Iranian Journal of Basic Medical Sciences最新文献

{"title":"Melittin alleviates bleomycin-induced pulmonary fibrosis <i>in vivo</i> through regulating TGF-β1/Smad2/3 and AMPK/SIRT1/PGC-1α signaling pathways.","authors":"Jia-Wang Yu, Wei-Hua Lu","doi":"10.22038/ijbms.2024.81986.17740","DOIUrl":"10.22038/ijbms.2024.81986.17740","url":null,"abstract":"<p><strong>Objectives: </strong>The present study investigated the protective effect of melittin (MEL) against bleomycin (BLM)- induced pulmonary fibrosis (PF) in mice and the mechanism underlying this effect.</p><p><strong>Materials and methods: </strong>A mouse model of PF was established by intratracheal injection of 3.5 mg/kg BLM. Twenty-four hours after the model was established, the mice in the treatment groups were intraperitoneally injected with MEL, and specimens were collected 28 days later. The body weight, survival rate, and pulmonary index (PI) of the mice were determined. Haematoxylin and eosin (HE) staining, Masson's trichrome staining, immunohistochemical staining, kit assays, and Western blot (WB) analysis were performed.</p><p><strong>Results: </strong>Our study indicated that MEL significantly increased the body weight and survival rate, reduced PI, and improved lung histopathology in mice. In addition, MEL inhibited epithelial-mesenchymal transition (EMT) and extracellular matrix (ECM) deposition. Attenuated mitochondrial damage and reduced oxidative stress (OS) were also observed in MEL-treated mice. We further showed that MEL inhibited the TGF-β1/Smad2/3 pathway and activated the AMPK/SIRT1/PGC-1α pathway.</p><p><strong>Conclusion: </strong>MEL is a promising future therapeutic agent for PF. Its multifaceted and complex mechanism of action inhibits both EMT and ECM production by modulating the TGF-β1/Smad2/3 pathway. It also improves mitochondrial function and reduces OS at least partially through the activation of the AMPK/SIRT1/PGC-1α signaling pathway.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 4","pages":"426-433"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11831745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448902","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":"Yavar-70A, a novel water-in-oil adjuvant: A potency study in HPV-16E7d vaccine model.","authors":"Zeinab Mirzaei, Soyar Sari, Masoud Moghaddam Pour, Seyed Mehdi Hassanzadeh, Benjamin Damizadeh, Morteza Taghizadeh, Mehdi Mahdavi","doi":"10.22038/ijbms.2024.81654.17671","DOIUrl":"10.22038/ijbms.2024.81654.17671","url":null,"abstract":"<p><strong>Objectives: </strong>Adjuvants are some of the most important components used for vaccine formulation. In addition, the efficacy of vaccines is highly dependent on the nature of the adjuvants used. Therefore, new adjuvant formulations may help develop more potent vaccines. In the present study, the potency of an in-house and water-in-oil adjuvant (Yavar-70A) was compared with Montanide ISA 206 and Montanide ISA 266 in an HPV-16E7d vaccine model.</p><p><strong>Materials and methods: </strong>Three HPV-16 E7d vaccines were formulated using three different adjuvants, Montanide ISA 206, Montanide ISA 266, and Yavar-70A, with standard protocols. Afterward, each formulation containing 10 μg of the E7d protein was administered thrice at two-week intervals to C57BL/6 mice. Serum levels of IFN-γ and IL-4 cytokines secreted from spleen cells, total IgG, and specific IgG1 and IgG2a isotypes were assessed using ELISA two weeks after the last immunization. Lymphocyte proliferative responses were also evaluated using the BrdU method.</p><p><strong>Results: </strong>The results indicated that the vaccine formulated using the Yavar-70A adjuvant showed the highest lymphocyte proliferation responses compared with other groups and higher IFN-γ cytokine release compared with that formulated using Montanide ISA 206. However, the vaccine formulated using Montanide ISA 206 induced the highest total IgG responses compared with other groups. Importantly, the vaccine formulated using Yavar-70A decreased IL-4 secretion compared with other vaccinated groups.</p><p><strong>Conclusion: </strong>The present study demonstrated that Yavar-70A induces cellular and humoral immunologic parameters against the HPV-16 E7d vaccine model comparable to commercialized oil-based adjuvants.