Exosomes that deliver specific mirnas can regulate osteogenesis and promote angiogenesis北大核心

BACKGROUND: Exosomes are nanoscale paracrine vesicles containing a variety of bioactive factors, such as miRNAs. Exosome miRNAs play an important role in intercellular communication. In recent years, more and more studies have focused on whether miRNAs in exosomes promote bone regeneration. OBJECTIVE: To review research status of exosomal miRNAs promoting bone regeneration in the recent years so as to provide a theoretical basis for further research and application in the field of bone regeneration. METHODS: Using “bone regeneration, bone repair, exosomes, miRNA” in Chinese and English as search terms, biomedical literature database, CNKI, and PubMed were retrieved for articles on exosomal miRNA and bone regeneration published from 2010 to 2021. RESULTS AND CONCLUSION: Exosomes derived from different cells can effectively regulate osteogenesis and promote angiogenesis through the delivery of specific miRNAs, which has a broad prospect in bone tissue engineering. © 2022, Publishing House of Chinese Journal of Tissue Engineering Research. All rights reserved.     

Biological characteristics and immunoregulation of exosomes derived from mesenchymal stem cells北大核心

BACKGROUND: Clarifying the synthesis and regulation of exosomes derived from mesenchymal stem cells is of great significance to the research and application of exosomes in the future. OBJECTIVE: To summarize the biological characteristics in exosomes derived from different mesenchymal stem cells and the role of these exosomes in the immune regulation, which hopes to find new breakthroughs in the study of exosomes in the future and provide ideas for cell-free therapy. METHODS: The articles were searched on PubMed, CNKI and Wanfang using the keywords of “stem cells, mesenchymal stem cells, exosomes, immunomodulation, inflammatory mediator, biological characteristics of exosomes, biological characteristics of mesenchymal stem cells, regeneration” in Chinese and English. Finally, 105 articles were included for review. RESULTS AND CONCLUSION: Mesenchymal stem cells are a type of pluripotent stem cells that exist widely in various tissues of the body. Mesenchymal stem cells not only have stem cell characteristics, but also play an important role in the immunosuppressive properties. Mesenchymal stem cells had been clinically applied for the treatment of many diseases. Therefore, mesenchymal stem cells were used to manage novel coronavirus pneumonia, and had ideal treatment effect. Exosomes are endosome-derived nanometer-scale vesicles (40–200 nm in diameter). Exosomes derived from mesenchymal stem cells have the same immune regulation function as its maternal cells, including that carrying immunosuppressive factors, promoting macrophages polarization into M2 type, preventing differentiation of pro-inflammatory T cell subsets and inhibiting antigen presentation. © 2022, Publishing House of Chinese Journal of Tissue Engineering Research. All rights reserved.     

MicroRNAs,immune cells and pregnancy

MicroRNAs （miRNAs） are a recently discovered class of non-coding RNAs that are expressed in many cell types, where they regulate the expression of complementary RNAs, thus modulating the stability and translation of mRNAs, miRNAs are predicted to regulate the expression of -50% of all protein coding genes in mammals. Therefore, they participate in virtually all cellular processes investigated so far. Altered miRNAs expressions are associated with both physiological （pregnancy） and pathological processes （cancer）. As the dynamic maternal-fetal interface plays a critical role in the maintenance of successful pregnancy, it is not surprising that the miRNAs that are unique to reproductive tissues are abundantly expressed. Research in this field has demonstrated the presence and dysregulation of a distinct set of pregnancy-associated miRNAs; however, most studies have centered on localizing various miRNAs in reproductive microdomains associated with normal or complicated pregnancies. Although several independent miRNA regulatory mechanisms associated with endometrial receptivity, immune cells, angiogenesis and placental development have been studied, miRNA-mediated regulation of pregnancy remains poorly understood. This review provides a summary of the current data on miRNA regulation as well as functional profiles of miRNAs that are found in the uterus, in immune cells associated with maternal tolerance to the fetus, and those involved in angiogenesis and placental development.     

