Iranian Journal of Basic Medical Sciences最新文献

{"title":"Introduction of <i>LPIN1</i> as a potential diagnostic and prognostic biomarker for gastric cancer via integrative bioinformatics analysis of a competing endogenous RNA network and experimental validation.","authors":"Milad Daneshmand-Parsa, Parvaneh Nikpour","doi":"10.22038/ijbms.2024.74686.16216","DOIUrl":"10.22038/ijbms.2024.74686.16216","url":null,"abstract":"<p><strong>Objectives: </strong>Identification of effective biomarkers is crucial for the heterogeneous disease of gastric cancer (GC). Recent studies have focused on the role of pseudogenes regulating gene expression through competing endogenous RNA (ceRNA) networks, however, the pseudogene-associated ceRNA networks in GC remain largely unknown. The current study aimed to construct and analyze a three-component ceRNA network in GC and experimentally validate a ceRNA.</p><p><strong>Materials and methods: </strong>A comprehensive analysis was conducted on the RNA-seq and miRNA-seq data of The Cancer Genome Atlas (TCGA) stomach adenocarcinoma (STAD) dataset to identify differentially-expressed mRNAs (DEMs), pseudogenes (DEPs), and miRNAs (DEMis). Pseudogene-associated ceRNA and protein-protein interaction (PPI) networks were constructed, and functional enrichment analyses were performed. DEMs and DEPs with degree centralities≥2 were selected for survival analysis. A ceRNA was further selected for experimental validation.</p><p><strong>Results: </strong>10,145 DEMs, 3576 DEPs, and 66 DEMis were retrieved and a ceRNA network was then constructed by including DEMis with concurrent interactions with at least a DEM and a DEP. Functional enrichment analysis demonstrated that DEMs of the ceRNA network were significantly enriched in cancer-associated pathways. <i>LPIN1</i> and <i>WBP1L</i> were two mRNAs showing an association with STAD patients overall survival. Expression analysis of <i>LPIN1</i> showed a significant decrease in GC tumors compared to non-tumor tissues (<i>P</i>=0.003).</p><p><strong>Conclusion: </strong>Our research emphasizes the significant implications of ceRNA networks in the development of new biomarkers for the detection and prognosis of cancer. Further examination is necessary to explore the functional roles of <i>LPIN1</i> in the pathogenesis of GC.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11459342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390531","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":"Isolated <i>Lactobacillus fermentum</i> Ab.RS22 from traditional dairy products inhibits HeLa cervical cancer cell proliferation and modulates apoptosis by the PTEN-Akt pathway.","authors":"Abbas Asoudeh-Fard, Mitra Salehi, Dariush Ilghari, Asghar Parsaei, Peyman Heydarian, Hossein Piri","doi":"10.22038/IJBMS.2023.72825.15846","DOIUrl":"10.22038/IJBMS.2023.72825.15846","url":null,"abstract":"<p><strong>Objectives: </strong>It is worthwhile to note that, some probiotics such as <i>Lactobacilli</i> and <i>Bifidobacteria</i> isolated from dairy products have significant therapeutic effects against cancer cells. Here, we evaluated anti-proliferation and the apoptotic effects of isolated <i>Lactobacillus fermentum</i> Ab.RS22 from traditional dairy products on the HeLa cervical cancer cells <i>in vitro.</i></p><p><strong>Materials and methods: </strong>The viability of treated HeLa cells with supernatant of <i>Lactobacillus</i> in 0.5, 0.75, 1, 1.5, and 2 ng/ml concentrations, and IC₅₀ values were detected by tetrazolium bromide. The <i>L. fermentum</i> Ab.RS22-induced cell death by flow cytometry was confirmed through evaluation of the expression of <i>caspase-3</i>, <i>P53</i>, <i>PTEN</i>, and <i>AKT</i> genes by quantitative reverse transcription-polymerase chain reactions (qRT-PCR).