Journal of Molecular Histology最新文献

{"title":"In vivo and in silico analysis of anti inflammatory, antipyretic and analgesic activity of methanolic extract of Nigella sativa","authors":"Nureen Zahra,&nbsp;Saher Fatima,&nbsp;Anum Nazir,&nbsp;Syeda Yumna Farrukh,&nbsp;Ayesha Anwer,&nbsp;Abid Sarwar,&nbsp;Tariq Aziz,&nbsp;Fahad Al Asmari,&nbsp;Aziza Mahdy Nahari,&nbsp;Rewa S. Jalal,&nbsp;Fakhria A. Al-Joufi,&nbsp;Maher S. Alwethaynani","doi":"10.1007/s10735-025-10399-2","DOIUrl":"10.1007/s10735-025-10399-2","url":null,"abstract":"<div><p><i>Nigella Sativa</i> (<i>N. sativa</i>) belongs to the family of Ranunculaceae and is an annual herb which is also known as black cumin or black seed. Since ancient times <i>N. sativa</i> has been used because of its widespread therapeutic properties which has been proven effective in respiratory, cardiovascular, gastrointestinal, inflammatory conditions and in inflammation. This study investigates the antiinflammatory, antipyretic, and analgesic properties of <i>Nigella sativa</i> (<i>N. sativa</i>) methanol extract using albino rats (n = 36). Diclofenac and paracetamol were used as standard medications in the trial, and the four concentrations of the methanolic extract (250, 500, 1000, and 2000 mg/kg) were tested for their effects on inflammation, pain, and fever. The methanolic extract of <i>N. sativa</i> seeds showed significant inhibition of fever (96%), inflammation (89%), and pain (85%). In addition, bioactive compounds in the seeds, including thymol, p-cymene, and limonene, were examined through <i>in-silico</i> studies. Ligand molecules and proteins associated with anti-inflammatory, analgesic, and antipyretic effects were 1DFN, 1A06, and 3LN0, respectively. The molecular docking results indicated significant binding interactions, with effective binding energy values corresponding to analgesic, antipyretic, and anti-inflammatory properties. Both in-silico and in-vivo results demonstrate the efficacy of <i>N. sativa</i> methanol extract in alleviating pain, inflammation, and fever.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676413","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":"Ramipril ameliorates endometriosis by inducing oxidative stress-mediated apoptosis in the wistar rat","authors":"Piyali Mazumdar,&nbsp;Shampa Sarkar Biswas","doi":"10.1007/s10735-025-10397-4","DOIUrl":"10.1007/s10735-025-10397-4","url":null,"abstract":"<div><p>Endometriosis is illustrated by the presence of ectopic endometrial cells capable of evading apoptosis outside the uterus. Apoptotic and anti-apoptotic factors in the extra uterine microenvironment can be compromised by the impairment in oxidative status. Angiotensin Converting Enzyme (ACE) Inhibitors and Nitric Oxide (NO) modulators play pivotal role in inflammation, angiogenesis, apoptosis and in abrogating oxidative imbalance. Therefore, in the current study we investigate the role of ACE inhibitor and or NO modulators in mitigating the proliferation of ectopic endometrial lesions in rat model. Sixty adult female virgin wistar rats were utilized; out of which fifteen were used as donor rats and rest forty-two were randomly divided into seven groups after surgical implantation of endometrial explants into rats (group II–VII). Histomorphometric assessment of uteri and ectopic lesions was performed by Hematoxylin and eosin (H-E) staining, followed by immunohistochemical study for Proliferating cell nuclear antigen (PCNA), Bax and Bcl-2. Oxidative stress parameters were evaluated by biochemical estimations, succeeded by immunoblotting of Poly [ADP-ribose] polymerase 1 (PARP1). Additionally, immunoblotting of Vascular endothelial growth factor (VEGF), Bax, Bcl-2 and caspase-3 was also performed. Significant decrease in the diameter of lesions with diffused staining at the extracellular spaces of stromal cells for PCNA accompanied by significant decrease in the expression of VEGF (<i>p</i> &lt; 0.00001) was observed in group III. Furthermore, increased expression of Bax:Bcl-2 ratio (<i>p</i> &lt; 0.001) and cleaved caspase-3 (<i>p</i> ≤ 0.0001) in ectopic lesions of group III was also observed. Administration of ramipril alone results in triggering oxidative stress mediated cleavage of PARP1, augmenting apoptosis in the ectopic lesions.