Oxidative Stress During Antituberculous Therapy in Young and Elderly Patients

Using allantoin (ATN ) as a marker for reactive oxygen species (ROS), oxidative stress during antituberculous (anti-TB) therapy was compared in 10 young and 9 elderly patients.Before treatment, ATN plasma concentrations in patients were similar to that of volunteers. Administration of a combination of isoniazid (INH ), rifampicin (RIF) and pyrazinamid e (PZA) increased plasma ATN in both groups of patients. ATN concentrations (M± SE) at six hours were higher (P <0.05 ) in elderly than in young patients on day one,8.22 ± 1.50 vs 1.89 ± 0.98 μg/mL); day 30, (5.85 ± 0.82 vs 0.87 ± 0.57 μg/mL; and day 90, (4.84 ± 1.24 vs 0.52 ± 0.50μg/mL). Because total amount of ATN excreted was similar in both groups on the three occasions, more ATN was formed in elderly than young patients. In conclusion, there was more oxidative stress in elderly than young patients. It is thereby suggested that Anti-TB drugs induce formation of ROS and elderly patients are at a greater risk of toxicity probably because of poor antioxidant mechanisms

Effects of ganglioside + aspirin + atorvastatin triple therapy on oxidative stress and inflammatory response in patients with cerebral infarction

Objective: To investigate the effects of ganglioside + aspirin + atorvastatin triple therapy on oxidative stress and inflammatory response in patients with cerebral infarction. Methods:A total of 138 patients with acute cerebral infarction between July 2016 and July 2017 were divided into control group (n=69) and triple group (n=69) by random number table method. Control group accepted conventional symptomatic treatment combined with aspirin and atorvastatin therapy, triple group accepted conventional symptomatic treatment combined with ganglioside, aspirin and atorvastatin triple therapy, and both groups were treated for 1 month. The differences in oxidative stress and inflammatory response were compared between the two groups before and after treatment. Results: Immediately after admission, There was no statistically significant difference in serum levels of oxidative stress indexes and inflammatory mediators between the two groups. After 1 week of treatment and after 4 weeks of treatment, serum oxidative stress indexes ROS and AOPPs levels of triple group were lower than those of control group whereas SOD and CAT contents were higher than those of control group;serum inflammatory mediators IL-6, TNF-α and TGF-β levels were lower than those of control group whereas IL-4, IL-10 and IL-13 levels were higher than those of control group. Conclusion: ganglioside + aspirin + atorvastatin triple therapy can effectively inhibit the systemic oxidative stress and inflammatory response in patients with cerebral infarction.

Effects of Ticagrelor on oxidative stress, coagulation function, platelet function and related factors in patients with coronary artery disease undergoing interventional therapy

Objective: To explore the effects of Ticagrelor on oxidative stress, coagulation function, platelet function and related factors in patients with coronary artery disease undergoing interventional therapy. Methods: A total of 140 patients with coronary artery disease who underwent percutaneous coronary intervention in our hospital from October 2016 to March 2018 were selected as the study subjects and were divided into control group (70 cases) and observation group (70 cases) by drawing lots. Both groups were treated with symptomatic routine therapy before operation. On this basis, the control group was treated with clopidogrel before operation, and the observation group was treated with Ticagrelor before operation on the basis of routine treatment. The changes of oxidative stress, coagulation index, platelet function and related factors were compared between the two groups before and after treatment. Results: Before treatment, there were no significant differences in oxidative stress factors, coagulation parameters, platelet parameters and related factors factors between the two groups. After treatment, the levels of MDA, MPAR, VEGF and MMP-9 in the two groups were lower than those before treatment, while the levels of SOD, APTT, TT and PT were higher than those before treatment;and the levels of MDA, MPAR, VEGF, MMP-9, APTT and PT in the observation group were significantly lower than those in the control group after treatment, while the levels fo SOD, TT and IPA in the observation group were significantly higher than those in the control group. Conclusions: Ticagrelor can better reduce oxidative stress injury, improve coagulation function and coronary stenosis, and inhibit platelet aggregation in patients with coronary heart disease undergoing PCI than clopidogrel. It has clinical popularization significance.

