MSCs relieve lung injury of COPD mice through promoting proliferation of endogenous lung stem cells / 华中科技大学学报（医学）（英德文版）

Bone marrow mesenchymal stem cells (MSCs) transplantation could repair injury tissue, but no study confirms whether MSCs can promote the proliferation of endogenous lung stem cells to repair alveolar epithelial cells of mice with chronic obstructive pulmonary disease (COPD). This study was designed to investigate the effect of MSCs on the proliferation of endogenous lung stem cells in COPD mice to confirm the repair mechanism of MSCs. The mice were divided into control group, COPD group, and COPD+MSCs group. The following indexes were detected: HE staining of lung tissue, the mean linear intercept (MLI) and alveolar destructive index (DI), the total cell number in bronchoalveolar lavage fluid (BALF), pulmonary function, alveolar wall apoptosis index (AI) and proliferation index (PI), the number of CD45(-)/CD31(-)/Sca-1(+) cells by flow cytometry (FCM), and the number of bronchoalveolar stem cells (BASCs) in bronchoalveolar duct junction (BADJ) by immunofluorescence. As compared with control group, the number of inflammatory cells in lung tissue was increased, alveolar septa was destroyed and the emphysema-like changes were seen, and the changes of lung function were in line with COPD in COPD group; AI of alveolar wall was significantly increased and PI significantly decreased in COPD group. There was no significant difference in the number of CD45(-)/CD31(-)/Sca-1(+) cells and BASCs between control group and COPD group. As compared with COPD group, the number of inflammatory cells in BALF was decreased, the number of CD45(-)/CD31(-)/Sca-1(+) cells and BASCs was increased, AI of alveolar wall was decreased and PI was increased, and emphysema-like changes were relieved in COPD+MSCs group. These findings suggested that MSCs transplantation can relieve lung injury by promoting proliferation of endogenous lung stem cells in the cigarette smoke-induced COPD mice.

Characteristics of antisense non-coding RNA in the INK4 locus and its roles in disease / 中国医学科学杂志(英文版)

With the development of genome-wide sequencing technology, 195 types of functional long non-coding RNAs (lncRNAs) have so far been found, and their cellular roles are gradually being revealed. Now lncRNAs have become a hotspot in the life science. These small molecules exist in almost all higher eukaryotes, and have very important regulatory roles in these organisms. This review briefly summarizes recent progress in researches on antisense non-coding RNA in the INK4 locus.

Correlation between distributions of pathogenic bacteria on hands and the position of funeral staffs / 中华预防医学杂志

<p><b>OBJECTIVE</b>This study aims to investigate the bacteria contamination on hands of funeral staffs in different positions.</p><p><b>METHODS</b>Bacterial samples were collected from the hands of 105 funeral staffs in different positions (including 90 frontline staffs and 15 administrative workers) from 13 funeral parlors nationwide, and were subsequently tested by bacterium inspection.</p><p><b>RESULTS</b>In total, 1783 strains of bacteria were isolated, including 1027 Gram-positive bacteria, most of which were Staphylococcus; and 756 Gram-negative bacteria, most of which were Pseudomonas. Out of the 1783 strains of bacteria, 570 pathogens and opportunistic pathogens were isolated, accounted to 31.96%. The isolated ratio of pathogens and conditional pathogens in embalmed/cosmetologist of cadavers was 35.67% (370/1037), which was higher than those in the funeral workers in other positions, such as cremators, pick-up and administrative workers, whose ratios were 24.42% (95/389), 22.41% (52/232) and 10.40% (12/125), respectively (χ(2) were 13.682, 10.967 and 32.263, respectively; P values were all < 0.05). And the isolated ratios of pathogens and conditional pathogens in cremators and pick-up workers were significantly higher than that in administrative workers (χ(2) were 11.206 and 7.873, respectively; P values were all < 0.05).</p><p><b>CONCLUSION</b>Lots of bacteria were found in the samples from hands of funeral staffs. The isolated ratio of pathogens and conditional pathogens was different between the funeral staffs in different positions; while the highest was from embalmed/cosmetologist of cadavers and the lowest was from administrators.</p>

