Clinical and Experimental Pharmacology and Physiology最新文献

{"title":"Metformin ameliorates endometrial thickness in a rat model of thin endometrium","authors":"M. Imran,&nbsp;Aditya Khandvilkar,&nbsp;Siddhanath Metkari,&nbsp;Geetanjali Sachdeva,&nbsp;Uddhav Chaudhari","doi":"10.1111/1440-1681.13862","DOIUrl":"https://doi.org/10.1111/1440-1681.13862","url":null,"abstract":"<p>Metformin, a well-established anti-diabetic drug, is also used in managing various other metabolic disorders including polycystic ovarian syndrome (PCOS). There are evidences to show that metformin improves endometrial functions in PCOS women. However, fewer studies have explored the direct effects of metformin on endometrium. Previous in vitro studies have shown that therapeutic serum concentrations of metformin enhance endometrial epithelial cell proliferation. The present study was undertaken to investigate in vivo effects of metformin on endometrial proliferation in a rat model of thin endometrium. Toward this, a rat model of thin endometrium was developed. Metformin (0.1% or 1% w/v) was administrated orally for 15 days in rats with thin endometrium. Oral metformin administration for three consecutive estrous cycles (15 days) in the thin endometrium rat model led to an increase in endometrial thickness compared to sham endometrium. Histological analysis showed a significant increase in the number of endometrial glands (<i>P</i> &lt; 0.05), stromal cells (<i>P</i> &lt; 0.01) and blood vessels (<i>P</i> &lt; 0.01) in metformin-treated (n = 10 in each group) uterine horns compared to sham (saline-treated) uterine horns in rats. The expression of proliferating cell nuclear antigen and vascular epithelial growth factor was found to be upregulated on treatment with 1% metformin-treated group (n = 7). However, pregnancy outcomes in the rats treated with metformin remained unaltered despite the restoration of endometrial thickness. In conclusion, the study demonstrated that metformin ameliorates endometrial thickness in a rat model of thin endometrium by increasing endometrial proliferation and angiogenesis, without restoration of embryo implantation.</p>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"51 6","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140556154","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":"Colorectal cancer cells with stably expressed SIRT3 demonstrate proliferating retardation by Wnt/β-catenin cascade inactivation","authors":"Tianyu Li,&nbsp;Leqi Fan,&nbsp;Yijiang Jia,&nbsp;Chen Xu,&nbsp;Wei Guo,&nbsp;Yuji Wang,&nbsp;Ye Li","doi":"10.1111/1440-1681.13856","DOIUrl":"https://doi.org/10.1111/1440-1681.13856","url":null,"abstract":"<p>Colorectal cancer (CRC) is a typical and lethal digestive system malignancy. In this study, we investigated the effect of sirtuin 3 (SIRT3) expression, a fidelity mitochondrial protein, on the proliferation of CRC cells and the mechanisms involved. Using the University of Alabama at Birmingham Cancer Data Analysis Portal database and the Clinical Proteomic Tumour Analysis Consortium database, we discovered that low expression of <i>SIRT3</i> in CRC was a negative factor for survival prognosis (<i>P &lt;</i> .05). Meanwhile, SIRT3 expression was correlated with distant metastasis and tumour, node, metastasis stage of CRC patients (<i>P &lt;</i> .05). Subsequently, we observed that CRC cells with stable <i>SIRT3</i> expression exhibited a significant decrease in proliferative capacities both in vitro and in vivo, compared to their counterparts (<i>P &lt;</i> .05). Further investigation using western blot, immunoprecipitation and TOPflash/FOPflash assay showed the mechanism of growth retardation of these cells was highly associated with the degradation of β-catenin in cytosol, and the localization of β-catenin/α-catenin complex in the nucleus. In conclusion, our findings suggest that the inhibition of CRC cell proliferation by SIRT3 is closely associated with the inactivation of the Wnt/β-catenin signalling pathway.