Research advances on extracellular vesicles-based regulation by traditional Chinese medicines and the relationship with TCM "Qi" / 药学学报

Extracellular vesicles (EVs) are an important type of active microvesicles. EVs encapsulate and transfer functional substances such as miRNAs, transcription factors and proteins, which are important vectors for cell communication and organ dialogue. In recent years, studies have shown that quite a number of Chinese medicinal herbs have the pharmacological effect of regulating EVs, and play a unique trans-organ and remote role in the treatment of diseases. Some Chinese medicinal herbs also contain plant-derived EVs themselves, which can be directly involved in the treatment of diseases. As one of the core theories of raditional Chinese medicines (TCM), Qi plays a variety of important roles in the physiological and pathological processes of human body and pharmacology. However, the scientific connotation of Qi′s role and the potential material carrier are still unclear. The latest research suggests that the effect of EVs is potentially related to that of Qi. Therefore, this paper reviews the effect of Qi nourishing Chinese medicinal herbs in regulating EVs in the treatment of cardiovascular diseases, nervous system diseases, liver diseases, renal diseases, malignant tumors and other diseases in recent years. EVs may play an important role in the pharmacological effect of some Chinese medicinal herbs in the treatment of diseases as an intermediary substance. EVs have the characteristics of long-distance transportation, which is consistent with the movement of Qi in TCM. EVs carry a variety of functional molecules, which is consistent with the function of Qi. As the potential material basis of Qi in TCM, the function of EVs is worth further study.

Therapeutic effect of small extracellular vesicles derived from mesenchymal stem cells on retinal light injury and its mechanism / 中华实验眼科杂志

Objective:To investigate the effect of small extracellular vesicles (sEVs) derived from mesenchymal stem cells (MSCs) in mouse model of retinal light injury and the possible mechanism.Methods:Human umbilical cord derived MSCs were identified by flow cytometry.Supernatants of passage 3-5 MSCs were collected.sEVs were harvested by ultracentrifugation and were identified by transmission electron microscopy.Sixty-five healthy female SPF-grade BALB/c mice aged 8-10 weeks were randomly divided into normal group (17 mice), phosphate buffered saline (PBS) group (24 mice) and sEVs group (24 mice). Mice in PBS and sEVs groups were intravitreally injected with 2 μl of PBS and sEVs, respectively, and were exposed to 930 lx blue light for 6 hours.No intervention was administered to the normal group.Three days after lighting, mice retinal structure was observed by hematoxylin-eosin staining.Apoptotic retinal cells were detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). Retinal function was tested by electroretinogram.Differentially expressed mRNAs between PBS group and sEVs group were assayed by mRNA transcriptome sequencing and were analyzed through KEGG cluster analysis.The differential mRNAs were verified via real-time quantitative PCR.The study protocol was approved by the Animal Ethics Committee of Tianjin Medical University Eye Hospital (No.TJYY20201221035).Results:MSCs were positive for CD90 and CD105, negative for CD34 and CD45.The extracted MSC-sEVs showed a bilayer membrane vesicle with a diameter of 80-140 nm.Hematoxylin-eosin staining showed the arrangement of photoreceptor nuclei was disordered in outer nuclear layer in PBS group.The disorder of photoreceptor nuclei arrangement of sEVs group was slighter than that of PBS group.The apoptotic cell number of sEVs group was (14.60±4.04)/visual field, which was lower than (24.00±8.52)/visual field of PBS group, with a statistically significant difference ( t=2.37, P<0.05). The a-wave amplitude of sEVs group was (64.38±16.70)μV, which was higher than (16.78±6.37) μV of PBS group, showing a statistically significant difference ( P<0.05). The b-wave amplitudes of PBS and sEVs groups were (132.40±39.41) μV and (154.86±34.08) μV, respectively, which were lower than (338.38±27.41) μV of normal group, and the differences were statistically significant (both at P<0.05). A total of 110 differentially expressed mRNAs were detected.There were 109 downregulated mRNAs in sEVs group.Differentially expressed mRNAs were mainly inflammation- and immune-related pathways.PCR showed that the expression level of C-C motif chemokine ligand 2, C-C motif chemokine receptor 2, leukotriene B4, leukocyte Ig-like receptor A6 and interleukin-1β in sEVs group were significantly decreased in comparison with PBS group (all at P<0.05). Conclusions:MSC-sEVs can ameliorate blue light-induced retinal structural and functional damage.The protective effect may be achieved through inhibiting inflammatory response.

