Tea consumption and risk of bone health: an updated systematic review and meta-analysis.

INTRODUCTION: Current research evaluating the association between tea consumption and bone health still has inconsistent findings. MATERIALS AND METHODS: The electronic databases of Embase, PubMed, Scopus, and Web of Science were systematically searched from inception until December 2022 to identify eligible studies. The calculation of summary relative risks (RRs) and 95% confidence intervals (CIs) was carried out using random-effects models. I2 statistics and Forest plots were used to assess the heterogeneity of RR values across studies. RESULTS: The pooled relative risks for bone health-related outcomes of interest among tea drinkers, compared to non-drinkers, were 0.910 (95% confidence interval 0.845 to 0.980) for fractures, based on 20 studies, 0.332 (0.207-0.457) for BMD (13 studies), 0.800 (0.674-0.950) for osteoporosis (10 studies), and 1.006 (0.876-1.156) for osteopenia (5 studies). Subgroup analysis of locations showed that the pooled relative risks were 0.903 (0.844-0.966) for the hip, 0.735 (0.586-0.922) for the femur, 0.776 (0.610-0.988) for the lumbar, 0.980 (0.942-1.021) for the forearm and wrist, 0.804 (0.567-1.139) for the phalanges, and 0.612 (0.468-0.800) for Ward's triangle. One-stage dose-response analysis revealed that individuals who consumed less than 4.5 cups of tea per day had a lower risk of bone health-related outcomes than those who did not consume tea, with statistically significant results. CONCLUSION: There is an association between tea consumption and a reduced risk of fractures, osteoporosis, hip, femur, and lumbar, as well as increased BMD.

Meat Intake and the Risk of Bladder Cancer: A Systematic Review and Meta-Analysis of Observational Studies.

The evidence for the association between meat intake and the risk of bladder cancer (BC) is still inconclusive. A total of 29 studies involving 1,475,125 participants and 18,836 cases of BC were included in the meta-analysis. Among these studies, 11 reported total meat intake, 20 reported red meat intake, 19 reported processed meat intake, 15 reported white meat intake, and 15 reported fish intake. The results suggested that there was an overall increase in BC risk associated with total meat intake (RR = 1.10; 95% confidence interval: 0.92-1.31; I2 = 55.20%; P = 0.014), and a higher red meat (RR = 1.23; 95% CI: 1.08-1.39; I2 = 51.30%; P = 0.004) or processed meat (RR = 1.16; 95% CI: 1.08-1.25; I2 = 28.00%; P = 0.125) intake may increase the risk of BC. In contrast, a higher intake of fish (RR = 0.80; 95% CI: 0.67-0.95; I2 = 62.90%; P = 0.001) was inversely associated with the risk of BC. Moreover, we did not observe an association between white meat (RR = 0.96; 95% CI: 0.83-1.10; I2 = 53.70%; P = 0.007) and the risk of BC. Our findings suggested that dietary intervention may be an effective approach to preventing BC, which still needs to be confirmed by further well-designed observational studies.

Coffee, Green Tea Intake, and the Risk of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis of Observational Studies.

Several studies suggest an inverse relationship between coffee intake and risk of hepatocellular carcinoma (HCC), but the association between green tea intake and the risk of HCC is still inconclusive. We performed a meta-analysis of observational studies to clarify the association. We identified eligible studies published from January 1, 1992, to February 28, 2022, by searching PubMed, Web of Science, and EMBASE. A total of 32 studies were included in the meta-analysis. Among them, 21 studies involving 2,492,625 participants and 5980 cases of HCC reported coffee intake, 18 studies involving 1,481,647 participants and 6985 cases of HCC reported green tea intake, and seven studies reported both coffee intake and green tea intake. The results showed that a higher coffee (RR = 0.53; 95% CI: 0.47-0.59; I2 = 0.0%; Pheterogeneity = 0.634) or green tea (RR = 0.80; 95% CI: 0.67-0.95; I2 = 72.30%; Pheterogeneity < 0.001) intake may be associated with a lower risk of HCC. The same results were observed in both cohort and case-control subgroups. Our findings suggest that drinking coffee or green tea may be a potentially effective approach for the prevention or mitigation of HCC, but this still needs to be confirmed by further well-designed observational studies and clinical experimental research.

Meat Intake and the Risk of Hepatocellular Carcinoma: A Meta-Analysis of Observational Studies.

