{"title":"Recent advancements in the role of phytochemicals and medicinal plants in prophylaxis and management of Alzheimer's disease.","authors":"Akanksha Mishra, Sairam Krishnamurthy","doi":"10.22038/ijbms.2024.77760.16826","DOIUrl":"10.22038/ijbms.2024.77760.16826","url":null,"abstract":"<p><p>Medicinal plants and phytochemicals are some of the major sources in the treatment of various neurodegenerative disorders including Alzheimer's disease (AD). There is no FDA-approved drug to target AD pathology directly. Full cognitive restoration and management of psychosis-like symptoms are still to be achieved. Being comparatively safer with fewer side effects, medicinal plants have been among the major areas of interest to be researched. Several mechanistic pathways are involved in AD including anticholinesterase activity, glutamate toxicity, free radicals generation, Amyloid β (Aβ) toxicity, inflammation, and mitochondrial dysfunction. Various phytochemicals such as paenol, andrographolide, isoquercitrin, flavonoids, and saponins obtained from different plant sources, various medicinal plants like <i>Spirulina maxima, Salicornia europaea, Curcuma longa, Citrus Junos Tanaka, Cassiae semen, Centella asiatica</i> as well as various traditional medicinal plants of China, Asia, Europe, Turkey, and Iran have been found effective against one or more of these targets. Large numbers of clinical trials are under process to evaluate the role of different phytoconstituents in AD management. Out of 143 agents under clinical trials, 119 have been categorized as disease-modifying agents. The present review extensively covers the recent advancements in the usage of phytochemicals and medicinal plants in various experimental AD models. It involves clinical trials and other research works divided into three sections, including those performed <i>in vitro, in vivo</i>, and in humans mainly from the last five years along with disease markers and mechanistic pathways involved. However, phytochemicals should be explored further in order to achieve neurorestoration in AD.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"27 11","pages":"1357-1369"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11459346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390542","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}
Rizwan Ahamad, Uma Bhandari, Sayima Nabi, Shweta Sharma
{"title":"Saroglitazar suppresses KIM-1 and type IV collagen in high fat diet and low-dose streptozotocin-induced diabetic nephropathy in Wistar rats.","authors":"Rizwan Ahamad, Uma Bhandari, Sayima Nabi, Shweta Sharma","doi":"10.22038/ijbms.2024.78221.16908","DOIUrl":"10.22038/ijbms.2024.78221.16908","url":null,"abstract":"<p><strong>Objectives: </strong>Nephropathy is the most common comorbidity linked to T2D. The present study aimed to examine the potential of saroglitazar in the context of a high-fat diet and low-dose streptozotocin-induced diabetic nephropathy in Wistar rats.</p><p><strong>Materials and methods: </strong>Molecular docking simulation investigations were conducted on the ligand-binding region of type IV collagen and Kidney injury molecule-1 (KIM-1), using saroglitazar and fenofibrate as the subjects. The rats were fed either a conventional rodent diet or a high-fat diet <i>ad libitum</i> for two weeks. Following a two-week period, the rats given an HFD were administered with a low-dose of STZ (35 mg/kg, IP). Rats with experimentally induced diabetes were categorized into five groups: normal control; diabetic control; HFD+STZ+saroglitazar (2 mg/kg); HFD+STZ+saroglitazar (4 mg/kg); HFD+STZ+fenofibrate (100 mg/kg) treated orally for 21 days with continuation on HFD. After 21 days, rats were kept on fasting overnight, blood and urine was acquired for various biochemical analysis. Animals were sacrificed, and kidney tissues were removed for histopathological studies.