease with high mortality. The excessive release of cytokines from macrophages is the main cause of out-of-control immune response in sepsis. Mesenchymal stem cells (MSCs) are thought to be useful in adjunctive therapy of sepsis and related diseases, due to their function in immune regulation, anti-inflammatory, antibacterial, and tissue regeneration. Also there have been several successful cases in clinical treatment. Some previous studies have shown that MSCs regulate the function of macrophages through secreting cytokines and extracellular vesicles, or transferring mitochondria directly to target cells, which affects the progress of sepsis. Here, we review the regulation of MSCs on macrophages in sepsis, mainly focus on the regulation ways. We hope that will help to understand the immunological mechanism and also provide some clues for the clinical application of MSCs in the biotherapy of sepsis.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"37 ","pages":"3946320221150722"},"PeriodicalIF":3.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/18/66/10.1177_03946320221150722.PMC9969469.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10860980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A high pan-immune-inflammation value before chemoradiotherapy indicates poor outcomes in patients with small-cell lung cancer.","authors":"Ahmet Kucuk, Erkan Topkan, Emine Elif Ozkan, Duriye Ozturk, Berrin Pehlivan, Ugur Selek","doi":"10.1177/03946320231187759","DOIUrl":"10.1177/03946320231187759","url":null,"abstract":"<p><p><b>Objectives:</b> The objective of our study was to assess the prognostic significance of the Pan-Immune-Inflammation Value (PIV) before concurrent chemoradiation (C-CRT) and prophylactic cranial irradiation (PCI) in patients with limited-stage small-cell lung cancer (SCLC). <b>Methods:</b> The medical records of LS-SCLC patients who underwent C-CRT and PCI between January 2010 and December 2021 were retrospectively analyzed. PIV values were calculated using the peripheral blood samples obtained within the past 7 days before the initiation of treatment: PIV = [neutrophils × platelets × monocytes] ÷ lymphocytes. Using receiver operating characteristic (ROC) curve analysis, the optimal pretreatment PIV cutoff values that can partition the study population into two groups with substantially distinct progression-free survival (PFS) and overall survival (OS) outcomes were determined. The relationship between PIV values and OS outcomes was the primary outcome measure. <b>Results:</b> Eighty-nine eligible patients were divided into two PIV groups at an optimal cutoff of 417 [Area under curve (AUC): 73.2%; sensitivity: 70.4%; specificity: 66.7%]: Group 1: PIV < 417 (<i>N</i> = 36) and Group 2: PIV ≥ 417 (<i>N</i> = 53). Comparative analyses revealed that patients with PIV < 417 had significantly longer OS (25.0 vs 14.0 months, <i>p</i> < .001) and PFS (18.0 vs 8.9 months, <i>p</i> = .004) compared to patients with PIV ≥ 417. The outcomes of the multivariate analysis have verified the independent significance of pretreatment PIV concerning PFS (<i>p</i> < .001) and OS (<i>p</i> < .001) outcomes. <b>Conclusion:</b> The findings of this retrospective study indicate that the pretreatment PIV is a reliable and independent prognostic biomarker for patients with LS-SCLC who were treated with C-CRT and PCI.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"37 ","pages":"3946320231187759"},"PeriodicalIF":3.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/82/d4/10.1177_03946320231187759.PMC10331221.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9798663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Guillain-Barré syndrome following COVID-19 vaccination.","authors":"Selia Chowdhury,&nbsp;Samia Chowdhury","doi":"10.1177/03946320231199349","DOIUrl":"10.1177/03946320231199349","url":null,"abstract":"<p><p><b>Background:</b> Among the various side-effects of COVID-19 vaccinations, Guillain-Barré syndrome (GBS) has been found to have some interesting association with the vaccinations. This paper mainly focuses on exploring different associations between COVID-19 vaccination and GBS.<b>Method:</b> A systematic search was conducted on electronic databases including PubMed, Google Scholar, Cochrane, and Embase for case reports published until July 2022. A total of 42 case reports involving 67 individuals from 16 different countries were documented. Reports were analyzed to identify presenting symptoms, diagnosis, treatment, and pathophysiological mechanisms related to the relevant issues.<b>Results:</b> The studies included a diverse range of individuals with ages ranging from 13 to 87 years, with an average age of 51.66 years and a male predominance. The average time between vaccination and symptom onset was 12.67 days. Prominent clinical features observed in the case reports included back pain, facial diplegia, weakness, and paresthesia. Diagnostic studies primarily involved cerebrospinal fluid (CSF) analysis and electromagnetic studies. A key diagnostic clue was the presence of albuminocytological dissociation in CSF. Available treatment options consisted of intravenous immunoglobulin (IVIG), plasmapheresis, and steroids.