中药诱导骨髓间充质干细胞的定向分化：研究与进展

BACKGROUND: In recent years, in-depth studies that single Chinese herbs or extracts, compound traditional Chinese medicine and medicated serum are used to regulate the directional differentiation of bone marrow mesenchymal stem cells into myofibroblasts, chondrocytes, osteoblasts, myocardial cells and nerve cells, which have become a highlight in the tissue engineering research.OBJECTIVE: To review the latest progress in the directional differentiation of bone marrow mesenchymal stem cells induced by Chinese herbs or their extracts.METHODS: The first author searched the CNKI, Wanfang and PubMed databases using the keywords of “Chinese herb, directional differentiation, mesenchymal stem cells” in Chinese and English, respectively, to retrieve relevant articles published from January 2010 to January 2016. Repetitive articles or those with no originality were eliminated. Totally 99 articles were searched initially, and then 43 articles were included in result analysis.RESULTS AND CONCLUSION: As the strongest seed cells in the bone differentiation system, bone marrow mesenchymal stem cells have a wide range of directional differentiation potential, and highlight the important value in combination with Chinese herbs for clinical treatment of various refractory diseases, especially for treatment of metabolic bone diseases, bone defects, nonunion and delayed union, which is not only conducive to in-depth, multi-angle studies on effects and mechanisms of Chinese herbs, but also to clinical treatment of various refractory diseases using bone marrow mesenchymal stem cells.   中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程     

Role of leptin in immunity

Leptin, a protein hormone produced by the adipocytes, has long been recognized to regulate metabolism, neuroendorine and other physiological functions. Early findings of increased leptin production during infection and inflammation and dysregulated immune response in leptin signaling-deficient mice provide strong evidence for the involvement of leptin in the immune responses. Recent data have established the regulatory function for leptin in immunity similar to the function of a pro-inflammatory cytokine, while gene-targeting studies also demonstrated an essential role of leptin in regulating hematopoiesis and lymphopoiesis. Moreover, there has been increasing evidence that leptin is involved in the pathogenesis of various autoimmune diseases. This review discusses recent advances in understanding the role of leptin in immunity and leptin-signaling pathways involved in modulating immune homeostasis and autoimmune pathogenesis. Cellular ＆ Molecular Immunology. 2007;4（1）：1-13.     

Heart＇omicsin＇AGEing （HOMAGE）：design,research objectives and characteristics of the common database

Heart failure is common in older people and its prevalence is increasing.The Heart ＇omics＇ in AGEing（HOMAGE） project aims to provide a biomarker approach that will improve the early diagnosis of heart failure.A large clinical database,based on（1） prospective population studies or（2） cross-sectional,prospective studies or randomized controlled trials（RCTs） of patients at risk for or with overt cardiovascular disease will be constructed to determine most promising ＇omics＇-based biomarkers to identify the risk of developing heart failure and/or comorbidities.Population studies,patient cohorts and RCTs are eligible for inclusion in the common database,if they received ethical approval to obtain and share data and have baseline information on cardiovascular risk factors.Currently,the HOMAGE database includes 43,065 subjects,from 20 studies in eight European countries,including healthy subjects from three population studies in France,Belgium and Italy（n = 7,124）,patients with heart failure（n = 4,312） from four cohorts in the UK,Spain and Switzerland and patients at high risk for cardiovascular disease（n = 31,629） in 13 cohorts.It is anticipated that more partners will join the consortium and enlarge the pooled data.This large merged database will be a useful resource with which to identify candidate biomarkers that play a role in the mechanism underlying the onset and progression of heart failure.     

The role of TNF related apoptosis-inducing ligand in neurodegenerative diseases

A hallmark of all forms of neurodegenerative diseases is impairment of neuronal functions,and in many casesneuronal cell death.Although the etiology of neurodegenerative diseases may be distinct,different diseases displaya similar pathogenesis,for example abnormal immunity within the central nervous system(CNS),activation ofmacrophage/microglia and the involvement of proinflammatory cytokines.Recent studies show that neurons in aneurodegenerative state undergo a highly regulated programmed cell death,also called apoptosis.TNF-relatedapoptosis-inducing ligand(TRAIL),a member of the TNF family,has been shown to be involved in apoptosisduring many diseases.As one member of a death ligand family,TRAIL was originally thought to target only tumorcells and was not present in CNS.However,recent data showed that TRAIL was unregulated in HIV-1-infected andimmune-activated macrophages,a major disease inducing cell during HIV-1-assoeiated dementia(HAD).TRAIL isalso induced on neuron by β-amyloid protein,an important pathogen for Alzheimer's disease.In this review,wesummarize the possible common aspects that TRAIL involved those neurodegenerative diseases,TRAIL inducedapoptosis signaling in the CNS cells,and specific role of TRAIL in individual diseases.Cellular & MolecularImmunology.2005;2(2):113-122.     