Effect of rehabilitation training combined with neurotrophic therapy on the nerve cytokine secretion and oxidative stress in rehabilitation period of patients with traumatic brain injury

Objective:To study the effect of rehabilitation training combined with neurotrophic therapy on the nerve cytokine secretion and oxidative stress in rehabilitation period of patients with traumatic brain injury.Methods:A total of 98 patients in rehabilitation period of traumatic brain injury who were treated in our hospital between July 2013 and September 2016 were collected and divided into control group and observation group according to the random number table method, and 49 cases in each group. Control group received regular neurotrophic therapy, and observation group received rehabilitation training combined with neurotrophic therapy. The differences in the contents of nerve cytokines and oxidative stress indexes were compared between the two groups before and after intervention.Results:Before intervention, differences in serum levels of nerve injury indexes, neurotrophy indexes, amino acid neurotransmitters and oxidative stress indexes were not statistically significant between the two groups of patients. After intervention, serum nerve injury indexes MBP, NGB, NSE and S-100B levels as well as excitatory amino acids Glu and Asp levels of observation group were lower than those of control group;neurotrophy indexes BDNF and GDNF levels as well as inhibitory amino acids GABA and Gly levels were higher than those of control group;serum oxidative stress indexes SOD and CAT levels were higher than those of control group;MDA level was lower than that of control group.Conclusions:Rehabilitation training combined with neurotrophic therapy can effectively optimize the nerve function and reduce the systemic oxidative stress state of patients in rehabilitation period of traumatic brain injury.

Effect of mid-frequency pulse therapy combined with external fixation on bone metabolism, inflammatory response and oxidative stress in patients with osteoporotic distal radial fractures

Objective:To study the effect of mid-frequency pulse therapy combined with external fixation on bone metabolism, inflammatory response and oxidative stress in patients with osteoporotic distal radial fractures.Methods: A total of 72 patients with osteoporotic distal radial fractures who were treated in the hospital between September 2015 and January 2017 were collected and divided into control group (n=36) and observation group (n=36) according to the random number table method. Control group received routine external fixation, and observation group received mid-frequency pulse therapy combined with external fixation. The differences in serum levels of bone metabolism indexes, inflammatory factors and oxidative stress indexes were compared between two groups of patients before and after treatment.Results: Before treatment, differences in serum levels of bone metabolism indexes, inflammatory factors and oxidative stress indexes were not statistically significant between the two groups. After 1 month of treatment, serum BGP, TAC and SOD levels of both groups of patients were higher than those before treatment whileβ-CTX, AKP, TRAP, CRP, IL-1β, IL-6 and MDA levels were lower than those before treatment, and serum BGP, TAC and SOD levels of observation group were higher than those of control group whileβ-CTX, AKP, TRAP, CRP, IL-1β, IL-6 and MDA levels were lower than those of control group.Conclusion: Mid-frequency pulse therapy combined with external fixation can promote fracture healing and reduce postoperative inflammatory response and oxidative stress response in patients with osteoporotic distal radial fracture.

Oxidative stress in neurodegenerative diseases

Reactive oxygen species are constantly produced in aerobic organisms as by-products of normal oxygen metabolism and include free radicals such as superoxide anion （02-） and hydroxyl radical （OH-）, and non-radical hydrogen peroxide （H202）. The mitochondrial respiratory chain and enzymatic reactions by various enzymes are endogenous sources of reactive oxygen species. Exogenous reactive oxygen species -inducing stressors include ionizing radiation, ultraviolet light, and divergent oxidizing chemicals. At low concentrations, reactive oxygen species serve as an important second messenger in cell signaling; however, at higher concentrations and long-term exposure, reactive oxygen species can damage cellular macromolecules such as DNA, proteins, and lipids, which leads to necrotic and apoptotic cell death. Oxidative stress is a condition of imbalance between reactive oxygen species formation and cellular antioxidant capacity due to enhanced ROS generation and/or dysfunction of the antioxidant system. Biochemical alterations in these macromolecular components can lead to various pathological conditions and human diseases especially neurodegenerative diseases. Neurodegenerative diseases are morphologically featured by progressive cell loss in specific vulnerable neuronal cells, often associated with cytoskeletal protein aggregates forming inclusions in neurons and/or glial cells. Deposition of abnormal aggregated proteins and disruption of metal ions homeostasis are highly associated with oxidative stress. The main aim of this review is to present as much detailed information as possible that is available on various neurodegenerative disorders and their connection with oxidative stress. A variety of therapeutic strategies designed to address these pathological processes are also described. For the future therapeutic direction, one specific pathway that involves the transcription factor nuclear factor erythroid 2-related factor 2 is receiving considerable attention.

