Latest Issue
Issue 12 ， 2022
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Circular RNAs: typical biomarkers for bone-related diseases
Abstract：Bone is a connective tissue that has important functions in the human body. Cells and the extracellular matrix (ECM) are key components of bone and are closely related to bone-related diseases. However, the outcomes of conventional treatments for bone-related diseases are not promising, and hence it is necessary to elucidate the exact regulatory mechanisms of bone-related diseases and identify novel biomarkers for diagnosis and therapy. Circular RNAs (circRNAs) are single-stranded RNAs that form closed circular structures without a 5' cap or 3' tail and polycyclic adenylate tails. Due to their high stability, circRNAs have the potential to be typical biomarkers. Accumulating evidence suggests that circRNAs are involved in bone-related diseases, including osteoarthritis, osteoporosis, osteosarcoma, multiple myeloma, intervertebral disc degeneration, and rheumatoid arthritis. Herein, we summarize the recent research progress on the characteristics and functions of circRNAs, and highlight the regulatory mechanism of circRNAs in bone-related diseases.Keywords：Circular RNA;Bone-related disease;Competing endogenous RNA (ceRNA);MicroRNA- 77
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Published：2022-12-15
Review
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Macrophage migration inhibitory factor protects bone marrow mesenchymal stem cells from hypoxia/ischemia-induced apoptosis by regulating lncRNA MEG3
Abstract：ObjectiveThis research was performed to explore the effect of macrophage migration inhibitory factor (MIF) on the apoptosis of bone marrow mesenchymal stem cells (BMSCs) in ischemia and hypoxia environments.MethodsThe cell viability of BMSCs incubated under hypoxia/ischemia (H/I) conditions with or without pretreatment with MIF or triglycidyl isocyanurate (TGIC) was detected using cell counting kit-8 (CCK-8) analysis. Plasmids containing long noncoding RNA (lncRNA) maternally expressed gene 3 (MEG3) or β-catenin small interfering RNA (siRNA) were used to overexpress or downregulate the corresponding gene, and the p53 signaling pathway was activated by pretreatment with TGIC. The influences of MIF, overexpression of lncRNA MEG3, activation of the p53 signaling pathway, and silencing of β-catenin on H/I-induced apoptosis of BMSCs were revealed by western blotting, flow cytometry, and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) staining.ResultsFrom the results of CCK-8 assay, western blotting, and flow cytometry, pretreatment with MIF significantly decreased the H/I-induced apoptosis of BMSCs. This effect was inhibited when lncRNA MEG3 was overexpressed by plasmids containing MEG3. The p53 signaling pathway was activated by TGIC, and β-catenin was silenced by siRNA. From western blot results, the expression levels of β-catenin in the nucleus and phosphorylated p53 (p-p53) were downregulated and upregulated, respectively, when the lncRNA MEG3 was overexpressed. Through flow cytometry, MIF was also shown to significantly alleviate the increased reactive oxygen species (ROS) level of BMSCs caused by H/I.ConclusionsIn summary, we conclude that MIF protected BMSCs from H/I-induced apoptosis by downregulating the lncRNA MEG3/p53 signaling pathway, activating the Wnt/β-catenin signaling pathway, and decreasing ROS levels.Keywords：Macrophage migration inhibitory factor (MIF);Long noncoding RNA (lncRNA);Maternally expressed gene 3 (MEG3);Bone marrow mesenchymal stem cells (BMSCs);β-Catenin;Apoptosis- 74
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Published：2022-12-15 -
Changes in the gut microbiota of osteoporosis patients based on 16S rRNA gene sequencing: a systematic review and meta-analysis
Abstract：BackgroundOsteoporosis (OP) has become a major public health issue, threatening the bone health of middle-aged and elderly people from all around the world. Changes in the gut microbiota (GM) are correlated with the maintenance of bone mass and bone quality. However, research results in this field remain highly controversial, and no systematic review or meta-analysis of the relationship between GM and OP has been conducted. This paper addresses this shortcoming, focusing on the difference in the GM abundance between OP patients and healthy controls based on previous 16S ribosomal RNA (rRNA) gene sequencing results, in order to provide new clinical reference information for future customized prevention and treatment options of OP.MethodsAccording to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), we comprehensively searched the databases of PubMed, Web of Science, Embase, Cochrane Library, and China National Knowledge Infrastructure (CNKI). In addition, we applied the R programming language version 4.0.3 and Stata 15.1 software for data analysis. We also implemented the Newcastle-Ottawa Scale (NOS), funnel plot analysis, sensitivity analysis, Egger’s test, and Begg’s test to assess the risk of bias.ResultsThis research ultimately considered 12 studies, which included the fecal GM data of 2033 people (604 with OP and 1429 healthy controls). In the included research papers, it was observed that the relative abundance of Lactobacillus and Ruminococcus increased in the OP group, while the relative abundance for Bacteroides of Bacteroidetes increased (except for Ireland). Meanwhile, Firmicutes, Blautia, Alistipes, Megamonas, and Anaerostipes showed reduced relative abundance in Chinese studies. In the linear discriminant analysis Effect Size (LEfSe) analysis, certain bacteria showed statistically significant results consistently across different studies.ConclusionsThis observational meta-analysis revealed that changes in the GM were correlated with OP, and variations in some advantageous GM might involve regional differences.Keywords：Osteoporosis;Microbiome;Intestinal;16S ribosomal RNA (rRNA) sequencing- 23