Review：Optical Methods for Tumors Diagnosing

The rapid development in the field of optic in the past decade demonstrates a potential for cancer diagnosis using optical technologies. This review highlights the principle and advantages of using optical technologies, and focuses on their application in tumor diagnosis and their limitation in clinical uses. These optical technologies are rapid methods,which can provide a great deal of different information from conventional methods, while, it still requires clinical trial studies to develop and ensure the applicability of these optical technologies for clinical cancer diagnosis.     

Progress of non-coding RNAs in stem cell abnormality of idiopathic pulmonary fibrosis北大核心

BACKGROUND: With the development of high-throughput technology, non-coding RNAs have gradually attracted attention and are widely involved in the course of various respiratory diseases. The progression of idiopathic pulmonary fibrosis is accompanied by stem cell abnormality and recent studies have shown that non-coding RNAs are associated with stem cell abnormality, thus affecting the progression of pulmonary fibrosis. Gene therapy that targets non-coding RNAs hints at the possibility of blocking the fibrosis process. OBJECTIVE: To summarize the research progress of non-coding RNAs in stem cell dysfunction and treatment of idiopathic pulmonary fibrosis. METHODS: English search terms included “IPF, stem cells, miRNA, lncRNA, circRNA, treatment” and Chinese search terms contained “idiopathic pulmonary fibrosis, stem cells, miRNA, lncRNA, circRNA, treatment”. Databases including PubMed, Wiley InterScience, CNKI, and Wanfang were used for retrieval, covering articles in the past decade. Screening was performed based on the inclusion and exclusion criteria. Finally, 82 articles were included for analysis. RESULTS AND CONCLUSION: (1) The recent studies on the correlation between non-coding RNAs and the mechanisms of stem cell abnormality in idiopathic pulmonary fibrosis were summarized, revealing that miRNAs, lncRNAs, and circRNAs jointly regulate the abnormal activation and differentiation of stem cells, and miRNAs are often the central link of the mechanisms of lncRNAs and circRNAs. (2) Existing trials have confirmed the safety of transplantation therapy to a certain extent, but in terms of efficacy, the diffusion function of patients has only been slightly improved, but the degree of fibrosis has not been significantly alleviated. Most importantly, the trials were non-randomized and lack of placebo controls, so more placebo-controlled randomized trials are needed. (3) The most important advantage of non-coding RNA-targeted gene therapy is that it has the characteristics of multi-gene regulation, which can intervene stem cell abnormalities from the upstream pathways. Based on the breakthroughs made in vivo and in vitro research, non-coding RNAs have been confirmed to be related to the targets of several drugs for idiopathic pulmonary fibrosis. (4) However, the disadvantages of gene therapy include that it still can only produce short-term effects, and it also faces problems such as effective dose, drug stability, and delivery in the human body. These problems need to be further resolved by future research. (5) In conclusion, although non-coding RNA-targeted therapy is difficult, it can be regarded as a novel way to improve the abnormality of stem cells in idiopathic pulmonary fibrosis, and combining this therapy with stem cell transplantation may achieve better efficacy. © 2023, Publishing House of Chinese Journal of Tissue Engineering Research. All rights reserved.     

MicroRNA在脑胶质瘤中的作用

icroRNAs (miRNAs) are critical regulators of gene expression. These small, non-coding RNAs are believed to regulate more than one third of protein-coding genes, and have been implicated in the control of many biological processes, including the biology of glioma. The functional significance in some of the miRNAs begins to emerge. This paper reviews the biogenesis of miRNAs, their roles in neuronal development and tumorigenesis of gliomas, and their contribution as tumor biomarkers. Research in this area is quickly gathering pace and is illuminating important aspects of the diseases that may ultimately lead to novel therapeutic interventions, as well as diagnostic and prognostic tools for brain tumors.     

Secondary metabolite credentials of Evolvulus alsinoides by high performance thin layer chromatography (HPTLC)

Plants and plant-based products are the bases of many modern pharmaceuticals that are current in use today for various diseases.The aim of the study was to investigate the biochemical constituents and high performance thin layer chromatography(HPTLC) finger printing of the ethanolic extract of Evolvulus alsinoides.Phytochemical screening was done by standard procedures and HPTLC method was also established to analyze alkaloids,flavonoids and phenolic compounds from the ethanolic extract of Evolvulus alsinoides.Preliminary phytochemical screening showed that ethanol extracted more secondary metabolites than other solvents.HPTLC fingerprinting analysis showed the presence of various alkaloids,flavonoids and phenols(quercetin) in the ethanolic extract.It can be concluded that Evolvulus alsinoides may serve as a source of potent antioxidants that may be used in the prevention of various diseases such as cancer,diabetes and cardiovascular diseases due to the presence of phenolic compounds.HPTLC finger print of Evolvulus alsinoides may be useful in the differentiation of the species from adulterants and act as a biochemical marker for this medicinally important plant in the pharmaceutical industry and plant systematic studies.     

