Targeting ferroptosis for treatment of Alzheimer' s disease / 中国药理学通报

Alzheimer' s disease (AD) is a progressive neurodegenerative disorder histologically characterized by the presence of senile plaques and neurofibrillary tangles (NFTs) found in and around pyramidal neurons in cortical tissue. Mounting evidence suggests regional increased iron load and dyshomeostasis have been associated with oxidative stress, oxidation of proteins and lipids, and cell death, and appears to be a risk factor for more rapid cognitive decline, thereby involved in multiple aspects of the pathophysiology of AD. Ferroptosis is a newly identified iron-dependent lipid peroxidation-driven cell death and emerging evidences have demonstrated the involvement of ferroptosis in the pathological process of AD. Notably, some novel compounds targeting ferroptosis can relieve AD-related pathological symptoms in AD cells and animal model and exhibit potential clinical benefits in AD patients. This review systematically summarizes the growing molecular and clinical evidence implicating ferroptosis in the pathogenesis of AD, and then reviews the application of ferroptosis inhibitors in mouse/cell models to provide valuable information for future treatment and prevention of AD.

Therapeutic potential of targeting SIRT1 for the treatment of Alzheimer's disease / 生理学报

Silent information regulator 1 (SIRT1) is one of the seven mammalian proteins of the sirtuin family of NAD+-dependent deacetylases. SIRT1 plays a pivotal role in neuroprotection and ongoing research has uncovered a mechanism by which SIRT1 may exert a neuroprotective effect on Alzheimer's disease (AD). Growing evidence demonstrates that SIRT1 regulates many pathological processes including amyloid-β precursor protein (APP) processing, neuroinflammation, neurodegeneration, and mitochondrial dysfunction. SIRT1 has recently received enormous attention, and pharmacological or transgenic approaches to activate the sirtuin pathway have shown promising results in the experimental models of AD. In the present review, we delineate the role of SIRT1 in AD from a disease-centered perspective and provides an up-to-date overview of the SIRT1 modulators and their potential as effective therapeutics in AD.

Recent progress of epigallocatechin 3-gallate for treatment of Parkinson's disease / 中国药理学通报

Epigallocatechin 3-gallate (EGCG) is an abundant polyphenolie component originating from green tea extract that has exhibited versatile bioactivities in combating several diseases. During the last decade, EGCG are effective in experimental models of Parkinson's disease (PD). Several experimental studies suggest the pleiotropic neuroprotective effects, aiding to EGCG as an appealing therapeutic strategy in PD. Therefore, in this review we focus on the effects of EGCG on anti-apoptosis, anti-oxidant, anti-inflammation, modulation of dopamine production, and the aggregation of a-synuclein. We aim to compile the recent updates and cellular and molecular mechanisms of neuroprotection of EGCG in PD. This review highlights the pharmacological features of EGCG and its therapeutic implications in PD.

Recent progress of neuroprotective mechanisms of luteolin in Alzheimer's disease / 中国药理学通报

Luteolin is a widely distributed type of flavone herbsand vegetables, which has diverse pharmacological activities against human ailments including Alzheimer's disease(AD). Recently, luteolin has been the most widely studied phytochemicals for their neuroprotective effects against experimental models of AD. Luteolin also improves brain insulin sensitivity and neuroinflammation, which attenuates the phosphorylation of tau and the formation of tangles, and the tendency of Aβ to form deposits. Furthermore, luteolin has anti-oxidative stress and anti-apoptosis effect in AD. The present study aims at reviewing experimental studies and describing the possible underlying molecular mechanisms by which luteolin and the related compounds protect against AD.

Effects of Exosomes Derived from miR-486 Gene Modified Umbilical Cord Mesenchymal Stem Cells on Biological Characteristics of Rat Cardiomyocytes / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effects of exosomes derived from miR-486 gene-modified umbilical cord mesenchymal stem cells (UC-MSCs) on biological characteristics of rat cardiomyocytes.</p><p><b>METHODS</b>The human umbilical cord mesenchymal stem cells (UC-MSCs) were isolated and cultured, then the immunophenotypes and ability of osteogenic and adipogenic differentiation of UC-MSC were identified. The structure of exosomes was observed by electron microscopy; the effect of exosomes on cell migration was detected by transwell cell migration test; the miR-486 high expression of UC-MSC was mediated by using recombinant adenovirus vector, moreover the UC-MSC with high expression of miR-486 were identified by qPT-PCR. The exosomes were isolated from cell culture supernatant by ultracentrifugation and the miR-486 expression level of UC MSC exosomes was detected by qRT-PCR. The effect of exosomes on the proliferation of cardiomyocytes was evaluated by Dye670 marking. The HO-induced cardiomyocyte apoptosis model was established, and the effect of exosomes on apoptosis of cardiomyocytes was detected by flow cytometry with Annexin V/PI double staining.</p><p><b>RESULTS</b>The exosomes derived from UC-MSCs had the diameter between 40-100 nm and double membrane stracture. The recombinant adenovirus could effectively mediate the expression of miR-486 in UC-MSC, and the expression level of miR-486 in exosomes of miR-486-modified UC-MSC significantly increased. The exosomes with miR-486 high expression possessed the pro-proliferation and pro-migration effects on cardiomyocytes, moreover the preventive effect on apoptosis of cardiomyocytes.</p><p><b>CONCLUSION</b>The exosomes derived from UC-MSC and accompamied by high expression of miR-486 can promote the proliferation and migration of cardio myocytes, yet can prevent the apoptosis of cardiomyocytes.</p>

Research Advance on Promoting Angiogenesis of Mesenchymal Stem Cells-Review / 中国实验血液学杂志

Mesenchymal stem cells (MSC) possess important biological characteristics of tissue repair and regeneration. MSC exert the properties promoting endogenous angiogenesis and have been widely applied in treatment of ischemia diseases. The therapeutic potency of MSC for ischemia diseases is owing to their secretion of angiogenic growth factors and release of exosomes. MSC promote angiogenesis stronger in hypoxia environment, and their miRNA played an important role in mediating regulation. This review summarizes recent advances in treatment of angiogenesis using MSC and their mechanisms. The angiogenic activities of MSC under hypoxia condition and their regulation by a miRNA network were discussed.

