Biological principles for "homotherapy for heteropathy" / 药学学报

Non-infectious chronic diseases in human including diabetes, non-alcoholic fatty liver disease (NAFLD), atherosclerosis (AS), neurodegenerative diseases, osteoporosis, as well as malignant tumors may have some common pathogenic mechanisms such as non-resolved inflammation (NRI), gut microbiota dysfunction, endoplasmic reticulum stress, mitochondria dysfunction, and abnormality of the mammalian target of rapamycin (mTOR) pathway. These pathogenic mechanisms could be the basis for "homotherapy for heteropathy" in clinic. Some commonly used clinical drugs, such as metformin, berberine, aspirin, statins, and rapamycin may execute therapeutic effect on their targeted diseases,and also have the effect of "homotherapy for heteropathy". The mechanisms of the above drugs may include anti-inflammation, modulation of gut microbiota, suppression of endoplasmic reticulum stress, improvement of mitochondria function, and inhibition of mTOR. For virus infectious diseases, as some viruses need certain commonly used replicases, the inhibitors of the replicases become examples of "homotherapy for heteropathy" for antiviral therapy in clinic (for example tenofovir for both AIDS and HBV infection). Especially, in case of outbreak of new emerging viruses, these viral enzyme inhibitors such as azvudine and sofibuvir, could be rapidly used in controlling viral epidemic or pandemic, based on the principle of "homotherapy for heteropathy". In this review article, we show the research progress of the biological basis for "homotherapy for heteropathy" and the possible mechanisms of some well-known drugs, in order to provide insights and new references for innovative drug R&D.

A new combination of naringin and trimetazidine protect kidney Mitochondria dysfunction induced by renal Ischemia / Reperfusion injury in rat

Abstract Ischemia/reperfusion (IR) injury leads to overproduction of Reactive Oxygen Species (ROS), and disrupts membrane potential that contributes to cell death. The aim of this study was to determine if naringin (NAR), trimetazidine (TMZ) or their combination, protect the kidney mitochondrial from IR injury. Forty rats were randomly allocated into five groups, harboring eight rats each: Sham, IR, NAR (100 mg/kg), TMZ (5 mg/kg) and NAR plus TMZ. Ischemia was induced by obstructing both renal pedicles for 45 min, followed by reperfusion for 4 hours. The mitochondria were isolated to examine the ROS, Malondialdehyde (MDA), Glutathione (GSH), mitochondrial membrane potential (MMP) and mitochondrial viability (MTT). Our findings indicated that IR injury resulted in excessive ROS production, increased MDA levels and decreased GSH, MMP and MMT levels. However, NAR, TMZ or their combination reversed these changes. Interestingly, a higher protection was noted with the combination of both, compared to each drug alone. We speculate that this combination demonstrates a promising process for controlling renal failure, especially with the poor clinical outcome, acquired with NAR alone. This study revealed that pretreatment their combination serves as a promising compound against oxidative stress, leading to suppression of mitochondrial stress pathway and elevation of GSH level.

Expression of gC1qR gene in ovarian cancer and its apoptotic mechanism / 临床与实验病理学杂志

Purpose To investigate the expression of globular C1q receptor (gC1qR) in ovarian cancer and to explore its potential molecular mechanism.Methods Retrospective analysis was made on 48 ovarian cancer tissues and ovarian cancer cell line SKOV3.Real time PCR and Western blot analysis were applied to detect the levels of gC1qR mRNA and gC1qR protein expression.The abilities of SKOV3 cells proliferation activity and quantity,migration and apoptosis were respectively assessed by M'TT,transwell assay and flow cytometry.Besides,the intracellular ROS was estimated via the fluorescence of H2DCFDA,the mitochondrial membrane potential was tested using a JC-1 probe,and the intracellular Ca2+ was assessed via Fluo-3/AM.Results The expressions of gC1qR gene was obviously decreased in the group of ovarian cancer tissues when compared with normal ovarian tissues group (2.61 ±0.34 vs 7.32 ± 1.25,0.20 ± 0.02 vs 0.67-± 0.06,P ＜ 0.001).Overexpression of gC1qR gene could result in significant up-regulation of ovarian cancer cell apoptosis and down-regulation in proliferation and migration,and showed significant cell apoptosis morphology.Simultaneously,the intracellular ROS and Ca2+ were obviously increased,and the mitochondrial membrane potential was obviously decreased.Conclusion gC1qR gene may play an important role in the apoptosis of ovarian cancer cells.In this process,gC1qR gene can induce apoptosis of ovarian cancer cells by inducing mitochondrial dysfunction.