Research progress in role of exosomes exosomes in mental disorders / 中南大学学报(医学版)

Exosomes are a class of extracellular vesicles with a structure of lipid bilayer-membrane. In the central nervous system (CNS), exosomes can be secreted from both neurons and glial cells. Exosomes released into the extracellular matrix can freely cross the blood-brain barrier and function as crucial carriers of cellular communication and substance exchange in the CNS. Exosomes play a key role in the pathological process of mental disorders such as schizophrenia, depression, and bipolar disorder, and they have the potential to be used as a targeted carrier of antipsychotic medications. Exosomes are likely to become a new tool in the future to aid in the early prevention, accurate diagnosis, and effective treatment for people with mental disorders.

Brain endothelial cell-derived extracellular vesicles with a mitochondria-targeting photosensitizer effectively treat glioblastoma by hijacking the blood‒brain barrier

Glioblastoma (GBM) is the most aggressive malignant brain tumor and has a high mortality rate. Photodynamic therapy (PDT) has emerged as a promising approach for the treatment of malignant brain tumors. However, the use of PDT for the treatment of GBM has been limited by its low blood‒brain barrier (BBB) permeability and lack of cancer-targeting ability. Herein, brain endothelial cell-derived extracellular vesicles (bEVs) were used as a biocompatible nanoplatform to transport photosensitizers into brain tumors across the BBB. To enhance PDT efficacy, the photosensitizer chlorin e6 (Ce6) was linked to mitochondria-targeting triphenylphosphonium (TPP) and entrapped into bEVs. TPP-conjugated Ce6 (TPP-Ce6) selectively accumulated in the mitochondria, which rendered brain tumor cells more susceptible to reactive oxygen species-induced apoptosis under light irradiation. Moreover, the encapsulation of TPP-Ce6 into bEVs markedly improved the aqueous stability and cellular internalization of TPP-Ce6, leading to significantly enhanced PDT efficacy in U87MG GBM cells. An in vivo biodistribution study using orthotopic GBM-xenografted mice showed that bEVs containing TPP-Ce6 [bEV(TPP-Ce6)] substantially accumulated in brain tumors after BBB penetration via transferrin receptor-mediated transcytosis. As such, bEV(TPP-Ce6)-mediated PDT considerably inhibited the growth of GBM without causing adverse systemic toxicity, suggesting that mitochondria are an effective target for photodynamic GBM therapy.

Extracellular vesicle-carried GTF2I from mesenchymal stem cells promotes the expression of tumor-suppressive FAT1 and inhibits stemness maintenance in thyroid carcinoma / 医学前沿

Through bioinformatics predictions, we identified that GTF2I and FAT1 were downregulated in thyroid carcinoma (TC). Further, Pearson's correlation coefficient revealed a positive correlation between GTF2I expression and FAT1 expression. Therefore, we selected them for this present study, where the effects of bone marrow mesenchymal stem cell-derived EVs (BMSDs-EVs) enriched with GTF2I were evaluated on the epithelial-to-mesenchymal transition (EMT) and stemness maintenance in TC. The under-expression of GTF2I and FAT1 was validated in TC cell lines. Ectopically expressed GTF2I and FAT1 were found to augment malignant phenotypes of TC cells, EMT, and stemness maintenance. Mechanistic studies revealed that GTF2I bound to the promoter region of FAT1 and consequently upregulated its expression. MSC-EVs could shuttle GTF2I into TPC-1 cells, where GTF2I inhibited TC malignant phenotypes, EMT, and stemness maintenance by increasing the expression of FAT1 and facilitating the FAT1-mediated CDK4/FOXM1 downregulation. In vivo experiments confirmed that silencing of GTF2I accelerated tumor growth in nude mice. Taken together, our work suggests that GTF2I transferred by MSC-EVs confer antioncogenic effects through the FAT1/CDK4/FOXM1 axis and may be used as a promising biomarker for TC treatment.

Cross - species regulation and underlying mechanisms of parasite - derived non-coding RNAs: a review / 中国血吸虫病防治杂志

Parasite-derived non-coding RNAs (ncRNAs) not only contribute to life activities of parasites, and microRNA (miRNA), long non-coding RNA (lncRNA), and circular RNA (circRNA) may generate a competitive endogenous RNA (ceRNA) regulatory network with host miRNAs and mRNAs via extracellular vesicles, thereby participating in infection and pathogenic processes. This article presents an overview of characterizing ncRNAs derived from parasites and the cross-species regulatory role of parasite-derived ncRNAs in host gene expression and its underlying mechanisms.

