Journal of Cellular and Molecular Medicine最新文献

{"title":"IL-38: A novel cytokine in systemic lupus erythematosus pathogenesis.","authors":"Wang-Dong Xu,&nbsp;Lin-Chong Su,&nbsp;Xiao-Yan Liu,&nbsp;Jia-Min Wang,&nbsp;Zhi-Chao Yuan,&nbsp;Zhen Qin,&nbsp;Xi-Ping Zhou,&nbsp;An-Fang Huang","doi":"10.1111/jcmm.15737","DOIUrl":"https://doi.org/10.1111/jcmm.15737","url":null,"abstract":"<p><p>IL-38 is a newly identified cytokine that belongs to the IL-1 family. In our previous study, we found elevated plasma levels of IL-38 in patients with systemic lupus erythematosus (SLE). However, the clear relationship of IL-38 expression in plasma, peripheral blood mononuclear cells (PBMCs) and clinical and laboratory features needs elucidation. Additionally, we evaluated the possible role of IL-38 in regulating production of inflammatory cytokines in PBMCs in vitro. A pristane-induced murine lupus model was used to further demonstrate the effects of IL-38 on cytokines in vivo and discuss the significance of IL-38 in lupus development. The results showed that mRNA expression of IL-38 in PBMCs of patients with SLE was elevated compared with volunteers, and expression of IL-38 in both plasma and PBMCs was strongly related to clinical features, such as haematuria and proteinuria, and correlated with a SLEDAI score. Plasma levels of TNF-α, IL-1β, IL-6 and IL-23 were elevated in patients with SLE and were related to plasma levels of IL-38. In vitro, PBMCs of patients with SLE stimulated with IL-38 showed a decreased expression of the four inflammatory cytokines compared with PBMCs of patients without treatment. Interestingly, IL-38 administration in lupus mice significantly reduced the development of lupus, such as reduced proteinuria, improved histological examinations of the kidneys and down-regulated inflammatory cytokines. In conclusion, IL-38 may suppress synthesis of pro-inflammatory cytokines and therefore regulate lupus pathogenesis.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/jcmm.15737","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38507567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroRNA-497 elevation or LRG1 knockdown promotes osteoblast proliferation and collagen synthesis in osteoporosis via TGF-β1/Smads signalling pathway.","authors":"ZhengTao Gu,&nbsp;DengHui Xie,&nbsp;CaiQiang Huang,&nbsp;Rui Ding,&nbsp;RongKai Zhang,&nbsp;QingChu Li,&nbsp;ChuangXin Lin,&nbsp;YiYan Qiu","doi":"10.1111/jcmm.15826","DOIUrl":"https://doi.org/10.1111/jcmm.15826","url":null,"abstract":"<p><p>MicroRNAs (miRNAs) have been corroborated to engage in the process of cellular activities in osteoporosis. However, few researches have been conducted to expose the integrated role of miR-497, leucine-rich alpha-2-glycoprotein-1 (LRG1) and transforming growth factor beta 1 (TGF-β1)/Smads signalling pathway in osteoporosis. Thereafter, the study is set out to delve into miR-497/LRG1/TGF-β1/Smads signalling pathway axis in osteoporosis. Osteoporosis bone tissues and normal bone tissues were collected. Rat osteoporosis models were constructed via ovariectomy. Model rats were injected with restored miR-497 or depleted LRG1 to explore their roles in osteoporosis. Rat osteoblasts were extracted from osteoporosis rats and transfected with restored miR-497 or depleted LRG1 for further verification. MiR-497 and LRG1 expression in femoral head tissues and osteoblasts of osteoporosis rats were detected. TGF-β1/Smads signalling pathway-related factors were detected. MiR-497 was poorly expressed while LRG1 was highly expressed and TGF-β1/Smads signalling pathway activation was inhibited in osteoporosis. MiR-497 up-regulation or LRG1 down-regulation activated TGF-β1/Smads signalling pathway, promoted collagen type 1 synthesis and suppressed oxidative stress in femoral head tissues in osteoporosis. MiR-497 restoration or LRG1 knockdown activated TGF-β1/Smads signalling pathway, promoted viability and suppressed apoptosis of osteoblasts in osteoporosis. Our study suggests that miR-497 up-regulation or LRG1 down-regulation promotes osteoblast viability and collagen synthesis via activating TGF-β1/Smads signalling pathway, which may provide a novel reference for osteoporosis treatment.