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676403","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-378d suppresses gastric cancer metastasis by targeting METTL4 to inhibit epithelial-mesenchymal transition","authors":"Danjie Xing,&nbsp;Jiapeng Bao,&nbsp;Jiancheng He,&nbsp;Hanxu Gao,&nbsp;Wanjiang Xue,&nbsp;Junjie Chen,&nbsp;Jia Li","doi":"10.1007/s10735-025-10392-9","DOIUrl":"10.1007/s10735-025-10392-9","url":null,"abstract":"<div><p>Metastasis is a major determinant of prognosis in gastric cancer (GC), and microRNAs (miRNAs) play crucial roles in driving the metastatic process. This study aimed to identify key miRNAs involved in GC metastasis and elucidate their underlying mechanisms. GC tissues from patients with and without metastasis were subjected to miRNA sequencing to identify differentially expressed miRNAs. Expression differences between GC and normal tissues, as well as their correlation with patient survival, were analyzed using data from The Cancer Genome Atlas and an internal cohort. miR-378d expression was measured by RT-qPCR in the internal cohort, and its association with clinicopathological features and prognosis was analyzed. Gene Set Enrichment Analysis (GSEA) was performed to investigate the potential mechanisms by which miR-378d influences GC metastasis. The findings were validated through in vitro wound healing, transwell assays, western blotting, and immunofluorescence, as well as in vivo models. MiRNA sequencing identified miR-378d as significantly downregulated in GC tissues and associated with poor prognosis. GSEA showed that miR-378d was negatively correlated with epithelial-mesenchymal transition (EMT). In vitro and in vivo experiments demonstrated that upregulation of miR-378d inhibited GC cell migration and invasion. Mechanistically, miR-378d suppressed EMT by downregulating METTL4 expression. miR-378d inhibits GC metastasis by suppressing EMT through the downregulation of METTL4, offering novel insights into the role of miRNAs in GC progression and highlighting potential therapeutic targets for intervention.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143667980","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":"Taraxasterol attenuates inflammatory responses in a 2,4-dinitrochlorobenzene-induced atopic dermatitis mouse model via inactivation of the MAPK and NF-κB pathways","authors":"Yu Zhang,&nbsp;Guoping Peng,&nbsp;Rusheng Zhang","doi":"10.1007/s10735-025-10391-w","DOIUrl":"10.1007/s10735-025-10391-w","url":null,"abstract":"<div><p>Atopic dermatitis (AD) is an inflammatory skin disease. Taraxasterol has anti-inflammatory effects in various pathological processes. In this study, our goal is to detect the biological functions of taraxasterol and its related mechanisms in AD development. The mouse model of experimental AD was established through application of 2’,4-dintrochlorobenzene (DNCB) onto the mouse dorsal skin. Taraxasterol (2.5, 5, and 10 mg/kg) was orally administrated to AD mice. Effects of taraxasterol on AD-like skin symptoms were examined through assessment of ratios of skin lesion area/dorsal skin region, skin thickness, skin hydration, and starching number. Histopathological changes were detected by performing H&amp;E staining. ELISA kits were obtained to measure serum TNF-α and IgE levels. RT-qPCR was conducted to measure mRNA levels of proinflammatory factors. Expression of MAPKs and NF-κB signaling was evaluated by western blotting. Taraxasterol alleviated AD-like skin symptoms (erosions, erythema, scaling, dryness, pruritus) and reduced lesion area and skin thickness in mice with DNCB-induced AD. Taraxasterol decreased epidermal thickness and serum levels of IgE and TNF-α and prevented the release of proinflammatory factors in lesion sites in of DNCB-induced AD mice. Mechanistically, taraxasterol inactivated the MAPK and NF-κB pathways. Taraxasterol alleviates AD-like skin symptoms and inflammation in a DNCB-induced AD mouse model via inactivation of the MAPK and NF-κB pathways.