Research Progress of HO1 on AntiOxidative Stress Injury of MSC --Review / 中国实验血液学杂志

Mesenchymal stem cell (MSC) is widely used in cell therapy because of its high proliferative and multi directional differentiation potential as well as its low immunogenicity. The transplantation of MSC can help the repair of the injured organs, however, the MSC transplanted to the local organs are affected by oxidative stress and lead to premature aging or apoptosis. Heme oxygenase 1 (HO1) is a key ratelimiting enzyme in the process of heme metabolism, which has the functions of antiinflammation, antioxidation, antiapoptosis, antiaging, reducing cell damage and promoting angiogenesis. Induced high expression of HO1 in MSC could increase the ability of MSC against oxidative stress injury, delay the senescence and apoptosis of MSC, and alleviate cell injury. In this reviews, the research progress of HO1 on antioxidative stress injury of MSC.

Flavonoids in myocardial ischemia-reperfusion injury: Therapeutic effects and mechanisms / 中草药·英文版

Ischemic heart diseases are one of the major causes of death worldwide. Effective restoration of blood flow can significantly improve patients’ quality of life and reduce mortality. However, reperfusion injury cannot be ignored. Flavonoids possess well-established antioxidant properties; They also have other benefits that may be relevant for ameliorating myocardial ischemia-reperfusion injury (MIRI). In this review, we focus on flavonoids with cardiovascular-protection function and emphasize their pharmacological effects. The main mechanisms of flavonoid pharmacological activities against MIRI involve the following aspects: a) antioxidant, b) anti-inflammatory, c) anti-platelet aggregation, d) anti-apoptosis, and e) myocardial-function regulation activities. We also summarized the effectiveness of flavonoids for MIRI.

Neuroprotective Effects of Molecular Hydrogen: A Critical Review / 神经科学通报·英文版

Molecular hydrogen (H

Anti-asthmatic effect of agarwood alcohol extract in mice and its mechanism / 中国中药杂志

As recorded, agarwood has the function of improving qi reception and relieving asthma, but the underlying mechanism is unclear and rarely reported. Therefore, this study explored the anti-asthmatic effect of the alcohol extract of agarwood produced by the whole-tree agarwood-inducing technique(Agar-Wit) in the asthma mouse model induced by intraperitoneal injection of ovalbumin(OVA) + Al(OH)_3 combined with intranasal administration of OVA and the mechanism, and compared the anti-asthmatic effects of agarwood induced with different methods. Firstly, the anti-inflammatory and anti-asthmatic effects of Agar-Wit agarwood in mice were evaluated based on the asthma frequency, lung tissue injury, and peripheral inflammatory white blood cell(WBC) count and eosinophil count. Then, the levels of interleukin-1β(IL-1β), IL-17, and IL-10 in serum of mice were detected by enzyme-linked immunoassay(ELISA) and the expression of inflammation-and apoptosis-related genes in tissues was measured by reverse transcription polyme-rase chain reaction(RT-PCR) so as to preliminarily explore the anti-asthmatic mechanism. RESULTS:: showed that the alcohol extract of Agar-Wit agarwood significantly reduced asthma frequency, relieved pathological injury, improved peripheral WBC count and eosinophil count, decreased the levels of inflammatory cytokines IL-1β and IL-17, elevated the level of anti-inflammatory cytokine IL-10, and down-regulated the mRNA expression of IL-1 R, tumor necrosis factor receptor R(TNFR), nuclear transcription factor-kappa B(NF-κB), Bax, and caspase 3, but had no significant influence on the expression of high-mobility group box 1(HMGB1) protein, caspase 8, and Bcl-2. The effect of Agar-Wit agarwood alcohol extract was better than that of wild agarwood alcohol extract and alcohol extract of agarwood induced with the burning-chisel-drilling method at the same dose. In conclusion, Agar-Wit agarwood can significantly alleviate inflammation and asthma, which is related to its anti-inflammation and anti-apoptosis activity.

