Journal of Molecular Histology最新文献

{"title":"Subcellular localization of SARS-CoV-2 E and 3a proteins along the secretory pathway","authors":"Joshua J. Hinkle,&nbsp;Kathleen A. Trychta,&nbsp;Emily S. Wires,&nbsp;Raven M. Osborn,&nbsp;Justin R. Leach,&nbsp;Zoha F. Faraz,&nbsp;Reinis Svarcbahs,&nbsp;Christopher T. Richie,&nbsp;Stephen Dewhurst,&nbsp;Brandon K. Harvey","doi":"10.1007/s10735-025-10375-w","DOIUrl":"10.1007/s10735-025-10375-w","url":null,"abstract":"<div><p>SARS-CoV-2 E and 3a proteins are important for the assembly, budding, and release of viral particles. These two transmembrane proteins have been implicated in forming channels in the membrane that allow the transport of ions to favor viral replication. During an active infection, both proteins generally localize to the endoplasmic reticulum (ER), ER-Golgi intermediate compartment (ERGIC), and the Golgi where viral assembly occurs. The ER and Golgi are critical for the proper packaging and trafficking of cellular proteins along the secretory pathways which determine a protein’s final destination inside or outside of the cell. The SARS-CoV-2 virus primarily infects epithelial cells that are highly secretory in nature such as those in the lung and gut. Here we quantified the distribution of SARS-CoV-2 E and 3a proteins along the secretory pathways in a human intestinal epithelial cell line. We used NaturePatternMatch to demonstrate that epitope-tagged E and 3a proteins expressed alone via transient transfection have a similar immunoreactivity pattern as E and 3a proteins expressed by wild-type viral infection. While E and 3a proteins localized with all selected cellular markers to varying degrees, 3a protein displayed a higher correlation coefficient with the Golgi, early/late endosome, lysosome, and plasma membrane when compared to E protein. This work is the first to provide quantification of the subcellular distribution of E and 3a proteins along the multiple components of the secretory pathway and serves as a basis to develop models for examining how E and 3a alter proteostasis within these structures and affect their function.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10735-025-10375-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143521705","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":"Nebivolol attenuates acute systemic inflammation induced testicular dysfunction by decreasing transendothelial migration via VCAM-1/MMP-9 signaling","authors":"Ercan Bas,&nbsp;Halil Asci,&nbsp;Yalcin Erzurumlu,&nbsp;Halil Ibrahim Buyukbayram,&nbsp;Deniz Catakli,&nbsp;Adem Milletsever,&nbsp;Orhan Imeci,&nbsp;Ozlem Ozmen","doi":"10.1007/s10735-025-10376-9","DOIUrl":"10.1007/s10735-025-10376-9","url":null,"abstract":"<div><p>Nebivolol (NB), which is a commonly used β₁ adrenoreceptor blocker, shows protective effects against oxidative stress and inflammation-related processes. In this study, we aimed to evaluate the possible protective effects of NB via the vascular cell adhesion molecule-1/matrix metalloproteinases-9 (VCAM-1/MMP-9) signaling pathway on systemic inflammation induced testicular dysfunction. Four groups of 32 male Wistar Albino rats were divided as (<i>n</i> = 8 for each) the control; lipopolysaccharide (LPS; 5 mg/kg on the third day); LPS + NB (NB: 10 mg/kg for three days and 5 mg/kg LPS 30 min following the last NB dose); NB (10 mg/kg for three days). Six hours following the LPS administration, rats were sacrificed, then testicular tissues were collected for evaluating total oxidant status (TOS), total antioxidant status and oxidative stress index (OSI) levels biochemically, VCAM-1 and MMP-9 mRNA expression levels, caspase-3 (cas-3), tumor necrosis factor-alpha (TNF-α) expressions by immunohistochemically. Systemic inflammation caused significant increases in TOS and OSI levels, VCAM-1, MMP-9, cas-3, TNF-α expressions, and a decrease of the spermatozoa count compared to the control group. NB administration successfully restored all these changes significantly. Thus, NB can be a protective drug candidate for testicular dysfunction secondary to systemic inflammation with its potent antioxidant and anti-inflammatory mechanisms.