</p>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"51 6","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140556306","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":"NPAS2, transcriptionally activated by ARRB1, promotes the malignant behaviours of lung adenocarcinoma cells and regulates the reprogramming of glucose metabolism","authors":"Shenglan Wang,&nbsp;Chunhong Huang,&nbsp;Yanbin Zheng,&nbsp;Xinjie Wu,&nbsp;Yutong Zhong","doi":"10.1111/1440-1681.13860","DOIUrl":"https://doi.org/10.1111/1440-1681.13860","url":null,"abstract":"<p>Lung adenocarcinoma (LUAD) is a serious threat to public health and is accompanied by increased morbidity and mortality worldwide. <i>Neuronal PAS domain protein2</i> (<i>NPAS2</i>) has been confirmed as an oncogene in LUAD; however, little is known about its molecular mechanism. Here, the expression level of NPAS2 was detected in LUAD cell lines and 16HBE cells. Gain- and loss-of-function experiments were performed. Cell Counting Kit-8, colony formation, flow cytometry, wound-healing and Transwell assays were conducted to assess cell proliferation, apoptosis, migration and invasion, respectively. Reprogramming of glucose metabolism was evaluated via oxygen consumption rate (OCR), complexes activities, lactic production and glucose consumption. The expression of critical proteins was examined by western blot. We demonstrated aberrant upregulation of NPAS2 and β-arrestin-1 (ARRB1) in LUAD cell lines. ARRB1 was found to be a critical transcription factor of NPAS2 with binding sites within the promoter region of NPAS2, thereby causing its transcriptional activation. Functional experiments revealed that NPAS2 depletion significantly inhibited the malignant behaviours of A549 cells by suppressing cell proliferation, migration, invasion and epithelial-mesenchymal transition and promoting cell apoptosis. Meanwhile, NPAS2 depletion increased OCR and activities of complexes (I, II, III and V), and reduced lactic acid production and glucose uptake in A549 cells, indicating that NPAS2 depletion inhibited aerobic glycolysis, accompanied by reduced expression of glycolytic enzymes. However, the changes caused by NPAS2 knockdown were partly restored by ARRB1 overexpression. In conclusion, our study suggests that ARRB1 could transcriptionally activate NPAS2, facilitating malignant activities and glycolysis, and ultimately promoting the progression of LUAD, proving a novel therapeutic strategy for the treatment of LUAD.</p>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"51 5","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140537728","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 HSP27 accelerates stress-induced gastric ulcer healing via the CXCL12/CXCR4 axis","authors":"Qiaoyan Lu,&nbsp;Hua Tang","doi":"10.1111/1440-1681.13857","DOIUrl":"https://doi.org/10.1111/1440-1681.13857","url":null,"abstract":"<p>Chronic stress often triggers gastrointestinal complications, including gastric injury and ulcers. Understanding the role of heat shock protein 27 (HSP27) in stress-induced gastric ulcers could unveil novel therapeutic targets. Here, we established a stress-induced gastric ulcer rat model using water immersion restraint stress and administered adenovirus-packaged HSP27 overexpression vector. Gastric ulcer severity was scored, and mucosal changes were assessed. Gastric epithelial and endothelial cells were treated with lipopolysaccharide and transfected with HSP27 overexpression vectors to evaluate cell viability, migration and angiogenesis. Expression levels of HSP27, C-X-C motif chemokine ligand 12 (CXCL12) and C-X-C motif chemokine receptor 4 (CXCR4) were measured in tissues and cells. HSP27 expression was initially low during stress-induced gastric ulceration but increased during ulcer healing. HSP27 overexpression accelerated ulcer healing in rats, promoting gastric epithelial cell proliferation and migration and gastric endothelial cell angiogenesis through the CXCL12/CXCR4 axis. Inhibitor IT1t reversed the effects of HSP27 overexpression on cell proliferation, migration and angiogenesis. In summary, HSP27 overexpression facilitated ulcer healing, which was partially mediated by the CXCL12/CXCR4 axis.