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/jcmm.15826","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38514990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endoplasmic reticulum stress remodels alveolar bone formation after tooth extraction.","authors":"Yun Chen,&nbsp;Yue Guo,&nbsp;Jun Li,&nbsp;Ying-Yi Chen,&nbsp;Qiong Liu,&nbsp;Li Tan,&nbsp;Zheng-Rong Gao,&nbsp;Shao-Hui Zhang,&nbsp;Ying-Hui Zhou,&nbsp;Yun-Zhi Feng","doi":"10.1111/jcmm.15753","DOIUrl":"https://doi.org/10.1111/jcmm.15753","url":null,"abstract":"<p><p>Bone healing in tooth extraction sockets occurs in a complex environment containing saliva and many microorganisms and is affected by many factors. Endoplasmic reticulum (ER) stress affects bone metabolism, but the role of ER stress in bone healing after tooth extraction remains unclear. We utilized a rat tooth extraction model, in which we promoted wound healing by using salubrinal to regulate the ER stress response. Western blot analysis showed increased expression of p-eIF2α/eIF2α, Runx2 and alkaline phosphatase (ALP) in bone tissue, and histological assays showed irregularly arranged and new bone with more collagen fibres 14 days after tooth extraction and after modulating the degree of ER stress. Micro-CT showed that modulating ER stress to an appropriate degree increases bone filling in regards to the density in the bottom and the surrounding bone wall of the tooth extraction wounds. Transmission electron microscopy showed rough ER expansion and newly formed collagen fibrils in osteoblasts after modulating ER stress to an appropriate degree. We also used different concentrations of salubrinal to evaluate the resistance to tunicamycin-induced ER stress in an osteogenic induction environment. Salubrinal restored the tunicamycin-induced decrease in the viability of primary calvarial osteoblasts and increased the expression of Runx2 and ALP, and decreased p-eIF2α/eIF2α in a dose-dependent manner. Taken together, the results demonstrate that ER stress occurred after tooth extraction, and regulating the degree of ER stress can promote bone healing in tooth extraction sockets, providing clinical evidence for bone healing.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/jcmm.15753","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38533428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Curcumin alleviates oxidative stress and inhibits apoptosis in diabetic cardiomyopathy via Sirt1-Foxo1 and PI3K-Akt signalling pathways.","authors":"Bin-Cheng Ren,&nbsp;Yu-Fei Zhang,&nbsp;Shan-Shan Liu,&nbsp;Xiao-Jing Cheng,&nbsp;Xin Yang,&nbsp;Xiao-Guang Cui,&nbsp;Xin-Rui Zhao,&nbsp;Hui Zhao,&nbsp;Min-Feng Hao,&nbsp;Meng-Dan Li,&nbsp;Yuan-Yuan Tie,&nbsp;Li Qu,&nbsp;Xue-Yi Li","doi":"10.1111/jcmm.15725","DOIUrl":"https://doi.org/10.1111/jcmm.15725","url":null,"abstract":"<p><p>Diabetes is a disorder of glucose metabolism, and over 90% are type 2 diabetes. Diabetic cardiomyopathy (DCM) is one of the type 2 diabetes complications, usually accompanied by changes in myocardial structure and function, together with cardiomyocyte apoptosis. Our study investigated the effect of curcumin on regulating oxidative stress (OS) and apoptosis in DCM. In vivo, diabetes was induced in an experimental rat model by streptozoticin (STZ) together with high-glucose and high-fat (HG/HF) diet feeding. In vitro, H9c2 cardiomyocytes were cultured with high-glucose and saturated free fatty acid palmitate. Curcumin was orally or directly administered to rats or cells, respectively. Streptozoticin -induced diabetic rats showed metabolism abnormalities and elevated markers of OS (superoxide dismutase [SOD], malondialdehyde [MDA], gp91^phox , Cyt-Cyto C), enhanced cell apoptosis (Bax/Bcl-2, Cleaved caspase-3, TUNEL-positive cells), together with reduced Akt phosphorylation and increased Foxo1 acetylation. Curcumin attenuated the myocardial dysfunction, OS and apoptosis in the heart of diabetic rats. Curcumin treatment also enhanced phosphorylation of Akt and inhibited acetylation of Foxo1. These results strongly suggest that apoptosis was increased in the heart of diabetic rats, and curcumin played a role in diabetic cardiomyopathy treatment by modulating the Sirt1-Foxo1 and PI3K-Akt pathways.