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143667981","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":"Notch 2 from bone marrow mesenchymal stem cells alleviates smoke inhalation-induced lung injury by mediating alveolar cell differentiation","authors":"Cunping Yin,&nbsp;Xiaoyan Wang,&nbsp;Yanmei Tao,&nbsp;Xiaoqing Wu,&nbsp;Yuan Li,&nbsp;Haiping Li,&nbsp;Yuan Liang","doi":"10.1007/s10735-025-10393-8","DOIUrl":"10.1007/s10735-025-10393-8","url":null,"abstract":"<div><h3>Background</h3><p>Smoke inhalation-induced lung injury (SILI) is the major fatality in fire- and blast-related accidents. Bone marrow mesenchymal stem cells (BMSCs) have a potential therapeutic role in SILI through directional differentiation into AT1, AT2, and pulmonary vascular endothelial cells. The present study proposes to evaluate the effect of Notch 2 on the directional differentiation of BMSCs and to characterize its reparative role in a SILI model.</p><h3>Methods</h3><p>pGMLV-SC5 RNAi and pcDNA 3.1 lentivirus exogenously regulate Notch 2 expression in rat-derived BMSCs and BMSCs were injected into the tail vein of the SILI rat model. H&amp;E, Masson and TUNEL stains characterized pathological changes in rat lung tissue. ELISA, western blot, and RT-qPCR identified inflammatory factors (IL-1β, IL-6 and TNF-α), Notch 2 pathway- (Notch 2 and Hes1), lung fibrosis- (α-SMA and E-cadherin), AT1- (AQP5), and AT2- (SPC and SPD) associated markers.</p><h3>Results</h3><p>pGMLV-SC5 RNAi or pcDNA 3.1 lentivirus could decrease or increase Notch 2 expression in BMSCs. In vivo imaging showed that BMSCs could be localized in the lungs of the SILI model at 24 h after model development. Treatment with BMSCs alleviated diffuse congestion, lung fibrosis, and alveolar cell apoptosis in lung tissues of the SILI model. Treatment of BMSCs decreased the levels of IL-1β, IL-6, TNF-α, and α-SMA and increased the expression of Notch 2, Hes1, E-cadherin, AQP5, SPC, and SPD in the SILI model. Overexpression of Notch 2 enhances the therapeutic effect of BMSCs on lung injury in the SILI model. Notably, overexpression of Notch 2 attenuated the BMSCs-induced upregulation of AQP5 expression and enhanced the BMSCs-induced upregulation of SPC and SPD expression.</p><h3>Conclusion</h3><p>Notch 2 contributes to lung injury repair in the SILI rat model by facilitating the differentiation of BMSCs to AT2. This study provides a new idea and target for the treatment of BMSCs for SILI.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143667990","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":"Direct exposure with exogenous mitochondria reduce colistin-induced mitochondrial dysfunction and cellular damages in isolated rat renal proximal tubular cells","authors":"Abdollah Arjmand,&nbsp;Ahmad Salimi,&nbsp;Maryam Mohammadabadi,&nbsp;Mehrdad Faizi,&nbsp;Amir Fakhri,&nbsp;Zhaleh Jamali,&nbsp;Jalal Pourahmad","doi":"10.1007/s10735-025-10389-4","DOIUrl":"10.1007/s10735-025-10389-4","url":null,"abstract":"<div><p>Kidney damage caused by colistin (polymyxin E) can bring about a decrease in creatinine clearance, potential proteinuria, cylindruria and oliguria in treated patients. It is therefore imperative to develop a new therapeutic strategy for reducing kidney damage after treatment with colistin. Mitochondrial damage is one of contributing factors in colistin-induced nephrotoxicity. Given the therapeutic benefits of mitochondrial transplantation by exogenous healthy mitochondria, we hypothesized that this strategy would be capable of ameliorating renal proximal tubular cells damage following exposure with colistin. For this purpose, we isolated rat renal proximal tubular cells (RPTCs) form kidney and exposed them with toxic concertation of colistin with/without rat healthy isolated mitochondria for 4 h. Cellular parameters such as lactate dehydrogenase (LDH), reactive oxygen species (ROS) formation, mitochondrial membrane potential (MMP), caspase 3 activation, lysosomal damage, glutathione and ATP content were measured. The results showed that administration of isolated mitochondria could improve colistin-induced nephrotoxicity and reduce mitochondrial dysfunction. Exogenous mitochondria reduced the activity of LDH, production of ROS, ATP and GSH depletion, loss of MMP, lysosomal damages and cell death. To the best of our knowledge, these results provide the first direct experimental evidence that direct exposure with exogenous mitochondria is capable of ameliorating cellular damage following treatment with colistin. These findings support that mitochondrial transplantation may be a promising therapeutic strategy for colistin-associated mitochondrial dysfunction in kidney cells.