Antioxidant and Antiapoptotic Polyphenols from Green Tea Extract Ameliorate CCl-Induced Acute Liver Injury in Mice / 中国结合医学杂志

OBJECTIVE@#To investigate the phenolic composition, antioxidant properties, and hepatoprotective mechanisms of polyphenols from green tea extract (GTP) in carbon tetrachloride (CCl)-induced acute liver injury mouse model.@*METHODS@#High-performance liquid chromatography was used to analyze the chemical composition of the extract. Antioxidant activity of GTP was assessed by O, OH, DPPH, and ferric-reducing antioxidant power (FRAP) assay in vitro. Sixty Kunming mice were divided into 6 groups including control, model, low-, medium-, and high-doses GTP (200, 400, 800 mg/kg) and vitamin E (250 mg/kg) groups, 10 in each group. GTP and vitamin E were administered at a level of abovementioned doses twice per day for 7 days prior to exposure to a single injection of CCl. Hepatoprotective effects of GTP were evaluated in a CCl-induced mouse model of acute liver injury, using commercial enzyme linked immunosorbent assay kits, histopathological observation, terminal deoxynucleotidyl transferase-mediated dUTPNick-end labeling (TUNEL) assay and Western blot.@*RESULTS@#GTP contained 98.56 µg gallic acid equivalents per milligram extract total polyphenols, including epicatechingallate, epigallocatechin gallate, epicatechin, and epigallocatechin. Compared with the model group, low-, medium-, or high doses GTP significantly decreased serum levels of alanine aminotransferase and aspartate transaminase (P<0.01). Histopathological observation confirmed that pretreatment of GTP prevented swelling and necrosis in CCl-exposed hepatocytes. Hepatoprotective effects of low-, medium-, and high-dose GTP were associated with eliminating free radicals and improving superoxide dismutase, catalase, and glutathione peroxidase activity in the liver. Additionally, low-, medium-, and high-dose GTP decreased cell apoptosis in the CCl-exposed liver (P<0.01). Phosphorylated nuclear factor kappa-B (NF-κB), p53, Bcl-2 associated x protein/B-cell lymphoma/leukemia-2 gene, cytochrome C, and cleaved caspase-3 levels were downregulated compared with the model group (P<0.01).@*CONCLUSION@#GTP achieves hepatoprotective effects by improving hepatic antioxidant status and preventing cell apoptosis through caspase-3-dependent signaling pathways.

Measles virus phosphoprotein inhibits apoptosis and enhances clonogenic and migratory properties in HeLa cells

Measles virus is the causative agent of measles, a major cause of child mortality in developing countries. Two majorproteins, coded by the viral genome, are nucleocapsid protein (N) and phosphoprotein (P). The N protein protects the viralgenomic RNA and forms ribonucleoprotein complex (RNP) together with P protein. MeV-P protein recruits the largeprotein (L), i.e. viral RNA-depended RNA polymerase (RdRp), to ensure viral replication in host cell. Apoptogenicproperties of N protein of Edmonston vaccine strain have been established in our lab previously. We investigated the role ofMeV-P protein of Edmonston vaccine strain as modulator of apoptosis in cervical cancer cell line (HeLa) and found thatMeV-P protein is anti-apoptotic and enhances cell proliferation. Measles virus is considered to be innately oncotropic virus.However, the anti-apoptotic property of MeV-P protein raises important concerns while adopting this virus as an anti-cancertherapeutic tool.

“Hairiness” is a Facsimile of Reorganized Cytoskeletons: A Cytopathic Effect of Coxiella burnetii

