Negin Masoomabadi, Ali Gorji, Tahereh Ghadiri, Safieh Ebrahimi
{"title":"Regulatory role of circular RNAs in the development of therapeutic resistance in the glioma: A double-edged sword.","authors":"Negin Masoomabadi, Ali Gorji, Tahereh Ghadiri, Safieh Ebrahimi","doi":"10.22038/ijbms.2024.81644.17669","DOIUrl":"10.22038/ijbms.2024.81644.17669","url":null,"abstract":"<p><p>Gliomas are the most common lethal tumors of the brain associated with a poor prognosis and increased resistance to chemo-radiotherapy. Circular RNAs (circRNAs), newly identified noncoding RNAs, have appeared as critical regulators of therapeutic resistance among multiple cancers and gliomas. Since circRNAs are aberrantly expressed in glioma and may act as promoters or inhibitors of therapeutic resistance, we categorized alterations of these specific RNAs expression in therapy resistant-glioma in three different classes, including chemoresistance, radioresistance, and glioma stem cell (GSC)-regulation. circRNAs act as competing endogenous RNA, sponging target microRNA and consequently affecting the expression of genes related to glioma tumorigenesis and resistance. By doing so, circRNAs can modulate the critical cellular pathways and processes regulating glioma resistance, including DNA repair pathways, GSC, epithelial-mesenchymal transition, apoptosis, and autophagy. Considering the poor survival and increased resistance to currently approved treatments for glioma, it is crucial to increase the knowledge of the resistance regulatory effects of circRNAs and their underlying molecular mechanisms. Herein, we conducted a comprehensive search and discussed the existing knowledge regarding the important role eof circRNAs in the emergence of resistance to therapeutic interventions in glioma. This knowledge may serve as a basis for enhancing the effectiveness of glioma therapeutic strategies.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 1","pages":"3-15"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059076","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}
Doha Abdou Mohamed, Rasha Salah Mohamed, Karem Fouda, Hoda Bakr Mabrok
{"title":"Dietary supplements for prevention of Alzheimer's disease: <i>In vivo</i> and <i>in silico</i> molecular docking studies.","authors":"Doha Abdou Mohamed, Rasha Salah Mohamed, Karem Fouda, Hoda Bakr Mabrok","doi":"10.22038/ijbms.2024.79960.17320","DOIUrl":"10.22038/ijbms.2024.79960.17320","url":null,"abstract":"<p><strong>Objectives: </strong>Alzheimer's disease (AD) is one of the most common neurodegenerative diseases in people over 65. The present research aimed to investigate the potential of different dietary supplements (DS) in preventing AD in an experimental animal model and <i>in silico</i> study.</p><p><strong>Materials and methods: </strong>Three DS containing a mixture of wheat-germ oil and black pepper extract/or turmeric extract were prepared. Total phenolic content, HPLC-phenolic profile, phytosterols content, fatty-acids profile, and anti-oxidant activity were evaluated in all DS. The protective effect of the prepared DS was assessed through their impact on cholinergic neurotransmission and the gene expression of GSK3β, APP, and Akt. Oxidative stress and inflammatory markers were evaluated. The inhibition activities against acetylcholinesterase (AChE) and reduction of amyloid-β aggregation of the major phytochemicals present in the studied DS were evaluated using <i>in silico</i> molecular docking study.</p><p><strong>Results: </strong>Molecular docking revealed that rosmarinic acid and β-Sitosterol exhibited the strongest binding affinities for AChE and Amyloid-β, respectively. The results showed that all DS reduced cholinergic neurotransmission, decreased TNF-α as an inflammatory marker, and improved oxidative stress status. All DS down-regulated the expression of GSK3β and APP while significantly up-regulating the expression of the Akt gene.