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143496812","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":"Effects of simulated microgravity on dental pulp stem cell stemness","authors":"Huailong Hou,&nbsp;Zhengjun Qiu,&nbsp;Jingyi Che,&nbsp;Yanping Li,&nbsp;Jingxuan Sun,&nbsp;Weiwei Zhang,&nbsp;Jinjie Ma,&nbsp;Shuang Zhang,&nbsp;Mengdi Li,&nbsp;Yumei Niu,&nbsp;Lina He","doi":"10.1007/s10735-025-10377-8","DOIUrl":"10.1007/s10735-025-10377-8","url":null,"abstract":"<div><p>Dental pulp stem cells (DPSCs), a subset of tooth-derived mesenchymal stem cells (MSCs), demonstrate significant promise in clinical stem cell therapy. However, prolonged in vitro expansion commonly results in compromised stemness, limiting therapeutic efficacy. Thus, maintaining the stemness of DPSCs during expansion and culture is a key challenge for regenerative medicine. In the current study, the impact of simulated microgravity (SMG) on DPSC stemness was investigated using the three-dimensional clinostat Cellspace-3D. After SMG treatment for 3 days, DPSCs demonstrated markedly enhanced replicative activity, proliferation efficiency, self-renewal capacity, and effective inhibition of the senescence process. Under specific differentiation induction conditions, DPSCs in the SMG group exhibited superior osteogenic, adipogenic, chondrogenic, and neural differentiation potentials. Additionally, DPSCs exhibited higher expression levels of the MSC surface markers Stro-1 and CD146 and stemness maintenance-related genes Oct4, Nanog, and Sox2 in the SMG group compared to those from the normal gravity (NG) group. To elucidate the potential molecular mechanisms by which SMG influences the stemness of DPSCs, transcriptome sequencing of total RNA was performed, and identified that differentially expressed genes (DEGs) are closely associated with the MAPK signaling pathway. Further verification experiments demonstrated that the MAPK/ERK signaling pathway was activated in the SMG group. In conclusion, SMG effectively maintains the stemness of DPSCs cultivated in vitro, and its mechanism of action may be associated with the activation of the MAPK/ERK signaling pathway.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143496813","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":"FAM64A regulates the malignant phenotype and tumor microenvironment of non-small cell lung cancer by activating the JAK/STAT3/PDL1 axis","authors":"Shuo Shi,&nbsp;Jiahui Han,&nbsp;Qianbiao Wu,&nbsp;Haoqiu Zhong,&nbsp;Binfeng Lei,&nbsp;Yibo Yan","doi":"10.1007/s10735-024-10339-6","DOIUrl":"10.1007/s10735-024-10339-6","url":null,"abstract":"<div><p>Non-small cell lung cancer (NSCLC) is a life-threatening disease that still lacks effective targeted treatment. Family with sequence similarity 64, member A (FAM64A) is dysregulated in different malignancies and participates in the cancer progression. To address the role of FAM64A in NSCLC. The FAM64A expression was detected by reverse transcription quantitative polymerase chain reaction and western blotting. Short-hairpin RNAs (shRNAs) against FAM64A were transfected into A549 and H460 cells. The role of FAM64A in vitro was evaluated by cell counting kit-8, transwell, enzyme-linked immunosorbent assay, immunofluorescence and western blotting. In vivo role of FAM64A was addressed in xenografted mice using immunohistochemistry and western blotting. FAM64A was upregulated in NSCLC that predicted a dismal prognosis for NSCLC patients. Knockdown of FAM64A diminished cell viability, invaded cell numbers, the Vimentin expression and the concentrations of TGF-β and IL-10, but fostered the E-cadherin expression and the concentrations of IL-2 and IFN-γ in NSCLC cells. Mechanistically, silencing of FAM64A declined the expression of JAK/STAT3/PD-L1 pathway, which was restored with the application of RO8191, an activator of JAK/STAT3 pathway. The inhibitory role of FAM64A knockdown in NSCLC cell proliferation, invasion, EMT and immune escape was inverted by the management of RO8191. In vivo, knockdown of FAM64A reduced tumor size and weight, the level of Vimentin and PD-L1, and the expression of JAK/STAT3/PD-L1 pathway, but enhanced the IFN-γ level. Upregulation of FAM64A promoted proliferation, invasion, EMT and immune escape through activating JAK/STAT3/PD-L1 axis.