</p><p><strong>Results: </strong><i>In-silico</i> investigation showed a substantial affinity between saroglitazar and fenofibrate with KIM-1 and type IV collagen. Saroglitazar produced a significant (<i>P</i><0.01) reduction in weight of the body, serum blood sugar, albumin, creatinine, and BUN levels. Further, saroglitazar significantly (<i>P</i><0.01) reduced the KIM-1 and type IV collagen levels in the urine of diabetic rats. Histopathological results showed improvement in tubular degeneration, necrosis, and dilatation of Bowman's space in kidney tissue.</p><p><strong>Conclusion: </strong>Saroglitazar attenuated renal injury by improving renal function in HFD+STZ-induced DN in Wistar rats.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"27 11","pages":"1447-1455"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11459336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390543","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}
Azin Alizadehasl, Maryam Sadat Alavi, Mohaddeseh Sadat Alavi, Ali Roohbakhsh
{"title":"TRPA1 as a promising target in ischemia/reperfusion: A comprehensive review.","authors":"Azin Alizadehasl, Maryam Sadat Alavi, Mohaddeseh Sadat Alavi, Ali Roohbakhsh","doi":"10.22038/IJBMS.2023.74590.16198","DOIUrl":"10.22038/IJBMS.2023.74590.16198","url":null,"abstract":"<p><p>Ischemic disorders, including myocardial infarction, cerebral ischemia, and peripheral vascular impairment, are the main common reasons for debilitating diseases and death in Western cultures. Ischemia occurs when blood circulation is reduced in tissues. Reperfusion, although commanded to return oxygen to ischemic tissues, generates paradoxical tissue responses. The responses include generating reactive oxygen species (ROS), stimulating inflammatory responses in ischemic organs, endoplasmic reticulum stress, and the expansion of postischemic capillary no-reflow, which intensifies organ damage. Multiple pathologic processes contribute to ischemia/reperfusion; therefore, targeting different pathologic processes may yield an effective therapeutic approach. Transient Receptor Potential A1 (TRPA1) belongs to the TRP family of ion channels, detects a broad range of chemicals, and promotes the transduction of noxious stimuli, e.g., methylglyoxal, ROS, and acrolein effects are attributed to the channel's sensitivity to intracellular calcium elevation or phosphoinositol phosphate modulation. Hypoxia and ischemia are associated with oxidative stress, which activates the TRPA1 channel. This review describes the role of TRPA1 and its related mechanisms that contribute to ischemia/reperfusion. Relevant articles were searched from PubMed, Scopus, Web of Sciences, and Google Scholar electronic databases, up to the end of August 2023. Based on the evidence presented here, TRPA1 may have protective or deteriorative functions during the ischemia/reperfusion process. Its function depends on the activation level, the ischemic region, the extent of lesions, and the duration of ischemia.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"27 3","pages":"270-278"},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10849207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139706745","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}
Saeed Mustapha, Rabiu Abdussalam Magaji, Mohammed Garba Magaji, Ibrahim Bako Gaya, Baraka Umar, Yusuf Yusha'u, Abubakar Bishir Daku, Samaila Musa Chiroma, Aliyu Jaafar, Mohamad Zulfadli Mehat, Che Norma Mat Taib, Mohamad Aris Moh'd Moklas
{"title":"Neuroprotective roles of flavonoid \"hispidulin\" in the central nervous system: A review.","authors":"Saeed Mustapha, Rabiu Abdussalam Magaji, Mohammed Garba Magaji, Ibrahim Bako Gaya, Baraka Umar, Yusuf Yusha'u, Abubakar Bishir Daku, Samaila Musa Chiroma, Aliyu Jaafar, Mohamad Zulfadli Mehat, Che Norma Mat Taib, Mohamad Aris Moh'd Moklas","doi":"10.22038/IJBMS.2024.76605.16573","DOIUrl":"10.22038/IJBMS.2024.76605.16573","url":null,"abstract":"<p><p>Interest in naturally occurring phytochemicals has been on the increase, they are believed to reduce the risk of brain disorders. Hispidulin (HN) is a phenolic flavonoid compound with various pharmacological and biological