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Published：2022-12-15 -
Globular adiponectin-mediated vascular remodeling by affecting the secretion of adventitial-derived tumor necrosis factor-α induced by urotensin II
Abstract：ObjectivesIn this study, we explored how adiponectin mediated urotensin II (UII)-induced tumor necrosis factor-α (TNF-α) and α-smooth muscle actin (α-SMA) expression and ensuing intracellular signaling pathways in adventitial fibroblasts (AFs).MethodsGrowth-arrested AFs and rat tunica adventitia of vessels were incubated with UII and inhibitors of signal transduction pathways for 1‒24 h. The cells were then harvested for TNF-α receptor (TNF-α-R) messenger RNA (mRNA) and TNF-α protein expression determination by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Adiponectin and adiponectin receptor (adipoR) expression was measured by RT-PCR, quantitative real-time PCR (qPCR), immunohistochemical analysis, and cell counting kit-8 (CCK-8) cell proliferation experiments. We then quantified TNF-α and α-SMA mRNA and protein expression levels by qPCR and immunofluorescence (IF) staining. RNA interference (RNAi) was used to explore the function of the adipoR genes. To investigate the signaling pathway, we applied western blotting (WB) to examine phosphorylation of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK). In vivo, an adiponectin (APN)-knockout (APN-KO) mouse model mimicking adventitial inflammation was generated to measure TNF-α and α-SMA expression by application of qPCR and IF, with the goal of gaining a comprehensive atlas of adiponectin in vascular remodeling.ResultsIn both cells and tissues, UII promoted TNF-α protein and TNF-α-R secretion in a dose- and time-dependent manner via Rho/protein kinase C (PKC) pathway. We detected marked expression of adipoR1, T-cadherin, and calreticulin as well as a moderate presence of adipoR2 in AFs, while no adiponectin was observed. Globular adiponectin (gAd) fostered the growth of AFs, and acted in concert with UII to induce α-SMA and TNF-α through the adipoR1/T-cadherin/calreticulin/AMPK pathway. In AFs, gAd and UII synergistically induced AMPK phosphorylation. In the adventitial inflammation model, APN deficiency up-regulated the expression of α-SMA, UII receptor (UT), and UII while inhibiting TNF-α expression.ConclusionsFrom the results of our study, we can speculate that UII induces TNF-α protein and TNF-α-R secretion in AFs and rat tunica adventitia of vessels via the Rho and PKC signal transduction pathways. Thus, it is plausible that adiponectin is a major player in adventitial progression and could serve as a novel therapeutic target for cardiovascular disease administration.Keywords：Urotensin II;Adiponectin;Signal transduction;Adventitial fibroblast;RNA interference (RNAi);Adiponectin-knockout (APN-KO)- 18
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Published：2022-12-15 -
Development and validation of novel inflammatory response-related gene signature for sepsis prognosis
Abstract：Due to the low specificity and sensitivity of biomarkers in sepsis diagnostics, the prognosis of sepsis patient outcomes still relies on the assessment of clinical symptoms. Inflammatory response is crucial to sepsis onset and progression; however, the significance of inflammatory response-related genes (IRRGs) in sepsis prognosis is uncertain. This study developed an IRRG-based signature for sepsis prognosis and immunological function. The Gene Expression Omnibus (GEO) database was retrieved for two sepsis microarray datasets, GSE64457 and GSE69528, followed by gene set enrichment analysis (GSEA) comparing sepsis and healthy samples. A predictive signature for IRRGs was created using least absolute shrinkage and selection operator (LASSO). To confirm the efficacy and reliability of the new prognostic signature, Cox regression, Kaplan-Meier (K-M) survival, and receiver operating characteristic (ROC) curve analyses were performed. Subsequently, we employed the GSE95233 dataset to independently validate the prognostic signature. A single-sample GSEA (ssGSEA) was conducted to quantify the immune cell enrichment score and immune-related pathway activity. We found that more gene sets were enriched in the inflammatory response in sepsis patient samples than in healthy patient samples, as determined by GSEA. The signature of nine IRRGs permitted the patients to be classified into two risk categories. Patients in the low-risk group showed significantly better 28-d survival than those in the high-risk group. ROC curve analysis corroborated the predictive capacity of the signature, with the area under the curve (AUC) for 28-d survival reaching 0.866. Meanwhile, the ssGSEA showed that the two risk groups had different immune states. The validation set and external dataset showed that the signature was clinically predictive. In conclusion, a signature consisting of nine IRRGs can be utilized to predict prognosis and influence the immunological status of sepsis patients. Thus, intervention based on these IRRGs may become a therapeutic option in the future.Keywords：Gene signature;Inflammatory response-related gene (IRRG);Prognosis;Immune function;Sepsis- 22