Oxidative stress factors in Parkinson's disease

Parkinson's disease(PD) is the second most common cause of neurodegeneration.Over the last two decades, various hypotheses have been proposed to explain the etiology of PD.Among these is the oxidant-antioxidant theory, which asserts that local and systemic oxidative damage triggered by reactive oxygen species and other free radicals may promote dopaminergic neuron degeneration.Excessive reactive oxygen species formation, one of the underlying causes of pathology in the course of PD has been evidenced by various studies showing that oxidized macromolecules including lipids, proteins, and nucleic acids accumulate in brain tissues of PD patients.DNA oxidation may produce various lesions in the course of PD.Mutations incurred as a result of DNA oxidation may further enhance reactive oxygen species production in the brains of PD patients, exacerbating neuronal loss due to defects in the mitochondrial electron transport chain, antioxidant depletion, and exposure to toxic oxidized dopamine.The protein products of SNCA, PRKN, PINK1, DJ1, and LRRK2 genes are associated with disrupted oxidoreductive homeostasis in PD.SNCA is the first gene linked with familial PD and is currently known to be affected by six mutations correlated with the disorder: A53T, A30P, E46K, G51D, H50Q and A53E.PRKN encodes Parkin, an E3 ubiquitin ligase which mediates the proteasome degradation of redundant and disordered proteins such as glycosylated α-synuclein.Over 100 mutations have been found among the 12 exons of PRKN.PINK1, a mitochondrial kinase highly expressed in the brain, may undergo loss of function mutations which constitute approximately 1–8% of early onset PD cases.More than 50 PD-promoting mutations have been found in PINK1.Mutations in DJ-1, a neuroprotective protein, are a rare cause of early onset PD and constitute only 1% of cases.Around 20 mutations have been found in DJ1 among PD patients thus far.Mutations in the LRRK2 gene are the most common known cause of familial autosomal dominant PD and sporadic PD.Treatment of PD patients, especially in the advanced stages of the disease, is very difficult.The first step in managing progressive PD is to optimize dopaminergic therapy by increasing the doses of dopamine agonists and L-dopa.The next step is the introduction of advanced therapies, such as deep brain stimulation.Genetic factors may influence the response to L-dopa and deep brain stimulation therapy and the regulation of oxidative stress.Consequently, research into minimally invasive surgical interventions, as well as therapies that target the underlying etiology of PD is warranted.

Aquatic exercise program-modulated oxidative stress markers in patients with Parkinson's disease

Parkinson's disease is a neurodegenerative disease.Oxidative stress,i.e.,the imbalance between the generation of reactive oxygen species and the antioxidant defense capacity of the body,plays an important role in the pathogenesis of this disease.Physical exercise can regulate oxidative stress.The purpose of this study was to analyze the short-and long-term effects of an aquatic exercise program on oxidative stress levels in patients with Parkinson's disease.The aquatic exercise program was carried out during 1 month with two sessions per week(1 hour/session).Blood samples were collected at four different time points:pre-intervention,immediately,48 hours,and 30 days after the first session of aquatic exercise program.Our results revealed that water-based programs modulated antioxidant enzyme activity,increased superoxide dismutase activity,reduced catalase activity,and increased the ratio of superoxide dismutase activity to catalase activity in patients with Parkinson's disease.Compared with pre-intervention and 48 hours after the first session of aquatic exercise program,superoxide dismutase activity was higher and catalase activity was lower immediately and 30 days after the first session.Our results demonstrated that aquatic exercise program could modulate oxidative stress,mainly by the effect of antioxidant enzyme activity.These results could better help understand the target of oxidative stress in Parkinson's disease.This study was approved by the Ethics Committee of Centro Universitário Metodista IPA(approval No.1.373.911)on August 9,2019 and registered with REBEC(registration number:RBR-6 NJ4 MK).