Research progress on emerging biomarkers in kidney transplantation / 器官移植

The hosts could show complex and diverse immune responses to the allografts. Whether biomarkers can be employed to explain the complexity of graft immune responses and the degree of disease damage are of significance. Conventional biomarkers, such as estimated glomerular filtration rate and blood concenrtation of immunosuppressant, lack of sensitivity and specificity in accurately identifying between immune and non-immune renal allograft injuries. Although renal biopsy is the "gold standard" for the diagnosis of postoperative complications, it still has disadvantages, such as invasiveness and high price, etc. Emerging biomarkers have potential advantages in the non-invasive diagnosis of subclinical injury of renal allograft, prediction of treatment response and individualized adjustment of immunosuppressive regimen. In this article, emerging biomarkers including blood, urine and tissue biomarkers that have been applied and are expected to be applied in clinical practice in the field of kidney transplantation were reviewed, and the range of application and effect of these biomarkers were evaluated, aiming to promote appropriate and rational application of these promising emerging biomarkers in clinical practice.

Protective effect and mechanism of mesenchymal stem cell-derived extracellular vesicle on radiation-induced liver injury / 器官移植

Objective To evaluate the protective effect and the underlying mechanism of mesenchymal stem cell-derived extracellular vesicle (MSC-EV) on radiation-induced liver injury and liver cell line injury in mouse models. Methods C57BL/6 mice were randomly divided into the blank group, model group and MSC-EV treatment group (treatment group), with 9 mice in each group. AML12 cells were randomly divided into the control group, irradiation group and MSC-EV intervention group (intervention group). Animal and cell models with radiation-induced injury were established by one-time 15 Gy and 6 Gy X-ray irradiation, respectively. At 48 h after irradiation, liver tissues and serum samples of mice were collected and prepared for subsequent experiments. At 15 h post-irradiation, cell experiment was carried out. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and content of malondialdehyde (MDA) in liver tissues and cells were measured. The relative expression levels of interleukin (IL)-1β, IL-6, transforming growth factor (TGF)-β and CXC chemokine ligand (CXCL)10 messenger RNA (mRNA) were detected by real-time fluorescent quantitative polymerase chain reaction (RT-qPCR). Liver tissues were prepared for hematoxylin-eosin (HE) staining to calculate liver pathological injury score. The apoptosis of liver tissues and cells was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and propidiumiodide (PI) staining, respectively. The expression levels of glutathione peroxidase 4 (GPX4) and ferroptosis suppressor protein 1 (FSP1) proteins were detected by Western blot. The production level of reactive oxygen species (ROS) was detected by dihydroethidine (DHE) staining. The fluorescence intensity of mitochondrial permeability transition pore (mPTP) was determined. Results Compared with the blank group, serum levels of AST and ALT were up-regulated, and the relative expression levels of IL-1β, TGF-β and CXCL10 mRNA in the mouse liver tissues were up-regulated, and MDA content was increased, liver injury score was elevated, cell apoptosis rate was increased, intracellular ROS level was elevated, and the relative expression levels of GPX4 and FSP1 proteins in the mouse liver tissues were down-regulated in the model group, and the differences were statistically significant (all P<0.05). Compared with the model group, serum levels of AST and ALT were decreased, and the relative expression levels of IL-1β, TGF-β and CXCL10 mRNA in the liver tissues of mice were down-regulated, MDA content was declined, liver injury score was declined, cell apoptosis rate was decreased, intracellular ROS level was decreased, and the relative expression levels of GPX4 and FSP1 proteins in the liver tissues of mice were up-regulated in the treatment group, and the differences were statistically significant (all P<0.05). Compared with the control group, cell apoptosis rate was increased, intracellular ROS level was elevated, the fluorescence intensity of mPTP was weakened, the relative expression levels of IL-1β, TGF-β and IL-6 mRNA were up-regulated, MDA content was increased, and the relative expression levels of GPX4 and FSP1 proteins were down-regulated in the irradiation group, and the differences were statistically significant (all P<0.05). Compared with the irradiation group, cell apoptosis rate was declined, intracellular ROS level was decreased, the fluorescence intensity of mPTP was strengthened, the relative expression levels of IL-1β, TGF-β and IL-6 mRNA were down-regulated, MDA content was decreased and the relative expression levels of GPX4 and FSP1 proteins were up-regulated in the intervention group, and the differences were statistically significant (all P<0.05). Conclusions MSC-EV may effectively alleviate radiation-induced liver injury by reducing ferroptosis of liver cells, enhancing antioxidant level and decreasing the production of lipid peroxide, thereby effectively alleviating radiation-induced liver injury.

