Journal of Molecular Histology最新文献

{"title":"Carboxylesterase 1 regulates peroxisome proliferator-activated receptor gamma to inhibit the growth and metastasis of breast cancer cells","authors":"Jingli Wen,&nbsp;Lei Geng,&nbsp;Ruohan Wang,&nbsp;Xiaolei Zhang,&nbsp;Yanmin Sui,&nbsp;Xiaofang Liu,&nbsp;Xin Han","doi":"10.1007/s10735-025-10446-y","DOIUrl":"10.1007/s10735-025-10446-y","url":null,"abstract":"<div><p>Breast cancer is a common malignancy in women, and it has an absence of effective therapies. Carboxylesterase 1 (CES1), a member of the carboxylesterase family, has anti-tumor properties in several types of cancer. However, the function of CES1 in breast cancer remains unclear. Peroxisome proliferator-activated receptor gamma (PPARG) is a downstream regulator of CES1 and exhibits anti-breast cancer properties. Both CES1 and PPARG were downregulated in breast cancer tissues. Low CES1 and PPARG expression were linked to poorer breast cancer survival. We constructed CES1 knockdown and overexpression models of breast cancer cells by CES1 overexpressing plasmids and plasmids containing short hairpin RNA. High expression of CES1 inhibited breast cancer cell proliferation, evidenced by diminished cell viability, decreased DNA replication, and G1 phase arrest. CES1 overexpression decreased the protein levels of CDK2, CDK6 and cyclin B1 in breast cancer cells. CES1 inhibited the Bcl-2/Bax axis and increased Cleaved caspase-3 levels. Transwell assays showed that CES1 inhibited cell migration and invasion. CES1 increased E-cadherin protein expression and decreased Vimentin protein expression. CES1 knockdown facilitated the proliferation, migration, and invasion of breast cancer cells. CES1 was found to regulate PPARG expression in breast cancer cells positively. We transfected PPARG-interfering plasmids into breast cancer cells with CES1 overexpression. Inhibition of PPARG abrogated the anti-growth and anti-metastasis functions of CES1 in breast cancer cells. This study elucidates that CES1 inhibits the malignant progression of breast cancer by up-regulating the expression of PPARG.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10735-025-10446-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hsa-miR-194-5p regulates TRAF6-mediated M1 macrophage apoptosis in recurrent spontaneous abortion","authors":"Xin Qi,&nbsp;Yueping Ding,&nbsp;Jundi Zheng,&nbsp;Xia Geng,&nbsp;Jie Zhang,&nbsp;Yan Xu","doi":"10.1007/s10735-025-10464-w","DOIUrl":"10.1007/s10735-025-10464-w","url":null,"abstract":"<div><p>Recurrent spontaneous abortion (RSA) is linked to pro-inflammatory responses driven by macrophage M1 polarization. miR-194-5p can affect the migration and infiltration of macrophages, and significantly inhibit the release of pro-inflammatory cytokines. However, whether miR-194-5p can affect RSA through M1 macrophage-related pathway remains to be further explored. To induce human monocytic leukemia THP-1 into M1 macrophages, PMA and LPS were used. Then detect the effects of transfection with miR-194-5p mimics on the migration, invasion, cell cycle and apoptosis of M1 macrophages. Two databases, DIANA-microT and miRDB, were first used to predict the target gene of miR-194-5p, and TRAF6 was selected as the target gene of miR-194-5p, and then the binding sites of the two were predicted and verified by dual luciferase assay. Transfection of inhibitors, with or without TRAF6 siRNA (si-TRAF6), was performed on M1 macrophages to assess changes in viability, migration, aggressiveness, cell cycle, and apoptosis, as well as TRAF6, NF-κB, and Wnt5a mRNA and protein levels. Compared with the miR-NC group, transfection with the miR-194-5p mimic significantly reduced the viability, migration, and invasion abilities of M1 macrophages, arrested them in the S phase, and promoted apoptosis. miR-194-5p bound to TRAF 3’UTR-WT and reduced the viability, migration ability, and aggressiveness of M1 macrophages, increased