<b>Conclusion:</b> This review highlights the diverse and clinically relevant associations between COVID-19 vaccination and GBS. The findings underscore the importance of conducting further studies to explore the causative links in this correlation and gain a better understanding of the relationship.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"37 ","pages":"3946320231199349"},"PeriodicalIF":3.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3e/65/10.1177_03946320231199349.PMC10492469.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10208560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of GPR30 sensitized gefitinib to NSCLC cells via regulation of epithelial-mesenchymal transition.","authors":"Xiaomin Yang,&nbsp;Hongyan Jiang,&nbsp;Jiang Ning,&nbsp;Shufen Zhang,&nbsp;Ying Cai,&nbsp;Liang Wang,&nbsp;Jinsong Yang,&nbsp;Guodong Xu,&nbsp;Wei Chen,&nbsp;Jianfei Wang","doi":"10.1177/03946320231210737","DOIUrl":"10.1177/03946320231210737","url":null,"abstract":"<p><p><b>Introduction:</b> G-protein coupled receptor 30 (GPR30) is associated with cell metastasis and drug resistance in many different cancer cells. The present study aimed to reveal the sensitivity of GPR30 to gefitinib in non-small cell lung cancer (NSCLC) cells.<b>Methods:</b> Cell viability and proliferation were detected using cell counting kit 8 and 5-ethynyl-2'-deoxyuridine assays, respectively. Western blotting and quantitative real-time reverse transcription PCR were used to detect GPR30 or epithelial-mesenchyme transition (EMT)-related mRNA and protein expression.<b>Results:</b> The results showed that GPR30 expression is associated with gefitinib sensitivity. G15, as a GPR30 antagonist, reduced GPR30 expression. We chose the maximum concentration of G15 with minimal cytotoxicity to detect cell viability after combined treatment with gefitinib in NSCLC cells, which indicated that G15 could increase sensitivity to gefitinib. However, the effect of G15 on gefitinib sensitivity disappeared after treatment with a small interfering RNA targeting <i>GPR30.</i> Further research showed that G15 or GPR30 siRNA treatment could upregulate E-cadherin and downregulate vimentin levels.<b>Conclusion:</b> Taken together, these data suggested that G15 could enhance NSCLC sensitivity to gefitinib by inhibition of GPR30 and EMT.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"37 ","pages":"3946320231210737"},"PeriodicalIF":3.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10612443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"61565613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of GPR81 aggravated intestinal ischemia/reperfusion injury-induced acute lung injury via HMGB1-mediated neutrophil extracellular traps formation.","authors":"Sun Yili,&nbsp;Dai Xinyi,&nbsp;Fan Kerui,&nbsp;Chen Kun,&nbsp;Yongqiang Yang,&nbsp;Li Zhang,&nbsp;Kai Hu","doi":"10.1177/03946320231193832","DOIUrl":"10.1177/03946320231193832","url":null,"abstract":"<p><strong>Introduction: </strong>Intestinal ischemia/reperfusion (II/R) injury is a life-threatening situation accompanied by severe organ injury, especially acute lung injury (ALI). A great body of evidence indicates that II/R injury is usually associated with hyperlactatemia. G-protein-coupled receptor 81 (GPR81), a receptor of lactate, has been recognized as a regulatory factor in inflammation, but whether it was involved in II/R injury-induced ALI is still unknown.</p><p><strong>Methods: </strong>To establish the II/R injury model, the superior mesenteric artery of the mice was occluded gently by a microvascular clamp for 45 min to elicit intestinal ischemia and then a 90-min reperfusion was performed. Broncho-alveolar lavage fluid (BALF) and lung tissues were obtained to evaluate the lung injury after II/R. The pulmonary histopathological alteration was evaluated by H&E staining. The concentration of proteins, the number of infiltrated cells, and the level of IL-6 were measured in BALF. The formation of neutrophil extracellular traps (NETs) was evaluated by the level of double-stranded DNA (dsDNA) and myeloperoxidase- double-stranded DNA (MPO-dsDNA) complex in BALF, and the content of citrullinated histone H3 (Cit-H3) in lung tissue. The level of HMGB1 in the BALF and plasma was measured by enzyme linked immunosorbent assay (ELISA).</p><p><strong>Results: </strong>Administration of the GPR81 agonist 3,5-dihydroxybenzoic acid (DHBA) aggravated II/R injury-induced lung histological abnormalities, upregulated the concentration of proteins, the number of infiltrated cells, and the level of IL-6 in BALF. In addition, DHBA treatment increased the level of dsDNA and MPO-dsDNA complex in BALF, and promoted the elevation of Cit-H3 in lung tissue and the release of HMGB1 in BALF and plasma.</p><p><strong>Conclusion: </strong>After induction of ALI by II/R, the administration of DHBA aggravated ALI through NETs formation in the lung.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"37 ","pages":"3946320231193832"},"PeriodicalIF":3.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ac/e8/10.1177_03946320231193832.PMC10498694.