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Shi M.,Hebei Medical University | Cui F.,Hebei Medical University | Liu A.-J.,Hebei Medical University | Ma H.-J.,Hebei Medical University | And 7 more authors.
Journal of Inflammation (United Kingdom) | Year: 2015

Objective: To explore the immunological mechanisms underlying the effect of chronic intermittent hypobaric hypoxia (CIHH) pretreatment on collagen-induced arthritis (CIA) in rat. Methods: Fifty-four adult male Sprague-Dawley rats were used in the experiment. Arthritis in CIA rats (n=18) was induced by injection of collagen. The CIHH+CIA rats (n=18) were treated with CIHH (simulated 3000 m altitude, 5 hours per day for 28 days, PO2=108.8 mmHg) before CIA. The control rats (n=18) were not given any treatment. Results: (1) Incidence rate of CIA in CIHH+CIA rats was significantly lower than that in CIA rats (P<0.05). (2) The paw thickness and arthritis index (AI) value in CIHH+CIA rats were lower than those in CIA rats (P<0.05). (3) The hyperplasia with inflammatory infiltration in synovial tissue of joints in CIHH+CIA rats was much alleviative compared with CIA rats. (4) TNF-α, IFN-γ, IL-4 and IL-17 in synovial tissue of joint and serum in CIHH+CIA rats were decreased compared with CIA rats (P<0.05). (5) The number of CD4-positive T-lymphocytes and the ratio of CD4/CD8 T-lymphocytes in peripheral blood in CIHH+CIA rats were lower than those in CIA rats (P<0.05). (6) The protein expression of HIF-1α and NF-κB in synovial tissue of joint in CIHH+CIA rats was decreased compared with CIA rats (P<0.05). Conclusion: CIHH pretreatment has a protective effect against collagen-induced arthritis in rat through down-regulation of HIF-1α and NF-κB, inhibition of inflammatory cytokines TNF-α and IL-17, and balance in CD4/CD8 and Th1/Th2 T lymphocytes. © 2015 Shi et al.; licensee BioMed Central.

He W.,CAS Institute of Microbiology | He W.,Hebei Key Laboratory of Medical Biotechnology | Wang W.,CAS Institute of Microbiology | Wang W.,University of Chinese Academy of Sciences | And 8 more authors.
PLoS ONE | Year: 2013

Human influenza is a seasonal disease associated with significant morbidity and mortality. The most effective means for controlling infection and thereby reducing morbidity and mortality is vaccination with a three inactivated influenza virus strains mixture, or by intranasal administration of a group of three different live attenuated influenza vaccine strains. Comparing to the inactivated vaccine, the attenuated live viruses allow better elicitation of a long-lasting and broader immune (humoral and cellular) response that represents a naturally occurring transient infection. The cold-adapted (ca) influenza A/AA/6/60 (H2N2) (AA ca) virus is the backbone for the live attenuated trivalent seasonal influenza vaccine licensed in the United States. Similarly, the influenza A components of live-attenuated vaccines used in Russia have been prepared as reassortants of the cold-adapted (ca) H2N2 viruses, A/Leningrad/134/17/57-ca (Len/17) and A/Leningrad/134/47/57-ca (Len/47) along with virulent epidemic strains. However, the mechanism of temperature-sensitive attenuation is largely elusive. To understand how modification at genetic level of influenza virus would result in attenuation of human influenza virus A/PR/8/34 (H1N1,A/PR8), we investigated the involvement of key mutations in the PB1 and/or PB2 genes in attenuation of influenza virus in vitro and in vivo. We have demonstrated that a few of residues in PB1 and PB2 are critical for the phenotypes of live attenuated, temperature sensitive influenza viruses by minigenome assay and real-time PCR. The information of these mutation loci could be used for elucidation of mechanism of temperature-sensitive attenuation and as a new strategy for influenza vaccine development. © 2013 He et al.

Xu P.,Chinese Peoples Liberation Army | Cao X.-B.,Chinese Peoples Liberation Army | Gao L.,Hebei Medical University | Ma H.-J.,Hebei Medical University | And 3 more authors.
Chinese Journal of Physiology | Year: 2014