apoptosis, and blocked the S phase. miR-194-5p negatively regulated TRAF6, resulting in decreased mRNA and protein levels of NF-κB and Wnt5a. miR-194-5p inhibitors and mimics had opposite effects, but miR-194-5p inhibitor effects could be reversed by si-TRAF6. There is a close association between RSA and M1 macrophage polarization. Furthermore, miR-194-5p inhibits the NF-κB and Wnt5a signaling pathways by negatively regulating TRAF6, thereby impeding the function of M1 macrophages and affecting the occurrence of RSA. These findings provide new therapeutic targets for the prevention, diagnosis, and treatment of RSA.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive analysis of FAM83B in pan-cancer and preliminary exploration in esophageal squamous cell carcinoma","authors":"Wei Guo,&nbsp;Xixi Zhao,&nbsp;Xinran Huang,&nbsp;Ruijuan Zhang,&nbsp;Yuchen Wang,&nbsp;Xinyu He,&nbsp;Xiangyun Ma,&nbsp;Yu Hao,&nbsp;Shangyi Geng,&nbsp;Shupei Pan,&nbsp;Hongbing Ma","doi":"10.1007/s10735-025-10452-0","DOIUrl":"10.1007/s10735-025-10452-0","url":null,"abstract":"<div><p>FAM83B is a novel oncogene that mediates transformation. Despite emerging evidence supporting an association between FAM83B and cancer, a holistic view of FAM83B’s correlation with pan-cancer is limited and its carcinogenic and radioresistant roles in esophageal squamous cell carcinoma (ESCC) remain to be explored. Using data from the TCGA project, GTEx database, and other online resources, we comprehensively examined FAM83B expression, genetic mutation, copy number variations (CNV), methylation, prognosis, function, immune-associated analyses, and drug sensitivity in pan-cancer. In addition, the biological function of FAM83B in ESCC was verified by CCK-8, colony formation assays, and flow cytometry. We discovered aberrant expression of FAM83B affected prognosis in various malignant tumors. Abnormal FAM83B mRNA expression was associated with CNV and methylation. Significant correlations were also observed between FAM83B expression and immune cell infiltration, immune checkpoints, tumor mutational burden (TMB), and microsatellite instability (MSI) in malignancies. In vitro experiments indicated that FAM83B mRNA and protein were upregulated in ESCC, and knockdown of FAM83B significantly inhibited the proliferation while promoting apoptosis and radiosensitivity of ESCC. These results suggest the multiple functional roles of FAM83B in pan-cancer and provide an attractive diagnostic and therapeutic biomarker for certain cancer types, especially ESCC.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144140261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myoinositol improves sperm parameters in diabetic rats by reducing oxidative stress and regulating apoptosis-related genes","authors":"Mina Kiani,&nbsp;Malek Soleimani Mehranjani,&nbsp;Mohammad Ali Shariatzadeh","doi":"10.1007/s10735-025-10451-1","DOIUrl":"10.1007/s10735-025-10451-1","url":null,"abstract":"<div><p>Diabetes disrupts spermatogenesis and leads to low-quality sperm by causing oxidative stress, inducing apoptosis and reducing testosterone level. Myoinositol has antiglycemic, antioxidant, anti-apoptotic, and testosterone-regulating properties. This study aimed to evaluate the potential of myoinositol in improving sperm production and sperm quality in diabetic rats. Eighteen rats were divided into three groups (n = 6 per group): control, diabetic (Streptozotocin + Nicotinamide), and diabetic + myoinositol supplementation (300 mg/kg, for 56 days). Sperm parameters, including count, total motility, viability, and morphology, were evaluated. Additionally, several biochemical and molecular markers were measured including serum malondialdehyde (MDA), superoxide dismutase (SOD), total antioxidant capacity (TAC), testosterone, Follicle-stimulating hormone (FSH), Luteinizing hormone (LH), and Bax/Bcl2 gene expression ratio, Bax and Bcl2 protein expression, germinal