[The expression of serum endoplasmic reticulum stress protein-78 in obstructive sleep apnea patients].

OBJECTIVE: This study aimed to detect serum level of glucose regulated protein 78(GRP78) in patients with obstructive sleep apnea(OSA) and explore the relationship between endoplasmic reticulum stress and the pathophysiology of OSA. METHODS: A total of 91 patients with OSA were enrolled in this study, including 30 mild, 28 moderate and 33 severe. The other 27 obese subjects were of age, gender and BMI matched group. Eleven moderate or severe OSA patients were administrated with continuous positive airway pressure (CPAP) treatment for 24 hours. Polysomnography, apnea hypopnea index (AHI), lowest arterial oxygen saturation(SaO2) and percentage of time spent at SaO2 below 90% (SIT90) were measured before and after sleep. Serum GRP78 was measured by ELISA. RESULTS: The expression of GRP78 in mild(3.42±0.97)µg/L, moderate(2.67±1.14)µg/L and severe(2.62±1.11)µg/L OSA groups was significantly higher than in control group(1.75±0.41)µg/L (P<0.05). The GRP78 level in mild OSA group was significantly higher than either moderate or severe OSA group (P<0.05). After 24 h treatment of CPAP, serum GRP78 level decreased significantly [(1.77±0.39)µg/L vs(2.84±0.39)µg/L; P<0.05]. CONCLUSIONS: Endoplasmic reticulum stress involves in the pathophysiology of patients with OSA. Higher GRP78 level in mild OSA patients suggests that endoplasmic reticulum related protein GRP 78 might rise then fall during exacerbation of OSA.

Study of the methylation patterns of the EGFR gene promoter in non-small cell lung cancer.

We investigated the methylation state of the epidermal growth factor receptor (EGFR) gene promoter in non-small cell lung cancer (NSCLC) and analyzed its effect on tumor biology. We enrolled 120 patients with NSCLC who had been confirmed by pathologic diagnosis and had been operated on. The methylation states of the EGFR gene promoter were detected and analyzed and a prognosis was given. NSCLC cell lines and nude mice were used to study the treatment reactivity of gefitinib (an EGFR inhibitor) with or without 5-aza-2'-deoxycytidine (5-aza-CdR) intervention. EGFR expression was high when the methylation degree was lower in patients with adenocarcinoma and poor pathological differentiation of tumor than in patients with squamous cell carcinoma and good pathological differentiation. NSCLC cells with low expression of EGFR and high methylation in the promoter region were insensitive to EGFR-targeted therapy. However, apoptosis and proliferation inhibition of cancer cells were even more pronounced when 5-aza-CdR was used to inhibit methylation. An in vivo study confirmed that methylation adjuvant therapy can improve the sensitivity of cancer to EGFR-targeted therapy. Application of a demethylating agent could be an important supplement for improving EGFR inhibition in the treatment of NSCLC, especially in those who are insensitive to the use of an EGFR inhibitor alone.

Investigation of several biomarkers associated with diabetic nephropathy.

OBJECTIVE: The aim of this study was to facilitate the systematic discovery of diagnostic biomarkers of diabetic nephropathy (DN). METHODS: 3 publicly available independent cohorts were got from Gene Expression Omnibus database. Gene expression array were used to screen for genome-wide relative significance (GWRS) and genome-wide global significance (GWGS). The most significant up- and down-regulated top 100 gene signatures were identified using a fold change based model. Then the protein-protein interaction (PPI) network was constructed, while the hub genes in this PPI network were identified by centrality analysis. Modules detection was performed to explore the functions of the modules. Meanwhile, gene enrichment analysis was performed to illuminate the biological pathways and processes associated with DN. RESULTS: The most significant up- and down-regulated top 100 gene signatures were identified and a PPI network was established. Several hub genes (VEGFA, IL8, MYC, CD14, ALB) were discovered. Several functional modules were revealed. Biological pathways including cytokine-cytokine receptor interaction and p53 signaling pathway, and processes including inflammatory response, response to wounding and enzyme linked receptor protein signaling pathway were identified. CONCLUSION: Our study displayed underlying biomarkers including biological pathways and several hub genes of DN.

Myocardial ischemic preconditioning upregulated protein 1(Mipu1):zinc finger protein 667 - a multifunctional KRAB/C2H2 zinc finger protein.