</p><p><strong>Conclusion: </strong>The present study concluded that all DS enhanced cholinergic neurotransmission, reduced inflammation, and improved oxidative stress status by impacting the expression of GSK3β, Akt, and APP genes. Rosmarinic acid and β-sitosterol showed promising effects for treating AD, according to an <i>in silico</i> molecular docking study. The studied dietary supplements were considered promising candidates for the prevention of AD.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 2","pages":"170-180"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756737/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028804","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":"Scopolamine-induced memory impairment in mice: Soursop leaf extract and fractions protect the hippocampus and prefrontal cortex.","authors":"Faith Afolabi, Babatunde Adebola Alabi, Joseph Ayo Badejo, Okim Okim Nsor, Sodiq Kolawole Lawal, Ezekiel Olugbenga Iwalewa","doi":"10.22038/ijbms.2024.80289.17379","DOIUrl":"10.22038/ijbms.2024.80289.17379","url":null,"abstract":"<p><strong>Objectives: </strong><i>Annona muricata</i>\" (soursop) is a medicinal plant with diverse ornamental, consumptive, and pharmacological importance. This study was designed for its anti-amnesic potential in mice.</p><p><strong>Materials and methods: </strong>The crude extract was fractionated with n-hexane, ethyl acetate, and aqueous methanol. The crude and fractions were tested <i>in vitro</i> for the anti-oxidant radical scavenging activity (DPPH), total flavonoid and phenolic content, and their acetylcholinesterase inhibitory activity. Thin-layer chromatography was used to determine the phytochemicals contained in the fractions and their purity. Neurobehavioral models like the Open Field Test, Novel Object Recognition Test, Y-Maze, and Morris Water Maze were used to evaluate the action of AMME (<i>Annona muricata</i> methanol extract) and AMAMF (<i>Annona muricata</i> aqueous methanol fraction).</p><p><strong>Results: </strong>The AMME and AMAMF significantly reduced the serum levels of myeloperoxidase and arginine (<i>P</i><0.05). They also modulate the hippocampal and prefrontal acetylcholinesterase and glutamic acid decarboxylase activities (<i>P</i><0.05). The 25 mg/kg AMAMF significantly affected short-term memory (<i>P</i><0.05). The AMAMF and AMME significantly enhanced the prefrontal and hippocampal tissue levels of glutathione and superoxide dismutase. During the <i>in vitro</i> AchE assay on all fractions, the AMME and AMAMF consistently showed the greatest percentage of inhibitory activity. They inhibited 50% of the AchE enzymes with the lowest concentration.</p><p><strong>Conclusion: </strong>The study showed the neuroprotective effects of AMME and AMAMF in memory impairment models. The extracts showed potent AChE inhibition and positive effects on memory and anti-oxidant enzyme levels.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 3","pages":"355-365"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189091","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}
Leila Arabi, Ali Roohbakhsh, Bizhan Malaekeh-Nikouei, Bibi Sedigheh Fazly Bazzaz
{"title":"The impact of artificial intelligence (AI) in academic writing and publication: Iranian Journal of Basic Medical Sciences (IJBMS) policy.","authors":"Leila Arabi, Ali Roohbakhsh, Bizhan Malaekeh-Nikouei, Bibi Sedigheh Fazly Bazzaz","doi":"10.22038/ijbms.2025.25229","DOIUrl":"10.22038/ijbms.2025.25229","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to determine the effect of 8-week high-intensity interval training (HIIT) on oxidative stress and apoptosis in the hippocampus of male rats with type 2 diabetes (T2D). The study focused on examining the role of proliferator-activated receptor gamma co-activator 1α (PGC1α)/Kelch-like ECH-associated protein Keap1/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway.</p><p><strong>Materials and methods: </strong>Twenty-eight 8-week-old Wistar rats were randomly assigned to one of four groups (n=7): control (Con), type 2 diabetes (T2D), exercise (Ex), and exercise + type 2 diabetes (Ex+T2D). The Ex and Ex+T2D groups completed an 8-week exercise program consisting of 80-100% Vmax and 4-10 intervals. The homeostasis model assessment of insulin resistance (HOMA-IR) index was used to assess insulin resistance. The levels of Bcl2, BAX, musculoaponeurotic fibrosarcoma (Maf), Nrf2, Keap1, and PGC1α in the hippocampus were assessed using the western blot method. Additionally, the levels of antioxidant enzymes in the hippocampus were measured using ELISA.</p><p><strong>Results: </strong>The findings indicated that the T2D group had lower levels of antioxidant enzymes, Maf, Bcl2, PGC1α, and Nrf2, and higher levels of BAX and Keap1 in the hippocampus. Conversely, the HIIT group exhibited increased levels of antioxidant enzymes, Maf, Bcl2, Nrf2, and PGC1α, along with decreased levels of BAX and Keap1 in the hippocampus.</p><p><strong>Conclusion: </strong>The study demonstrated that 8-week HIIT was effective in reducing hippocampal apoptosis and oxidative stress induced by T2D by activating the PGC1α-Keap1-Nrf2 signaling pathway. The metabolic changes induced by exercise may lead to an increase in PGC1 expression, which is the primary stimulator of the Keap1-Nrf2 signaling pathway.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 1","pages":"1-2"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059079","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}
Xiao-Ping Jin, Yi-Fei Ren, Li-Guo Wang, Hao Xie, Lu Huang, Juan Zhang, Zuo-Ying Hu
{"title":"Pim3 up-regulation by YY1 contributes to diabetes-induced cardiac hypertrophy and heart failure.","authors":"Xiao-Ping Jin, Yi-Fei Ren, Li-Guo Wang, Hao Xie, Lu Huang, Juan Zhang, Zuo-Ying Hu","doi":"10.22038/ijbms.2024.78688.17016","DOIUrl":"10.22038/ijbms.2024.78688.17016","url":null,"abstract":"<p><strong>Objectives: </strong>The close relationship of proto-oncogenes to myocardial hypertrophy has long been recognized, and cardiac hypertrophy leads to heart failure (HF). However, whether proviral insertion of Moloney virus 3 kinase (Pim3), a proto-oncogene, contributes to cardiac hypertrophy in diabetes mellitus (DM) remains unknown. This study aims to investigate whether Pim3 is involved in DM-induced cardiac hypertrophy and HF and to elucidate its underlying mechanisms.</p><p><strong>Materials and methods: </strong>DM was induced in mice by intraperitoneal injection of streptozotocin. Cardiac function was evaluated by echocardiography, and cardiac hypertrophy was determined through histological analysis, quantitative real-time polymerase chain reaction, and western blotting. Silencing RNA transfection and lentivirus-mediated gene knockdown were performed both in vitro and in vivo. Transcriptional activity was analyzed using chromatin immunoprecipitation and luciferase reporter assay.</p><p><strong>Results: </strong>Compared with C57BL/6J mice, cardiac hypertrophy and dysfunction were observed in mice with DM. Pim3 mRNA and protein expression were significantly up-regulated in diabetic hearts and high glucose-cultured H9C2 cells. Yin Yang 1 (YY1), which translocated from the cytoplasm into the nucleus under hyperglycemia, bound to the Pim3 promoter and enhanced Pim3 transcriptional activity. Pim3 or YY1 knockdown profoundly reduced cell size and inhibited the mRNA and protein expression of cardiac hypertrophy markers, as well as markedly attenuating myocardial hypertrophy and cardiac dysfunction.</p><p><strong>Conclusion: </strong>Hyperglycemia induced nuclear translocation of YY1, leading to Pim3 up-regulation, eventually developing into cardiac hypertrophy and HF. Targeting YY1-Pim3 signaling may be a promising therapeutic avenue for DM-induced cardiac hypertrophy and HF.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 2","pages":"245-253"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028257","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}