Roles of SPK in Regulation of Hypoxia Induced Proliferation and Glucose Consume of Leukemia Cells / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To clarify the roles of SPK pathway in the regulation of proliferation, survival and glucose consume of human erythroleukemia TF-1 cells.</p><p><b>METHODS</b>The interfering in SPK expression of TF-1 cells was performed using leutivirus vector-mediated shRNA, the interference efficacy of SPK in TF-1 cells was detected by RT-qPCR and Western blot, the viability of TF-1 cell proliferation was detected by using CCK-8 method, the apoptosis of TF-1 cells was determined by flow cytmetry with Annexin V staining.</p><p><b>RESULTS</b>Hypoxia up-regulated the expression of HIF-1α, HIF-2α, and SPK in TF-1 cells. SPK treatment resulted in reduced proliferation and induced apoptosis in TF-1 cells. Furthermore, knockdown of the SPK significantly reduced utilization and consumption of glucose.</p><p><b>CONCLUSION</b>The SPK is key signalling molecule involved in regulation of hypoxia-induced proliferation and glucose metabolism in TF-1 cells, and plays an important rote in proliferation and energy metabolism of leukemia cells.</p>

Assessment of Function of a Single Limb after Injury / 法医学杂志

OBJECTIVE@#To explore the method for the objective evaluation of single limb function after in- jury in forensic medical practice.@*METHODS@#The score of activities of daily living (ADL) were graded for a single limb function after injury from 47 cases. All cases were simultaneously evaluated using the different methods including Fugl-Meyer motor function assessment (FMA), weighting, look-up table (LUT). The correlation were compared between ADL and the other three methods.@*RESULTS@#Injured part and the score using the three methods were correlated with ADL score (P < 0.05). The correlation coeffi- cient (|r| value) showed highest using LUT method, and lowest using FMA method.@*CONCLUSION@#The loss function of limb is affected by the injuried parts. The methods of FMA, weighting and LUT show a good accuracy for evaluating the limb function after injury and the correlation presents higher using LUT method.

Effect of aurora inhibitor VX-680 on proliferation and apoptosis of CML cells / 中国实验血液学杂志

This study was aimed to explore the effect of VX-680, an aurora inhibitor, on proliferation and apoptosis of K562, KCL22 cell lines and CD34⁺ cells from chronic myeloid leukemia (CML) patients in vitro. The proliferation of K562 and KCL22 cell was detected by CCK-8 method. Apoptosis of cells was detected by Annexin V-PI labeling and flow cytometry. The colony forming ability of bone marrow CD34⁺ cells derived from CML patients and donors was determined by the colony forming test. The results showed that the treatment of K562, KCL22 and CML CD34⁺ cells with VX-680 of 20-100 nmol/L for 3 days could obviously inhibit the cell proliferation in a concentration-dependent manner (P < 0.01). VX-680 treatment significantly induced apoptosis of K562 and KCL22 cells. Compared to bone marrow CD34⁺ cells derived from the healthy donors, the colony forming ability of CML CD34⁺ cells derived from bone marrow of CML patients was remarkably reduced (P < 0.01). It is concluded that VX-680, an aurora inhibitor, can inhibit the proliferation and induce apoptosis of CML cells in vitro.

Effect of microRNA-17-92 cluster on the biological characteristics of K562 cells and its mechanisms / 中国实验血液学杂志

The objective of this study was to explore the effects of microRNA-17-92 on the biological characteristics of K562 cells. The expression of miR-17-92 in K562 cells transfected with miRNA-17-92 mimic was detected by real time PCR. The effect of microRNA-17-92 on K562 cell proliferation was detected by CCK-8 method. Apoptosis of K562 cells was detected by Annexin V-PI labeling. Cell cycle distribution was determined by using flow cytometry. Western blot was performed to determine the protein levels of Crk. The results indicated that the transfection with miR-17-92 mimic increased expression of mature miR-17-92 in K562 cells. Compared with control group, cell proliferation and cell amount in S-phase of miR-17-92 mimic transfected group significantly increased, cell apoptosis decreased. The expression of signal connector protein Crk was greatly up-regulated in miR-17-92-mimic-transfected K562 cells. It is concluded that miR-17-92 can promote proliferation, inhibit apoptosis and regulate the cell cycle of K562 cells.

Influencing factors of psychopath's civil litigation / 法医学杂志

OBJECTIVE@#To explore the influencing factors of schizophrenic patient's capability in civil litigation, and to establish the base of quantitative study about execution of civil litigation.@*METHODS@#To study questionnaires completed from patients with and without civil litigation capabilities and to determine the influencing factors from medical and forensic aspects.@*RESULTS@#One hundred patients were admitted to the study and were divided into two groups based on capability in civil litigation. There were significant differences in psychiatric and legal aspects between the groups.@*CONCLUSION@#Capability of schizophrenic patients in perusing civil litigation had been impaired or even complete lost.

Application of Case Discussion in Pathophysiological Teaching / 中华医学教育探索杂志

Case discussion is an effective approach,which combines basic theory with clinical medicine.It can evoke students' interest and cultivate their creative thinking capacity.Moreover,it can improve teachers' general ability in teaching pathophysiolo- gy.In this article,we discuss the application of case discussion in pathophysiology teaching.