In 1993, I reported that Coxiella burnetii transforms human B cells into hairy cells (cbHCs), the first hairy cell reported outside of hairy cell leukemia (HCL). Over last few decades, advances in molecular biology have provided evidence supporting that C. burnetii induces hairiness and inhibits the apoptosis of host cells. The present review summarizes new information in support of cbHC. C. burnetii was shown to induce reorganization of the cytoskeleton and to inhibit apoptosis in host cells. Peritoneal B1a cells were found to be permissive for virulent C. burnetii Nine Mile phase I (NMI) strains in mice. C. burnetii severely impaired E-cad expression in circulating cells of Q fever patients. B-cell non-Hodgkin lymphoma was linked to C. burnetii. Mutation of BRAF V600E was pronounced in HCL, but “hairiness” was not linked to the mutation. Risk factors shared among coxiellosis and HCL in humans and animals were reported in patients with Q-fever. Accordingly, I propose that C. burnetii induces reorganization of the cytoskeleton and inhibits apoptosis as cytopathic effects that are not target cell specific. The observed hairiness in cbHC appears to be a fixed image of dynamic nature, and hairy cells in HCL are distinct among lymphoid cells in circulation. As the cytoskeleton plays key roles in maintaining cell structural integrity in health and disease, the pathophysiology of similar cytopathic effects should be addressed in other diseases, such as myopathies, B-cell dyscrasias, and autoimmune syndromes.

Research progress in mesenchymal stem cells modified by Heme oxygenase 1 / 中国修复重建外科杂志

Objective: To review the literature reports on research progress of Heme oxygenase 1 (HO-1) modified mesenchymal stem cells (MSCs). Methods: The significance, effects, and related mechanism of HO-1 modification of MSCs were summarized by consulting the related literatures and reports of HO-1 modification of MSCs. Results: HO-1 modification of MSCs has important research value. It can effectively enhance the anti-oxidative stress and anti-apoptotic properties of MSCs in complex internal environment after transplantation into vivo. It can also effectively enhance the immune regulation function of MSCs. It can improve the anti-injury, repair, and immune regulation effect of MSCs in various disease models and research fields. Conclusion: The basic research of HO-1 modified MSCs has made remarkable progress, which is expected to be applied in clinical trials and provide theoretical basis and reference value for stem cell therapy.

Protective effects of extracts of Schisandra chinensis stems against acetaminophen-induced hepatotoxicity via regulation of MAPK and caspase-3 signaling pathways / 中国天然药物

The present study was designed to evaluate protective activity of an ethanol extract of the stems of Schisandra chinensis (SCE) and explore its possible molecular mechanisms on acetaminophen (APAP) induced hepatotoxicity in a mouse model. The results of HPLC analysis showed that the main components of SCE included schisandrol A, schisandrol B, deoxyschisandrin, schisandrin B, and schisandrin C and their contents were 5.83, 7.11, 2.13, 4.86, 0.42 mg·g, respectively. SCE extract was given for 7 consecutive days before a single hepatotoxic dose of APAP (250 mg·kg) was injected to mice. Our results showed that SCE pretreatment ameliorated liver dysfunction and oxidative stress, which was evidenced by significant decreases in aspartate transaminase (AST), alanine aminotransferase (ALT), malondialdehyde (MDA) contents and elevations in reduced glutathione (GSH) and superoxide dismutase (SOD) levels. These findings were associated with the result that the SCE pretreatment significantly decreased expression levels of 4-hydroxynonenal (4-HNE) and 3-nitrotyrosine (3-NT). SCE also significantly decreased the expression levels of Bax, mitogen- activated protein kinase (MAPK), and cleaved caspase-3 by APAP exposure. Furthermore, supplementation with SCE suppressed the expression levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), suggesting alleviation of inflammatory response. In summary, these findings from the present study clearly demonstrated that SCE exerted significant alleviation in APAP-induced oxidative stress, inflammation and apoptosis mainly via regulating MAPK and caspase-3 signaling pathways.

Advances in study of pharmacological effects of ginsenoside Rg1 in hepatic diseases / 药学学报

Ginsenoside Rg1 is one of the main active components of ginseng with various pharmacological activities including anti-inflammatory, anti-oxidation, anti-aging, anti-tumor and anti-apoptosis. Ginsenoside Rg1 plays a protective role in multiple tissues and organs, which shows the multiple targeting properties of the pharmacological effects. Recently, a number of studies have demonstrated that ginsenoside Rg1 has a protective role in the liver due to its multiple pharmacological effects. In chemical liver injury models, or in other liver injury models, ginsenoside Rg1 can alleviate liver necrosis induced by oxidative stress and inflam-mation. This article provides a review of the recent studies on the efficacy of ginsenoside Rg1 in the treatment of various liver damage and the molecular mechanism.