</p><p><strong>Results: </strong>Most cytotoxicity effects of <i>Lactobacillus</i> on HeLa cells were detected in 2 ng/ml at 24 hr (<i>P</i><0.01); also, the IC₅₀ value was measured as 1.5 ng/ml. The findings of the flow cytometry assay showed that <i>L. fermentum</i> Ab.RS22 in 1.5 ng/ml concentration at 24 hr increased the percentage of both apoptosis and necrosis cells. Lactobacillus-induced cell death was verified through results of Real-time PCR; where expression of <i>caspase-3</i>, <i>P53</i>, and <i>PTEN</i> genes was increased (<i>P</i><0.01), and also expression of <i>AKT</i> gene (anti-apoptotic) was decreased (<i>P</i><0.05).</p><p><strong>Conclusion: </strong>Our findings showed that <i>L. fermentum</i> Ab.RS22 could dose-dependently inhibit the proliferation of the HeLa cells. Its apoptotic effect was confirmed via modulating <i>PTEN/p53</i>/<i>Akt</i> gene expression and activation of the caspase-3 mediated apoptosis pathway. Therefore, <i>L. fermentum</i> Ab.RS22 can be considered a valuable anticancer candidate against cervical cancer progression in subsequent studies.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10897561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139990055","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":"<i>In vitro</i> pro-apoptotic and anti-metastatic potentials of harmaline-silver containing folate-linked chitosan nano-drug delivery system.","authors":"Ali Hussein Wannas Al-Harmooshee, Masoud Homayouni Tabrizi, Nasim Hayati Roodbari","doi":"10.22038/IJBMS.2023.71731.15602","DOIUrl":"10.22038/IJBMS.2023.71731.15602","url":null,"abstract":"<p><strong>Objectives: </strong>Harmaline and green-synthesized silver nanoparticles were encapsulated by folate-linked chitosan molecules as a receptor-mediated drug delivery system to evaluate its pro-apoptotic and anti-metastatic potentials on human ovarian (A2780) and epithelioid (PANC) cancer cells.</p><p><strong>Materials and methods: </strong>The Ag nanoparticles (AgNP) were synthesized utilizing an herbal bio-platform (Bistorta officinalis) and embedded with harmalin. The Harmaline-ag containing folate-linked chitosan nanoparticles (HA-fCNP) were synthesized utilizing the ionic gelation method. Both the AgNP and HA-fCNP nanoparticles were characterized by DLS, FESEM, and Zeta potential analysis. Moreover, the chemical properties of HA-fCNP and the crystallinity of AgNPs were determined by applying FTIR and XRD methods, respectively. The HA-fCNP cytotoxicity was analyzed on A2780, PANC, and HFF cell lines. Moreover, pro-apoptotic and anti-metastatic potentials of HA-fCNP were studied by analyzing the BAX-BCL2 and MMP2-MMP9 gene expression profiles, respectively. The A2780 cellular death was determined by AO/PI and flow cytometry methods.</p><p><strong>Results: </strong>The HA-fCNP significantly exhibited a selective cytotoxic impact on A2780 and PANC cancerous cell lines compared with normal human foreskin fibroblast (HFF) cells. The increased SubG1-arrested A2780 cells and up-regulated BAX gene expression following the increased treatment concentrations of hA-fCNP indicated its selective pro-apoptotic activity on A2780 cells. Also, the notable down-regulated expressions of MMP2 and MMP9 metastatic genes following the increasing doses of HA-fCNP treatment on A2780 cells confirmed its anti-metastatic activity.</p><p><strong>Conclusion: </strong>The cancer-selective cytotoxicity, apoptotic, and anti-metastatic properties of HA-fCNP are considered the appropriate properties of an anticancer compound.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10790289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139485568","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":"Fabrication and evaluation of the regenerative effect of a polycaprolactone/chitosan nanofibrous scaffold containing bentonite nanoparticles in a rat model of deep second-degree burn injury.","authors":"Seyedeh-Sara Hashemi, Ali-Akbar Mohammadi, Mehdi Kian, Alireza Rafati, Mojtaba Ghaedi, Behzad Ghafari","doi":"10.22038/IJBMS.2023.69930.15210","DOIUrl":"10.22038/IJBMS.2023.69930.15210","url":null,"abstract":"<p><strong>Objectives: </strong>In the present study, we evaluated the effect of a nanofibrous scaffold including polycaprolactone (PCL), chitosan (CHT), and bentonite nanoparticles (Ben-NPS) on wound healing in order to introduce a novel dressing for burn wounds.