The association between meat intake and hepatocellular carcinoma (HCC) risk is still unclear. We conducted a meta-analysis with observational studies to clarify this relationship. A total of 17 studies involving 2,915,680 participants and 4,953 cases of HCC were included in the meta-analysis. Ten studies reported red meat intake, nine reported white meat intake, nine reported fish intake, seven reported processed meat intake, and five reported total meat intake. The results showed that the consumption of red meat (relative risk [RR] = 1.04; 95% confidence interval [CI]: 0.91-1.18; I2=50.50%; P = 0.033) and total meat intake (RR = 1.01; 95% CI: 0.90-1.13; I2 = 15.50%; P = 0.316) were not associated with risk of HCC. However, a higher dietary intake of processed meat (RR = 1.20; 95% CI: 1.02-1.41; I2 = 26.30%; P = 0.228) may increase the risk of HCC. In contrast, the intake of white meat (RR = 0.76; 95% CI: 0.63-0.92; I2 = 68.30%; P = 0.001) and fish (RR = 0.91; 95% CI: 0.86-0.96; I2 =40.90%; P = 0.095) were inversely associated with risk of HCC. Our findings suggest that dietary intervention may be an effective approach to preventing HCC. These need to be verified with further well-designed observational studies and experimental clinical research.

Estradiol mediates vasculoprotection via ERRα-dependent regulation of lipid and ROS metabolism in the endothelium.

The estrogen-mediated vasculoprotective effect has been widely reported in many animal studies, although the clinical trials are controversial and the detailed mechanisms remain unclear. In this study, we focused on the molecular mechanism and consequence of 17ß-estradiol (E2)-induced ERRα (estrogen-related receptor alpha) expression in endothelium and its potential beneficial effects on vascular function. The human aorta endothelial cells were used to identify the detailed molecular mechanism and consequences for E2-induced ERRα expression through estrogen receptors (ER), where ERα responses E2-induced ERRα activation, and ERß responses basal ERRα expression. E2-induced ERRα expression increases fatty acid uptake/oxidation with increased mitochondrial replication, ATP generation and attenuated reactive oxygen species (ROS) formation. We have obtained further in vivo proof from high-fat diet mice that the lentivirus-carried endothelium-specific delivery of ERRα expression on the vascular wall normalizes E2 deficiency-induced increased plasma lipids with ameliorated vascular damage. ERRα knockdown worsens the problem, and the E2 could only partly restore this effect. This is the first time we report the detailed mechanism with direct evidence that E2-induced ERRα expression modulates the fatty acid metabolism and reduces the circulating lipids through endothelium. We conclude that E2-induced ERRα expression in endothelium plays an important role for the E2-induced vasculoprotective effect.

Characteristics of qacA/B-positive Staphylococcus aureus isolated from patients and a hospital environment in China.

OBJECTIVES: This study was designed to demonstrate the characteristics of qacA/B-positive Staphylococcus aureus in China. METHODS: One hundred and forty-five MRSA and 178 MSSA from clinical specimens from seven hospitals in different regions of China, 70 MRSA from superficial sites of patients and 106 MRSA from environmental samples from an ICU were collected and screened for the presence of the qacA/B gene. The qacA/B-positive isolates and 72 randomly selected qacA/B-negative control isolates were further characterized by MLST, spa typing and detection of toxin genes, as well as antimicrobial and chlorhexidine susceptibility. SCCmec typing was conducted for MRSA. PFGE was conducted for qacA/B-positive isolates. RESULTS: Twenty-five (7.8%) of the 321 MRSA isolates harboured qacA/B, including 11 isolates from clinical specimens (7.6%), 12 isolates from patients' superficial sites (17.1%) and 2 isolates from an ICU environment (1.9%). Ten and five qacA/B-positive MRSA were identified as ST239-t030-MRSA-III and ST239-t037-MRSA-III, respectively. Six PFGE clusters and five singletons were identified among the 25 qacA/B-positive MRSA. Only one (0.6%) of the 178 MSSA isolates harboured qacA/B. qacA/B carriage in MRSA was statistically associated with spa-t037 and the presence of mupA. Compared with qacA/B-negative MRSA, the qacA/B-positive MRSA exhibited a lower susceptibility to chlorhexidine and higher resistance rates to clindamycin and trimethoprim/sulfamethoxazole. CONCLUSIONS: Carriage of qacA/B, although it had a low prevalence, might be the main reason for declining susceptibility to chlorhexidine in MRSA from Chinese patients and is probably associated with spa-t037 and the presence of the mupA gene.

Involvement of activation of C-met signaling pathway in CD151-induced HUVECs angiogenesis.