Protective effects of extracts of Schisandra chinensis stems against acetaminophen-induced hepatotoxicity via regulation of MAPK and caspase-3 signaling pathways / 中国天然药物

The present study was designed to evaluate protective activity of an ethanol extract of the stems of Schisandra chinensis (SCE) and explore its possible molecular mechanisms on acetaminophen (APAP) induced hepatotoxicity in a mouse model. The results of HPLC analysis showed that the main components of SCE included schisandrol A, schisandrol B, deoxyschisandrin, schisandrin B, and schisandrin C and their contents were 5.83, 7.11, 2.13, 4.86, 0.42 mg·g, respectively. SCE extract was given for 7 consecutive days before a single hepatotoxic dose of APAP (250 mg·kg) was injected to mice. Our results showed that SCE pretreatment ameliorated liver dysfunction and oxidative stress, which was evidenced by significant decreases in aspartate transaminase (AST), alanine aminotransferase (ALT), malondialdehyde (MDA) contents and elevations in reduced glutathione (GSH) and superoxide dismutase (SOD) levels. These findings were associated with the result that the SCE pretreatment significantly decreased expression levels of 4-hydroxynonenal (4-HNE) and 3-nitrotyrosine (3-NT). SCE also significantly decreased the expression levels of Bax, mitogen- activated protein kinase (MAPK), and cleaved caspase-3 by APAP exposure. Furthermore, supplementation with SCE suppressed the expression levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), suggesting alleviation of inflammatory response. In summary, these findings from the present study clearly demonstrated that SCE exerted significant alleviation in APAP-induced oxidative stress, inflammation and apoptosis mainly via regulating MAPK and caspase-3 signaling pathways.

Apoptosis in response to heat stress is positively associated with heat-shock protein 90 expression in chicken myocardial cells in vitro

To determine heat-shock protein (Hsp)90 expression is connected with cellular apoptotic response to heat stress and its mechanism, chicken (Gallus gallus) primary myocardial cells were treated with the Hsp90 promoter, aspirin, and its inhibitor, geldanamycin (GA), before heat stress. Cellular viability, heat-stressed apoptosis and reactive oxygen species level under different treatments were measured, and the expression of key proteins of the signaling pathway related to Hsp90 and their colocalization with Hsp90 were detected. The results showed that aspirin treatment increased the expression of protein kinase B (Akt), the signal transducer and activator of transcription (STAT)-3 and p-IKKα/β and the colocalization of Akt and STAT-3 with Hsp90 during heat stress, which was accompanied by improved viability and low apoptosis. GA significantly inhibited Akt expression and p-IKKα/β level, but not STAT-3 quantity, while the colocalization of Akt and STAT-3 with Hsp90 was weakened, followed by lower cell viability and higher apoptosis. Aspirin after GA treatment partially improved the stress response and apoptosis rate of tested cells caused by the recovery of Akt expression and colocalization, rather than the level of STAT-3 (including its co-localization with Hsp90) and p-IKKα/β. Therefore, Hsp90 expression has a positive effect on cellular capacity to resist heat-stressed injury and apoptosis. Moreover, inhibition of Hsp90 before stress partially attenuated its positive effects.

Improvement Effects of Baicalein against Myocardial Ischemia/Reperfusion Injury in Rats / 中国药房

OBJECTIVE:To study the improvement effects of baicalein against myocardial ischemia/reperfusion(I/R)injury in rats. METHODS:I/R injury model was induced by Langendorff method. Isolated heart of 40 rats were randomly divided into nor-mal group(continuous perfusion),model group(perfusion withdrawal 20 min)and baicalein high,medium and low concentration groups (K-H solution of baicalein 40,10 and 2.5 μmol/ml 10 min before perfusion withdrawal). The myocardial infarction rate, the activity of creatine kinase(CK)and lactate dehydrogenase(LDH)in coronary effluent liquid,SOD activity and MDA content, GSH/GSSG and apoptosis rate of cardiac muscle cell in myocardial tissue were detected. RESULTS:Compared with normal group, the myocardial infarction rate,apoptosis rate of cardiac muscle cell,the activities of CK and LDH and the content of MDA in myo-cardial tissue were increased in model group,while SOD activity and GSH/GSSG of myocardial tissue decreased(P0.05). CONCLUSIONS:Baicalein has cer-tain improvement effect on myocardial I/R injury in rats,and its mechanism may be associated with antioxidant and anti-apoptosis effect of baicalein.