Somayyeh Rahmani, Ebrahim Najdegerami, Mazdak Razi, Mehdi Nikoo
{"title":"Potential therapeutic effects of shrimp protein hydrolysates on NAFLD-induced infertility disorders: Insights into redox balance, heat shock protein expression, and chromatin compaction in male rats.","authors":"Somayyeh Rahmani, Ebrahim Najdegerami, Mazdak Razi, Mehdi Nikoo","doi":"10.22038/ijbms.2024.76649.16589","DOIUrl":"10.22038/ijbms.2024.76649.16589","url":null,"abstract":"<p><strong>Objectives: </strong>Nonalcoholic fatty liver disease (NAFLD) is known to disrupt testicular anti-oxidant capacity, leading to oxidative stress (OS) that can negatively affect male fertility by damaging sperm DNA. Heat shock proteins (HSP70 and HSP90), in association with transitional proteins (TP1 and TP2), play crucial roles in protecting sperm DNA integrity in oxidative conditions. Whiteleg shrimp protein hydrolysates (HPs) exhibit anti-oxidant properties, prompting this study to explore the potential of HPs in ameliorating NAFLD-induced testicular damage.</p><p><strong>Materials and methods: </strong>The study divided rats into four groups: control, a group subjected to a high-fat diet (HFD) to induce NAFLD without supplementation, and two HFD-induced NAFLD groups receiving HP doses (20 and 300 mg/kg). After 70 days, the testicular total anti-oxidant capacity (TAC), malondialdehyde (MDA), glutathione (GSH), glutathione disulfide (GSSG), HSP70-2a, HSP90 expression, and TP mRNA levels were assessed.</p><p><strong>Results: </strong>The results showed that HFD-induced NAFLD significantly increased GSH and MDA levels and disrupted the GSH/GSSG ratio (<i>P</i><0.05) while also reducing HSP70-2a, HSP90, TP1, and TP2 expression (<i>P</i><0.05). However, HP administration effectively restored testicular redox balance, reduced oxidative stress, and enhanced these protective proteins' expression compared to HFD (<i>P</i><0.05).</p><p><strong>Conclusion: </strong>NAFLD negatively affects the testicular redox system and HSP and TP expression, disrupting male fertility potential. In contrast, HP-treated rats showed a marked effect on NAFLD-induced damage by improving testicular anti-oxidant status and regulating the expression of HSPs and TP proteins. These findings suggest a potential therapeutic role for HP in safeguarding male fertility against the damaging effects of NAFLD.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 2","pages":"158-169"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028401","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}
Majid Keshavarzi, Bibi Marjan Razavi, Hossein Hosseinzadeh
{"title":"Trans-sodium crocetinate ameliorates Parkinson-like disease caused by bisphenol A through inhibition of apoptosis and reduction of α-synuclein in rats.","authors":"Majid Keshavarzi, Bibi Marjan Razavi, Hossein Hosseinzadeh","doi":"10.22038/ijbms.2024.81157.17567","DOIUrl":"10.22038/ijbms.2024.81157.17567","url":null,"abstract":"<p><strong>Objectives: </strong>Trans-sodium crocetinate (TSC) is one of the crocetin derivations that is more soluble and stable than crocetin and its cis form. It easily crosses the blood-brain barrier. TSC has neuroprotective effects. Bisphenol A (BPA) is an endocrine-mimicking compound that induces Parkinson-like disease by impacting the dopaminergic system. In this research, the effects of TSCs on BPA-induced Parkinson-like symptoms via behavioral and molecular assays have been investigated.</p><p><strong>Materials and methods: </strong>Male Wistar rats received BPA (75 mg/kg, gavage), TSC (10, 20, and 40 mg/kg), and levodopa (L-dopa) (10 mg/kg) via intraperitoneal injection (IP) for 28 days. Parkinsonian-like motor features were evaluated using bar test, rotarod, and open field experiments. Malondialdehyde (MDA) and glutathione (GSH) levels were also measured as the most important indicators of oxidative stress. Western blotting was performed for the molecular assays of alpha-synuclein (α-syn), Bcl-2, Bax, caspase-3, Beclin, and LC3 I/II proteins.