Myocardial ischemic preconditioning upregulated protein 1 (Mipu1) is a newly discovered upregulated gene produced in rats during the myocardial ischemic preconditioning process. Mipu1 cDNA contains a 1824-base pair open reading frame and encodes a 608 amino acid protein with an N-terminal Krüppel-associated box (KRAB) domain and classical zinc finger C2H2 motifs in the C-terminus. Mipu1 protein is located in the cell nucleus. Recent studies found that Mipu1 has a protective effect on the ischemia-reperfusion injury of heart, brain, and other organs. As a nuclear factor, Mipu1 may perform its protective function through directly transcribing and repressing the expression of proapoptotic genes to repress cell apoptosis. In addition, Mipu1 also plays an important role in regulating the gene expression of downstream inflammatory mediators by inhibiting the activation of activator protein-1 and serum response element.

Effect of batroxobin against dog heart ischemia/reperfusion injury.

AIM: To study the effect of batroxobin(Bat) on dog heart ischemia/reperfusion (I/R) injury. METHODS: Dog heart I/R injury was induced by occluding the left anterior descending coronary artery for 30 min and restoring blood perfusion for 90 min. Bat was intravenously injected before heart ischemia and 15 min before reperfusion. Plasma creatine kinase (CK), lactate dehydrogenase (LDH), and myocardial malondiaedehyde (MDA) concentrations were measured. The pathologic changes of I/R myocardium were observed. RESULTS: Bat reduced the mortality rate of I/R dog (I/R group 65.0% vs Bat-I group 30.0% and Bat-II group 28.6%, P < 0.05). Myocytes of I/R heart showed intracellular edema, damaged mitochondria, and concentrated nucleus. Bat decreased these changes. In Bat-I and Bat-II group, plasma CK and LDH level were reduced, the +dp/dtmax and -dp/dtmax at 30 min after ischemia and 90 min after reperfusion were elevated, and left ventricular end dilation pressure (LVEDP) was lowered. The myocardial MDA contents were decreased by 42.3% and 38.1% (P < 0.01) in Bat-I and Bat-II group, respectively. CONCLUSION: Bat may exert an apparent role against dog heart ischemia/reperfusion injury and improve myocardial function.

[Plasmid pcDNA3 enhances Ca(2+) transport of sarcoplasmic reticulum in ischemic skeletal muscle of rats].

The effects of plasmid pcDNA3 on Ca(2+) transport of sarcoplasmic reticulum (SR) in ischemic skeletal muscle was investigated. The results show that Ca(2+) transport (including Ca(2+) uptake and Ca(2+) release) rate of SR in ischemic skeletal muscle was markedly increased compared with that in non-ischemic muscle (P<0.01 or P<0.05). After plasmid pcDNA3 bound to the DNA binding proteins of SR, Ca(2+) transport of SR was further increased. The results suggest that the effect of plasmid DNA on the ability of Ca(2+) transport in SR of ischemic skeletal muscle is the same as is observed in normal skeletal muscle. The pathophysiological significance of the present finding deserves further exploration.

Basic fibroblast growth factor increases nitric oxide and endothelin production in rat aorta.

The study was undertaken to investigate the effect of basic fibroblast growth factor (bFGF) on aortic production of nitric oxide (NO) and endothelin of aorta in spontaneously hypertensive rats (SHR) and WKY rats. Rat aortas were cut into vessel slices and incubated with 10 or 100 ng/ml bFGF for 6 hours. Nitric oxide synthase (NOS) activity in aortic slices and contents of NO(-)(2) and endothelin in the medium were determined. The results showed that NOS activity in aortic slices of SHR was 17.6% lower than that of WKY (P<0.01). NO(-)(2) and endothelin contents in the medium of SHR aortic slices were 59.7% lower and 37.4% higher than those of WKY aortic slices. Upon the exposure of low and high doses of bFGF, NOS activity in the aorta of SHR was increased by 29.7% and 59.6% (both P<0.01),respectively, while the NO(-)(2) contents in the medium were increased respectively by 28.2% (P<0.05) and 70.5% (P<0.01). Aortic endothelin production was increased by 24.1% and 44.5% (both P<0.01) respectively while the NOS activity in the aorta of WKY was increased by 24.4% and 53.7% (both P<0.01). NO(-)(2) contents in the medium were augmented by 18.8% (P<0.05)and 25.9% (P<0.01), respectively. Aortic endothelin production was increased by 84.1% and 93.1% (both P<0.01). It is concluded that bFGF may modulate the production of NO and endothelin in both SHR and WKY rats.

[Involvement of calcineurin-dependent signal pathway in the angiotensin II-induced cardiac myocyte hypertrophy].