Mitochondrial ultrastructure and function changes in SH?SY5Y induced by manganese / 实用医学杂志

Objective To explore the mechanism of SH?SY5Y mitochondrial dysfunction treated by manganese to find a new potential therapeutic target. Methods Transmission Electron Microscopy(TEM)to observe the morphology of mitochondria. Cell treated with 250μmol/L for periods of time(2 h, 4 h, 6 h)while mitochondrial membrane potential(MMP)and ROS can be detected by FCM and fluorescence microplate reader. Results After treating with MnCl2 in 6 h, TEM images showed early vacuoles, lamellar structures of SH?SY5Y cells. Then test the mitochondrial membrane potential and showed that MMP would be decreased gradually. Meanwhile, analysis showed that in comparison with control, treatment group had a higher ROS level respectively (P < 0.05). Conclusion MnCl2 can cause mitochondrial damage through a mechanism closely related to disrupt the MMP or generate abundant ROS.

Research progress of microRNA in mitochondrial dysfunction of children with sepsis / 中华实用儿科临床杂志

Sepsis is the systemic inflammatory respond syndrome and autoimmunity injury caused by pathogenic microorganism or any other immunogenicity.Mitochondria,an important organelle,which has an essential role in cellular growth,metabolism,occurrence and development of disease by generating ATP following the oxidative phosphorylation from glycolysis.There had been some progresses on the research of sepsis in several decades.A number of studies had shown that the degree of mitochondrial dysfunction was related to the eventual outcome of sepsis.microRNA are endogenous small noncoding RNAs that post-transcriptionally regulate gene and bio-protein expression,and then adjust mitochondrial oxidative stress,has important influence on the process of sepsis and prognosis.Here,a current review of how microRNA impinge on mitochondrial dysfunction in sepsis was performed.

Apoptosis Induced by Manganese on Neuronal SK-N-MC Cell Line: Endoplasmic Reticulum (ER) Stress and Mitochondria Dysfunction

OBJECTIVES: Manganese chloride (MnCl2) is one of heavy metals for causing neurogenerative dysfunction like Manganism. The purpose of this study was to determine the acute toxicity of MnCl2 using different times and various concentrations including whether manganese toxicity may involve in two intrinsic pathways, endoplasmic reticulum (ER) stress and mitochondria dysfunction and lead to neuronal apoptosis mediated by organelle disorders in neuroblastoma cell line SK-N-MC. METHODS: In the acute toxicity test, five concentrations (200, 400, 600, 800, 1,000 uM) of MnCl2 with 3, 6, 12, 24, 48 hours exposure were selected to analyze cell viability. In addition, to better understand their toxicity, acute toxicity was examined with 1,000 uM MnCl2 for 24 hours exposure via reactive oxygen species (ROS), mitochondria membrane potential, western blotting and mitochondrial complex activities. RESULTS: Our results showed that both increments of dose and time prompt the increments in the number of dead cells. Cells treated by 1,000 microM MnCl2 activated 265% (+/-8.1) caspase-3 compared to control cell. MnCl2 induced intracellular ROS produced 168% (+/-2.3%) compared to that of the control cells and MnCl2 induced neurotoxicity significantly dissipated 48.9% of mitochondria membrane potential compared to the control cells. CONCLUSIONS: This study indicated that MnCl2 induced apoptosis via ER stress and mitochondria dysfunction. In addition, MnCl2 affected only complex I except complex II, III or IV activities.

Study of the damage effects of Helicobacter pylori on dopaminergie cell line SH-SY5Y in vitro / 临床神经病学杂志

Objective To study the damage effects and its mechanism of Helicobacter pylori(HP) on dopaminergie cell line SH-SY5Y in vitro.Methods The cellular survival rate,the level of cellular activated oxygen and the activity of mitochondrion respiratory chain complexes were measured in dopaminergic cell line SH-SY5Y after adding secretory components of HP(HP group),MPP+(PD group) and culture solution(control group).Results The cellular survival rates in the HP group and PD group were decreased,the cellular survival rate of high concentration HP subgroup was dramatically decreased than those in the middle and low concentration subgroups(all P