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143667989","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":"Serum proteomic profiling reveals potential predictive indicators for coronary artery calcification in stable ischemic heart disease","authors":"Haiyan Wu,&nbsp;Mingjie Pang,&nbsp;Haoqiang Chen,&nbsp;Ke Zhuang,&nbsp;Hong Zhang,&nbsp;Yan Zhao,&nbsp;Xiaoxue Ding","doi":"10.1007/s10735-025-10388-5","DOIUrl":"10.1007/s10735-025-10388-5","url":null,"abstract":"<div><p>Coronary artery calcification (CAC) is a common complication in patients with stable ischemic heart disease (SIHD). However, the early diagnosis and understanding of the pathogenesis of CAC in SIHD patients remain underdeveloped. This study aimed to analyze aberrant alterations in the serum proteome of SIHD patients, as well as SIHD patients with severe CAC (CAC_SIHD), and to explore the potential risk factors of CAC in SIHD patients. Serum proteomic profiles were obtained from individuals with SIHD (n = 6), CAC_SIHD (n = 6), and healthy controls (n = 9), and were analyzed using nano liquid chromatography tandem mass spectrometry (LC–MS/MS). The aberrant alterations in proteins and immune cells in the serum of SIHD and CAC_SIHD patients were characterized through differential protein expression analysis and single-sample gene set enrichment analysis analysis, respectively. Differentially expressed proteins (DEPs) were further subjected to gene ontology functional enrichment and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Finally, Receiver Operating Characteristic analysis was performed on the DEPs between SIHD and CAC_SIHD to identify potential predictive factors of CAC. Abnormalities in multiple complement pathways and lipid metabolism were observed in SIHD and CAC_SIHD patients. Moreover, SIHD and CAC_SIHD were characterized by an increased presence of T cells and natural killer cells, along with a reduced presence of B cells. Subsequent analysis of serum proteins revealed that RNASE1 and MSLN may be potential predictive indicators for the early detection and diagnosis of CAC in SIHD patients. In conclusion, our research extensively examined the variations in serum proteins in patients with SIHD and CAC_SIHD, identifying key indicators and metabolic pathways associated with these conditions. These findings not only provide new insights into the pathological mechanisms of SIHD and CAC_SIHD, but also suggest potential factors for the early diagnosis of CAC in SIHD patients, which imply potential clinical applications.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10735-025-10388-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143645492","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":"Protective effects of N-acetylcysteine against titanium dioxide nanoparticles-induced kidney damage in rats","authors":"Cengiz Yuksel,&nbsp;Yesim Hulya Uz","doi":"10.1007/s10735-025-10395-6","DOIUrl":"10.1007/s10735-025-10395-6","url":null,"abstract":"<div><p>The objective of this study was to evaluate the potential protective effect of <i>N</i>-acetylcysteine (NAC) against kidney damage induced by titanium dioxide nanoparticles (TiO₂NP) through biochemical, histological, and immunohistochemical analyses. Forty rats were randomly divided into four groups of 10 animals each. Saline was administered intragastrically to control group for 14 days. In NAC group, 150 mg/kg NAC was injected intraperitoneally for 21 days. In TiO₂NP group, TiO₂NP at a dose of 50 mg/kg/day, dissolved in saline, was administered intragastrically for 14 days. TiO₂NP + NAC group received 50 mg/kg/day TiO₂NP for 14 days and 150 mg/kg NAC for 21 days, starting 7 days before TiO₂NP administration. At the end of experiment, rats were anesthetized, serum samples were collected for biochemical analysis, and kidney tissue was removed for histological and immunohistochemical analyses. There was no significant change in body weight, kidney weight, or serum urea-creatinine levels between the groups. TiO₂NP caused a significant increase in vacuolization and brush border loss scores in tubular cells, as well as scores for congestion and leukocyte infiltration. However, NAC supplementation significantly ameliorated these impairments. Additionally, TiO₂NP significantly increased NF-kB, TNF-α, and caspase-3 immunoreactivities, as well as the number of PCNA-positive and TUNEL-positive cells. NAC treatment decreased all immunoreactivities and TUNEL-positive cells, but did not change the number of PCNA-positive cells after TiO₂NP exposure. The results of the study showed that the toxic effects of TiO₂NP on the kidneys, commonly encountered in daily life, can be mitigated by the anti-inflammatory and anti-apoptotic properties of NAC.