</p>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"51 5","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140342953","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":"Exploring the modulatory effects of sotagliflozin on dyslipidemia in mice: The role of glucagon, fibroblast growth factor 21 and glucagon-like peptide 1","authors":"Nitin J. Deshmukh,&nbsp;M. S. Kalshetti,&nbsp;Mohan Patil,&nbsp;Pankaj Autade,&nbsp;Ganesh V. Sangle","doi":"10.1111/1440-1681.13854","DOIUrl":"10.1111/1440-1681.13854","url":null,"abstract":"<p>Sotagliflozin is the first dual SGLT1/2 inhibitor antidiabetic drug approved by the US Food and Drug Administration for the management of heart failure. SGLT1/2 inhibition is observed to potentiate the secretion of the incretin hormone, glucagon-like peptide-1 (GLP-1). The current preclinical research sought to investigate the effect of sotagliflozin on the secretion of fat-regulating peptides such as GLP-1, glucagon and fibroblast growth factor 21 (FGF21) and their prospective association with sotagliflozin's potential beneficial effects on dyslipidaemia. During an oral fat tolerance test in mice, sotagliflozin substantially increased GLP-1 and insulin concentrations. Although sotagliflozin alone did not ameliorate postprandial lipemia, its combination with linagliptin (DPP-IV inhibitor) significantly improved lipid tolerance comparable to orlistat (lipase inhibitor). In a triton-induced hypertriglyceridemia model, sotagliflozin, along with other medications (fenofibrate, exenatide and linagliptin) reduced fat excursion; however, co-administration with linagliptin provided no extra advantage. Furthermore, sotagliflozin stimulated glucagon secretion in the alpha TC1.6 cells and healthy mice, which resulted in an increased circulating FGF21 and β-hydroxybutyrate concentration. Finally, chronic treatment of sotagliflozin in high-fat diet (HFD)-fed obese mice resulted in reduced body weight gain, liver triglyceride, cholesterol, interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-α) levels compared with the placebo group. However, the addition of linagliptin did not provide any additional benefit. In conclusion, sotagliflozin was found to have an effect on GLP-1 and also stimulate the release of glucagon and FGF21, which are important for regulating fat metabolism. Therefore, sotagliflozin might represent a potential therapeutic approach for the treatment of diabetic dyslipidemia and steatohepatitis.</p>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"51 5","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140287089","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":"Differential responses of cerebral and renal oxygenation to altered perfusion conditions during experimental cardiopulmonary bypass in sheep","authors":"Roger G. Evans,&nbsp;Andrew D. Cochrane,&nbsp;Sally G. Hood,&nbsp;Bruno Marino,&nbsp;Naoya Iguchi,&nbsp;Rinaldo Bellomo,&nbsp;Peter R. McCall,&nbsp;Nobuki Okazaki,&nbsp;Alemayehu H. Jufar,&nbsp;Lachlan F. Miles,&nbsp;Taku Furukawa,&nbsp;Connie P. C. Ow,&nbsp;Jaishankar Raman,&nbsp;Clive N. May,&nbsp;Yugeesh R. Lankadeva","doi":"10.1111/1440-1681.13852","DOIUrl":"10.1111/1440-1681.13852","url":null,"abstract":"<p>We tested whether the brain and kidney respond differently to cardiopulmonary bypass (CPB) and to changes in perfusion conditions during CPB. Therefore, in ovine CPB, we assessed regional cerebral oxygen saturation (rSO₂) by near-infrared spectroscopy and renal cortical and medullary tissue oxygen tension (PO₂), and, in some protocols, brain tissue PO₂, by phosphorescence lifetime oximetry. During CPB, rSO₂ correlated with mixed venous SO₂ (r = 0.78) and brain tissue PO₂ (r = 0.49) when arterial PO₂ was varied. During the first 30 min of CPB, brain tissue PO₂, rSO₂ and renal cortical tissue PO₂ did not fall, but renal medullary tissue PO₂ did. Nevertheless, compared with stable anaesthesia, during stable CPB, rSO₂ (66.8 decreasing to 61.3%) and both renal cortical (90.8 decreasing to 43.5 mm Hg) and medullary (44.3 decreasing to 19.2 mm Hg) tissue PO₂ were lower. Both rSO₂ and renal PO₂ increased when pump flow was increased from 60 to 100 mL kg⁻¹ min⁻¹ at a target arterial pressure of 70 mm Hg. They also both increased when pump flow and arterial pressure were increased simultaneously. Neither was significantly altered by partially pulsatile flow. The vasopressor, metaraminol, dose-dependently decreased rSO₂, but increased renal cortical and medullary PO₂. Increasing blood haemoglobin concentration increased rSO₂, but not renal PO₂. We conclude that both the brain and kidney are susceptible to hypoxia during CPB, which can be alleviated by increasing pump flow, even without increasing arterial pressure. However, increasing blood haemoglobin concentration increases brain, but not kidney oxygenation, whereas vasopressor support with metaraminol increases kidney, but not brain oxygenation.