1.Research advances in mesenchymal stem cells from various sources in treatment of liver fibrosis
Dongdong WANG ; Gang CHEN ; Zongqiang HU
Journal of Clinical Hepatology 2016;32(3):597-600
Mesenchymal stem cells (MSC) are derived from the mesoderm, and exhibit multipotential differentiation. MSC can alleviate liver fibrosis and improve liver function through paracrine cytokines and cell-cell interactions, but their therapeutic mechanism remains unknown. MSC are derived from various tissues, such as bone marrow, umbilical cord tissue, umbilical cord blood, peripheral blood, and adipose tissue. However, there are different advances in MSC with various sources in experimental studies and clinical treatment of liver fibrosis. This paper summarizes the possible therapeutic mechanisms of MSC in alleviating liver fibrosis, as well as the advances in experimental studies and clinical application of MSC with various sources. MSC transplantation is a new therapeutic method for liver fibrosis and has a broad application prospect in this field.
2.Potential value of mesenchymal stem cells and their derivatives in repairing donor liver
Yiting WANG ; Jie JIANG ; Li MA ; Zongqiang HU ; Li LI
Organ Transplantation 2023;14(4):592-
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.
3.LncRNA SNHG12 regulates miR-138-5p/HIF-1α axis to improve hypoxia/reoxygenation human vascular endothelial cell damage
Zongqiang WEI ; Linru WANG ; Wenxian HU ; Juanzi ZHANG ; Xianming HUANG ; Lin LI ; Qiang LI
Chinese Journal of Immunology 2023;39(12):2494-2500
Objective:To study the effect of Long non-coding RNA(LncRNA)small nucleolar RNA host gene 12(SNHG12)regulating miR-138-5p/hypoxia inducible factor-1(HIF-1α)axis on improving the damage of hypoxia/reoxygenation(H/R)human vas-cular endothelial cells.Methods:Human umbilical vein endothelial cells(HUVECs)were cultured in vitro and randomly divided into control group,H/R model group,H/R+LncRNA SNHG12 overexpression group,H/R+miR-138-5p mimics group,H/R+co-transfec-tion group and H/R+co-transfection negative control group,each transfection group was transfected separately,and except for control group,the remaining groups were given hypoxia for 5 hours and then reoxygenated for 1 hour to induce the cell models,and then the cell viability of each group was detected by CCK-8 experiment;the cell apoptosis in each group was detected by flow cytometry experi-ment,and the apoptosis rate of each group was compared;the levels of reactive oxygen species(ROS),lactate dehydrogenase(LDH)and inflammatory factors IL-6,IL-17 and IL-18 in each group were measured by the kit;the expressions of miR-138-5p and HIF-1α mRNA in cells of each group were measured by real-time quantitative PCR(qRT-PCR)experiment;the expressions of apoptotic pro-teins caspase-9,Bcl-2-associated X protein(Bax)and HIF-1α in each group were evaluated by Western blot.Results:Compared with control group,the apoptosis rate,cellular ROS,LDH,IL-6,IL-17 and IL-18 levels,cellular HIF-1α mRNA and protein levels,cellular caspase-9,Bax and HIF-1α protein levels were increased in H/R model group(P<0.05),the cell viability and miR-138-5p level were decreased(P<0.05).Compared with H/R model group and H/R+co-transfection group,the cell viability,cell HIF-1αmRNA and protein levels were increased in H/R+LncRNA SNHG12 overexpression group(P<0.05),the apoptosis rate,cellular ROS,LDH,IL-6,IL-17 and IL-18 levels,cellular caspase-9 and Bax protein levels,and miR-138-5p level were decreased(P<0.05);the cell viability,cellular HIF-1α mRNA and protein levels were decreased in H/R+miR-138-5p mimics group(P<0.05),the apoptosis rate,cellular ROS,LDH,IL-6,IL-17 and IL-18 levels,cellular caspase-9 and Bax protein levels were increased(P<0.05).Com-pared with H/R model group,there was no significant difference in cell index levels between the H/R+co-transfection negative control group and the H/R+co-transfection group(P>0.05).Conclusion:LncRNA SNHG12 can upregulate HIF-1α expression by downregulat-ing miR-138-5p expression,inhibit H/R-induced inflammation and oxidative stress in HUVECs,and reduce cell damage and apoptosis.
4.Research advances in conversion therapy for primary liver cancer
Jie JIANG ; Zongqiang HU ; Gang CHEN ; Yuantong XU ; Guang CHU
Journal of Clinical Hepatology 2020;36(8):1870-1873
Radical hepatectomy and liver transplantation are the best choices to improve the long-term prognosis of patients with primary liver cancer; however, most of the patients in China have lost the opportunity for surgical treatment at the time of confirmed diagnosis. Therefore, conversion therapy has become a research hotspot in improving the survival rate of patients with advanced liver cancer. This article briefly describes the evaluation of conversion therapy for liver cancer and summarizes the current conversion treatment regimens for unresectable liver cancer. With the deepening of the understanding of primary liver cancer and individualized treatment, the group of precise treatment combined with multidisciplinary diagnosis and treatment develops the regimens for individualized conversion therapy, which is considered to effectively improve the surgical resection rate, treatment outcome, and long-term prognosis of patients with advanced liver cancer.
5.Evolution and innovation of preservation fluid for donor liver
Guotao YU ; Yanfeng YIN ; Chuntao YAN ; Guangxu ZOU ; Huangyan ZHANG ; Li MA ; Zongqiang HU
Organ Transplantation 2024;15(1):131-137
Organ preservation fluid could mitigate cold ischemia injury and maintain normal function of the grafts. At present, how to reduce a series of injury caused by cold ischemia of donor liver and improve the preservation quality of grafts are the hot and challenging spots in this field. Currently, preservation fluid in clinical practice has not achieved ideal preservation effect, especially for the protection of marginal donor organs. In the context of severe donor shortage, the key solution is still to explore the optimal preservation protocol for donor liver to prevent grafts from cold ischemia injury. In this article, the mechanism of donor liver injury during cold ischemia, the classification and evolution of donor liver preservation fluid were summarized, the development direction and challenges of donor liver preservation fluid were discussed, aiming to provide novel ideas and references for the research and development of donor liver preservation fluid.