</p><p><strong>Materials and methods: </strong>PCL, PCL/CHT, and PCL/CHT/Ben-NPS nanofibrous scaffolds were fabricated by the electrospinning technique. Their structural and physiochemical characteristics were investigated by Fourier-transform infrared spectroscopy (FTIR) analysis, scanning electron microscopy (SEM), tensile strength, water contact angle, as well as, swelling and degradation profiles test. The disc diffusion assay was carried out to investigate the antibacterial potential of the scaffolds. In addition, the cell viability and proliferation ability of human dermal fibroblasts (HDFs) on the scaffolds were assessed using MTT assay as well as SEM imaging. The wound-healing property of the nanofibrous scaffolds was evaluated by histopathological investigations during 3,7, and 14 days in a rat model of burn wounds.</p><p><strong>Results: </strong>SEM showed that all scaffolds had three-dimensional, beadles-integrated structures. Adding Ben-NPS into the PCL/CHT polymeric composite significantly enhanced the mechanical, swelling, and antibacterial properties. HDFs had the most cell viability and proliferation values on the PCL/CHT/Ben-NPS scaffold. Histopathological evaluation in the rat model revealed that dressing animal wounds with the PCL/CHT/Ben-NPS scaffold promotes wound healing.</p><p><strong>Conclusion: </strong>The PCL/CHT/Ben-NPS scaffold has promising regenerative properties for accelerating skin wound healing.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10790295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139485589","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":"Effect of thymoquinone on transient receptor potential melastatin (TRPM) channels in rats with liver ischemia reperfusion model in rats.","authors":"Kerem Caglar, Recep Dokuyucu, Gokhan Agturk, Cemil Tumer, Okan Tutuk, Hatice Dogan Gocmen, Hasan Gokce, Zeynel Abidin Tas, Oguzhan Ozcan, Bulent Gogebakan","doi":"10.22038/IJBMS.2023.71990.15647","DOIUrl":"10.22038/IJBMS.2023.71990.15647","url":null,"abstract":"<p><strong>Objectives: </strong>We aimed to investigate the levels of transient receptor potential melastatin (TRPM) gene expression, and the antioxidant and histopathologic effect of thymoquinone (Tmq) in the hepatic I/R rat model.</p><p><strong>Materials and methods: </strong>Fifty Wistar rats were divided into 5 groups. Group 1: Control; Group 2: Sham; Group 3: Hepatic I/R (45 min/45 min); Group 4: Tmq (50 mg/kg); Group 5: Tmq+I/R (ten days before I/R at the dose of 50 mg/kg of Tmq). The hepatic I/R (45min/45min) model was performed at the portal vein and the hepatic artery with atraumatic vascular clamp in the ischemia groups. The liver tissues and blood samples that were taken at the end of the study were evaluated for histopathologic and biochemical analysis. Besides <i>TRPM</i> gene expression levels were determined in liver tissues. It was seen that cellular swelling, congestion, PNL, and apoptosis parameters statistically decreased in Tmq and Tmq+I/R groups in comparison with the I/R group in histopathological evaluation.</p><p><strong>Results: </strong>It was observed that biochemical parameters, AST, ALT, GGT, LDH, creatinine, and urea levels significantly increased in the I/R group as compared with, sham, Tmq, and Tmq+I/R groups. It was found that <i>TRPM2,6,7,8</i> gene expression decreased significantly in Tmq+I/R groups as compared to the I/R group.