Human umbilical cord mesenchymal stem cell-derived extracellular vesicles enhance the regenerative capability of fibrotic liver / 器官移植

Objective To investigate the role of human umbilical cord mesenchymal stem cell-derived extracellular vesicle (hUC-MSC-EV) in the regeneration of fibrotic liver. Methods C57BL/6 mice were randomly divided into the 70% normal liver resection group (Oil+PHx group), 70% liver fibrosis resection group (CCl4+PHx group) and 70% liver fibrosis resection+mesenchymal stem cell-derived extracellular vesicle (MSC-EV) treatment group (CCl4+PHx+MSC-EV group), with 8 mice in each group. LX-2 cell lines were assigned into the phosphate buffer solution (PBS) group, transforming growth factor (TGF)-β group and TGF-β+MSC-EV group. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) in mice after partial liver resection were detected in each group. The expression levels of liver fibrosis and proliferation-related parameters were analyzed in each group. The messenger RNA (mRNA) expression levels of epidermal growth factor (EGF), fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) in LX-2 cells were detected in each group, and their effects on HGF expression in mouse liver were observed. Results Compared with the Oil+PHx group, the serum levels of AST, ALT and LDH were up-regulated, and the degree of fibrosis was more severe, the positive area of Sirius red and α-smooth muscle actin (α-SMA) staining was larger, and the expression level of α-SMA protein was up-regulated in the CCl4+PHx group. Compared with the CCl4+PHx group, the serum levels of AST, ALT and LDH were decreased, the degree of fibrosis was slighter, the positive area of Sirius red and α-SMA staining was decreased, and the expression level of α-SMA protein was down-regulated in the CCl4+PHx+MSC-EV group, and the differences were statistically significant (all P < 0.05). Compared with the Oil+PHx group, the protein expression levels of Ki67 and proliferating cell nuclear antigen (PCNA) were lower in the CCl4+PHx group. Compared with the CCl4+PHx group, the protein expression levels of Ki67 and PCNA were increased in the CCl4+PHx+MSC-EV group, and the differences were statistically significant (all P < 0.05). Compared with the PBS group, the expression level of CollagenⅠ mRNA in LX-2 cells was increased, the expression level of α-SMA protein was up-regulated and the expression level of HGF protein was decreased in the TGF-β group. Compared with the TGF-β group, the expression level of CollagenⅠ mRNA in LX-2 cells was decreased, the expression levels of HGF mRNA and protein were increased, and the expression level of α-SMA protein was decreased in the TGF-β+MSC-EV group, the differences were statistically significant (all P < 0.05). The expression level of HGF protein in the CCl4+PHx group was lower than that in the Oil+PHx group, whereas the difference was not statistically significant (P > 0.05). The expression level of HGF protein in the CCl4+PHx+MSC-EV group was higher than that in the CCl4+PHx group, and the difference was statistically significant (P < 0.05). Conclusions The regenerative capacity of fibrotic liver is weaker than that of normal liver. hUC-MSC-EV may alleviate liver fibrosis and improve liver regeneration by promoting HGF secretion from actived hepatic stellate cells and effectively enhancing the regenerative capacity of fibrotic liver.

Progress on the cell therapy strategy of mesenchymal stem cells / 口腔疾病防治

@#Cell therapy based on mesenchymal stem cells (MSCs) has been a hot research topic in recent years, including the traditional cell therapy strategy based on living cells and the new cell-free therapy strategy based on soluble proteins or bioactive molecules such as extracellular vesicles (EVs). At present, MSC-induced cells have mature functions and specific structures, and insitu transplantation combined with biomaterials or organic technology has greatly improved the settlement rate and function. On the other hand, as the large-scale culture technique and EVs separation technique evolve, it is possible to obtain a large number of pure EVs, and EVs are gradually becoming a hot spot of current research. An increasing number of studies have shown that the therapeutic effect of MSCs not only occurs by implantation and differentiation but also manifests as the paracrine effect of MSCs. In this review, we discuss the emerging outcomes of cell therapies and acellular therapies to alleviate these pathological conditions.