epithelium apoptosis. In the diabetic group, sperm count, viability, and normal morphology significantly decreased, along with lower levels of SOD, TAC, testosterone, FSH, and LH. Conversely, MDA levels and the Bax/Bcl2 gene ratio significantly increased compared to the control group. In the diabetic + myoinositol group, sperm count, viability, morphology, and motility significantly improved (P &lt; 0.001), as did TAC, testosterone, and FSH levels (P &lt; 0.001), with a significant increase in LH levels (P &lt; 0.05). Additionally, MDA levels (P &lt; 0.01) and the Bax/Bcl2 gene ratio (P &lt; 0.05) were significantly reduced compared to the diabetic group. This study showed that diabetes impairs sperm quality, antioxidant capacity, and hormones while increasing oxidative stress and apoptosis. Myoinositol improves sperm parameters, boosts antioxidants, and reduces apoptosis, suggesting its therapeutic potential for diabetes-induced reproductive dysfunction.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144108466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesenchymal stem cell exosomes regulate TGFβ/Smad3 by decreasing the METTL3-NEAT1 axis to inhibit scar progression after breast surgery","authors":"Juan Du,&nbsp;Jincheng Wu,&nbsp;Qinqin Song,&nbsp;Shuangru Li,&nbsp;Youwang Hong,&nbsp;Aizaz Anwar,&nbsp;Quanyou Fu,&nbsp;Jisong Liu","doi":"10.1007/s10735-025-10441-3","DOIUrl":"10.1007/s10735-025-10441-3","url":null,"abstract":"<div><h3>Background</h3><p>Scars are traces of tissue loss left behind by connective tissue overgrowth and repair. Studies in recent years have shown that mesenchymal stem cell exosomes (MSC-Exo) have the ability to inhibit and repair cutaneous scarring, but their specific role in post-breast surgery scar formation and the mechanisms behind it remain enigmatic.</p><h3>Methods</h3><p>Extraction and characterization of exosomes from mesenchymal stem cells (MSCs). Western Blot and RT-qPCR were used to evaluate the expression of fibrillar protein and TGF-β/Smad3 in mammary hypertrophic scar fibroblasts (MHSFs) stimulated with MSC-Exo, sh-METTL3, sh-NEAT1 and their negative controls. Construction of a mouse model of proliferative scar formation using mechanical tension and detection of fibronectin and pathway protein expression using Western Blot and RT-qPCR. Pathologic changes of mammary scarring in mice using HE staining, Masson staining and immunofluorescence.</p><h3>Results</h3><p>Both in vitro and in vivo, MSC-Exo, sh-METTL3 and sh-NEAT1 were shown to decrease the expression of COL1A1, COL3A1, α-SMA, fibronectin, TGF-β, p-Smad2/Smad2, p-Smad3/Smad3, by Western Blot and RT-qPCR. In addition, improved lesions and reduced collagen deposition were observed in mice by HE and Masson assays.</p><h3>Conclusions</h3><p>In summary, our study revealed that exosomes of MSCs function through the m6A methyltransferase METTL3, which regulates the NEAT1/TGF-β/Smad3 axis to slow down the rate of scar formation after breast surgery.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144090976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Arsenic-induced neurocardiac toxicity and protective role of Resveratrol: histopathological and molecular insights","authors":"Saroj,&nbsp;Kamakshi Mehta,&nbsp;Kamlesh Kumar Pandey,&nbsp;Balpreet Kaur,&nbsp;Saroj Kaler,&nbsp;Pushpa Dhar","doi":"10.1007/s10735-025-10439-x","DOIUrl":"10.1007/s10735-025-10439-x","url":null,"abstract":"<div><p>Arsenic toxicity is a global health problem chiefly targeting soft tissues of the body like the brain and heart. The major mechanism underlying arsenic-induced neurotoxicity is oxidative stress. Particularly, the neurons and cardiac myocytes show limitless susceptibility to oxidative stress. Herein, we examined the impact of prolonged arsenic exposure and resveratrol post-treatment on the cardiac and neuronal [Ventromedial hypothalamic nucleus (VMH)] morphology. Adult mice were segregated into