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/jcmm.15725","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38406382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IFI30 expression is an independent unfavourable prognostic factor in glioma.","authors":"Xiu Liu,&nbsp;Chunyan Song,&nbsp;Shoubo Yang,&nbsp;Qiang Ji,&nbsp;Feng Chen,&nbsp;Wenbin Li","doi":"10.1111/jcmm.15758","DOIUrl":"https://doi.org/10.1111/jcmm.15758","url":null,"abstract":"<p><p>Gamma-interferon-inducible lysosomal thiol reductase, the only known lysosomal thiol reductase, is encoded by gene IFI30 and expressed constitutively in antigen-presenting cells. Our comprehensive study on IFI30 in gliomas found its expression to be high in glioblastomas and in gliomas with a mesenchymal subtype or wild-type isocitrate dehydrogenase, all of which indicated the malignancy and poor outcomes of gliomas. Kaplan-Meier survival analysis ascertained that high IFI30 expression conferred poor outcomes. The IFI30 expression levels also showed high efficiency in predicting 1-, 3- and 5-year overall survival. Univariable and multivariable Cox regression analyses were performed to define IFI30 as an independent prognostic marker. Biological process analysis suggested that IFI30 was involved in immune responses. ESTIMATE and CIBERSORT were applied to evaluate immune cell infiltration, with results indicating that samples with higher IFI30 expression had higher infiltration of immune cells, including regulatory T cells and M0 macrophages. Correlation analysis showed that IFI30 was significantly positively correlated with immune checkpoints that suppress effective antitumour immune responses. Immunohistochemical staining was also performed to confirm the association between IFI30 expression and the immune phenotype. The suggested correlation between high IFI30 expression and an immunosuppressive phenotype contributes to our knowledge about the glioma microenvironment and might provide clues for the development of novel therapeutic targets.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/jcmm.15758","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38416207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CircFOXP1/FOXP1 promotes osteogenic differentiation in adipose-derived mesenchymal stem cells and bone regeneration in osteoporosis via miR-33a-5p.","authors":"Wanxiang Shen,&nbsp;Bin Sun,&nbsp;Chenghong Zhou,&nbsp;Wenyi Ming,&nbsp;Shaohua Zhang,&nbsp;Xudong Wu","doi":"10.1111/jcmm.15792","DOIUrl":"https://doi.org/10.1111/jcmm.15792","url":null,"abstract":"<p><p>Osteoporosis (OP) is defined by bone mass loss and structural bone deterioration. Currently, there are no effective therapies for OP treatment. Circular RNAs (circRNAs) have been reported to have an important function in stem cell osteogenesis and to be associated with OP. Most circRNA roles in OP remain unclear. In the present study, we employed circRNA microarray to investigate circRNA expression patterns in OP and non-OP patient bone tissues. The circRNA-miRNA-mRNA interaction was predicted using bioinformatic analysis and confirmed by RNA FISH, RIP and dual-luciferase reporter assays. ARS and ALP staining was used to detect the degree of osteogenic differentiation in human adipose-derived mesenchymal stem cells (hASCs) in vitro. In vivo osteogenesis in hASCs encapsulated in collagen-based hydrogels was tested with heterotopic bone formation assay in nude mice. Our research found that circFOXP1 was significantly down-regulated in OP patient bone tissues and functioned like a miRNA sponge targeting miR-33a-5p to increase FOXP1 expression. In vivo and in vitro analyses showed that circFOXP1 enhances hASC osteogenesis by sponging miR-33a-5p. Conversely, miR-33a-5p inhibits osteogenesis by targeting FOXP1 3'-UTR and down-regulating FOXP1 expression. These results determined that circFOXP1 binding to miR-33a-5p promotes hASC osteogenic differentiation by targeting FOXP1. Therefore, circFOXP7ay prevent OP and can be used as a candidate OP therapeutic target.