</p><p><strong>Conclusion: </strong>We showed that thymoquinone can inhibit the entry of Ca+2 into the cell by decreasing <i>TRPM2,6,7,8</i> gene expression. Based on our findings, we think that Tmq application in the treatment of liver diseases due to I/R damage may be important in terms of both ischemia and apoptosis and can also be used in the treatment of liver-related diseases.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10849204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139706771","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":"Alpha-pinene alleviates CCl₄-induced renal and testicular injury in rats by targeting oxidative stress, inflammation, and apoptosis.","authors":"Fatemeh Noroozi, Masoumeh Asle-Rousta, Rahim Amini, Zeinab Sahraeian","doi":"10.22038/IJBMS.2024.73116.15890","DOIUrl":"https://doi.org/10.22038/IJBMS.2024.73116.15890","url":null,"abstract":"<p><strong>Objectives: </strong>Renal and testicular disorders are primarily associated with oxidative damage and inflammation. Here, alpha-pinene (a type of monoterpene) was investigated for its effect on oxidative/nitrosative stress and the expression of inflammatory and apoptotic factors in the kidneys and testes of rats treated with CCl₄.</p><p><strong>Materials and methods: </strong>CCl₄ was injected intraperitoneally (IP) at a dose of 2 ml/kg (twice a week for six weeks). Alpha-pinene (50 mg/kg/day, IP) was also treated during the same period.</p><p><strong>Results: </strong>CCl₄ increased the level of malondialdehyde (<i>P</i><0.01 in the kidney and <i>P</i><0.001 in the testis) and nitric oxide (<i>P</i><0.001 in the kidney and <i>P</i><0.01 in the testis) and decreased the levels of glutathione (<i>P</i><0.05) in the kidneys and testicles of rats. CCl₄ also reduced the catalase enzyme activity in the kidneys (<i>P</i><0.05) but did not affect its activity in the testis. In addition, CCl₄ enhanced the mRNA expression of TNF-α (<i>P</i><0.01), nuclear factor-κB (P<0.05), and Bax (<i>P</i><0.05 in the kidney and <i>P</i><0.01 in the testis) and decreased the expression of Bcl-2 (<i>P</i><0.05) in both organs. Alpha-pinene prevented all the mentioned changes, but it did not influence the expression of Bcl-2 in the kidneys of rats receiving CCl₄.</p><p><strong>Conclusion: </strong>Alpha-pinene may have the potential to prevent renal and testicular diseases by strengthening the antioxidant system in the kidneys and testis, and inhibiting oxidative/nitrosative stress, inflammation, and apoptosis caused by CCl₄.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11024401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140857366","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":"Assessment of the neuroprotective effect of green synthesized iron oxide nanoparticles capped with curcumin against a rat model of Parkinson's disease.","authors":"Yasser Ashry Khadrawy, Eman Nasr Hosny, Haitham Sharf Eldein Mohamed","doi":"10.22038/IJBMS.2023.73124.15892","DOIUrl":"10.22038/IJBMS.2023.73124.15892","url":null,"abstract":"<p><strong>Objectives: </strong>The current study aims to investigate the protective effect of iron oxide nanoparticles capped with curcumin (FeONPs-Cur) against motor impairment and neurochemical changes in a rat model of Parkinson's disease (PD) induced by reserpine.</p><p><strong>Materials and methods: </strong>Rats were grouped into control, PD model induced by reserpine, and PD model treated with FeONPs-Cur (8 rats/group). The open field test was used to assess motor activity. The concentration of dopamine (DA), norepinephrine (NE), serotonin (5-HT), lipid peroxidation (MDA), reduced glutathione (GSH), and nitric oxide (NO), and the activities of Na⁺,K⁺,ATPase, acetylcholinesterase (AchE), and monoamine oxidase (MAO) were determined in the midbrain and striatum. Data were analyzed by ANOVA at <i>P</i>-value<0.05.