Anti-apoptotic effects of cobalt proporphyrin-induced overexpression of heme oxygenase-1 in a mouse ;model of liver ischemia-reperfusion injury / 中华微生物学和免疫学杂志

Objective To investigate the anti-apoptosis effects of heme oxygenase-1 (HO-1) in a mouse model of liver ischemia-reperfusion ( IR ) injury and to analyze the possible mechanisms . Methods A cell model of hypoxia/reoxygenation injury was established after transfecting mouse liver AML12 cells with HO-1 small interfering RNA ( siRNA) . Real-time PCR and Western blot assay were performed to detect the changes of HO-1, B-cell lymphoma 2 (Bcl2) and caspase-3 at the cellular level. The mouse models of liver ischemia-reperfusion injury were established with/without pretreatments with cobalt proporphyrin (CoPP), CoPP+znic proporphyrin ( ZnPP) and/or ZnPP. The levels of aspartate transaminase ( AST) and alanine transaminase ( ALT) in serum samples were measured. Immunohistochemistry was used to analyze the chan-ges of caspase-3. Western blot assay was used to detect the expression of HO-1 and Bcl2 at protein level. The pathological changes of liver tissues were observed under light microscope. The apoptosis of hepatocytes was observed by using Tunel assay. Results Decreased expression of HO-1 and Bcl2 and increased expres-sion of caspase-3 were observed in the model of hypoxia/reoxygenation injury by pre-transfecting the AML12 cells with HO-1 siRNA. Compared with the IR injury group, the CoPP pretreatment group showed lower lev-els of AST and ALT (P<0. 05) and alleviated pathological damages in liver tissues. Moreover, the expres-sion of caspase-3 was inhibited, but the expression of HO-1 and Bcl2 were enhanced. Less apoptotic cells was detected by the Tunel assay (P<0. 05). However, these protective effects could be suppressed by adding ZnPP. Conclusion HO-1 has anti-apoptotic effects in the in vitro model of hypoxia/reoxygenation. CoPP can upregulate the expression of HO-1 and play the role of anti-apoptosis in a mouse model of liver is-chemia-reperfusion injury.

Brain-Derived Neurotrophic Factor (BDNF) Exerts a Protective Effect via an Anti-Apoptotic Mechanism on Hypoxic-Ischemic Injury in the Rat Brain / 대한주산의학회잡지

PURPOSE: Perinatal hypoxic-ischemic (HI) brain injury remains a common cause of chronic handicapping conditions of cerebral palsy, mental retardation, learning disability, and epilepsy. HI brain injury induces cell death via either necrosis or apoptosis. Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family. It plays key roles in survival, differentiation, and maintenance of neurons. This study was to investigate the neuroprotective effects of BDNF via the mechanisms of anti-apoptosis in HI brain injury by using cortical astrocyte and neuronal cell culture. METHODS: Cortical astrocytes culture of 1-day-old Sprague-Dawley (SD) rat pups and embryonic cortical neuronal cell culture of SD rats at 14-day gestation were done. The Normoxia group was prepared in 5% CO2 incubators and the Hypoxia group and Hypoxia+BDNF group (after treatment with BDNF for 24 hours) were placed in 1% O2 incubators (94% N2, 5% CO2) for 6 or 18 hours. The expression of Bcl-2 and Bax were assessed by real-time PCR and western blot. The caspase-3 activation was evaluated by caspase activity assay kit. RESULTS: In astrocyte and neuronal cell, the expressions of Bcl-2 in the hypoxia groups were reduced compared to the normoxia groups, whereas, those in the Hypoxia+BDNF groups were increased compared to the hypoxia groups. However, the expressions of Bax and caspase-3 and the ratio of Bax/Bcl-2 were revealed reversely. In astrocyte, Hypoxia group for 6 hours was not significantly altered in Bcl-2, Bax expressions. CONCLUSION: BDNF neuroprotective effects on HI brain injury in neonatal rats may occur via anti-apoptotic mechanism.