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/jcmm.15792","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38437575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thrombospondin-2 stimulates MMP-9 production and promotes osteosarcoma metastasis via the PLC, PKC, c-Src and NF-κB activation.","authors":"Ju-Fang Liu,&nbsp;Po-Chun Chen,&nbsp;Tsung-Ming Chang,&nbsp;Chun-Han Hou","doi":"10.1111/jcmm.15874","DOIUrl":"https://doi.org/10.1111/jcmm.15874","url":null,"abstract":"<p><p>Osteosarcoma is an extremely common primary bone malignancy that is highly metastatic, with most deaths resulting from pulmonary metastases. The extracellular matrix protein thrombospondin-2 (TSP-2) is key to many biological processes, such as inflammation, wound repair and tissue remodelling. However, it is unclear as to what biological role TSP-2 plays in human metastatic osteosarcoma. The immunochemistry analysis from osteosarcoma specimens identified marked up-regulation of TSP-2 in late-stage osteosarcoma. Furthermore, we found that TSP-2 increased the levels of matrix metallopeptidase 9 (MMP-9) expression and thereby increased the migratory potential of human osteosarcoma cells. Osteosarcoma cells pre-treated with an MMP-9 monoclonal antibody (mAb), an MMP-9 inhibitor, or transfected with MMP-9 small interfering RNA (siRNA) reduced the capacity of TSP-2 to potentiate cell migration. TSP-2 treatment activated the PLCβ, PKCα, c-Src and nuclear kappa factor B (NF-κB) signalling pathways, while the specific siRNA, inhibitors and mutants of these cascades reduced TSP-2-induced stimulation of migration activity. Knockdown of TSP-2 expression markedly reduced cell metastasis in cellular and animal experiments. It appears that an interaction between TSP-2 and integrin αvβ3 activates the PLCβ, PKCα and c-Src signalling pathways and subsequently activates NF-κB signalling, increasing MMP-9 expression and stimulating migratory activity amongst human osteosarcoma cells.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/jcmm.15874","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38458253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological rationale for antihypertensive drug choice on COVID-19-affected patients: ACEI/ARB might not increase their susceptibility.","authors":"Hong-Jin Zhao, Xiao-Mei Yang, Ai-Hong Wang, Yan Li","doi":"10.1111/jcmm.15850","DOIUrl":"10.1111/jcmm.15850","url":null,"abstract":"Dear Editor, The novel coronavirus outbreak is threatening human health globally mainly through causing severe acute respiratory syndrome (SARS), and this coronavirus is named as SARS-CoV-2 (severe acute respiratory coronavirus 2) to be differentiated from SARS-CoV in 2003. SARS-CoV-2 spreads mainly through the respiratory route and uses membrane-bound ACE2 (angiotensin-converting enzyme 2) as the receptor to enter into the cells for replication.1 The receptor ACE2 is a single-pass membrane protein, and its extracellular enzymatic domain is classically known to convert Ang II (angiotensin II) to Ang1-7 in RAS (renin-angiotensin systems).2 When cleaved from the cell membrane, ACE2 enters into the blood and this secreted ACE2 loses the ability to mediate the coronavirus infection. The membranebound ACE2-mediated SARS infection consumes a large proportion of ACE2 molecules, leading to the down-regulation of ACE2/Ang1-7 and up-regulation of Ang II. This imbalance of the RAS system eventually results in exacerbation of inflammation in lung tissues and cardiovascular dysfunction.3 To avoid the adverse effects of Ang II on the cardiovascular system, ACEI/ARB (angiotensin-converting enzyme inhibitors/Ang II receptor blockers) is used as the first-line medicine in the treatment of hypertension and heart failure through inhibiting the production or function of Ang II.4 Considering the large consumption of ACE2 due to the SARS infection and the subsequent increased Ang II accumulation, the drug choice ACEI/ARB should be more suitable for the treatment of hypertensive COVID19 (coronavirus disease 2019) patients. This drug strategy will rebalance the RAS system and prevent the progression from pneumonia to severe ARDS in theory. Recently, Fang et al5 have suggested the conversion of ACEI/ ARB to CCB (calcium channel blockers) for hypertensive patients based on studies reporting the up-regulatory effects of ACEI/ARB on ACE2 expression, which could contribute to increased sensitivity to SARS-CoV-2 infection. A study has shown the increased cardiac ACE2 mRNA levels by ACEI/ARB administration.6 Moreover, ARB has been implicated in up-regulating the cardiac and renal ACE2 protein levels.7,8 However, Western blot data are lacking to experimentally distinguish ACE2 molecules in full-length membrane form from those in cleaved/secreted form due to their similar molecular weight. As a result, a note of caution is needed when interpreting the roles of ACE2 expression levels in SARS-CoV-2 infection as the cleaved ACE2 could not function as the