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475274","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":"Molecular roles in membrane receptor signaling pathways and cascade reactions in chondrocytes: a review","authors":"Yingkang Zhu,&nbsp;Jingjing Zhu,&nbsp;Xu Wang,&nbsp;Pengbo Wang,&nbsp;Ruiyu Liu","doi":"10.1007/s10735-025-10368-9","DOIUrl":"10.1007/s10735-025-10368-9","url":null,"abstract":"<div><p>Articular cartilage (AC) is a specialized connective tissue with unique biological and mechanical properties, which depends on the biological effects of each resident chondrocyte and its surrounding extracellular matrix (ECM) to form a unit that operates in a constant and balanced feedback loop. The surface membrane receptors of chondrocytes play a crucial role in the feedback balance of this biological unit. Various biological signals outside chondrocytes, such as water-soluble chemical signal molecules and mechanical signals, are unable to directly enter the cell and must first bind to the plasma membrane receptors to induce changes in the level and activity of intracellular signal transduction molecules. These changes then transmit through signaling cascade pathways into the nucleus, changing the cell phenotype, and producing physiological or pathological changes. Specific chemical and mechanical signals break the feedback balance of cartilage tissue units through membrane receptors. In the ECM environment, the molecular actions of chondrocyte membrane receptors in response to these specific signals, along with associated ion channel receptors, collectively regulate the biological effects of chondrocytes. This leads to decreased chondrocyte survival and an imbalance in ECM regulation, ultimately disrupting the tissue’s molecular framework and physiological feedback mechanisms, and resulting in pathological changes in cartilage tissue. To provide insights into addressing the complexities associated with cartilage tissue injury and repair engineering, this review provides a comprehensive overview of the molecular mechanisms and biological implications of chondrocyte membrane receptor-mediated signal transduction, including G protein-coupled receptors (GPCRs), enzyme-linked receptors (tyrosine kinase receptors (TKRs)), and integrin receptors.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475135","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 Dalbergiella welwitschi alkaloid-rich leaf extracts on testicular damage in streptozotocin-induced diabetic rats","authors":"B. O. Ajiboye,&nbsp;F. I. Ayemoni,&nbsp;C. D. Famusiwa,&nbsp;O. E. Lawal,&nbsp;J. A. Falode,&nbsp;S. A. Onikanni,&nbsp;M. F. Akhtar,&nbsp;S. Gupta,&nbsp;B. E. Oyinloye","doi":"10.1007/s10735-025-10366-x","DOIUrl":"10.1007/s10735-025-10366-x","url":null,"abstract":"<div><p>Diabetes mellitus is a chronic disease affecting young and old, even though it can be managed with orthodox medicine, which has a series of side effects. Therefore, <i>Dalbergiella welwitschi</i> is one of the medicinal plants that is commonly used for the management of diabetes mellitus and its associated complications. Hence, this study was designed to assess the testicular-protective ability of alkaloid-rich leaf extract of <i>D. welwitschi</i> in streptozotocin-induced type 2 diabetic rats <i>D. welwitshii</i> leaf alkaloid-rich extract was obtained using standard procedure. Streptozotocin was injected into the experimental animals intraperitoneally at a dose of 45 mg/kg body weight to induce type 2 diabetes mellitus. Prior to this, the animals were given 20% (w/v) fructose for one week. Thus, the animals were grouped into five (n = 8), comprising of un-induced rats (NC), diabetic control (DC), diabetic rats treated with low (50 mg/kg body weight) and high (100 mg/kg body weight) doses of <i>D. welwitschi</i> alkaloid-rich leaf extracts (i.e., DWL and DWH respectively) and 200 mg/kg body weight dose of metformin (MET). The animals were sacrificed on the 21st day, blood and testis were harvested and used for the determination of ions (Fe, Cu and Zn), sialic acid, some hormones (testosterone, luteinizing and follicle stimulating), oxidative stress biomarkers [malondialdehyde<b> (</b>MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and glutathione (GSH)] as well as histological examination. In addition, the results show that diabetic rats placed on DWL, and DWH significantly (p &lt; 0.05) decreased ion levels (Fe, Cu and Zn) and ameliorated oxidative stress biomarkers such as MDA, SOD, CAT, GPx, GST, and GSH. These were supported by the histological examination by improving testicular-protective effects in diabetic rats administered DWL, and DWH. Therefore, it is that assume that the alkaloid-rich leaf extracts of <i>D. welwitschi</i> may offer potential benefits in the treatment of diabetic testicular dysfunction.