</p>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"51 4","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1440-1681.13852","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140058818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epidemiology and risk factors of bloodstream infections among adolescents and young adults with acute lymphoblastic leukaemia: An 11-year retrospective cohort study","authors":"Longlong Xue,&nbsp;Yishu Tang,&nbsp;Liwen Wang,&nbsp;Cong Xu,&nbsp;Qian Cheng,&nbsp;Xin Li","doi":"10.1111/1440-1681.13850","DOIUrl":"10.1111/1440-1681.13850","url":null,"abstract":"<p>Adolescent and young adults (AYAs) belong to a unique category of patients diagnosed with acute lymphoblastic leukaemia (ALL). Bloodstream infection (BSI) is a leading cause of treatment-related mortality in ALL patients. However, the epidemiology and risk factors for mortality from BSIs in AYA patients remain unclear. In this study, we analysed these aspects in AYAs patients and compared similarities and differences with children (&lt;15 years old) and older adults (&gt;39 years old). We analysed the pathogenic epidemiology, antibiotic resistance and BSI risk factors of 73 children, 180 AYAs, and 110 older adults with ALL in three comprehensive hospitals from January 2010 to August 2021. The data on BSIs in AYAs were compared to that of the other two groups. In this study, the epidemiology of BSIs in AYAs was similar to that of older adult patients. Concerning clinical characteristics, most AYAs and older adults with BSIs were in a relapsed or uncontrolled state (34.5% vs. 35.4%, p = 0.861). In terms of pathogen distribution, Gram-negative bacteria (GNB) were the most common causative pathogens in AYAs and older adult groups. Extended-spectrum beta-lactamase (ESBL)-producing bacteria were more commonly found in AYAs than in children (32.8% vs. 16.4%, p = 0.09). Regarding risk factors, the length of hospitalization (&gt;14 days) and renal inadequacy (creatinine ≥ 177 μmol/L) were influencing factors for 30-day mortality in AYAs patients with BSIs. In our study, AYA patients with BSIs showed clinical characteristics and pathogen distributions similar to those of older adult patients but quite different from those of children.</p>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"51 4","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140058819","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":"A 2-week treatment with 5-azacytidine improved the hypercontractility state in prostate from obese mice: Role of the nitric oxide-cyclic guanosine monophosphate signalling pathway","authors":"Ana Carolina Ghezzi,&nbsp;Gabriela Reolon Passos,&nbsp;Mariana Gonçalves de Oliveira,&nbsp;Akila Lara Oliveira,&nbsp;Guilherme Rossi Assis-Mendonça,&nbsp;Glaucia Coelho de Mello,&nbsp;Edson Antunes,&nbsp;Fabiola Zakia Monica","doi":"10.1111/1440-1681.13851","DOIUrl":"10.1111/1440-1681.13851","url":null,"abstract":"<p>Benign prostatic hyperplasia (BPH) is characterised by increases in prostate volume and contraction. Downregulation of the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) signalling pathway contributes to prostate dysfunctions. Previous studies in cancer cells or vessels have shown that the epigenetic mechanisms control the gene and protein expression of the enzymes involved in the production of NO and cGMP. This study is aimed to evaluate the effect of a 2-week treatment of 5-azacytidine (5-AZA), a DNA-methyltransferase inhibitor, in the prostate function of mice fed with a high-fat diet. Functional, histological, biochemical and molecular assays were carried out. Obese mice presented greater prostate weight, α-actin expression and contractile response induced by the α-1adrenoceptors agonist. The relaxation induced by the NO-donor and the protein expression of endothelial nitric oxide synthase (eNOS) and soluble guanylate cyclase (sGC) were significantly decreased in the prostate of obese mice. The treatment with 5-AZA reverted the higher expression of α-actin, reduced the hypercontractility state of the prostate and increased the expression of eNOS and sGC and intraprostatic levels of cGMP. When prostates from obese mice treated with 5-AZA were incubated in vitro with inhibitors of the NOS or sGC, the inhibitory effect of 5-AZA was reverted, therefore, showing the involvement of NO and cGMP. In conclusion, our study paves the way to develop or repurpose therapies that recover the expression of eNOS and sGC and, hence, to improve prostate function in BPH.