Genetic susceptibility of cervical cancer

Epidemiological and laboratory-based studies have identified infection with one of 15 high-risk human papillo-mavirus (HPV) types as a necessary but not sufficient cause of cervical cancer. The prevalence of genital HPV in-fections is high in young women, but most of the infections regress without interventions. Host genetic variations in genes involved in immune response pathways may be related to HPV clearance, and HPV E6/E7 oncoproteins interacting or downstream genes, both coding and non-coding, may contribute to the outcome of high risk HPV infection and cervical cancer. Of specific interest for this review has been the selection of genetic variants in genes involved in the above-referred pathways with a summary of their applications in association studies. Because the supportive and opposing data have been reported in different populations, well-designed international collabora-tive studies need to be conducted to define the consistency of the associations, paving the way to better define the patients at high risk of developing cervical cancer.     

Hsa-mir-499 rs3746444 polymorphism and cancer risk: a meta-analysis

MicroRNAs(miRNAs) are gene regulators involved in numerous diseases including cancer,heart disease,neurological disorders,vascular abnormalities and autoimmune conditions.Although hsa-mir-499 rs3746444 polymorphism was shown to contribute to the susceptibility of multiple genes to cancer,the data have yielded conflicting results.Therefore,this meta-analysis was performed to provide a comprehensive assessment of potential association between hsa-mir-499 rs3746444 polymorphism and cancer risk.In this meta-analysis,a total of 9 articles regarding 10 eligible case-control studies in English(including 6134 cases and 7141 controls) were analyzed.No significant association between hsa-mir-499 rs3746444 polymorphism and overall cancer risk was demonstrated.However,an increased risk was observed in the subgroup of breast cancer patients(G allele vs A allele:OR = 1.10,95% CI = 1.00-1.20;P heterogeneity = 0.114;I 2 = 53.9%) and population-based studies(G allele vs A allele:OR = 1.12,95% CI = 1.00-1.25;P heterogeneity = 0.062;I 2 = 64.0%).The findings suggested an association between hsa-mir-499 rs3746444 polymorphism and increased risk to breast cancer.     

Application of engineered exosomes in bone repair and regeneration北大核心

BACKGROUND: Bone defect caused by disease or accident is very common in clinic. The current main treatment method for bone defect repair is autologous bone grafting. Autologous bone grafting may cause complications, such as secondary infections and scars. The other treatments, such as allogeneic bone transplantation, may have risks of immune rejection and disease transmission. Furthermore, safety considerations and the performance of biomaterials and cell-based treatment require further clarification. In recent years, engineered exosomes have shown good application potential in bone repair and bone regeneration, and have become a current research hotspot. OBJECTIVE: To review the research progress of engineering exosomes in promoting bone defect repair and bone regeneration. METHODS: The PubMed, CNKI and Wanfang databases were searched for relevant articles with the key words of “exosome; engineered exosomes; bone repair; bone regeneration” in English and Chinese, respectively. The search time was from January 1980 to September 2020. Articles that were not related to the purpose of the research and repetitive articles were excluded, and 56 articles that met the criteria were finally included for review. RESULTS AND CONCLUSION: The engineered exosomes can not only promote bone differentiation of osteoblast-related cells and new blood vessel formation, but also target tissues and cells. A large number of experiments have proven that the engineered exosomes for repairing bone defect and promoting bone regeneration is a feasible strategy. © 2022, Publishing House of Chinese Journal of Tissue Engineering Research. All rights reserved.     

One Gene,Three Diseases： How Small Changes Cause Big Differences

Two recent studies have discovered a surprising link between three seemingly different clinical diseases： one that destroys bone marrow, another that prevents sun damage from being repaired, and a third which causes children to show signs of aging extremely early. It has been found that all three diseases are caused by mutations in the same gene. Mutations come in a number of different flavors, with effects ranging from no consequence to catastrophic failure or entirely new functions. Mutations range from the humble point mutation, in which a single DNA ＂base＂ is altered or removed;     

Microglia modulate neurodegeneration in Alzheimer's and Parkinson's diseases

Dementia is a rapidly rising global health crisis that silently disables families and ends lives and livelihoods around the world.To date,however,no early biomarkers or effective therapies exist.It is now clear that brain microglia are more than mere bystanders or amyloid phagocytes;they can act as governors of neuronal function and homeostasis in the adult brain.Here,we highlight the fundamental role of microglia as tissue-resident macrophages in neuronal health.Then,we suggest how chronic impairment in microglia-neuron cross-talk may secure the permanence of the failure of synaptic and neuronal function and health in Alzheimer's and Parkinson's diseases.Understanding how to assess and modulate microglia-neuron interactions critical for brain health will be key to developing effective therapies for dementia.     