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143645510","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":"Curcumin protects rat endplate chondrocytes against IL-1β-induced apoptosis via Bcl-2/Bax regulation","authors":"Chao Wan,&nbsp;Shixing Liu,&nbsp;Long Zhao,&nbsp;Chengbing Chang,&nbsp;Hewen Li,&nbsp;Rui Li,&nbsp;Bin Chen","doi":"10.1007/s10735-025-10390-x","DOIUrl":"10.1007/s10735-025-10390-x","url":null,"abstract":"<div><p>The study aims to investigate the protective effect of curcumin on intervertebral disc degeneration by examining its influence on IL-1β-induced apoptosis in rat cartilage endplate cells. The rat primary chondrocytes treated by IL-1 β at 10 ng /mL was utilized as a rat model in intervertebral disc degeneration, followed by incubation with different concentration of curcumin (10, 15, 20 μmol/L). Cell apoptosis and cell proliferation were conducted through flow cytometry and CCK-8, respectively. Furthermore, immunofluorescence staining was used to visualize the expression of Bax and Bcl-2 inside the cells. Western blotting was performed to determine the expression of the Bax and Bcl-2. Curcumin promoted proliferation of chondrocytes treated by IL-1 β, but inhibited the apoptosis. Importantly, curcumin significantly downregulated the expression level of Bax but upregulated the expression level of Bcl-2. Strengths of this study include the use of multiple assays to validate the findings, while limitations include the in vitro nature and lack of in vivo data. Curcumin is capable of ameliorating IL-1β -induced intervertebral disc degeneration by Bcl-1 and Bax production. This study provides a foundation for future research into curcumin’s therapeutic potential in intervertebral disc degeneration.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143645553","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":"Nell-1 inhibits lipopolysaccharide-activated macrophages into M1 phenotype through the modulation of NF-κB pathway","authors":"Yue Chen,&nbsp;Qiang Wang,&nbsp;Mengyue Li,&nbsp;Yixuan Fang,&nbsp;Xiuting Bi,&nbsp;Jiameng Wu,&nbsp;Qi Han,&nbsp;Hongfan Zhu,&nbsp;Zhien Shen,&nbsp;Xiaoying Wang","doi":"10.1007/s10735-025-10385-8","DOIUrl":"10.1007/s10735-025-10385-8","url":null,"abstract":"<div><p>Nel-like molecule-1 (Nell-1), as a novel osteo-inductive molecule with great potential for clinical applications, has various functions including promoting chondrogenesis, suppressing osteoclastic activity, promoting osteogenesis, suppressing inflammation and promoting vascularization. Its anti-inflammatory potential has been widely studied. However, its anti-inflammatory potential in macrophage and possible underlying molecular mechanisms are poorly understood. Therefore, the present study aims to evaluate the anti-inflammatory potential and the regulation to macrophage polarization of Nell-1 in human myeloid cell line (THP-1) derived macrophages. M1-related markers and M2-related markers were studied in THP-1 derived macrophages. The suppressive potential of Nell-1 on lipopolysaccharide (LPS)-induced translocation of nuclear factor-kappa B (NF-κB) in THP-1 macrophage was studied. Results showed that Nell-1 significantly reduced M1 macrophage-related surface marker cluster of differentiation 86 (CD86) and inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β) and reversed the LPS-induced M1 polarization of macrophages by upregulating the M2-specific markers of vascular endothelial growth factor (VEGF), arginase-1(Arg-1), and cluster of differentiation 206 (CD206) in vitro. In addition, the possible mechanism of the anti-inflammatory effects of Nell-1 is via regulating NF-κB pathway. Hence, Nell-1 is a potential suppressor of inflammation and is involved in the regulation of macrophage polarization. Nell-1 may be a potential candidate for treating inflammatory diseases and promoting tissue regeneration.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143632499","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}