Research progress on kidney transplantation rejection associated with non-HLA antibody / 器官移植

Human leukocyte antigen (HLA) is a product encoded by HLA gene complex, which is located on the short arm of chromosome 6 and is the main target of alloimmunity. However, positive HLA antibody is not responsible for all kinds of rejections in kidney transplantation. Non-HLA antibody is the product of donor gene expression in allogeneic kidney transplantation. Intraoperative ischemia-reperfusion injury, the interaction between alloimmunity and autoimmunity and the mediation of extracellular vesicles may trigger immune system response and promote the production of non-HLA antibody. Multiple studies have demonstrated that non-HLA antibody is an important factor of inducing rejection and affecting the outcomes of kidney transplantation. Consequently, the types and formation mechanism of non-HLA antibody in kidney transplantation were reviewed, and research progress on kidney transplantation rejection associated with non-HLA antibody was summarized, aiming to provide reference for in-depth study of kidney transplantation rejection associated with non-HLA antibody.

Recent Progress on Pharmaceutical Properties of Extracellular Vesicles from Mesenchymal Stem Cells--Review / 中国实验血液学杂志

Mesenchymal stem cells (MSCs) have been officially approved in many countries to treat graft-versus-host disease, autoimmune disorders and those associated with tissue regeneration after hematopoietic stem cell transplantation. Studies in recent years have confirmed that MSC acts mainly through paracrine mechanism, in which extracellular vesicles secreted by MSC (MSC-EV) play a central role. MSC-EV has overwhelming advantages over MSC itself in the setting of adverse effects in clinical application, indicating that MSC-EV might take the place of its parent cells to be a potentially therapeutic tool for "cell-free therapy". The pharmaceutical properties of MSC-EV largely depend upon the practical and optimal techniques including large-scale expansion of MSC, the modification of MSC based on the indications and the in vivo dynamic features of MSC-EV, and the methods for preparing and harvesting large amounts of MSC-EV. The recent progresses on the issues above will be briefly reviewed.

Cellular nanovesicles for therapeutic immunomodulation: A perspective on engineering strategies and new advances

Cellular nanovesicles which are referred to as cell-derived, nanosized lipid bilayer structures, have emerged as a promising platform for regulating immune responses. Owing to their outstanding advantages such as high biocompatibility, prominent structural stability, and high loading capacity, cellular nanovesicles are suitable for delivering various immunomodulatory molecules, such as small molecules, nucleic acids, peptides, and proteins. Immunomodulation induced by cellular nanovesicles has been exploited to modulate immune cell behaviors, which is considered as a novel cell-free immunotherapeutic strategy for the prevention and treatment of diverse diseases. Here we review emerging concepts and new advances in leveraging cellular nanovesicles to activate or suppress immune responses, with the aim to explicate their applications for immunomodulation. We overview the general considerations and principles for the design of engineered cellular nanovesicles with tailored immunomodulatory activities. We also discuss new advances in engineering cellular nanovesicles as immunotherapies for treating major diseases.

Potential value of mesenchymal stem cells and their derivatives in repairing donor liver / 器官移植

In recent years, organ transplantation has developed rapidly in China, whereas the proportion of supply and demand of organs for donation is severely unbalanced. To resolve the shortage of donor livers, repairing extended criteria donor liver and improving the quality of donor liver are critical research directions. Mesenchymal stem cell (MSC) is a category of stem cells with self-renewal and differentiation potential, which possess the functions of immunomodulation and tissue repair. The derivatives of MSC have the advantages of low immunogenicity and high biocompatibility, which have been widely applied in the treatment of multiple diseases. In this article, research progress on the role of MSC, exosomes and extracellular vesicles in alleviating liver steatosis, repairing ischemia-reperfusion injury and promoting the regeneration of small-for-size liver allograft was reviewed, and the feasibility and safety of MSC and the derivatives in repairing donor liver were summarized, aiming provide novel ideas for repairing marginal donor liver and enhancing the quality of liver allograft.

Progress of mesenchymal stem cells in the treatment of bronchopulmonary dysplasia / 国际儿科学杂志

Bronchopulmonary dysplasia(BPD) is a chronic lung disease in the premature infants, which is an important cause of poor prognosis in the premature infants.The pathogenesis of BPD involves a variety of prenatal and postnatal mechanisms affecting the development of immature lungs.The combined effect of BPD alters lung morphogenesis, disrupts capillary gas exchange in the alveoli, and leads to pathological and clinical features of BPD.The current clinical methods used to treat BPD are still difficult to improve its prognosis.Mesenchymal stem/stromal cell(MSC) is a promising and innovative therapy for the treatment of a wide range of diseases due to the ease of extraction, low immunogenicity, anti-inflammatory properties and regenerative ability.In recent years, many experimental and clinical studies have found and proved that mesenchymal stem cell transplantation has a certain effect on BPD, so MSC may become the promising treatment for BPD in the future.However, the possibility that MSC may promote tumor growth, the presence of heterogeneous cell populations resulting in different efficacy, and ethical issues regarding the use of this treatment in humans make it a number of therapeutic challenges.This article reviews the mechanism of action and treatment of MSC in BPD, as well as the research progress in the treatment of BPD with MSC.