Immunological effects of silica and asbestos

Silicosis patients （SILs） and patients who have been exposed to asbestos develop not only respiratory diseases but also certain immunological disorders. In particular, SIL sometimes complicates autoimmune diseases such as systemic scleroderma, rheumatoid arthritis （known as Caplan syndrome）, and systemic lupus erythematoses. In addition, malignant complications such as lung cancer and malignant mesothelioma often occurr in patients exposed to asbestos, and may be involved in the reduction of tumor immunity. Although silica-induced disorders of autoimmunity have been explained as adjuvant-type effects of silica, more precise analyses are needed and should reflect the recent progress in immunomolecular findings. A brief summary of our investigations related to the immunological effects of silica/asbestos is presented. Recent advances in immunomolecular studies led to detailed analyses of the immunological effects of asbestos and silica. Both affect immuno-competent cells and these effects may be associated with the pathophysiological development of complications in silicosis and asbestos-exposed patients such as the occurrence of autoimmune disorders and malignant tumors, respectively. In addition, immunological analyses may lead to the development of new clinical tools for the modification of the pathophysiological aspects of diseases such as the regulation of autoimmunity or tumor immunity using cellmediated therapies, various cytokines, and molecule-targeting therapies. In particular, as the incidence of asbestosrelated malignancies is increasing and such malignancies have been a medical and social problem since the summer of 2005 in Japan, efforts should be focused on developing a cure for these diseases to eliminate nationwide anxiety.     

Application of graphene-based nanomaterials in stem cells北大核心

BACKGROUND: As a kind of newly-developing nanomaterial, graphene has been used in many fields. Many recent studies have found that graphene-based nanomaterials can affect the biological behaviors of stem cells. OBJECTIVE: To review the application and progress of graphene-based nanomaterials in stem cells. METHODS: We searched the articles about the application of graphene-based nanomaterials in stem cells published in PubMed, Web of Science, and CNKI databases with the search terms “graphene, nanomaterials, stem cell” in English and Chinese. Finally, 57 articles met the criteria for review. RESULTS AND CONCLUSION: Graphene-based nanomaterials have good stability and corrosion resistance, high mechanical strength, good biocompatibility, which are accepted as one of the most promising nanomaterials in biomedicine. Stem cells are undifferentiated cells that can differentiate into various mature cells in human body, which have a broad application prospect in tissue engineering, regenerative medicine and other fields. Many recent studies have applied graphene-based nanomaterials to stem cell research and found that they can affect the growth, proliferation, adhesion and differentiation of stem cells, and these nanomaterials may affect the biological behavior of stem cells by regulating the expression of related genes and various signaling pathways. However, graphene-based nanomaterials have biological toxicity, which restrict their application in biological aspects. Moreover, most researches only involved cellular level, and it needs further animal studies and in vivo experimental researches. © 2022, Publishing House of Chinese Journal of Tissue Engineering Research. All rights reserved.     

Baicalin modulates microRNA expression in UVB irradiated mouse skin

This study aimed to evaluate the effects of baicalin on ultraviolet radiation B (UVB)-mediated microRNA (miRNA) expression in mouse skin.We determined miRNA expression profiles in UVB irradiated mice,baicalin treated irradiated mice,and untreated mice,and conducted TargetScan and Gene Ontology analyses to predict miRNA targets.Three miRNAs (mmu-miR-125a-5p,mmu-miR-146a,and mmu-miR-141) were downregulated and another three (mmu-miR-188-5p,mmu-miR-223 and mmu-miR-22) were upregulated in UVB irradiated mice compared with untreated mice.Additionally,these miRNAs were predicted to be related to photocarcinogenesis,hypomethylation and apoptosis.Three miRNAs (mmu-miR-378,mmu-miR-199a-3p and mmu-miR-181b) were downregulated and one (mmu-miR-23a) was upregulated in baicalin treated mice compared with UVB irradiated mice,and they were predicted to be related to DNA repair signaling pathway.These deregulated miRNAs are potentially involved in the pathogenesis of photodamage,and may aid treatment and prevention of UVB-induced dermatoses.