control and experimental groups; controls received distilled water, while experimental groups received oral gavage of arsenic trioxide (ATO) at low (2 mg/kg bw) or high (4 mg/kg bw) doses for 45 days. Cardiac effects were assessed at the low dose (2 mg/kg bw), whereas neurological effects were evaluated at both low and high doses. Mice were sacrificed on day 45 to obtain perfusion-fixed hearts and brains for histological and morphometric studies. Long-term ATO exposure resulted in a higher heart-to-body weight ratio than controls, suggesting ATO-induced hypertrophy. Microscopic observations revealed a regular arrangement of cardiac muscle fibres, branching patterns of cardiomyocytes, and fibroblasts across all the treatment groups. However, increased cardiac myocyte diameter in ventricles and substantial fibrosis in vessel walls were noticed in ATO-alone exposed hearts relative to controls. Selective vulnerability of hypothalamic neurons following ATO exposure was evident by significant alterations in morphometric parameters (reduced cell density and soma size) in the VMH nucleus of animals receiving ATO (2 and 4 mg/kg) alone. These dramatic histopathological alterations were found to be restored after ATO + <i>Res</i> co-treatment. We also examined the expression of ER-α in the preoptic area of the hypothalamus and indicated downregulation of ER-α due to prolonged ATO exposure. Our findings highlight Resveratrol as a potent neurocardiac protector against ATO toxicity via estrogen signaling modulation, supporting its therapeutic potential in arsenic poisoning.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144090977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring neuro-glial interaction mechanisms in myelin plasticity for learning and memory enhancement","authors":"Reham M. Wahid,&nbsp;Nancy Husseiny Hassan,&nbsp;Walaa Samy,&nbsp;Aliaa Talaat,&nbsp;Amira Mokhtar Gobran,&nbsp;Shaimaa R. Abdelmohsen,&nbsp;Heba Atef Elsayed","doi":"10.1007/s10735-025-10431-5","DOIUrl":"10.1007/s10735-025-10431-5","url":null,"abstract":"<div><p>Neural plasticity was considered as the principal mechanism for learning and memory many decades ago. So our study aims to figure out the underlying mechanisms of myelin plasticity associated with learning and memory. Myelin was considered for a long time as static, inert insulator, irrelevant to learning. But recent studies showed that myelination is dynamically changed to enhance neuronal plasticity. The study was conducted on 24 rats, divided into 3 groups, with 8 rats in each: Group 1: control in cages; Group 2: control untrained; and Group 3: rats were trained using Barnez maze behavior test. The gene expression analysis for <i>Sox10</i>, <i>Myrf</i>, <i>Nrg1</i>, <i>Bdnf</i>, <i>Serpine2</i> and <i>Mbp</i> was evaluated by qRT-PCR in hippocampus tissues with correlation assessment, and histopathological and immunohistochemistry assessment were done. The present study showed improved spatial memory with increased myelination in the trained group, in addition to high expression of <i>Sox10</i>, <i>Myrf</i>, <i>Nrg1</i> and <i>Bdnf</i> in the trained group compared to all others (<i>P</i> &lt; 0.001). <i>Serpine2</i> and <i>GFAP</i> as markers of astrocytes showed high expression in the trained group in comparison with other groups (<i>P</i> &lt; 0.001) with strong positive correlation between <i>Serpine2</i> and <i>Mbp</i> (r = 0.76, <i>P</i> = 0.02). Myelin plasticity as one of the crucial learning mechanisms, was influenced by different neural and environmental signals. In addition, there was a significant role of astrocytes in promoting such myelination effect.