rAAV/ABAD-DP-6His attenuates oxidative stressinduced injury of PC12 cells

Our previous studies have revealed that amyloidβ（Aβ）-binding alcohol dehydrogenase （ABAD） decoy peptide antagonizes Aβ42-induced neurotoxicity. However, whether it improves oxidative stress injury remains unclear. In this study, a recombinant adenovirus constitutively secreting and expressing Aβ-ABAD decoy peptide （rAAV/ABAD-DP-6His） was successfully constructed. Our results showed that rAAV/ABAD-DP-6His increased superoxide dismutase activity in hydro-gen peroxide-induced oxidative stress-mediated injury of PC12 cells. Moreover, rAAV/ABAD-DP-6His decreased malondialdehyde content, intracellular Ca2＋concentration, and the level of reactive oxygen species. rAAV/ABAD-DP-6His maintained the stability of the mitochondrial membrane potential. In addition, the ATP level remained constant, and apoptosis was reduced. Overall, the results indicate that rAAV/ABAD-DP-6His generates the fusion peptide, Aβ-ABAD decoy peptide, which effectively protects PC12 cells from oxidative stress injury induced by hy-drogen peroxide, thus exerting neuroprotective effects.

Overview of angiogenesis and oxidative stress in cancer

Neoplasms can be considered as a group of aberrant cells that need more vascular supply to fulfill all their functions.Therefore,they promote angiogenesis through the same neovascularization pathway used physiologically.Angiogenesis is a process characterized by a heterogeneous distribution of oxygen caused by the tumor and oxidative stress;the latter being one of the most powerful stimuli of angiogenesis.As a result of altered tumor metabolism due to hypoxia,acidosis occurs.The angiogenic process and oxidative stress can be detected by measuring serum and tissue biomarkers.The study of the mechanisms underlying angiogenesis and oxidative stress could lead to the identification of new biomarkers,ameliorating the selection of patients with neoplasms and the prediction of their response to possible anti-tumor therapies.In particular,in the treatment of patients with similar clinical tumor phenotypes but different prognoses,the new biomarkers could be useful.Moreover,they may lead to a better understanding of the mechanisms underlying drug resistance.Experimental studies show that blocking the vascular supply results in antiproliferative activity in vivo in neuroendocrine tumor cells,which require a high vascular supply.

The emerging role of nitric oxide in the synaptic dysfunction of vascular dementia

With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic rate.However,few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia patients.Similarly in Alzheimer’s disease and other neurological disorders,synaptic dysfunction is recognized as the main reason for cognitive decline.Nitric oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous system.Recently,nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular dementia.This review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction,neuroinflammation,oxidative stress,and blood-brain barrier dysfunction that underlie the progress of vascular dementia.Additionally,we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.

Antioxidant therapy in the management of acute,chronic and post-ERCP pancreatitis:A systematic review

We systematically reviewed the clinical trials which recruited antioxidants in the therapy of pancreatitis and evaluated whether antioxidants improve the outcome of patients with pancreatitis. Electronic bibliographic databases were searched for any studies which investigated the use of antioxidants in the management of acute pancreatitis （AP） or chronic pancreatitis （CP） and in the prevention of post-endoscopic retrograde cholangio-pancreatography （post-ERCP） pancreatitis （PEP） up to February 2009. Twenty-two randomized, placebo-controlled, clinical trials met our criteria and were included in the review. Except for a cocktail of antioxidants which showed improvement in outcomes in three different clinical trials, the results of the administration of other antioxidants in both AP and CP clinical trials were incongruent and heterogeneous.Furthermore, antioxidant therapy including allopurinol and N-acetylcysteine failed to prevent the onset of PEP in almost all trials. In conclusion, the present data do not support a benefit of antioxidant therapy alone or in combination with conventional therapy in the management of AP, CP or PER Further double blind, randomized, placebo-controlled clinical trials with large sample size need to be conducted.