The present study was undertaken to observe the role of calcineurin (CaN)-dependent signaling pathway in the angiotensin II (Ang II)-induced cardiac myocyte hypertrophy. In cultured myocardial cells of neonatal rats, Ang II was used to stimulate hypertrophy and CaN-pathway blocked by CsA(an inhibitor of CaN). 3H-leucine incorporation, and activities of CaN, mitogen-activated protein kinase (MAPK) and protein kinase C (PKC) were investigated. The results showed that 3H-leucine incorporation of Ang II-stimulated myocardial cells was 46% higher than control (P < 0.01), which could be inhibited by CsA (0.5-5 micrograms/ml) and PD098059(an inhibitor of MAPK). CaN and PKC activities of Ang II-stimulated myocardial cells were 39% and 280% higher than control (P < 0.001) respectively, while no significant increase in MAPK activities was observed. CsA could reverse the increase of CaN activity, but had no effect on PKC. It is concluded that the CaN-dependent signaling pathway may play an important role in the development of the Ang II-induced cardiac myocyte hypertrophy.

[Effect of salvia miltiorrhiza composita on superoxide dismutase and malonyldialdehyde in treating patients with non-insulin dependent diabetes mellitus (NIDDM)].

OBJECTIVE: To assess the effect of Salvia Miltiorrhiza Composita (SMCo) in treating non-insulin-dependent diabetes mellitus (NIDDM). METHODS: The superoxide dismutase (SOD) and malonyldialdehyde (MDA) levels of 20 patients with NIDDM were observed before and after treatment with Salvia Miltiorrhiza Composita and 20 patients without using SMCo were studied as controls. RESULTS: The SOD levels were significantly lower than that of normal (P < 0.05), and MDA significantly increased (P < 0.01). After treatment with SMCo, the SOD levels were significantly increased (P < 0.01), there was no difference between the treatment group and the normal group. In the control group, the SOD levels had increase tendency and MDA had decrease tendency, but there was significant difference compared with the normal (P < 0.05, P < 0.01 respectively). The total effective rate of anti-lipid peroxidation injury in the group combined with intravenous SMCo was markedly higher than in the group without SMCo therapy (90% vs 60%, P < 0.01). CONCLUSION: SMCo could resist lipid peroxidation injury.

[Study on syndrome-type in TCM and its correlation with superoxide dismutase and malonyldialdehyde in patients with non-insulin dependent diabetes mellitus].

OBJECTIVE: To explore the possible relationship between Syndrome-Type in TCM and the superoxide dismutase (SOD) as well as malonyldialdehyde (MDA). METHODS: Serum SOD and MDA were measured in 61 patients with non-insulin dependent diabetes mellitus (NIDDM) and 20 normal subjects. RESULTS: SOD activity of the NIDDM patients blood were clearly lower than those of normal subjects, but MDA were markedly elevated. From the Syndrome-Type of Yin Deficiency with Hyperactivity of Heat, to both Qi and Yin Deficiency, to both Yin and Yang Deficiency, or from without hemostasis to with the appearance of hemostasis in order. The SOD activity decreased and meanwhile MDA increased gradually. CONCLUSIONS: SOD activity and MDA levels in patients with NIDDM were associated with Syndrome-Type in TCM, it might be responsible for the diagnosis of Syndrome-Type in TCM.

[Inhibitory effects of Chinese medicines on SOS responses in E. coli and their mechanism].

Sixty kinds of commonly used Chinese medicines have been examined for their ability to depress the release of Lambda phage from lysogenic strain in the inductest. 11 Chinese medicines showed an inhibitory effects. Among them, Codonopsis radix, Polygonatum radix and fractus Lycium were strong depressors. They also showed an inhibitory effect on SOS response in SOS chromotest with a dose-effect response. These medicines were also found to decrease the frequency of gene conversion in S. cerevisiae in the presence of hydroxyurea. The effective compound (s) of Polygonatum radix partially purified from the extract with Sephadex G-25 chromatography was a reductive carbohydrate with molecular weight less than 3,000. The compound was shown to exert an inhibitory effect on SOS response occurred at 42 degrees C in E. coli GW1060 (recA441), but has no effect on SOS network gene expression in E. coli GW 1107 (lexA51), suggesting that Polygonatum radix may contain an inhibitor of RecA protease.

[Preparation of human minisatellite DNA probes].

A 23-mer oligonucleotide based on the core sequence was chemically synthesized and used to screen the human genomic library. Fifteen positive recombinants containing the minisatellite sequences were identified, and one of them, C35.9, was used to perform Southern hybridization with the DNAs from unrelated Chinese individuals. Each sample has 3-11 hybridizing bands, and some of which are polymorphic. The band patterns detected under controlled condition are individual-specific in a limited population. This indicates that the minisatellites obtained by screening the library can be used to detect the polymorphisms of the minisatellites.

[Epidemic tendency of Kaschin-Beck disease in Shan Xi province for five years].

According to the continued observation on Kaschin-Beck disease situation in Shanxi province from 1982 to 1986, this paper clarifies that the epidemic tendency is tending to fall. Only in a few small areas the disease prevalence was steady. The cause of this tendency relates to the improvement of the living standard among the residents in the disease areas.