Testosterone alleviates tumor necrosis factor-alpha-mediated tissue factor pathway inhibitor downregulation via suppression of nuclear factor-kappa B in endothelial cells / 亚洲男科学杂志(英文版)

We have observed earlier that testosterone at physiological concentrations can stimulate tissue factor pathway inhibitor (TFPI) gene expression through the androgen receptor in endothelial cells. This study further investigated the impact of testosterone on TFPI levels in response to inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha). Cultured human umbilical vein endothelial cells were incubated in the presence or absence of testosterone or TNF-alpha. TFPI protein and mRNA levels were assessed by enzyme-linked immunosorbent assay and quantitative real-time reverse transcription polymerase chain reaction. To study the cellular mechanism of testosterone's action, nuclear factor-kappa B (NF-kappaB) translocation was confirmed by electrophoretic mobility shift assays. We found that after NF-kappaB was activated by TNF-alpha, TFPI protein levels declined significantly by 37.3% compared with controls (P < 0.001), and the mRNA levels of TFPI also decreased greatly (P < 0.001). A concentration of 30 nmol L(-1) testosterone increased the secretion of TFPI compared with the TNF-alpha-treated group. NF-kappaB DNA-binding activity was significantly suppressed by testosterone (P < 0.05). This suggests that physiological testosterone concentrations may exert their antithrombotic effects on TFPI expression during inflammation by downregulating NF-kappaB activity.

Hemin, a heme oxygenase-1 inducer, improves aortic endothelial dysfunction in insulin resistant rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Under an insulin resistance (IR) state, overproduction of reactive oxygen species (ROS) may be playing a major role in the pathogenesis of endothelial dysfunction, hypertension and atherosclerosis. Recently, increasing attention has been drawn to the beneficial effects of heme oxygenase-1 (HO-1) in the cardiovascular system. This study aimed to investigate the effects of HO-1 on vascular function of thoracic aorta in IR rats and demonstrate the probable mechanisms of HO-1 against endothelial dysfunction in IR states.</p><p><b>METHODS</b>Sprague-Dawley (SD) rats fed with high-fat diet for 6 weeks and the IR models were validated with hyperinsulinemic-euglycemic clamp test. Then the IR rat models (n = 44) were further randomized into 3 subgroups, namely, the IR control group (n = 26, in which 12 were sacrificed immediately and evaluated for all study measures), a hemin treated IR group (n = 10) and a zinc protoporphyrin-IX (ZnPP-IX) treated IR group (n = 8) that were fed with a high-fat diet. Rats with standardized chow diet were used as the normal control group (n = 12). The rats in IR control group, hemin treated IR group and ZnPP-IX treated IR group were subsequently treated every other day with an intraperitoneal injection of normal saline, hemin (inducer of HO-1, 30 micromol/kg) or ZnPP-IX (inhibitor of HO-1, 10 micromol/kg) for 4 weeks. Rats in the normal control group remained on a standardized chow diet and were treated with intraperitoneal injections of normal saline every other day for 4 weeks. Systolic arterial blood pressure (SABP) was measured by tail-cuffed microphotoelectric plethysmography. The blood carbon monoxide (CO) was measured by blood gas analysis. The levels of nitric oxide (NO), inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), blood glucose (BG), insulin, total cholesterol (TC) and triglyceride (TG) in serum, and the levels of total antioxidant capacity (TAOC), malondialdehyde (MDA) and superoxide dismutase (SOD) in the aorta were measured. The expression of HO-1 mRNA and HO-1 protein in aortal tissue were detected by semi-quantitative RT-PCR and Western blot. The vasoreactive tensometry was performed with thoracic aortic rings (TARs).</p><p><b>RESULTS</b>Compared with the normal control group, the levels of SABP, BG, insulin, TC, TG, NO, iNOS and MDA were higher, while the levels of CO, TAOC, SOD and eNOS were lower in IR control rats. After treatment of IR rats for 4 weeks a more intensive expression of HO-1 mRNA and HO-1 protein were observed in hemin treated IR group compared with the normal control group. And compared with 4-week IR control rats, the levels of CO, TAOC, SOD and eNOS were increased, while the levels of SABP and iNOS activity were lower in the hemin treated IR group. Administration of hemin in IR rats appeared to improve the disordered vasorelaxation of TARs to acetylcholine (ACh). Alternatively, the reverse results of SABP, CO, TAOC, SOD, iNOS and vasorelaxation responses to ACh were observed in IR rats with administration of ZnPP-IX.</p><p><b>CONCLUSIONS</b>The endothelial dysfunction in the aorta is present in the IR state. The protective effects of HO-1 against aortic endothelial dysfunction may be due to its antioxidation and regulative effect of vasoactive substances. It is proposed that hemin, inducer of HO-1, could be a potential therapeutic option for vascular dysfunction in IR states.</p>