effects on the central nervous system. It belongs to the flavone class of flavonoids. It can be found in different plant materials, especially fruits and vegetables. The literature used in this review was collected from credible scientific databases including ScienceDirect, Scopus, PubMed, Google Scholar, and Hindawi without time restriction, using relevant keywords, such as HN, brain, central nervous system, flavonoids, and flavones. HN was discovered to possess pro-apoptotic properties, act as an antioxidant, inhibit cytokine production and toll-like receptor 4 expression, as well as impede nuclear factor kappa beta and mitogen-activated protein kinase B. HN was also found to inhibit lipid peroxidation in vitro and reduce brain edema in mice. These pharmacological potentials suggest that HN is a promising candidate for neuroprotection in CNS disorders like depression and epilepsy. This review provides an update on the scientific literature concerning how these activities could help provide various forms of neuroprotection in the CNS. Additional experimental data on the effects of HN in models of neurological disorders and neuroprotection should be explored further. Based on the current study, HN is a promising candidate for neuroprotection of the CNS.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"27 9","pages":"1077-1084"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11266747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141758747","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":"Effects of <i>Crocus sativus</i> and its constituent, safranal, and pioglitazone, on systemic inflammation and oxidative stress induced by paraquat aerosol in rats.","authors":"Arghavan Memarzia, Seydeh Zahra Ghasemi, Fatemeh Amin, Zahra Gholamnezhad, Mohammad Hossein Boskabady","doi":"10.22038/IJBMS.2024.72996.15867","DOIUrl":"https://doi.org/10.22038/IJBMS.2024.72996.15867","url":null,"abstract":"<p><strong>Objectives: </strong>The effects of <i>Crocus sativus</i>, safranal, and pioglitazone on aerosolized paraquat (PQ)-induced systemic changes were examined.</p><p><strong>Materials and methods: </strong>Control (Ctrl) and PQ groups of rats were exposed to saline or PQ (27 and 54 mg/m3, PQ-L and PQ-H) aerosols eight times on alternate days. Nine PQ-H groups were treated with dexamethasone (0.03 mg/kg/day, Dexa), two doses of <i>C. sativus</i> extract (20 and 80 mg/kg/day, CS-L and CS-H), safranal (0.8 and 3.2 mg/kg/day, Saf-L and Saf-H), pioglitazone (5 and 10 mg/kg/day, Pio-L and Pio-H), and the combination of low dose of the pioglitazone and extract or safranal (Pio + CS and Pio + Saf) after the end of PQ exposure.</p><p><strong>Results: </strong>Interferon-gamma (INF-γ), interleukin 10 (IL-10), superoxide dismutase (SOD), catalase (CAT), and thiol serum levels were reduced, but tumor necrosis factor (TNF-α), malondialdehyde (MDA), and total and differential WBC were increased in both PQ groups (<i>P</i><0.05 to <i>P</i><0.001). All measured variables were improved in all treated groups (<i>P</i><0.05 to <i>P</i><0.001). The effects of high dose of C. sativus and safranal on measured parameters were higher than dexamethasone (<i>P</i><0.05 to <i>P</i><0.001). The effects of Pio + CS and Pio + Saf treatment on most variables were significantly higher than three agents alone (<i>P</i><0.05 to <i>P</i><0.001).</p><p><strong>Conclusion: </strong><i>C. sativus</i> and safranal improved inhaled PQ-induced systemic inflammation and oxidative stress similar to those of dexamethasone and showed synergic effects with pioglitazone suggesting the possible PPARγ receptor-mediated effects of the plant and its constituent.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"27 5","pages":"640-646"},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11017852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140860855","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}
Wahyu Widowati, Ahmad Faried, Achmad Adam, Deni Rahmat, Hanna Sari Widya Kusuma, Nindia Salsabila Mia Dewi, Marisca Evalina Gondokesumo, Rizal Rizal, Ita Margaretha Nainggolan, Massoud Vosough