</p><p><strong>Results: </strong>The PD model exhibited a decrease in motor activity. In the midbrain and striatum of the PD model, DA, NE, and 5-HT levels decreased significantly (<i>P</i>-value<0.05). However, an increase in MAO, NO, and MDA was observed. GSH, AchE and Na⁺,K⁺,ATPase decreased significantly in the two brain areas. FeONPs-Cur prevented the decline of dopamine and norepinephrine and reduced oxidative stress in both areas. It also prevented the increased MAO activity in the two areas and the inhibited activity of AchE and Na⁺,K⁺,ATPase in the midbrain. These changes were associated with improvements in motor activity.</p><p><strong>Conclusion: </strong>The present data indicate that FeONPs-Cur could prevent the motor deficits induced in the PD rat model by restoring dopamine and norepinephrine in the midbrain and striatum. The antioxidant activity of FeONPs-Cur contributed to its protective effect. These effects nominate FeONPs-Cur as an antiparkinsonian candidate.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10722487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139074065","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":"Evaluation of the influence of N-acetylcysteine and broccoli extract on systemic paraquat poisoning: Implications for biochemical, physiological, and histopathological parameters in rats.","authors":"Mahdieh Raeeszadeh, Sara Arvand, Danial Shojaee Moghadam, Loghman Akradi","doi":"10.22038/IJBMS.2024.75258.16311","DOIUrl":"10.22038/IJBMS.2024.75258.16311","url":null,"abstract":"<p><strong>Objectives: </strong>Paraquat (PQ), a potent environmental herbicide, is recognized for inducing irreparable toxic damage to biological systems. This study aimed to evaluate the effectiveness of N-acetylcysteine (NAC) and broccoli extract, individually and in combination, in alleviating PQ poisoning in rats, leveraging the exceptional anti-oxidant, anti-inflammatory, and anti-apoptotic properties of broccoli.</p><p><strong>Materials and methods: </strong>Seventy Wistar rats were categorized into seven groups: C (control, vehicle), PQ (paraquat at 40 mg/kg), BC (broccoli extract at 300 mg/kg), NC (N-acetylcysteine at the same dose of 300 mg/kg), and combined groups PQ+BC, PQ+NC, and NC+PQ+BC, all administered equivalent doses. After 42 days, blood samples were collected to evaluate liver and kidney parameters, proinflammatory biomarkers, caspase-3, and caspase-9. Lung tissues were excised, with one part preserved for hydroxyproline and oxidative stress parameter measurement and another sectioned and stained for histopathological analysis.</p><p><strong>Results: </strong>The PQ group exhibited the highest lung-to-body weight (LW/BW) ratio, while the PQ+BC+NC group demonstrated the lowest ratio. Results indicated an elevated lung hydroxyproline concentration and a significant reduction in anti-oxidant enzymes (catalase, glutathione peroxidase, superoxide dismutase, and total anti-oxidant capacity) (<i>P</i><0.001). The PQ+BC group showed modified malondialdehyde levels, reaching a peak in the PQ group. Additionally, a significant decrease in tumor necrosis factor, interleukin-1, caspase-3, and caspase-9 was observed in the PQ+BC+NC group (<i>P</i><0.01). Pulmonary edema, hyperemia, and severe hemorrhage observed in the PQ group were notably reduced in the PQ+BC+NC group.</p><p><strong>Conclusion: </strong>The combination of active compounds from broccoli and NAC demonstrated significant systemic and pulmonary effects in mitigating PQ-induced toxicity.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141154065","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":"Autophagy inhibitor 3-methyladenine attenuates renal injury in streptozotocin-induced diabetic mice.","authors":"Haiwen Ren, Mengxin Huang, Liwen Ou, Xuan Deng, Xin Wu, Quan Gong, Benju Liu","doi":"10.22038/IJBMS.2024.71378.15518","DOIUrl":"10.22038/IJBMS.2024.71378.15518","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate whether 3-methyladenine (3-MA) can protect the kidney of streptozotocin (STZ) - induced diabetes mice, and explore its possible mechanism.