Effect of ultrashort wave therapy combined with antioxidant and neurotrophy therapy on nerve conduction function and serum cytokines in patients with diabetic peripheral neuropathy

Objective: To study the effect of ultrashort wave therapy combined with antioxidant and neurotrophy therapy on nerve conduction function and serum cytokines in patients with diabetic peripheral neuropathy. Methods: A total of 128 patients who were diagnosed with DPN in South District of Guang'anmen Hospital of China Academy of Chinese Medical Sciences between May 2014 and February 2017 were selected as the research subjects and randomly divided into electrotherapy + drug group and routine drug group;the nerve conduction velocity as well as serum levels of nerve cytokines and inflammatory cytokines were measured before treatment and 8 weeks after treatment. Results: Median nerve and common peroneal nerve MNCV, median nerve and superficial peroneal nerve SNCV as well as serum CNTF, BDNF, SDF-1α, IGF-1, CAT and HO-1 levels of both groups 8 weeks after treatment were significantly higher than those before treatment while serum ICAM-1, TNF-α, IL-6, ET-1, MDA and 8-OHdG levels were significantly lower than those before treatment;median nerve and common peroneal nerve MNCV, median nerve and superficial peroneal nerve SNCV as well as serum CNTF, BDNF, SDF-1α, IGF-1, CAT and HO-1 levels of electrotherapy + drug group 8 weeks after treatment were significantly higher than those of routine drug group while serum ICAM-1, TNF-α, IL-6, ET-1, MDA and 8-OHdG levels were significantly lower than those of routine drug group. Conclusion: Ultrashort wave therapy combined with antioxidant and neurotrophy therapy for DPN can improve the nerve conduction function and neurotrophic state, and also inhibit the inflammatory response and oxidative stress response.

Self-shrinking supramolecular nanoparticles syndicate energy suppression and NIR-II mild photothermal amplification of mitochondrial oxidative stress for breast cancer therapy

Photothermal therapy(PTT)may lead to healthy tissue damage,tumor metastasis,and recurrence,which makes mild photothermal therapy(mild PTT)stand out.However,overcoming heat resistance,insufficient therapeutic effect,and poor photothermal conversion efficiency has become new challenge.Herein,we report a dynamic supramolecular nanocarrier formed from amide-sericin and aldehyde-polyhydroxy glucan(denoted as SDA),the loose cavity of which can be filled by using the pharmaceutical combination of lonidamine(LND)and NIR-II photothermal agent of IR-1061,producing SDLI with a tighter inner hole,smaller and uniform particle size and excellent stability due to multiple pulling forces.Moreover,the intricate internal network structure prevents the hydrophobic IR-1061 from forming aggregates in the small cavity,and the photothermal conversion efficiency(PCE)can reach 48.9%.At the acidic tumor microenvironment of pH 6.5,the controlled release of LND can solve the problem of heat resistance of NIR-II mild PTT and significantly improve the therapeutic effect of NIR-II mild PTT.Meanwhile,SDLI also shows a reasonable tumor inhibition rate,so the synergistic strategy of inhibiting tumor energy metabolism and NIR-II mild PTT to magnify mitochondrial oxidative stress,continuous cell stress state-induced immunogenic cell death to promote the induction of tumor apoptosis is proposed to achieve more effective cancer treatment.

Regulating Signal Pathway Triggers Circular Reactive Oxygen Species Production to Augment Oxidative Stress with Enzyme-Activated Nanoparticles

Regulating antioxidative stress pathways to augment oxidative stress and enhance antitumor therapy is highly desirable but very challenging.Herein,we initiated a multifunctional nanoparticle to regulate the Keap1-Nrf2 antioxidative stress pathway to promote cancer cell apoptosis.The OPFV-SnMP@GE11 nanoparticles were assembled by enzyme-activated OPFV-TLQ,tin mesoporphyrin(SnMP),and DSPEPEG-GE11.OPFV-SnMP@GE11 accumulated at tumor sites through specific targeting with GE11.OPFV-TLQ was specifically reduced to a photosensitizer OPFVNH2 by endocellular NAD(P)H:quinone oxidoreductase 1(NQO1).Under irradiation,OPFV-NH2 greatly produced reactive oxygen species(ROS)through a type I mechanism,which activated the Keap1-Nrf2 signal pathway and enhanced the transcription of NQO1,resulting in a continuous and explosive generation of ROS.Additionally,SnMP inhibited the activity of heme oxygenase-1(HO-1),further depressing antioxidative stress.This strategy provides insight into the regulation of the signal pathway to amplify oxidative stress,paving the way to studying the molecular mechanisms of cellular activities to enhance cancer therapy.