</p><p><strong>Results: </strong>Our analyses indicated that treatment with TSC at high dose reduces MDA levels and protects GSH reserves. TSC can also increase anti-apoptotic Bcl-2 and decrease pro-apoptotic Bax and caspase-3 proteins. While it does not affect autophagy markers, TSC decreased α-syn protein expression, reduced the catalepsy time, and improved the time spent staying on the rotating bar and the locomotor activity.</p><p><strong>Conclusion: </strong>Overall, TSC likely ameliorates BPA-mediated Parkinson' s-like symptoms by suppressing oxidative stress inhibition. This leads to reduced α-syn expression, which ultimately results in apoptosis inductions. Therefore, TSC can serve as a promising exploratory target for future research aimed at controlling Parkinson's disease.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 2","pages":"254-263"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028783","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":"Enhancing dermal collagen density towards youthfulness: A comparative study of PCL, PLLA, and PDO thread implantation in aging rats model.","authors":"Mary Soen, Meilinah Hidayat, Wahyu Widowati","doi":"10.22038/ijbms.2024.80494.17428","DOIUrl":"10.22038/ijbms.2024.80494.17428","url":null,"abstract":"<p><strong>Objectives: </strong>Both intrinsic and extrinsic factors cause skin aging. Intrinsic aging is characterized by decreased collagen density, particularly collagen types I (COL1A1) and III (COL3A1), and an increase in the COL1/COL3 ratio. Extrinsic aging, primarily due to ultraviolet light exposure, leads to photoaging, which causes collagen fragmentation and reduced production, leading to skin sagging. Thread lifts, a nonsurgical method, aim to tighten the skin and stimulate collagen production using biodegradable monofilament threads such as polydioxanone (PDO), poly-lactic acid (PLLA), and polycaprolactone (PCL). This study compared the effectiveness of PDO, PLLA, and PCL threads in reversing aging by enhancing dermal collagen, reducing the COL1/COL3 ratio, and increasing COL3A1 gene expression in UVB-exposed aging model rats.</p><p><strong>Materials and methods: </strong>Thirty female Wistar (<i>Rattus norvegicus</i>) rats were divided into six groups, and their back hair was shaved and exposed to 840 mJ/m<sup>2</sup> UVB for 4 weeks. Skin biopsy specimens were assessed using Sirius Red staining to determine dermal collagen density and the COL1/COL3 ratio. Furthermore, qRT-PCR was used to examine COL3A1 gene expression.</p><p><strong>Results: </strong>PDO, PLLA, and PCL threads enhanced skin quality, similar to the young negative control group, based on parameters such as dermal collagen density, COL1/COL3 ratio, and COL3A1 gene expression. PCL thread was more active than PDO and PLLA.</p><p><strong>Conclusion: </strong>Thread implantation may result in a more youthful collagen profile than negative control and may be used to support skin anti-aging. The most effective thread was PCL compared to PDO and PLLA.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 2","pages":"151-157"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028793","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}
Ameneh Mohammadi, Pedram Ebrahimnejad, Said Abediankenari, Zahra Kashi, Pooria Gill