{"title":"Potential antiaging activity of secretome gel of human Wharton's jelly mesenchymal stem cells (hWJ-MSCs) in UV-induced mice models.","authors":"Wahyu Widowati, Ahmad Faried, Achmad Adam, Deni Rahmat, Hanna Sari Widya Kusuma, Nindia Salsabila Mia Dewi, Marisca Evalina Gondokesumo, Rizal Rizal, Ita Margaretha Nainggolan, Massoud Vosough","doi":"10.22038/IJBMS.2024.70825.15385","DOIUrl":"10.22038/IJBMS.2024.70825.15385","url":null,"abstract":"<p><strong>Objectives: </strong>Skin aging is a degenerative process that can be induced by UV irradiation. UV radiation can produce reactive oxidate stress which causes premature aging. This study aims to examine the antiaging potential of secretome gel (SC) from human Wharton Jelly Mesenchymal Stem Cells (hWJ-MSCs) in a UVB-induced mice model.</p><p><strong>Materials and methods: </strong>The secretome was obtained from hWJ-MSCs and made in gel form. Male mice were radiated by UVB for 15 min twice daily for 14 days. The gel was topically applied to the mice's dorsal skin. Two treatments of secretome gel: secretome 1 is applied once and secretome 2 is applied twice daily after UVB radiation. TGF-β1, IL-10, and IL-18 gene expression was determined using RT-PCR. Hematoxylin Eosin staining was used to observe the inflammation and collagen density of skin tissue. An immunohistochemistry assay was used to analyze the protein expression of P53, COL4A1, MMP-2, and MMP-13. The data were statistically analyzed using the ANOVA test followed by the Tukey post hoc test (<i>P</i><0.05).</p><p><strong>Results: </strong>UVB induction caused loss of collagen, increasing inflammation and high expression of aging mediators. SC increased the gene expression of TGF-β1 and IL-10 and decreased IL-18 gene expression. Histopathological tests showed that SG increased collagen density, lowered inflammation, and repaired cell damage in skin tissue. Immunohistochemistry test showed that SC decreased MMP-2, MMP-13, and P53 expression, in contrast, increased COL4A1.</p><p><strong>Conclusion: </strong>The secretome gel of hWJ-MSCs showed antiaging activities with potential for preventing and curing skin aging.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"27 7","pages":"868-878"},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11127088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141154247","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}
Somayeh Yazdanparast, Davood Bashash, Amirsalar Nikkhah Bahrami, Mohammad Ghorbani, Mehrdad Izadirad, Mehdi Bakhtiyaridovvombaygi, Seyede Zahra Hasanpour, Ahmad Gharehbaghian
{"title":"Royal jelly induces ROS-mediated apoptosis in acute lymphoblastic leukemia (ALL)-derived Nalm-6 cells: Shedding light on novel therapeutic approaches for ALL.","authors":"Somayeh Yazdanparast, Davood Bashash, Amirsalar Nikkhah Bahrami, Mohammad Ghorbani, Mehrdad Izadirad, Mehdi Bakhtiyaridovvombaygi, Seyede Zahra Hasanpour, Ahmad Gharehbaghian","doi":"10.22038/IJBMS.2024.76261.16498","DOIUrl":"10.22038/IJBMS.2024.76261.16498","url":null,"abstract":"<p><strong>Objectives: </strong>Until recently, a conventional chemotherapy regimen for Acute lymphoblastic leukemia (ALL) is considered an efficient therapeutic method in children. However, suboptimal long-term survival rates in adults, disease relapse, and drug-induced toxicities require novel therapeutic agents for ALL treatments. Today, natural products with pharmacological benefits play a significant role in treating different cancers. Among the most valued natural products, honey bees' royal jelly (RJ) is one of the most appreciated which has revealed anti-tumor activity against different human cancers. This study aimed to evaluate anti-leukemic properties and the molecular mechanisms of RJ cytotoxicity on ALL-derived Nalm-6 cells.