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 2","pages":"224-229"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028714","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":"NMDA receptors antagonists alleviated the acute phase of traumatic brain injury.","authors":"Mehrdad Hajinejad, Ahmadreza Gharaeian Morshed, Abdolreza Narouiepour, Maryam Izadpanahi, Mohammad Mahdi Taheri, Mohammad Hossein Sadeghian, Fatemeh Forouzanfar, Sajad Sahab Negah","doi":"10.22038/ijbms.2024.80887.17500","DOIUrl":"10.22038/ijbms.2024.80887.17500","url":null,"abstract":"<p><strong>Objectives: </strong>Traumatic brain injury (TBI) is a significant cause of mortality and disability worldwide. TBI has been associated with factors such as oxidative stress, neuroinflammation, and apoptosis, which are believed to be mediated by the N-methyl-D-aspartate (NMDA)-type glutamate receptor. Two NMDA receptor antagonists, ketamine and memantine, have shown potential in mitigating the pathophysiological effects of TBI.</p><p><strong>Materials and methods: </strong>To conduct the study, a controlled cortical impact model was used to induce TBI in rats. The rats with TBI were then divided into three groups: a group receiving only TBI, a group receiving TBI along with memantine, and a group receiving TBI along with ketamine. After 24 hr, the levels of oxidative stress markers (such as SOD, MDA, and total thiol) in the brain tissue were measured. Immunohistochemical staining was also performed seven days after TBI to assess the activation of glial cells and the TLR-4/NF-κB neuroinflammatory pathway.</p><p><strong>Results: </strong>The results indicated that treatment with memantine led to a reduction in MDA levels and an increase in SOD and total thiol levels. Memantine also decreased astrogliosis and down-regulated the TLR-4/NF-κB pathway. On the other hand, ketamine increased the levels of anti-oxidant markers but did not significantly affect the MDA level. Additionally, ketamine decreased the expression of NF-κB seven days after TBI.</p><p><strong>Conclusion: </strong>The findings suggest that NMDA receptor antagonists, such as ketamine and memantine, may have therapeutic effects on TBI by inhibiting oxidative stress and inflammatory responses.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 2","pages":"181-186"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028809","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> effects of phytochemicals on adipogenesis with a focus on molecular mechanisms: A systematic review.","authors":"Niusha Kazemi, Elham Ramazani, Zahra Tayarani-Najaran","doi":"10.22038/ijbms.2025.78924.17090","DOIUrl":"10.22038/ijbms.2025.78924.17090","url":null,"abstract":"<p><p>Adipogenesis, the process of proliferation of adipocyte progenitor cells and their differentiation into mature adipocytes, plays a critical role in the development of obesity. In this context, exploring the effects of phytochemicals on adipogenesis is very promising, as nowadays, they are widely used as food, drink, or supplement and can significantly impact general health and obesity control. This systematic review attempts to evaluate new findings regarding the molecular mechanisms of different phytochemicals on adipogenesis in <i>in vitro</i> models. Between 2010 and July 2023, a comprehensive systematic search of PubMed and Scopus databases was conducted. The following keywords were used: (\"adipogenic\") AND (\"inhibit\" OR \"suppress\" OR \"reduce\" OR \"anti\" OR \"decrease\") AND (\"cell\" OR \"cell line\" OR \"adipocyte\") AND (\"phytochemical\" OR \"plant\" OR \"herb\"). In this review, 109 studies were comprehensively analyzed, which provided important insights into the process of adipogenesis. Among the numerous transcription factors studied, PPARγ, C/EBPα, and SREBP1c were found to be the most important regulators actively involved in adipocyte differentiation. These results highlight the critical role of these factors in the control of adipogenesis and suggest that they represent promising targets for therapeutic interventions aimed at reducing the excessive lipid accumulation associated with obesity. This study provides a compelling rationale for further exploring phytochemicals as potential therapeutics for treating obesity. The potential benefits of using natural products to influence adipogenesis are evident, and future studies should focus on translating these findings into clinical applications.