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144091181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A diet-driven metabolic dysfunction-associated steatohepatitis (MASH) mouse model resembles the corresponding human disease","authors":"Guilherme Ribeiro Romualdo,&nbsp;Letícia C. Valente,&nbsp;Gabriel P. Bacil,&nbsp;Luana Riechelmann-Casarin,&nbsp;Antônio R. B. da Fonseca,&nbsp;Miguel W. Fornes,&nbsp;Luís F. Barbisan","doi":"10.1007/s10735-025-10449-9","DOIUrl":"10.1007/s10735-025-10449-9","url":null,"abstract":"<div><p>Most of the available preclinical Metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatitis (MASH) models fail to resemble metabolic comorbidities and liver fibrosis. To establish a standard MASLD/MASH model, we characterized some morphological, biochemical, and transcriptomic features in a Western diet-induced MASLD model in mice, depicting its similarities to the corresponding human disease. Male C57BL/6J mice received a hypercaloric diet containing sucrose, saturated fat, and cholesterol-rich chow, and high sugar solution for 24 weeks. This model featured a distinct MASH phenotype with obesity, impaired glucose metabolism, hypercholesterolemia, extensive macro and microvesicular, liver steatosis, and slight-to-moderate pericellular/perisinusoidal fibrosis, which was in keeping with the increased hepatic levels of IL-6 and TNF-α, and upregulation of 18 collagen subunit genes (as <i>Col1a1</i>, <i>Col1a2</i>, <i>Col3a1</i>, <i>Col5a2</i>, <i>Col4a1</i>, <i>Col6a3</i>, <i>Col14a1</i>, <i>Col6a2</i>, <i>Col5a1</i>), 34 cytokines or chemokines or related receptors-coding genes (as <i>Il15</i>, <i>Cxcl9</i>, <i>Ccl22</i>), 18 TNF-related genes (as <i>Tnfaip8l3</i>, <i>Tnfrsf21</i>, <i>Tnfaip8</i>, <i>Tnfrfs12a</i>) and 12 metalloproteinase/tissue inhibitors of metalloproteinases-related genes (as <i>Mmp2</i>, <i>Mmp7</i>). The downregulated genes were negative regulators of gluconeogenesis, insulin secretion, and lipid biosynthesis, most belonging to the major urinary protein (MUP) family. The computational analysis of human samples revealed a similarity between our bioassay and human steatohepatitis, with the upregulation of fibrosis- and inflammation-associated orthologs (<i>COL1A1</i>, <i>COL1A2</i>, <i>COL3A1</i>, <i>COL5A2</i>, <i>COL4A1</i>, <i>COL6A3</i>, <i>COL14A1</i>, <i>COL6A2</i>, <i>COL5A1</i>, <i>TNFAIP8L3</i>, <i>TNFRSF21</i>, <i>TNFAIP8</i>, <i>TNFRFS12A</i>, <i>IL15</i>, <i>CXCL9</i>, <i>CCL22</i>, <i>MMP2</i>, <i>MMP7</i>). Our mouse model may be applied as a standard MASH translational bioassay, providing valuable insights into the inflammatory/fibrosis axis of this chronic disease, from the pathogenesis to therapeutic intervention.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144090975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysregulated autophagy in periodontal ligament stem cells of individuals with type 2 diabetes mellitus and periodontitis","authors":"Qian-Qian Chen,&nbsp;Jie Huang,&nbsp;Qi Liu,&nbsp;Kun Yang","doi":"10.1007/s10735-025-10455-x","DOIUrl":"10.1007/s10735-025-10455-x","url":null,"abstract":"<div><p>This study aimed to investigate autophagy and its associated mechanisms in periodontal ligament stem cells (PDLSCs) within the inflammatory microenvironment of type 2 diabetes mellitus (T2DM) and periodontitis. Periodontal ligament tissues were obtained from healthy individuals, individuals with T2DM, individuals with chronic periodontitis, and individuals with both T2DM and periodontitis. PDLSCs were isolated, cultured, and treated with the autophagy inhibitor 3-methyladenine (3-MA) and the autophagy activator rapamycin (Rapa). Cell proliferative capacity was evaluated, autophagic activity and organelle damage were assessed using transmission electron microscopy, and the relative expression levels of autophagy-related genes (<i>Beclin-1</i>,<i> LC3 II</i>,<i> P62</i>) were measured using real-time quantitative PCR. Compared to PDLSCs derived from healthy individuals, those from individuals with chronic periodontitis or T2DM exhibited no significant morphological differences but demonstrated reduced proliferative capacity. Treatment with 3-MA and Rapa did not significantly alter proliferative