</p><p><strong>Materials and methods: </strong>The metabolic activity was measured by MTT assay. Apoptosis, cell distribution in the cell cycle, and intracellular reactive oxygen species (ROS) level were investigated using flow cytometry analysis. Moreover, quantitative real-time PCR (qRT-PCR) was performed to scrutinize the expression of various regulatory genes.</p><p><strong>Results: </strong>RJ significantly decreased the viability of Nalm-6 cells but had no cytotoxic effect on normal cells. In addition, RJ induced ROS-mediated apoptosis by up-regulating pro-apoptotic genes while decreasing anti-apoptotic gene expression. The results outlined that ROS-dependent up-regulation of FOXO4 and Sirt1 inhibits the cells' transition to the S phase of the cell cycle through p21 up-regulation. The qRT-PCR analysis of autophagy-related gene expression also demonstrated that RJ induced BECN1 mediated autophagy in Naml-6 cells.</p><p><strong>Conclusion: </strong>Taken together, this study showed that RJ can be utilized as a potent natural substance to induce ALL cells' programmed cell death. However, further studies are required to examine this compound's pharmaceutical application.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"27 7","pages":"801-812"},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141154264","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":"Application of methylene blue for the prevention and treatment of COVID-19: A narrative review.","authors":"Elaheh Emadi, Daryoush Hamidi Alamdari, Davood Attaran, Soroush Attaran","doi":"10.22038/IJBMS.2024.71871.15617","DOIUrl":"10.22038/IJBMS.2024.71871.15617","url":null,"abstract":"<p><p>The newest virus from the SARS family of viruses called acute syndrome-coronavirus-2 (SARS-CoV-2), which causes COVID-19 disease, was identified in China at the end of 2019. In March 2020, after it spread to 29 additional countries, it was declared a pandemic by the World Health Organization (WHO). SARS-CoV-2 infection mainly starts through the respiratory tract and causes a wide spectrum of symptoms from asymptomatic infections to acute respiratory distress syndrome with multi-organ failure and vasoplegic shock. Among the many immunomodulatory and antiviral drugs that have been studied for the treatment of COVID-19, methylene blue (MB) may play an influential role. This article reviews the history of MB applications, the antiviral effects of MB against SARS-CoV-2, and the results of <i>in vivo</i> and <i>in vitro</i> studies of the use of MB in COVID-19. Based on studies, MB can simultaneously affect most of the host's harmful responses caused by SARS-CoV-2 infection due to its multiple properties, including anti-hypoxemia, anti-oxidant, immune system modulator, and antiviral. The use of MB is associated with a reduction in the possibility of getting infection, and mortality, and can be used as a safe, effective, cheap, and available treatment option with minimal side effects for the clinical management of COVID-19.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"27 7","pages":"780-792"},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141155264","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":"Effects of crocin on the enhancement of <i>in vitro</i> neurogenesis: Involvement of Notch and CREB/BDNF signaling pathways.","authors":"Shayan Vafaei, Vida Mirzaie, Masoumeh Baghalishahi, Elahe Mousanejad, Seyed Noureddin Nematollahi-Mahani","doi":"10.22038/IJBMS.2024.76308.16513","DOIUrl":"10.22038/IJBMS.2024.76308.16513","url":null,"abstract":"<p><strong>Objectives: </strong>Adult neurogenesis, the process of generating new neurons, continues throughout life. Unfortunately, this process is insufficient in pathological conditions and needs to be promoted. Crocin, the active component of saffron, affects neurogenesis <i>in vivo</i> and <i>in vitro</i>. We aimed to investigate the enhancing effects of crocin on the neurogenesis of adipose-derived mesenchymal stem cells in the presence of retinoic acid, as well as the molecular pathways involved.