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 4","pages":"409-425"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11831750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448833","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":"Pre- and post-traumatic boric acid therapy prevents oxidative stress-mediated neuronal apoptosis in spinal cord injury.","authors":"Turan Kandemir, Ibrahim Sogut, Zeki Serdar Ataizi, Betul Can, Aysegul Oglakci-Ilhan, Dilek Burukoglu-Donmez, Gungor Kanbak","doi":"10.22038/ijbms.2024.81531.17649","DOIUrl":"10.22038/ijbms.2024.81531.17649","url":null,"abstract":"<p><strong>Objectives: </strong>In our study, the neuroprotective efficacy of pre- and post-traumatic applications of boric acid (BA) in rats with experimentally induced spinal cord injury (SCI) was investigated.</p><p><strong>Materials and methods: </strong>The experimental animals were divided into four groups: control group (C), SCI group (SCI), BA-treated group before SCI (BA+SCI), and BA-treated group after SCI (SCI+BA). Forty-eight hours after SCI, biochemical levels of malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), and cytochrome c (Cytc) and caspase-3 (Casp3) expressions were measured in the spinal cord tissues and were examined histologically.</p><p><strong>Results: </strong>After SCI, oxidative stress markers, such as MDA, TOS, and OSI, and apoptosis markers Cytc and Casp3 showed an increase in levels compared to Group C. The oxidative stress markers that increased after SCI decreased with BA+SCI application, while Cytc level, one of the apoptosis markers that increased after SCI, decreased in both groups with BA application. Cell, myelin, ependymal damage, and hemorrhage levels increased after SCI compared to Group C. These histological markers increased after SCI and decreased after BA+SCI. BA was found to reduce SCI-induced oxidative stress and oxidative stress-induced apoptosis.</p><p><strong>Conclusion: </strong>BA administered before SCI was shown to be more effective in protecting neural damage.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 4","pages":"444-450"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11831752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448905","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 assessment of ethosomes for effective transdermal delivery of loxoprofen.","authors":"Sarah Jabbar Abd Alhur, Hasanain Shakir Mahmood","doi":"10.22038/ijbms.2025.84183.18206","DOIUrl":"https://doi.org/10.22038/ijbms.2025.84183.18206","url":null,"abstract":"<p><strong>Objectives: </strong>To formulate and evaluate ethosomes for the transdermal delivery of loxoprofen, a potent non-steroidal anti-inflammatory drug (NSAID).</p><p><strong>Materials and methods: </strong>Fifteen ethosomal formulations were created via thin-film hydration and probe sonication techniques, with variations in the amounts of egg yolk lecithin, ethanol, cholesterol (CHOL), Tween 80 (TW80), and propylene glycol (PG). The formulations were assessed for their particle size (PS), zeta potential (ZP), polydispersity index (PDI), pH, and entrapment efficiency (EE). Field scanning electron microscopy (FSEM) was utilized to evaluate their morphology. The <i>in vitro</i> drug release and <i>ex vivo</i> permeability of the ethosomal formulations were evaluated against those in a hydroethanolic drug solution.</p><p><strong>Results: </strong>The formulation labeled F14, comprising 1% loxoprofen, 1% egg yolk lecithin, 30% ethanol, 5% propylene glycol, and phosphate-buffered saline (PBS) up to 25 ml, was recognized as an optimized ethosomal formulation. These ethosomes demonstrated an average size of 164.2±19 nm, a PDI of 0.280±0.028, a ZP of +45.1±4.5 mV, and an EE of 96.8±0.43%. <i>In vitro</i> and <i>ex vivo</i> tests demonstrated that the ethosomal formulation (F14) showed superior drug release and penetration rates compared to a conventional hydroalcoholic solution. The differential scanning calorimetry (DSC) study showed that loxoprofen was completely trapped within ethosomes. On the other hand, the Fourier transform infrared (FTIR) study confirmed that the drug and the additives did not interact.</p><p><strong>Conclusion: </strong>The current study revealed that loxoprofen can be effectively delivered transdermally via the ethosomal system.