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Differential bone metabolism and protein expression in mice fed a high-fat diet versus Daurian ground squirrels following natural pre-hibernation fattening
Abstract：This study compared the effects on bone metabolism and morphology of pathological obesity induced by excessive fat intake in a non-hibernator (mice) versus healthy obesity due to pre-hibernation fattening in a hibernator (ground squirrels). Kunming mice were fed a high-fat diet to provide a model of pathological obesity (OB group). Daurian ground squirrels fattened naturally in their pre-hibernation season (PRE group) were used as a healthy obesity model. Micro-computed tomography (micro-CT) and three-point bending tests were used to determine the microstructure and mechanical properties of bone. Western blots were used to analyze protein expression levels related to bone metabolism (Runt-related transcription factor 2 (RunX2), osteocalcin (OCN), alkaline phosphatase (ALP), osteoprotegerin (OPG), receptor activator of nuclear factor-κB ligand (RANKL), cathepsin K, matrix metallopeptidase 9 (MMP9), patched protein homolog 1 (Ptch1), phosphorylated β-catenin (P-β-catenin), and glycogen synthase kinase-3β (GSK-3β)). Compared with controls, there was no obvious bone loss in the OB mice, and the stiffness of the femur was increased significantly. Compared with summer active squirrels, bone formation was enhanced but the mechanical properties did not change in the PRE group squirrels. In OB mice, western blots showed significantly increased expression levels of all proteins except RunX2, OPG, and Ptch1. PRE ground squirrels showed significantly increased expression of most proteins except OCN and Ptch1, which decreased significantly, and P-β-catenin and OPG, which did not change. In conclusion, for non-hibernating mice, moderate obesity had a certain protective effect on bones, demonstrating two-way regulation, increasing both bone loss and bone formation. For pre-hibernating ground squirrels, the healthy obesity acquired before hibernation had a positive effect on the microstructure of bones, and also enhanced the expression levels of proteins related to bone formation, bone resorption, and Wnt signaling.Keywords：High-fat diet;Pre-hibernation fattening;Bone formation;Bone loss;Wnt signaling- 21
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Published：2022-12-15
Research Article
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Prevalence and risk factors of cardiovascular diseases and psychological distress among female scientists and technicians
Abstract：This study aimed to explore the prevalence and risk factors of cardiovascular disease (CVD) and psychological distress among female scientists and technicians in China. Accordingly, we included scientists and technicians from representative research institutions, medical institutions, colleges, universities, and businesses in China, and the data were collected from July 1, 2019 to March 31, 2021 via online questionnaires. The parameters evaluated in this study included age, sex, marital status, educational background, monthly income, sleep hours, sleep problems, smoking, alcohol consumption, work-related stress, work burnout, cardiovascular symptoms, CVD, family history, and depressive and anxiety symptoms. A total of 14 530 scientists and technicians were included, comprising 7144 men and 7386 women. We found 34.9% men and 16.6% women with CVD, 35.1% men and 21.4% women with depressive symptoms, 28.7% men and 13.8% women with anxiety symptoms, and 22.0% men and 9.5% women with CVD combined with depressive or anxiety symptoms. This study focused on the details of women. Younger women (age≤35 years) had the highest prevalence of depressive symptoms (24.9%), anxiety symptoms (16.2%), and comorbidity (11.2%). It was established that, despite traditional risk factors, unmanageable work burnout, depressive symptoms, and anxiety symptoms were associated with a higher risk of CVD in women; insomnia, overwhelming work stress, unmanageable work burnout, and CVD were linked to a higher risk of depressive symptoms and anxiety; insomnia, overwhelming work stress, and unmanageable work burnout were related to CVD combined with depressive or anxiety symptoms. A bidirectional relationship was noted between CVD and depression or anxiety in female scientists and technicians, and insomnia and overwhelming work stress were positively associated with comorbidity. It is suggested that effective measures should be taken to protect female scientists and technicians from CVD and psychological distress.Keywords：Female scientist and technician;Depressive symptom;Anxiety;Insomnia;Cardiovascular disease (CVD)- 20
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Published：2022-12-15
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