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10241865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ischemia reperfusion myocardium injuries in type 2 diabetic rats: Effects of ketamine and insulin on LC3-II and mTOR expression.","authors":"Zhiguo Tao,&nbsp;Rongmu Lin,&nbsp;Rui Zhang,&nbsp;Peng He,&nbsp;Chengwen Lei,&nbsp;Yuanhai Li","doi":"10.1177/03946320231196450","DOIUrl":"10.1177/03946320231196450","url":null,"abstract":"<p><p><b>Objectives:</b> Myocardiopathy occurs in ischemia-induced injury caused by dysregulation of autophagy of cardiac tissues. The present report evaluates the protective effect of ketamine and insulin against myocardial injury in type 2 diabetic rats (T2DM).<b>Methods:</b> The effects of ketamine and its combination with insulin on biochemical parameters and inflammatory cytokines in the serum of I/R-induced myocardial injury in T2DM rats were evaluated. The parameters of reactive oxygen species and the expression of autophagosome signaling pathway proteins were also determined. Using transmission electron microscopy, we investigated autophagosomes. Western blots were used to detect autophagy-associated signaling pathways. Myocardial function was determined by echocardiography and histopathological changes in myocardial tissues were also determined in I/R-induced myocardial injury in type 2 diabetic rats.<b>Results:</b> There was a significant reduction in glucose, AST, LDH, and CK-MB levels and cytokines (IL-1β, IL-6, and TNF-α) in serum of the ketamine (<i>p</i> < .05) and ketamine + insulin (<i>p</i> < .01) groups than in the diabetic + I/R. MDA and ROS levels were reduced with a substantial (<i>p</i> < .05) increase in GSH levels through improved cardiac function in the ketamine (<i>p</i> < .05) and ketamine + insulin (<i>p</i> < .01) groups than the diabetic + I/R group. There was an increase in mature autophagosomes in diabetic+I/R+Kt+In compared to diabetic+I/R+Kt alone in infarction and marginal zones. It should be noted that the significant increase (<i>p</i> < .01) in protein levels of the autophagy-associated intracellular signaling pathways AMPK and mTOR, as well as an increase in LC3-II and BECLIN-1, suggests that ketamine combined with insulin-activated autophagy-associated intracellular signaling AMPK and mTOR.<b>Conclusion:</b> The findings of the study suggest that ketamine combined with insulin administration remarkably protects I/R-induced myocardial injury in rats with T2DM by reducing the dysregulation of autophagy.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"37 ","pages":"3946320231196450"},"PeriodicalIF":3.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/dc/18/10.1177_03946320231196450.PMC10467302.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10117739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 icariin on the H₂O₂-induced proliferation of mouse airway smooth muscle cells through miR-138-5p regulating SIRT1/AMPK/PGC-1α axis.","authors":"Yu-Fang Huang,&nbsp;Guo-Chun Ou,&nbsp;Shou-Hong Ma,&nbsp;Ming-Wei Liu,&nbsp;Wen Deng","doi":"10.1177/03946320231151515","DOIUrl":"https://doi.org/10.1177/03946320231151515","url":null,"abstract":"<p><p>Icariin exerts antioxidative and anti-inflammatory effects and is used in the treatment of bronchial asthma. However, the specific modes of action are uncertain. In this study, we investigated whether icariin could modulate the silencing information regulator 2-related enzyme 1 (SIRT1)/adenosine monophosphate-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor gamma co-activator 1α (PGC-1α) axis by regulating miR-138-5p during H₂O₂-induced proliferation of mouse airway smooth muscle cells (ASMCs). Primary BALB/c mouse ASMCs were cultured using the tissue block adherence method and were induced with hydrogen peroxide (H₂O₂; 200 μmol/L) to establish a bronchial asthma ASMC proliferation model. With the aid of Western Blot and quantitative real-time polymerase chain reaction (qRT-PCR) in H₂O₂-induced ASMCs, the expression of miR-138-5p, SIRT1, AMPK, PGC-1α, α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), collagen I, and collagen III protein and mRNA were investigated. The proliferation rate and activities of superoxide dismutase1 (SOD1), reduced glutathione (GSH), malonaldehyde (MDA), and reactive oxygen species (ROS) in ASMCs were determined. The results suggest Compared with the H₂O₂-induced group, icariin inhibited the miR-138-5p expression; enhanced SIRT1, p-AMPK, and PGC-1α expression; attenuated MDA activity and ROS level; lowered TGF-β1, collagen I, and collagen III expression levels; and decreased the proliferation of ASMCs induced by H₂O₂. The dual-luciferase reporter gene assay results showed that SIRT1 is a regulatory target of miR-138-5p.The results suggest that Icariin could improve the H₂O₂-induced proliferation of ASMCs. The mechanism may be related to the increase of activation of SIRT1/AMPK/PGC-1α axis by suppressing the expression of miR-138-5p. Thus, SIRT1 is the regulatory target of miR-138-5p.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"37 ","pages":"3946320231151515"},"PeriodicalIF":3.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d0/fe/10.1177_03946320231151515.PMC9926010.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10743516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}