Chronic intermittent hypobaric hypoxia (CIHH) facilitates carotid sinus baroreflex (CSB) in adult rats, but the effect of CIHH on CSB in young rats is not known. The purpose of present study was to investigate the effect of CIHH on CSB in the young rat treated with CIHH from neonatal age, and the role of nitric oxide (NO) and Ca2+ in the effect of CIHH. Neonatal male Sprague-Dawley rats were randomly divided into three groups: 42-day CIHH treatment group (CIHH42), 56-day CIHH treatment group (CIHH56), and an age-matched control group (control). CIHH neonatal rats with the maternal rats were exposed to a simulated high-altitude hypoxia in a hypobaric chamber mimicking 5,000-m altitude (O2 at 11.1%) for 42 or 56 days, 6 h per day, respectively. Isolated carotid sinus perfusion technique was used to test CSB of the rats. After 42-day and 56-day CIHH exposure, the CSB of the rats was inhibited significantly, manifesting as decrease of peak slope (PS) and reflex decrease (RD), and increase of threshold pressure (TP), equilibrium pressure (EP) and saturation pressure (SP). This inhibitory effect was canceled by L-type calcium channel activator Bay K 8644, but not by nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME). The data showed that CIHH inhibited CSB in anesthetized young rats through blocking L-type calcium channels in carotid sinus baroreceptor. © 2014 by The Chinese Physiological Society and Airiti Press Inc.

Cui F.,Hebei Medical University | Gao L.,Hebei Medical University | Yuan F.,Hebei Medical University | Dong Z.-F.,Hebei Medical University | And 6 more authors.
PLoS ONE | Year: 2012

Background: Hypobaric intermittent hypoxia (HIH) produces many favorable effects in the cardiovascular system such as anti-hypertensive effect. In this study, we showed that HIH significantly attenuated a depressor response induced by acute hypoxia. Methodology/Principal Findings: Sprague-Dawley rats received HIH in a hypobaric chamber simulating an altitude of 5000 m. The artery blood pressure (ABP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were recorded in anesthetized control rats and rats received HIH. The baseline ABP, HR and RSNA were not different between HIH and control rats. Acute hypoxia-induced decrease in ABP was significantly attenuated in HIH rat compared with control rats. However, acute hypoxia-induced increases in HR and RSNA were greater in HIH rat than in control rats. After removal of bilateral ascending depressor nerves, acute hypoxia-induced depressor and sympathoexcitatory responses were comparable in control and HIH rats. Furthermore, acute hypoxia-induced depressor and sympathoexcitatory responses did not differ between control and HIH groups after blocking ATP-dependent K+ channels by glibenclamide. The baroreflex function evaluated by intravenous injection of phenylephrine and sodium nitroprusside was markedly augmented in HIH rats compared with control rats. The pressor and sympathoexcitatory responses evoked by intravenous injection of cyanide potassium were also significantly greater in HIH rats than in control rats. Conclusions/Significance: Our findings suggest that HIH suppresses acute hypoxia-induced depressor response through enhancement of baroreflex and chemoreflex function, which involves activation of ATP-dependent K+ channels. This study provides new information and underlying mechanism on the beneficiary effect of HIH on maintaining cardiovascular homeostasis. © 2012 Cui et al.

Li B.,Hebei Key Laboratory of Medical Biotechnology | Li Y.,Hebei Medical University | Liu K.,Hebei Key Laboratory of Medical Biotechnology | Wang X.,Hebei Key Laboratory of Medical Biotechnology | And 3 more authors.
Endocrine Research | Year: 2016

Purpose/aim of the study: Claudins-5, -9, and -11 are tight-junction proteins that are mainly expressed in endothelial cells. Their deficiency may lead to cell barrier dysfunction, which is considered as the initiating process and pathological basis of cardiovascular disease in diabetes. We investigated whether high glucose (HG) affects claudins-5, -9, and -11 in human cardiac microvascular endothelial cells (HCMECs), and examined the effects of the traditional Chinese medication tongxinluo (TXL) on these tight junction proteins. Materials and methods: HCMECs were exposed to HG with and without TXL treatment, and then mRNA and protein levels of claudins-5, -9, and -11 were examined. The distribution of claudins-5 and -11 was also investigated. Histone H3K9 acetylation (H3K9ac) in claudin-5 and claudin-11 gene promoters, which functions in transactivation, was measured. Results: We found that HG suppressed claudins-5 and -11 gene expression in HCMECs, and TXL reversed the HG-mediated inhibition of claudins-5 and -11 mRNA and protein expressions. Treatment with high-dose of TXL promoted cell membrane localization of claudins-5 and -11 in HG-stimulated HCMECs. Furthermore, high-dose of TXL blocked the inhibition of H3K9ac in claudin-5 and claudin-11 gene promoters caused by exposure to HG, thus activating gene transcription. Conclusions: Our results show that HG suppressed claudins-5 and -11 in HCMECs, and TXL could reverse the HG-induced suppression of claudins-5 and -11 by increasing H3K9ac in their respective gene promoters. © 2016 Taylor & Francis

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