Antioxidants,inflammation and cardiovascular disease

Multiple factors are involved in the etiology of cardiovascular disease(CVD). Pathological changes occur in a variety of cell types long before symptoms become apparent and diagnosis is made. Dysregulation of physiological functions are associated with the activation of immune cells,leading to local and finally systemic inflammation that is characterized by production of high levels of reactive oxygen species(ROS). Patients suffering from inflammatory diseases often present with diminished levels of antioxidants either due to insufficient dietary intake or,and even more likely,due to increased demand in situations of overwhelming ROS production by activated immune effector cells like macrophages. Antioxidants are suggested to beneficially interfere with diseases-related oxidative stress,however the interplay of endogenous and exogenous antioxidants with the overall redox system is complex. Moreover,molecular mechanisms underlying oxidative stress in CVD are not fully elucidated. Metabolic dybalances are suggested to play a major role in disease onset and progression. Several central signalingpathways involved in the regulation of immunological,metabolic and endothelial function are regulated in a redox-sensitive manner. During cellular immune response,interferon γ-dependent pathways are activated such as tryptophan breakdown by the enzyme indoleamine 2,3-dioxygenase(IDO) in monocyte-derived macrophages,fibroblasts,endothelial and epithelial cells. Neopterin,a marker of oxidative stress and immune activation is produced by GTP-cyclohydrolase Ⅰ in macrophages and dendritic cells. Nitric oxide synthase(NOS) is induced in several cell types to generate nitric oxide(NO). NO,despite its low reactivity,is a potent antioxidant involved in the regulation of the vasomotor tone and of immunomodulatory signaling pathways. NO inhibits the expression and function of IDO. Function of NOS requires the cofactor tetrahydrobiopterin(BH4),which is produced in humans primarily by fibroblasts and endothelial cells. Highly toxic peroxynitrite(ONOO-) is formed solely in the presence of superoxide anion(O2-). Neopterin and kynurenine to tryptophan ratio(Kyn/Trp),as an estimate of IDO enzyme activity,are robust markers of immune activation in vitro and in vivo. Both these diagnostic parameters are able to predict cardiovascular and overall mortality in patients at risk. Likewise,a significant association exists between increase of neopterin concentrations and Kyn/Trp ratio values and the lowering of plasma levels of vitamin-C,-E and-B. Vitamin-B deficiency is usually accompanied by increased plasma homoycsteine. Additional determination of NO metabolites,BH4 and plasma antioxidants in patients with CVD and related clinical settings can be helpful to improve the understanding of redox-regulation in health and disease and might provide a rationale for potential antioxidant therapies in CVD.

Antioxidant and immunomodulatory effects of Viusid in patients with chronic hepatitis C

AIM:To investigate the efficacy of Viusid,a nutritional supplement,as an antioxidant and an immunomodulator in patients with chronic hepatitis C.METHODS:Sixty patients with chronic hepatitis C who were non-responders to standard antiviral treatment were randomly assigned to receive Viusid(3 sachets daily,n=30) or placebo(n=30) for 24 wk.The primary outcome was the change in serum malondialdehyde and 4-hydroxyalkenals(lipid peroxidation products).Secondary outcomes were changes in serum tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ) and interleukin-10(IL-10).RESULTS:Statistically significant reductions in serum 4-hydroxyalkenals and malondialdehyde levels were observed in both groups in comparison with pretreatment values,but the patients who received Viusid showed a more marked reduction as compared with the control group(P=0.001).TNF-α levels significantly increased from 6.9 to 16.2 pg/mL(P< 0.01) in the patients who received placebo in comparison with almost unchanged levels,from 6.6 to 7.1 pg/mL(P=0.26),in the patients treated with Viusid(P=0.001).In addition,IL-10 levels were markedly increased in the patients treated with Viusid(from 2.6 to 8.3 pg/mL,P=0.04) in contrast to the patients assigned to placebo(from 2.8 to 4.1 pg/mL,P=0.09)(P=0.01).Likewise,the administration of Viusid markedly increased mean IFN-γ levels from 1.92 to 2.89 pg/mL(P< 0.001) in comparison with a reduction in mean levels from 1.80 to 1.68 pg/mL(P=0.70) in the placebo group(P< 0.0001).Viusid administration was well tolerated.CONCLUSION:Our results indicate that treatment with Viusid leads to a notable improvement of oxidative stress and immunological parameters in patients with chronic hepatitis C.