Recent research on the mechanism of mesenchymal stem cells in the treatment of bronchopulmonary dysplasia / 中国当代儿科杂志

Bronchopulmonary dysplasia (BPD) is a chronic lung disease due to impaired pulmonary development and is one of the main causes of respiratory failure in preterm infants. Preterm infants with BPD have significantly higher complication and mortality rates than those without BPD. At present, comprehensive management is the main intervention method for BPD, including reasonable respiratory and circulatory support, appropriate enteral nutrition and parenteral nutrition, application of caffeine/glucocorticoids/surfactants, and out-of-hospital management after discharge. The continuous advances in stem cell medicine in recent years provide new ideas for the treatment of BPD. Various pre-clinical trials have confirmed that stem cell therapy can effectively prevent lung injury and promote lung growth and damage repair. This article performs a comprehensive analysis of the mechanism of mesenchymal stem cells in the treatment of BPD, so as to provide a basis for clinical applications.

The role of extracellular vesicles in human cytomegalovirus infection / 中华检验医学杂志

Extracellular vesicles (EV) are membrane structured vesicles containing proteins, lipids and nucleic acids. EVS produced by virus-infected cells are involved in communication between infected and uninfected cells. EV produced by human cytomegalovirus (HCMV) infected cells can promote the transmission and infection of HCMV and escape the host immune response. It can also activate the body′s immune response against HCMV infection. In-depth study of the mechanism and compositional changes of EV produced by HCMV infected cells will contribute to the prevention, diagnosis, and treatment of HCMV. The current research has achieved some results, but they are not deep enough. Future advancements in EV isolation and identification technologies and the reduction of economic costs will contribute to the extensive development and clinical application of the research.

Research progress on the regulatory mechanism of endothelial derived extracellular vesicles in acute respiratory distress syndrome / 中华危重病急救医学

Acute respiratory distress syndrome (ARDS) is a clinical syndrome caused by a variety of internal and external injury factors in the lung, and its morbidity and mortality have remained stubbornly high. Recent studies have shown that endothelial-derived extracellular vesicles are an important mediator of pathological signal transduction and play an important regulatory role in the occurrence, development and prognosis of ARDS. Now our paper reviewed the regulatory mechanism of endothelial-derived extracellular vesicles in ARDS.

Research progress of mesenchymal stem cells and their derivatives nebulization in the treatment of pulmonary diseases / 中华危重病急救医学

In acute or chronic lung diseases, inappropriate immune response and abnormal repair process can lead to irreversible damage to lung tissue, which in turn leads to decreased lung function and even respiratory failure or death. Mesenchymal stem cells (MSCs) and their derivatives have shown wide application prospects in cell therapy and acellular therapy of lung diseases and are entering the clinical transformation stage because of their unique physiological functions and characteristics, but the safety and efficacy of MSCs and their derivatives are still controversial. Nebulization therapy provides new opportunities and challenges for the innovative treatment of MSCs and their derivatives in lung diseases. In a number of preclinical studies and clinical trials, there have been evidence that atomization therapy of MSCs and their derivatives is safe and effective. This method could be an optimal solution for the treatment of various complex lung diseases. However, extensive research should be carried out on various strategies and their compatibility with different nebulizers before this method can be used in clinical setting. In this paper, we review the research progress of MSCs and their derivatives by nebulization in the treatment of pulmonary diseases.

Research progress on the molecular regulatory mechanism of exosome biogenesis / 中华危重病急救医学

Exosomes are small vesicles with a diameter of about 40-160 nm actively secreted by cells. They participate in a variety of pathophysiological processes and are closely related to the occurrence and development of diseases. As a newly carrier of intercellular communication and circulating biomarkers of disease diagnosis and prognosis, exosomes have attracted great attention for their potential clinical applications. However, many aspects such as exosome biogenesis, targeted transport, and mechanism of action are still unclear. This paper focuses on the exosome biogenesis, summarizes the exosome biogenesis pathways, and describes relevant molecular modulation mechanisms of importance. And this review provides a theoretical basis for disease treatment based on regulating exosome production.