receptor for coronavirus to invade the target cells. Importantly, the existing evidence does not support the exclusion of ACEI/ARB from the treatment of hypertensive patients without/with COVID-19. Hilliard et al9 have demonstrated the up-regulation of ACE2/ Ang1-7 pathways in pre-menopausal women, compared with older women, suggesting the lower expression and/or activity of ACE2 in ageing women. Similarly, Xie et al10 have display","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/jcmm.15850","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38490327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small RNA sequencing reveals a novel tsRNA-06018 playing an important role during adipogenic differentiation of hMSCs.","authors":"Tao Wang, Lingling Cao, Shan He, Kai Long, Xinping Wang, Hui Yu, Baicheng Ma, Xiaoyuan Xu, Weidong Li","doi":"10.1111/jcmm.15858","DOIUrl":"10.1111/jcmm.15858","url":null,"abstract":"<p><p>Transfer RNA-derived small RNAs (tsRNAs), a novel type of non-coding RNA derivative, are able to regulate a wide range of biological processes. What role these tsRNAs play in the regulation of human bone marrow mesenchymal stem cell (hMSCs) adipogenic differentiation remains uncertain. We induced the adipogenic differentiation of human bone marrow mesenchymal cells (hMSCs) and then performed small RNA transcriptomic sequencing, leading us to identify tsRNA-06018 as a target of interest based upon resultant the tsRNA expression profiles. When tsRNA-06018 was knocked down, this led to the inhibition of adipogenesis and a decrease in adipogenic marker expression. When STC2 was overexpressed, this impaired the adipogenic differentiation of these cells. We further used luciferase reporter assays to confirm that tsRNA-06018 directly binds the 3'-untranslated region (3'-UTR) of STC2. In addition, we determined that both knocking down tsRNA-06018 and overexpressing STC2 increased extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation within cells. We also assessed that the adipogenic differentiation of hMSCs in which tsRNA-06018 was knocked down was further enhanced upon the addition of the ERK1/2 inhibitor U0126 as compared tsRNA-06018 knockdown alone. Taken together, using small RNA sequencing we profiled tsRNAs in hMSCs during the process of adipogenesis, leading us to identify tsRNA-06018 as a novel regulator of this differentiation process. This tsRNA was able to regulate adipogenic differentiation by targeting STC2 via the ERK1/2 signalling pathway.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38485840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunomodulatory effects of berberine on the inflamed joint reveal new therapeutic targets for rheumatoid arthritis management.","authors":"Peng Shen, Yang Jiao, Li Miao, Ji-Hua Chen, Amir Abbas Momtazi-Borojeni","doi":"10.1111/jcmm.15803","DOIUrl":"10.1111/jcmm.15803","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is a chronic inflammatory syndrome designated by synovial joint inflammation leading to cartilage degradation and bone damage as well as progressive disability. Synovial inflammation is promoted through the infiltration of mononuclear immune cells, dominated by CD4⁺ T cells, macrophages and dendritic cells (DCs), together with fibroblast-like synoviocytes (FLS), into the synovial compartment. Berberine is a bioactive isoquinoline alkaloid compound showing various pharmacological properties that are mainly attributed to immunomodulatory and anti-inflammatory effects. Several lines of experimental study have recently investigated the therapeutic potential of berberine and its underlying mechanisms in treating RA condition. The present review aimed to clarify determinant cellular and molecular targets of berberine in RA and found that berberine through modulating several signalling pathways involved in the joint inflammation, including PI3K/Akt, Wnt1/β-catenin, AMPK/lipogenesis and LPA/LPA₁ /ERK/p38 MAPK can inhibit inflammatory proliferation of FLS cells, suppress DC activation and modulate Th17/Treg balance and thus prevent cartilage and bone destruction. Importantly, these molecular targets may explore new therapeutic targets for RA treatment.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7687014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38412740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}