Study progress of Danshensu and its derivatives in cardiovascular mechanism / 药学实践杂志

Danshensu is one of the main water soluble active ingredients of Salvia miltiorrhiza ,which has many phar-macological activities ,especially in cardiovascular system .T he cardiovascular pharmacological mechanism of Danshensu and its derivatives from the view of anti-apoptosis ,antioxidant ,inhibiting calcium overload and role in the inflammatory reaction path-ways etc .were summarized in this article .

Research progress on effects of hypoxia inducible factors on main-tenance of cancer stem cell biological characteristics / 中国肿瘤临床

Hypoxic microenvironment is a typical characteristic of solid tumors and is considered an independent risk factor in tu-mor progression and poor prognosis. Hypoxic microenvironment is a critical part of cancer stem cell (CSC) niche and plays an impor-tant role in the evolution of cancer stem cells in tumors and in apoptosis resistance. As a key factor in the tumor's adaption to hypoxic microenvironment, hypoxia inducible factors (HIFs) can induce biological behavioral changes in CSCs that can accelerate tumor malig-nant transformation. Such behavioral changes include anti-apoptosis, enhancement of drug-resistance gene expression, and tumor inva-sion and metastasis. HIFs are also among the main factors affecting the capacity of CSCs to maintain their biological characteristics. In this review, the authors focus on recent advances in our understanding of the role that HIFs play in maintaining the biological character-istics of CSCs.

Functional research advances of the protection of alpha crystallin to the lens transparency / 中华实验眼科杂志

α-Crytallin,composed of two menbers of the small heat shock protein,is the major component of the cytoplasm in lens.α-Crytallin not only possesses chaperone-like activity,but also plays important roles in regulation of cell cycle,enhancing genome stability and prevention of the stress-induced apoptosis.The gene mutation associated with α-crytallin is a common cause of hereditary cataract,which is the major cause of childhood blindness.Whereas various changes of the α-crytallin can result in the most common cause of blindness in the world—age-related cataract.Understanding of the function of α-crytallin helps to comprehend the development of lens and how the lens maintain its normal function,and to provide a theoretical basis for the prevention and treatment of the cataract related to the malfunction of α-crytallin.The genetic mapping and mechanism of cataract and the function of α-crytallin are summarized here.

Effects of taurine on the development of the mammalian brain and anti-hypoxic ischemic brain damage / 国际儿科学杂志

As an inhibitory amino acid similar to gama-aminobutyric acid,taurine can activate the corticostriatal pathway as an endogenous ligand for glycine receptors,establishing equilibrium between the excitatory and inhibitory processes in the brain.In mammalian brains,taurine concentrations increase during the developmental period of the brain until weaning,and subsequently decline reaching stable concentrations in adulthood.With abilities of anti-oxidative stress,anti-inflammatory and anti-apoptosis,taurine can improve the hypoxic-ischemic brain injury,promote the proliferation and differentiation of neurons and affect brain development,It needs more investigations to prove when and how taurine supplementation during gestation,baby,children or adult can assist the development of the brain and prevent the damage of the brain from hypoxic and ischemic damage.

Current progress of erythropoietin in depression / 中国药理学通报

Erythropoietin (EPO),which is routinely used in clinic to treat anemia,has been implicated in a wide range of activities on diverse tissues.Recently,accumulating evidence shows that EPO has antidepressant-like effects and may be a po-tential drug candidate for treating mood symptoms and memory dysfunction in depression.This review summarizes the current progress on EPO’s antidepressant-like effects,and explores its potential mechanism and clinical application in the future,provi-ding a general view of the research and application status of EPO in depression.