capacity across groups. PDLSCs from individuals with chronic periodontitis and T2DM displayed increased autophagosome formation, more severe organelle damage, and upregulated expression of autophagy-related genes <i>Beclin-1</i> and <i>LC3 II</i>, while P62 expression was downregulated, compared to PDLSCs from healthy individuals. PDLSCs from individuals with T2DM and periodontitis exhibit excessive autophagy and organelle damage. Autophagy dysregulation in PDLSCs within a diabetic and inflammatory microenvironment may contribute to the severity of periodontal destruction observed in individuals with T2DM.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144090974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of autologous cytokine-rich serum and platelet-rich plasma administration on oxidative status, minerals and proinflammatory cytokines in brain and serum in cyclophosphamide-induced ovarian failure","authors":"Mustafa Ermiş,&nbsp;Erol Karakaş,&nbsp;Hanifi Erol,&nbsp;Gökhan Akcakavak,&nbsp;Recai Aci,&nbsp;Furkan Ümit,&nbsp;Özhan Karatas,&nbsp;Gülay Çiftci","doi":"10.1007/s10735-025-10448-w","DOIUrl":"10.1007/s10735-025-10448-w","url":null,"abstract":"<div><p>Cyclophosphamide (CP) is one of the most commonly used chemotherapy agents and carries a high risk of ovarian damage. This study aimed to evaluate the effects of autologous cytokine-rich serum (ACRS) and platelet-rich plasma (PRP) on brain oxidative status, mineral levels, and proinflammatory cytokines in rats with CP-induced ovarian failure. A total of 42 female Wistar rats (12-weeks-old) were used in the study. Six of these rats were allocated as donors, and the remaining 36 rats were randomly distributed into six groups (n = 6 per group). Group 1 received no treatment. On the 1st and 7th days, 75 mg/kg of CP was administered intraperitoneally to Groups 4, 5, and 6. On day 1, PRP was administered intraovarianly to Groups 2 and 5, while ACRS was administered intraovarianly to Groups 3 and 6. Additionally, PRP and ACRS were administered intraperitoneally to the respective groups on 7th and 14th days.The study was terminated at the end of the 31st day. Brain tissue and blood samples were collected for biochemical analyses and ovarian tissue samples were collected for histomorphological examinations. Morphological analysis using Hematoxylin–Eosin (HE) staining and immunohistochemical evaluation for AMH, α-SMA, and IL-1β were conducted on the ovaries. Proinflammatory cytokines and insulin levels were measured using ELISA test kits. TAS/TOS levels were assessed using Relassay Diagnostic kits. Biochemical parameters and mineral levels were measured using autoanalyzer. Histopathological evaluation revealed that follicular degeneration, congestion, hemorrhage, edema, and inflammatory cell infiltration, as well as the number of atretic follicles and IL-1β immunoreactivity, were observed at the highest levels in the CP group (Group 4). In contrast, the numbers of primordial, primary, secondary, and tertiary follicles, along with AMH and α-SMA immunoreactivity levels, were found to be the lowest in this group. However, positive therapeutic effects were observed in the CP-treated groups (Groups 5 and 6). In the serum, increased levels of AST, ALT, creatinine, glucose, LDL, TOS, Ca, Fe, Mg, IL-1β, IL-1α, TNF-α, and NF-kB were detected in the CP groups (G4, G5, G6) compared to the control groups (G1, G2, and G3). In brain tissue, a decrease of total protein and total cholesterol levels were observed in the CP groups (G4, G5, G6) compared to the control groups, while increases in Na, Cl, Fe, IL-1β, IL-1α, TNF-α, and NF-kB levels were detected. In conclusion, PRP and ACRS therapies from the patient's own blood have a potential as supportive or chemopreventive strategies with reduced side effects and treatment costs.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144084810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}