</p><p><strong>Materials and methods: </strong>Differentiation capacities and stemness potential of harvested ADSCs were evaluated by differentiating into osteocytes and adipocytes, and expression of mesenchymal CD markers by flow cytometry. The optimum dose of crocin was assessed with an MTT assay. Crocin, retinoic acid, CREB/BDNF, and Notch inhibitors and their combination were added to the culture medium. Jag1, Hes1, Notch, and BDNF gene expression were analyzed by RT-PCR on days 7, 14, and 21, while CREB, DCX, SOX2, and NeuN expression were analyzed by immunofluorescence.</p><p><strong>Results: </strong>Expression of mesenchymal CD markers as well as adipogenic and osteogenic differentiation confirmed the origin and properties of ADSCs. The optimal dose of crocin was 1 mM. Crocin significantly (<i>P</i><0.05) increased, while inhibitors (DATP&Naphthol) significantly (<i>P</i><0.05) decreased Jag1, Hes1, Notch, and BDNF expression. Immunofluorescent assessments showed that expression of DCX, BDNF, NeuN, and Sox2 proteins increased significantly (<i>P</i><0.05) after crocin administration and decreased significantly (<i>P</i><0.05) after inhibitor administration.</p><p><strong>Conclusion: </strong>Crocin can be used as an enhancer for neural differentiation of MSCs <i>in vitro</i> in the presence of retinoic acid. The mechanism is proposed through Notch and CREB/BDNF signaling pathways.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"27 7","pages":"914-922"},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141155306","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}
Mohammad Azimi-Alamouty, Mohammad Amin Habibi, Amin Ebrahimi Sadrabadi, Zahra Jamalpoor
{"title":"An <i>in situ</i> forming gelatin-based hydrogel loaded with soluble amniotic membrane promotes full-thickness wound regeneration in rats.","authors":"Mohammad Azimi-Alamouty, Mohammad Amin Habibi, Amin Ebrahimi Sadrabadi, Zahra Jamalpoor","doi":"10.22038/IJBMS.2024.74290.16140","DOIUrl":"10.22038/IJBMS.2024.74290.16140","url":null,"abstract":"<p><strong>Objectives: </strong>Early effective treatment and appropriate coverage are vital for full-thickness wounds. Amnion membrane-derived products have recently emerged in tissue engineering. However, the optimal concentration, carrier for controlled release, and handling have remained challenges. This study aims to develop and optimize an <i>in situ</i> forming, amniotic-based hydrogel for wound healing.</p><p><strong>Materials and methods: </strong>Here, a composite matrix was fabricated with gelatin hydrogel modified with methacrylate functional group conjugated (GelMA) and keratose (wt.1%), loaded with mesenchymal stem cells (MSCs, 1×10<sup>5</sup> cell/ml) and optimized soluble amniotic membrane (SAM, 0.5 mg/ml). The physicochemical properties of the final subject were evaluated <i>in vitro</i> and <i>in vivo</i> environments.</p><p><strong>Results: </strong>The results of the <i>in vitro</i> assay demonstrated that conjugation of the methacryloyl group with gelatin resulted in the formation of GelMA hydrogel (26.7±1.2 kPa) with higher mechanical stability. Modification of GelMA with a glycosaminoglycan sulfate (Keratose) increased controlled delivery of SAM (47.3% vs. 84.3%). Metabolic activity (93%) and proliferation (21.2 ± 1.5 µg/ml) of MSCs encapsulated in hydrogel improved by incorporation of SAM (0.5 mg/ml). Furthermore, the migration of fibroblasts was facilitated in the scratched assay by SAM (0.5 mg/ml)/MSCs (1×10<sup>5</sup> cell/ml) conditioned medium. The GelMA hydrogel groupes revealed regeneration of full-thickness skin defects in rats after 3 weeks due to the high angiogenesis (6.3 ± 0.3), cell migration, and epithelialization.</p><p><strong>Conclusion: </strong>The results indicated in situ forming and tunable GelMA hydrogels containing SAM and MSCs could be used as efficient substrates for full-thickness wound regeneration.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"27 8","pages":"1005-1014"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11193504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442638","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}