Effects of testosterone on extracellular signal-regulated kinase 1/2 phosphorylation in human umbilical vein endothelial cells / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the effects of testosterone on extracellular signal-regulated kinase l/2 ( ERK1/2) phosphorylation in human umbilical vein endothelial cells (HUVEC).</p><p><b>METHODS</b>Activations of ERK1/2 stimulated by physiological testosterone were detected by Western blotting in cultured HUVEC.</p><p><b>RESULTS</b>A rapid phosphorylation expression of ERK1/2 was observed by treatment of the HUVECs with 3 x 10(-8) mol/L testosterone, especially at 30 minutes. This phosphorylation was greatly inhibited by incubation with androgen receptor antagonist flutamide for 3 hours previously.</p><p><b>CONCLUSION</b>Testosterone at physiological concentrations induces the mitogen-activated protein kinase (MAPK, ERK1/2 and MEK1/2) phosphorylation within a short time, and flutamide could impair the process.</p>

The role of activation of nuclear factor-kappa B on the expression of heme oxygenase-1 induced by lipopolysaccharide in rat myocardium / 中国应用生理学杂志

<p><b>AIM</b>The role of activated nuclear factor-kappa B(NF-kappaB) on the expression of heme oxygenase-1 induced by lipopolysaccharide (LPS) in rats' myocardium was obversed, and the effect exerted in endotoxic shock was explored.</p><p><b>METHODS</b>The changes in mean arterial pressure within 12 hours were recorded on a polygraph. The protein expression of NF-kappaB p65 in rats'myocardium, which were induced by lipopolysaccharide were measured with immunochemistry. The changes both of protein and gene expression of heme oxygenase-1 in rats' myocardium, which were induced by injection of LPS or preadministration of the specific inhibitor of NF-kappaB, pyrrolidine dithiocarbamate(PDTC), were examined by immunochemistry of reverse transcripted polymerase chain reaction.</p><p><b>RESULTS</b>(1) LPS caused a rapid decrease of MAP within 12 h( P < 0.01). (2) After LPS was administration, the protein expression of NF-kappaB p65 in both of micrangium endothelium within myocardium markedly increased at 0.5 h and 2 h, while decreased gradually at 6 h and 12 h. (3) ES group expressed as migration of acute inflammatory cells and dilation and stagnation in blood capillary, while the increase of HO-1 mRNA induced by LPS didn't change at the first 0.5 h, began at 2 h, peaked at 6 h, and declined at 12 h, respectively. The protein expression of HO-1 in micrangium endothelium within myocardium markedly increased and emerged in myocardium, and kept a high level at 6 h and 12 h. (4) When a specific inhibitor of NF-kappaB, PDTC, was applied to inhibit the level of NF-kappaB, we found that the pathomorphological changes of myocardium in ES rats were improved and both HO-1 mRNA and protein expression in myocardium markedly failed at 6 h.</p><p><b>CONCLUSION</b>NF-kappaB was activated on the stimulation of LPS, which brought about its translocation to the nucleus to act on transcription activity of HO-1 gene. NF-kappaB might be involved in its signal transductive mechanisms, which might be one of the important mechanism of LPS inducing the refractory low arterial pressure in ES rats.</p>

Na+-H+ exchanger protein changes in vascular smooth muscle and effect of Na+-H+ exchange inhibitor on vessel stenosis after balloon injuries in rabbits / 中华心血管病杂志