{"title":"Nanomolecular silencing of TSC22D4 mRNA via a DNAsome-siRNA for enhancing insulin sensitization in hepatocytes.","authors":"Ameneh Mohammadi, Pedram Ebrahimnejad, Said Abediankenari, Zahra Kashi, Pooria Gill","doi":"10.22038/ijbms.2024.81998.17744","DOIUrl":"10.22038/ijbms.2024.81998.17744","url":null,"abstract":"<p><strong>Objectives: </strong>Insulin resistance (IR) is a critical component of metabolic syndrome, primarily linked to obesity. It contributes to impaired glucose metabolism, beta-cell dysfunction, and the onset of type 2 diabetes. This study aimed to develop a DNAsome nanocarrier designed for the targeted delivery of small interfering RNA (siRNA) to inhibit mRNA of Transforming growth factor beta-like Stimulated Clone 22 D4 (TSC22D4), thereby enhancing insulin sensitivity in hepatocytes.</p><p><strong>Materials and methods: </strong>The DNAsome was constructed using Y-DNA building blocks derived from three distinct DNA oligonucleotides. Its structural characteristics were analyzed through atomic force microscopy (AFM). The functional efficacy of the DNAsome in delivering siRNA was evaluated by measuring its cellular uptake and ability to down-regulate TSC22D4 expression in HepG2 cells via real-time PCR. Additionally, the cytotoxicity and safety of both the DNAsome and the DNAsome-siRNA complexes were assessed using the MTT assay on HepG2 cells.</p><p><strong>Results: </strong>Findings indicated successful fabrication of the DNAsome nanocarriers, although aggregation was observed at higher concentrations, yielding nanoparticle sizes between 116 and 740 nm. Real-time PCR results confirmed effective siRNA targeting, significant cellular uptake of the nanocomplexes, and successful silencing of TSC22D4 expression.</p><p><strong>Conclusion: </strong>This study suggests that DNAsome-based siRNA delivery systems hold promise for improving insulin sensitivity and addressing IR associated with obesity and metabolic syndrome.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 3","pages":"385-392"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189059","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":"Ellagic acid alleviates NLRP6/caspase-1/GSDMD-mediated inflammation and pyroptosis in rats post cerebral ischemia/reperfusion injury.","authors":"Ling Hu, Xiaoqiong Wei, Guofu Shen, Xiaohuan Huang","doi":"10.22038/ijbms.2024.78864.17057","DOIUrl":"10.22038/ijbms.2024.78864.17057","url":null,"abstract":"<p><strong>Objectives: </strong>Ellagic acid (EA) is a natural polyphenol with anti-cancer, anti-oxidant, anti-inflammatory, antibacterial, and other effects. However, the role of EA in cerebral ischemia/reperfusion injury (CIRI) remains unclear. This study aims to investigate the neuroprotective effects of EA in CIRI.</p><p><strong>Materials and methods: </strong>Forty male Wistar rats (260-300 g) were randomly divided into four groups with 10 rats per group: 1) Sham+Veh: Rats underwent I/R surgery, except that they were not inserted with thread plugs, and received solute treatment at the same time. 2) MCAO/R+Veh. 3) MCAO/R+EA: Rats were administered 200 mg/kg EA before undergoing MCAO. 4) MCAO/R+Nim: Rats were administered Nim before undergoing MCAO.</p><p><strong>Results: </strong>Cerebral MCAO/R damaged brain tissue, elevated neurological deficit score (<i>P<</i>0.01), cerebral infarction volume (<i>P<</i>0.01), inflammatory cell infiltration (<i>P<</i>0.01), NLRP6, ASC, caspase-1 and GSDMD mRNA level (<i>P<</i>0.01 and <i>P<</i>0.001), NLRP6, caspase-1, GSDMD-N and IL-1β protein level (<i>P<</i>0.01 and <i>P<</i>0.001), and inflammatory cytokines in brain tissue (<i>P<</i>0.01). Prophylactic administration of EA also significantly improved brain tissue damage, reduced neurological deficit score (<i>P<</i>0.01), cerebral infarction volume (<i>P<</i>0.01), inflammatory cell number (<i>P<</i>0.05), NLRP6, caspase-1, GSDMD-N mRNA and protein level (<i>P<</i>0.05 and <i>P<</i>0.01), ASC mRNA level and IL-1β protein level (<i>P<</i>0.01), and IL-1β and IL-18 level in brain tissue (<i>P<</i>0.01) compared to positive control.</p><p><strong>Conclusion: </strong>EA may serve as a potential drug for the treatment of brain I/R, which may exert an anti-inflammatory effect by inhibiting the activation of the inflammasome.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 1","pages":"105-112"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058959","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}