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 6","pages":"728-738"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12057754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002278","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":"Investigating the protective effects of fluvoxamine against sepsis-related acute lung injury through antiapoptotic, anti-inflammatory, and anti-oxidant features in rats.","authors":"Halil Asci, Suleyman Emre Akin, Hasan Ekrem Camas, Ahmet Bindal, Okan Kurtbolat, Serife Tasan, Abdurrahman Gulal, Rumeysa Taner, Turgut Kurt, Ozlem Ozmen","doi":"10.22038/ijbms.2024.80608.17444","DOIUrl":"10.22038/ijbms.2024.80608.17444","url":null,"abstract":"<p><strong>Objectives: </strong>Acute lung injury (ALI) is characterized by severe hypoxia and alveolar damage, often caused by oxidative stress, endoplasmic reticulum stress (ERS), and apoptosis. Fluvoxamine (FLV), an antidepressant, has tissue-protective properties through various intracellular mechanisms. This study investigates the anti-inflammatory effects of FLV used as an antidepressant in a lipopolysaccharide (LPS)-induced ALI model.</p><p><strong>Materials and methods: </strong>Thirty-two female Wistar Albino rats aged 14-16 weeks and weighing 300-350 g, with 8 animals in each group, were divided into four groups: control, LPS, LPS+FLV, and FLV. After LPS administration, rats were euthanized, and histopathological analysis, immunohistochemistry for tumor necrosis factor-α (TNF-α) and caspase-3 (Cas-3), ELISA for oxidative stress markers, and PCR for CHOP, Cas-12, and Cas-9 gene expressions were conducted.</p><p><strong>Results: </strong>In the LPS group, lung tissue damage, increased inflammatory cell infiltration, increased Cas-3 and TNF-α expressions, increased oxidative stress markers, and increased CHOP, Cas-9, and Cas-12 mRNA expressions were observed compared to the control group. FLV treatment in the LPS+FLV group significantly reversed these effects in the LPS group.</p><p><strong>Conclusion: </strong>FLV exhibits protective effects against ALI by mitigating inflammation, ERS, and apoptosis via the CHOP/Cas-9/Cas-12 pathway. Further studies are needed to explore additional pathways and potential clinical applications of FLV.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 3","pages":"323-331"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189050","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":"Preventing the rejection of skin allografts by immunomodulatory and regenerative effects of exosomes derived from bone marrow mesenchymal stem cells in mice.","authors":"Parham Soufizadeh, Gholamreza Nikbakht Brujeni, Mohammad Mehdi Dehghan, Massoumeh Jabbari Fakhr, Pouya Houshmand, Mahyar Mohebbi, Hossein Aminianfar, Sirous Sadeghian Chaleshtori","doi":"10.22038/ijbms.2025.82564.17841","DOIUrl":"10.22038/ijbms.2025.82564.17841","url":null,"abstract":"<p><strong>Objectives: </strong>Reducing the immune response to inflammation is vital for successful transplantation, yet chronic graft rejection remains a major issue despite immunosuppressive drugs. This study explored the effect of bone marrow mesenchymal stem cell-derived exosomes on the survival of skin allografts in mice.</p><p><strong>Materials and methods: </strong>C57BL/6 and BALB/c mice underwent skin allograft surgery, followed by intraperitoneal injection of exosomes, which were compared with groups receiving dexamethasone and no treatment group.</p><p><strong>Results: </strong>On day 3, mild signs of graft rejection appeared in both control groups, while none were seen in the exosome-treated group. By day 14, the grafts were completely rejected in the control groups but showed mild rejection in the treatment group. Histopathology revealed severe rejection signs in the control groups, including epithelial necrosis and inflammation, while the treatment group showed signs of angiogenesis and graft acceptance. Additionally, inflammatory cytokine levels (TNF-α, IL-1β, and IL-6) were lower in the treatment group than in the positive control group, particularly on days 3 and 14.</p><p><strong>Conclusion: </strong>The findings suggest that exosomes can prevent graft rejection and may offer a promising therapeutic approach for solid organ transplantation, though further research is needed to standardize exosome methods and evaluate cost-effectiveness.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 4","pages":"469-476"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11831755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449033","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":"Role of ENaC in gender-associated differences in blood pressure.","authors":"Guo-Feng Yu, Li-Qin Yu, Qin-Rui Lai, Wei Li","doi":"10.22038/ijbms.2025.81832.17701","DOIUrl":"10.22038/ijbms.2025.81832.17701","url":null,"abstract":"<p><strong>Objectives: </strong>Sexual dimorphism in blood pressure regulation has been extensively noted in humans, but the underlying mechanisms remain to be fully understood. Our research aims to investigate the possible correlation between gender-associated differences in blood pressure and renal sodium transport.