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143455560","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 the anti-diabetic properties of camel milk: effects on blood glucose, antioxidant defense, and organ histo-morphological features in rabbits","authors":"Muhammad Asif Arain,&nbsp;Gul Bahar Khaskheli,&nbsp;Ghulam Shabir Barham,&nbsp;Qurban Ali Shah,&nbsp;Fazul Nabi,&nbsp;Mikhlid H. Almutairi,&nbsp;Bader O. Almutairi,&nbsp;Illahi Bakhash Marghazani","doi":"10.1007/s10735-025-10371-0","DOIUrl":"10.1007/s10735-025-10371-0","url":null,"abstract":"<div><p>Camel milk (CM) has acquired substantial consideration in contemporary years owing to its potential prospective pharmaceutical benefits besides nutritional properties. As, CM retain inimitable composition and attain sophisticated concentration of bioactive compounds, thus helps in regulation of blood glucose level, and improves insulin sensitivity. Contemporary study intends to explore anti-diabetic inflictions of CM, besides body weight, blood profile, antioxidant defense and organ integrity in diabetic rabbits. To achieve this, a total of 36 rabbits was randomly alienated into six equal groups (<i>N</i> = 6), such as control, control + camel milk, diabetic control, insulin treated, camel milk treated, and CM + insulin. Diabetes was induced by injecting STZ (50-mg/kg). The diabetic rabbits were treated either with CM (100 ml/rabbit/day), or insulin (6 unit/kg/day) and their combination (CM-30 ml + insulin 3-unit/day) for 42 days. Body weight, blood glucose level and hematological indices were measured weekly. Reduced body weight, elevated blood glucose level and altered hematological indices were noticed in diabetes induced rabbits. On the contrary, improved weight gain, glycemic level, anti-oxidant defense and blood chemistry were noticed in groups treated with camel milk individually and insulin; conversely, non-significant changes were seen in CM + insulin treated group. Diabetic control group revealed gross-pathological changes in liver, kidney, intestine and pancreas. CM and insulin augmented organ integrity and stability. Convincingly, these outcomes strongly indicate therapeutic potential of CM that regulated hyperglycemic condition and mitigated the negative impact of diabetes in organ histomorphology.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143438607","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":"PBX1 attenuates inflammation and apoptosis of trophoblast cells induced by LPS through downregulating the transcription of TMUB1: PBX1 ameliorates RSA development","authors":"Xiuping Zhang,&nbsp;Shimin Wang,&nbsp;Lixia Liang,&nbsp;Fen Hu,&nbsp;Xueluo Zhang,&nbsp;Xiangrong Cui,&nbsp;Zhiping Zhang,&nbsp;Xueqing Wu","doi":"10.1007/s10735-025-10364-z","DOIUrl":"10.1007/s10735-025-10364-z","url":null,"abstract":"<div><p>Recurrent spontaneous abortion (RSA) brings tremendous difficulties to clinical treatment and prognosis. Pre-B-cell leukemia homeobox 1 (PBX1), as a functional transcription factor, involves in the regulation of cell apoptosis and proliferation. However, the underlying mechanism of PBX1 in RSA treatment has not been explored. We established a lipopolysaccharide (LPS)-induced abortion model and detected PBX1 expression with real-time PCR, western blot and immunohistochemistry. The PBX1-overexpressed adenovirus (AV-oePBX1) was infected into trophoblast cells treated with LPS to define the function of PBX1 on cell apoptosis, inflammation and NF-κB pathway. A luciferase reporter assay was conducted to validate the transcription regulation of PBX1 on transmembrane and ubiquitin like domain containing 1 (TMUB1). Compared to women with normal abortion, PBX1 was downregulated in the placental villous tissues of RSA patients. The placental tissues of LPS-treated mice also manifested notably reduction of PBX1 at mRNA and protein levels. PBX1 overexpression alleviated inflammation and apoptosis of trophoblast cells. Substantially, PBX1 was negatively correlated with TMUB1, which was highly expressed in RSA patients and LPS-treated mice. Moreover, PBX1 bound to TMUB1 promoter and inhibited its transcription. Interestingly, exogenous TMUB1 abolished the effects of PBX1 on apoptosis, inflammation, and NF-κB signal pathway. In total, PBX1 attenuated cell apoptosis and inflammation, and suppressed NF‐κB signal pathway induced by LPS through downregulating TMUB1 transcription. Therefore, PBX1 may be developed as a novel target for clinical treatment of RSA.