<p><b>OBJECTIVE</b>To explore the mechanism and effect of sodium/hydrogen exchanger (Na(+)-H(+) exchanger, NHE), amiloride, on vessel stenosis.</p><p><b>METHODS</b>Thirty-two adult male New Zealand white rabbits were randomly divided into groups of amiloride intervention (IG, n = 12), balloon injury (BG, n = 10) and sham-operation (SG, n = 10). A 2.5 mm x 20 mm Foley's tube was used to injury left side iliac artery in the IG and BG groups, whereas a same Foley's tube was inserted into the vessel without any injuries in the SG group. Amiloride (5 mg.kg(-1).d(-1)) was intraperitoneally injected 3 days before balloon injuries and the same dosage normal saline was used in the same way in the BG group for 28 days after operation. The rabbits were killed and the iliac arteries were stained with Hematoxylin-Eosin, alpha-actin and Masson's trichrome to observe the morphologic changes in the vessel cava, neointima, media layer, and vascular smooth muscle cells (VSMCs) migration into the neointima and extracellular matrixes (ECMs).</p><p><b>RESULTS</b>Four weeks after balloon injuries in rabbits, a cave narrow of the iliac artery and neointima were found and the media layer (VSM layer) was proliferated. The quantities of NHE-1 protein from artery smooth muscle in all the groups were 0.21 +/- 0.02, 0.25 +/- 0.04 and 0.11 +/- 0.03 (P < 0.01), respectively. The difference between the BG and SG groups was significant, which indicated that the NHE-1 proteins increased after balloon injury. The quantities of NHE-1 protein from the IG group were lower than those from the BG group. The cave areas were 0.91 mm(2) +/- 0.23 mm(2), 0.68 mm(2) +/- 0.19 mm(2) and 1.08 mm(2) +/- 0.17 mm(2) (P < 0.01), respectively. The intima areas were 0.27 mm(2) +/- 0.15 mm(2), 0.67 mm(2) +/- 0.24 mm(2) and 0.05 mm(2) +/- 0.03 mm(2), respectively (P < 0.01). The ratios of intima to media area were 1.21 +/- 0.24, 1.39 +/- 0.26 and 0.15 +/- 0.08 (P < 0.01), respectively. Amiloride increased vessel cave areas, but decreased intima areas and intima to media ratios in the IG group. In the IG group, alpha-actin positive areas in neointima was higher (16,328.31 microm(2) +/- 6220.27 microm(2)) than those in the SG group (4164.15 microm(2) +/- 1788.37 microm(2)) (P < 0.01). ECMs areas in neointima in the IG group were lower (8910.62 microm(2) +/- 7041.62 microm(2)) than those in the SG group (33,358.76 microm(2) +/- 7290.17 microm(2)) (P < 0.01).</p><p><b>CONCLUSIONS</b>Balloon injuries of iliac artery in rabbits induce VSMCs proliferation, migration, narrowed cave and vessel stenosis. Amiloride, a NHE-1 inhibitor, may relieve this vessel stenosis.</p>

Testosterone's effect on tPA and PAI-1 mRNA levels of HUVEC / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the effect of testosterone with varied concentrations on the tPA and PAI-1 mRNA levels of Human umbilical vein endothelial cells (HUVEC).</p><p><b>METHODS</b>HUVEC within 2 - 3 passages were cultured with testosterone (3, 30, 3 x 10(3), 3 x 10(4) nmol/L) , and the control confluent cells were cultured in the same medium without steroid for 48 hours. RT-PCR was carried out to detect tPA and PAI-1 mRNA levels.</p><p><b>RESULTS</b>tPA mRNA level increased, while PAI-1 mRNA levels decreased significantly, at the testosterone concentrations ranging from 3 to 3 x 10(3) nmol/L (P < 0.05). Both tPA and PAI-1 mRNA level decreased obviously of 3 x 10(4) nmol/L group.</p><p><b>CONCLUSION</b>The results indicated that testosterone could stimulate tPA gene expression, while decreased PAI-1 mRNA level of HUVEC, which suggested that testosterone might have beneficial effects on preventing male's thrombotic diseases.</p>