</p>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"51 4","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140058817","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":"Study on the mechanism underlying Trichosanthis peel injection-induced improvements in myocardial fibrosis markers in patients with chronic heart failure","authors":"Yue He,&nbsp;Xinsheng Gu,&nbsp;Zhou Yang,&nbsp;Hao Wang,&nbsp;Ping Liu","doi":"10.1111/1440-1681.13848","DOIUrl":"10.1111/1440-1681.13848","url":null,"abstract":"<p>In this research, we aimed to observe the changes in myocardial fibrosis indices in patients with chronic heart failure before and after treatment and to evaluate the anti-chronic heart failure and ventricular remodelling effects of Trichosanthis peel (TP) injection. This study was a single-center, open, single-blind, randomized controlled study with an optimal efficacy design. Patients were consecutively and randomly divided into two groups, with 36 patients in the TP injection group and 36 patients in the conventional treatment group. ELISA was used to measure changes in myocardial fibrosis indices before and after discharge, including transforming growth factor β (TGF-β), serum hyaluronic acid (HA), type I procollagen (PCI), laminin (LN) and type III procollagen (PCIII). There was no significant difference between the two groups in clinical data or baseline level of myocardial fibrosis before treatment. After treatment, compared with the conventional treatment group, the myocardial fibrosis index was significantly decreased following TP injection. Our findings indicate that TP injection combined with conventional medicine can attenuate myocardial fibrosis by reducing angiotensin II, aldosterone, TGFβ, HA, PCI, metallomatrix proteinase 2, connective tissue growth factor and LN and promote ventricular remodelling in patients with chronic heart failure.</p>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"51 4","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139995779","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":"Phosphatidylserine accelerates wound healing and reduces necrosis in the rats: Growth factor activation","authors":"Partow Mirzaee Saffari,&nbsp;Pooria Asili,&nbsp;Sadaf Eshraghi,&nbsp;Ahad Muhammadnejad,&nbsp;Ahmad Reza Dehpour,&nbsp;Ramin Goudarzi,&nbsp;Alireza Partoazar","doi":"10.1111/1440-1681.13849","DOIUrl":"10.1111/1440-1681.13849","url":null,"abstract":"<p>To examine the effect of topical phosphatidylserine (PS) on wound healing factors and tissue necrosis in in vivo models. Topical PS was applied to evaluate aspects of the wound healing process and growth factors production of vascular endothelial growth factors (VEGF) as well a necrosis reduction in the skin flap of rat models. Moreover, phenytoin (PHT) and cyclosporine A (CsA) were used topically as positive control treatments in wound and necrosis models, respectively. Immunohistochemistry (IHC) VEGF, transforming growth factor-β (TGF-β), fibroblast growth factor (FGF) and histopathology were analysed on the wounds of rats. In the necrosis assessment, necrotic areas were determined on photography taken from the back skin of rats. Results indicated that PS topically enhanced significantly (<i>P</i> &lt; 0.05) numbers of fibroblasts and endothelium while inhibiting the neutrophils and macrophages during the 14 days of wound treatment. Moreover, higher values of collagen deposition and epithelialization scores as well as wound recovery percentage (near 80%) were determined significantly (<i>P</i> &lt; 0.05) in the PS group compared with the control. IHC analysis determined that FGF and VEGF cytokine factors were elevated in the wound site by topical PS. Moreover, the necrotic area was significantly (<i>P</i> &lt; 0.05) improved in the PS group. Our experiment indicated that wound improvement and flap survival values in PS treatments were superior to PHT and CsA control groups, respectively. In conclusion, these findings suggest the potential of PS application in the healing of wounds and control of necrosis development after surgery or skin injuries.</p>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"51 4","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139971134","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}