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143430907","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":"miR-504-3p-HNF1B signaling axis aggravates podocyte injury in diabetic kidney disease","authors":"Yibo Zhuang,&nbsp;Lingtao Zhu,&nbsp;Chenlu Fu,&nbsp;Huiping Ni","doi":"10.1007/s10735-025-10369-8","DOIUrl":"10.1007/s10735-025-10369-8","url":null,"abstract":"<div><p>Recently, microRNAs (miRNAs) have been found to mediate the development of diabetic kidney disease (DKD) by regulating podocyte injury. The aim of this study was to investigate the influence of miR-504-3p on high glucose (HG)-treated mouse renal podocytes (MPC5) and its potential regulatory mechanisms. First, a DKD cell model was established. Next, RT-qPCR was performed to measure miR-504-3p and HNF1 Homeobox B (<i>HNF1B</i>) expression levels. Additionally, the proliferation and apoptosis of MPC5 cells were assessed using CCK-8 assay and Flow cytometry, respectively. The protein expression levels of cell fibrotic markers, podocyte injury marker, epithelial-mesenchymal transition (EMT) markers and HNF1B were measured by Western Blotting. ROS, MDA, SOD and GSH kits were used to assess oxidative stress levels. Furthermore, the interplay between miR-504-3p and <i>HNF1B</i> was confirmed by luciferase reporter experiments. The miR-504-3p expression was significantly upregulated in GEO database (GSE161884) and in HG-induced MPC5 cells. The results revealed that HG treatment decreased MPC5 cell proliferation, promoted cell apoptosis and fibrosis, and ultimately led to podocyte injury. However, miR-504-3p knockdown could reverse these phenotypes and reduce podocyte injury. Moreover, online database screening combined with dual luciferase reporter assay confirmed <i>HNF1B</i> as a specific target of miR-504-3p. Finally, overexpression of <i>HNF1B</i> mitigated the proliferation inhibition and apoptosis promotion induced by oxidative stress and inhibited EMT-mediated cell fibrosis, thereby counteracting the effects of miR-504-3p on podocyte injury under HG treatment. In summary, our data indicate that miR-504-3p regulates HG-induced podocyte injury by sponging <i>HNF1B</i>, providing a new direction for the treatment of DKD.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143423357","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":"Ciliary neurotrophic factor attenuates myocardial infarction-induced oxidative stress and ferroptosis via PI3K/Akt signaling","authors":"Jian Wang,&nbsp;Nan Wu,&nbsp;Jie Zhang,&nbsp;Xiaojing Li,&nbsp;Yingchu Hu,&nbsp;Jiating Dai,&nbsp;Caijie Shen,&nbsp;Xiaomin Chen","doi":"10.1007/s10735-025-10359-w","DOIUrl":"10.1007/s10735-025-10359-w","url":null,"abstract":"<div><h3>Background</h3><p>As a member of the interleukin-6 family, ciliary neurotrophic factor (CNTF) regulates inflammation, oxidative stress, and other processes to exhibit neurotrophic and differentiating effects over cells in the central nervous system. It has not yet been documented, therefore, if CNTF influences the cardiac remodeling brought on by myocardial infarction (MI). The purpose of the current investigation was to identify the function and underlying mechanisms of CNTF in cardiac remodeling brought on by MI.</p><h3>Methods</h3><p>Using an adeno-associated virus 9 (AAV9) system and tail vein injection, we overexpressed CNTF in the hearts. To create a model of MI, C57BL/6 mice underwent left anterior descending (LAD) ligation. The following techniques were employed to assess the impact of CNTF overexpression and the underlying mechanisms: quantitative real-time PCR, western blotting, histological analysis, immunofluorescence and immunohistochemistry analysis, and echocardiography. We used H9c2 cells to confirm CNTF’s in vitro effects.</p><h3>Results</h3><p>In MI mice, overexpression of CNTF prevents cardiac hypertrophy and cardiac fibrosis. Furthermore, oxidative stress and ferroptosis in response to MI damage were markedly reduced by CNTF overexpression. Mechanistically, overexpression of CNTF in both in vivo and in vitro markedly enhanced PI3K/Akt signaling. However, blocking this pathway effectively negated the beneficial impact of CNTF overexpression.</p><h3>Conclusions</h3><p>Our research indicates that via initiating the PI3K/Akt signaling pathway, CNTF controls myocardial dysfunction, oxidative stress, and ferroptosis in MI-induced cardiac remodeling. CNTF may have therapeutic potential in treating MI-induced cardiac remodeling.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143423306","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}