Advancement and prospects of tumor gene therapy

Gene therapy is one of the most attractive fields in tumor therapy. In past decades, significant progress has been achieved. Various approaches, such as viral and non-viral vectors and physical methods, have been developed to make gene delivery safer and more efficient. Several therapeutic strategies have evolved, including gene-based (tumor suppressor genes, suicide genes, antiangiogenic genes, cytokine and oxidative stress-based genes) and RNA-based (antisense oligonucleotides and RNA interference) approaches. In addition, immune response-based strategies (dendritic cell- and T cell-based therapy) are also under investigation in tumor gene therapy. This review highlights the progress and recent developments in gene delivery systems, therapeutic strategies, and possible clinical directions for gene therapy.

Comparison of Intraperitoneal and Intratesticular GY Y4137 Therapy for the Treatment of Testicular Ischemia Reperfusion Injury in Rats

The efficacy of intraperitoneal GY Y4137 therapy and intratesticular GY Y4137 therapy in an experimental rat model was investigated.Four groups were set up as the sham-operation group,torsion/detorsion(T/D)group,T/D plus intraperitoneal GY Y4137(G-IP)group,and T/D plus intratesticular GY Y4137(G-IT)group.In order to establish a testicular T/D model,the left testis was opcrated and the rotation reached 720°clockwise which lasted 1 h before reperfiusion.The G-IP group accepted 100 umol/kg of GY Y4137 intraperitoneally 30 min after testicular rotation,while the G-IT group was treated with the same dose by intratesticular injection.Six h after detorsion,the testis was collcted and subsequently asssed.The T/D group showed signifcant changes in histology and an enhancement in the level of oxidative stress and apoptosis compared to the sham-operation group.The expression of Caspase-3 and Bax turmed out to be strengthened by T/D and relatively decreased with GY Y4137 treatment in both the G-IP and G-IT groups.Moreover,the Bcl-2 expression was inhibited in the T/D group,and promoted by GYY4137 in the G-IP and G-IT groups.GYY4137,moderating these observed changes,displayed a more protective cffect with G-IT therapy than G-IP therapy.This study indicated that the efficacy of intratesticular therapy with GYY4137 is better than that of intraperitoneal therapy,which may provide a more valuable approach for testicular torsion therapy.

Insights on antioxidant therapeutic strategies in type 2 diabetes mellitus:A narrative review of randomized control trials

BACKGROUND Type 2 diabetes mellitus(T2DM)is a metabolic disease of impaired glucose utilization.Imbalance in generation and elimination of free radicals generate oxidative stress which modulates glucose metabolism and insulin regulation,resulting in the occurrence and progression of diabetes and associated complications.Antioxidant supplements in T2DM can be seen as a potential preventive and effective therapeutic strategy.AIM To compare randomized controlled trials(RCTs)in which antioxidants have been shown to have a therapeutic effect in T2DM patients.METHODS We systematically searched the electronic database PubMed by keywords.RCTs evaluating the effect of antioxidant therapy on glycaemic control as well as oxidant and antioxidant status as primary outcomes were included.The outcomes considered were:A reduction in blood glucose;changes in oxidative stress and antioxidant markers.Full-length papers of the shortlisted articles were assessed for the eligibility criteria and 17 RCTs were included.RESULTS The administration of fixed-dose antioxidants significantly reduces fasting blood sugar and glycated hemoglobin and is associated with decreased malondialdehyde,advanced oxidation protein products,and increased total antioxidant capacity.CONCLUSION Antioxidant supplements can be a beneficial approach for the treatment of T2DM.