</p><p><strong>Materials and methods: </strong>STZ was used to induce diabetes in C57BL/6J mice. The mice were divided into normal control group (NC), diabetes group (DM), and diabetes+3-MA intervention group (DM+3-MA). Blood glucose, water consumption, and body weight were recorded weekly. At the end of the 6th week of drug treatment, 24-hour urine was collected. Blood and kidneys were collected for PAS staining to evaluate the degree of renal injury. Sirius red staining was used to assess collagen deposition. Blood urea nitrogen (BUN), serum creatinine, and 24-hour urine albumin were used to evaluate renal function. Western blot was used to detect fibrosis-related protein, inflammatory mediators, high mobility group box 1 (HMGB1)/NF-κB signal pathway molecule, vascular endothelial growth factor (VEGF), and podocin, and immunohistochemistry (IHC) was used to detect the expression and localization of autophagy-related protein and fibronectin.</p><p><strong>Results: </strong>Compared with the kidney of normal control mice, the kidney of diabetes control mice was more pale and hypertrophic. Hyperglycemia induces renal autophagy and activates the HMGB1/NF-κB signal pathway, leading to the increase of inflammatory mediators, extracellular matrix (ECM) deposition, and proteinuria in the kidney. In diabetic mice treated with 3-MA, blood glucose decreased, autophagy and HMGB1/NF-κB signaling pathways in the kidneys were inhibited, and proteinuria, renal hypertrophy, inflammation, and fibrosis were improved.</p><p><strong>Conclusion: </strong>3-MA can attenuate renal injury in STZ-induced diabetic mice through inhibition of autophagy and HMGB1/NF-κB signaling pathway.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141155285","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":"N-acetylcysteine protects septic acute kidney injury by inhibiting SIRT3-mediated mitochondrial dysfunction and apoptosis.","authors":"Heng Fan, Jian-Wei Le, Min Sun, Jian-Hua Zhu","doi":"10.22038/IJBMS.2024.72882.15853","DOIUrl":"10.22038/IJBMS.2024.72882.15853","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the protective effect of N-acetylcysteine (NAC) on septic acute kidney injury (SAKI) via regulating Sirtuin3 (SIRT3)-mediated mitochondrial dysfunction and apoptosis.</p><p><strong>Materials and methods: </strong>By constructing SIRT3 knockout mice and culturing kidney tubular epithelial cells (KTECs), we assessed the changes of renal function and detected the protein expression of adenine nucleotide translocator (ANT), cyclophilin (CypD) and voltage-dependent anion channel (VDAC) using western-blotting, and simultaneously detected toll-like receptor 4 (TLR4), inhibitor of kappa B kinase (IKKβ), inhibitor of Kappa Bα (IκBα), and p65 protein expression. We observed mitochondrial damage of KTECs using a transmission electron microscope and assessed apoptosis by TdT-mediated dUTP Nick-End Labeling and flow cytometry.</p><p><strong>Results: </strong>SIRT3 deficiency led to the deterioration of renal function, and caused a significant increase in inducible nitric oxide synthase production, a decrease in mitochondrial volume, up-regulation of TLR4, IκBα, IKKβ, and p65 proteins, and up-regulation of ANT, CypD and VDAC proteins. However, NAC significantly improved renal function and down-regulated the expression of TLR4, IκBα, IKKβ, and p65 proteins. Furthermore, SIRT3 deficiency led to a significant increase in KTEC apoptosis, while NAC up-regulated the expression of SIRT3 and inhibited apoptosis.</p><p><strong>Conclusion: </strong>NAC has a significant protective effect on SAKI by inhibiting SIRT3-mediated mitochondrial dysfunction and apoptosis of KTECs.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11127075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141154157","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}