</p><p><strong>Materials and methods: </strong>We measured male and female mice's blood pressure, urine, and plasma sodium concentration when fed a regular or high-Na⁺ diet. After that, their renal sodium transporters were assessed by western blot and immunofluorescence. For further investigation, male mice were castrated to observe the differences in blood pressure and renal sodium transporters compared to normal mice.</p><p><strong>Results: </strong>Male mice exhibited higher blood pressure and lower renal sodium excretion than female littermates. Furthermore, the blood pressure of male mice exhibited a more significant and rapid increase relative to female mice when the diet was switched from control sodium to high sodium. Western blot and immunofluorescent staining revealed that in male mice, the sodium transporters epithelial sodium channel (ENaC) and the upstream kinases SPAK (Ste20-related proline/alanine-rich kinase), OSR1 (oxidative stress response kinase 1), and WNK4 (Lysine-Deficient Protein Kinase 4) were elevated. Beyond that, male mice exhibited lowered blood pressure and reduced abundance of ENaC (α, β, and γ) after castration.</p><p><strong>Conclusion: </strong>ENaC plays a significant role in gender-associated differences in blood pressure and renal sodium reabsorption.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 4","pages":"527-532"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11831749/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449035","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":"Targeting dipeptidyl peptidase-8/9 to combat inflammation-induced osteoclastogenesis in RAW264.7 macrophages and analysis of anti-osteoclastogenesis potential of chrysin.","authors":"Syed Sufian Ahmad, Faraha Ahmed, Sayeed Ahmad, Anuja Krishnan, Mohammad Ahmed Khan","doi":"10.22038/ijbms.2025.82219.17784","DOIUrl":"10.22038/ijbms.2025.82219.17784","url":null,"abstract":"<p><strong>Objectives: </strong>Osteoclasts drive bone resorption under inflammation, with cytokines promoting osteoclastogenesis. The role of proline enzymes like dipeptidyl peptidase-8 and 9 (DPP-8/9) in this process remains unclear. This study aimed to explore the DPP-8/9 involvement in inflammation-driven osteoclastogenesis using the RAW264.7 macrophage model.</p><p><strong>Materials and methods: </strong>Receptor activator of nuclear factor-κB ligand (RANKL) and lipopolysaccharide (LPS) induced osteoclastogenesis, raising interleukin-6 (IL-6), tumor necrosis factor (TNF-α), and IL-23 levels. Using RAW264.7 cells, DPP-8/9 protein and tartrate-resistant acid phosphatase (TRAPc) were assayed. Antibodies for cluster of differentiation (CD86 and CD206) were used to analyze macrophage polarization, while molecular docking was used to assess flavonoid binding to DPP-8/9. Western blot confirmed DPP-8/9 expression in treated macrophages.</p><p><strong>Results: </strong>Administering RANKL and LPS increased IL-6 and TNF-α levels, significantly promoting osteoclastogenesis in RAW264.7 macrophages. This treatment also elevated the levels of the inflammatory macrophage marker IL-23. Osteoclast formation was confirmed by measuring TRAPc levels in the culture. Analysis of the cell supernatant revealed elevated DPP-8/9 levels in the RANKL+LPS group. Inhibition of DPP-8/9 with 1G244 decreased inflammatory cytokines and TRAPc levels in the cell culture. Molecular docking analysis of various flavonoids identified chrysin as a potential molecule with sufficient binding energy against DPP-8/9, a finding confirmed by blotting assay.</p><p><strong>Conclusion: </strong>This study emphasizes the involvement of DPP-8/9 in inflammatory osteoclastogenesis in RAW264.7 macrophages. Inhibition of DPP-8/9 reduced osteoclastogenesis markers and inflammatory cytokines levels, indicating decreased osteoclast formation. Additionally, chrysin demonstrated potential as an anti-DPP-8/9 agent, highlighting its possible role in future therapeutic strategies targeting inflammation-induced osteoclastogenesis.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 4","pages":"516-526"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11831742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449037","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}