CD151 is a member of the tetraspanin family that is implicated as a promoter of pathological or physiological angiogenesis. C-Met is expressed on a variety of cells including vascular endothelial cells (VECs) and up-regulated during angiogenesis. In this study, we investigated whether CD151 regulated migration, proliferation, tube formation and angiogenesis of human umbilical VECs (HUVECs) with activation of C-Met. Moreover, we studied whether CD151 could affect the angiogenic molecules such as nitric oxide (NO), vascular cell adhesion molecule-1 (VCAM-1) and vascular endothelial growth factor (VEGF). The expression of CD151 was determined by Western blotting. The cell proliferation assay was performed using the cell counting kit-8 (CCK-8) method and cell migration was assessed in microchemotaxis chambers by using fetal bovine serum (FBS) as the chemotactic stimulus. The angiogenic molecules were evaluated using ELISA. The NO level was detected using NO detection kit. The potential involvement of various signaling pathways was explored using relevant antibodies. We found that proliferation, migration and tube formation of HUVECs were promoted by CD151 with activation of C-Met, FAK and CDC42, while they were suppressed with CD151 knockdown by RNAi. Similarly, the levels of NO, VCAM-1 and VEGF in HUVECs were increased by CD151, but they were inhibited with CD151 knockdown by RNAi. These data suggested that CD151 could promote migration, proliferation, tube formation and angiogenesis of HUVECs, which was possibly related to the C-Met signaling pathways.

The p38 MAPK inhibitor SB203580 differentially modulates LPS-induced interleukin 6 expression in macrophages.

The p38 mitogen-activated protein kinase (MAPK) plays a key role in lipopolysaccharide (LPS)-induced signal transduction pathways that lead to inflammatory cytokine synthesis in macrophages; however, whether the inhibition of p38 MAPK regulates LPS-induced inflammatory cytokine expression in different types of macrophages remains the subject of debate. Herein, we assessed whether the inhibition of p38 MAPK by SB203580 regulates LPS-induced expression of the inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) in RAW264.7 and resident peritoneal macrophages. Lipopolysaccharide stimulation of RAW264.7 macrophages or mouse resident peritoneal macrophages significantly increased TNF-α and IL-6 production. The addition of SB203580 to cultures dramatically blocked LPS-induced TNF-α production in RAW264.7 and mouse resident peritoneal macrophages, and dramatically blocked LPS-induced IL-6 production in RAW264.7 macrophages, but not in mouse resident peritoneal macrophages. Additionally, high concentrations of SB203580 resulted in increased IL-6 production. However, LPS-stimulation significantly up-regulated the mRNA transcript levels of TNF-α and IL-6 in RAW264.7 and mouse resident peritoneal macrophages, whereas pretreatment with SB203580 dramatically down-regulated LPS-induced mRNA transcript levels of TNF-α and IL-6 in these cells. Our data show that SB203580 differentially modulates LPS-induced production of the inflammatory cytokine IL-6 in two different sources of macrophages, and that this course of regulation occurs at the IL-6 mRNA post-transcriptional stage.

[Corrigendum] The tetraspanin CD151­ARSA mutant inhibits angiogenesis via the YRSL sequence.

Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that, in Fig. 4A on p. 839, the 'CD151/24 h' and 'CD151­ARSA/48 h' panels appeared to contain overlapping sections of data, such that they were potentially derived from the same original source, where these panels were intended to show the results from differently performed experiments. The authors have re­examined their original data, and realize that the 'CD151­ARSA/48 h' panel was inadvertently placed incorrectly in the figure. The revised version of Fig. 4, now containing the correct data for the 'CD151­ARSA/48 h' experiment in Fig. 4A, is shown below. Note that this error did not adversely affect either the results or the overall conclusions reported in this study. All the authors agree with the publication of this corrigendum, and are grateful to the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this. They also wish to apologize to the readership of the Journal for any inconvenience caused. [Molecular Medicine Reports 7: 836­842, 2013; DOI: 10.3892/mmr.2012.1250].

Effects of different dietary patterns during pregnancy on birth outcomes and glucose parameters in women with gestational diabetes mellitus: A systematic review and meta-analysis.

PURPOSE: Dietary interventions are the cornerstone of gestational diabetes mellitus (GDM) treatment. This study aimed to evaluate the effects of dietary patterns during pregnancy on birth outcomes and glucose parameters in women with GDM. METHODS: PubMed, Embase, and The CoChrane Library were searched from the time of database creation to November 30, 2021, along with manual searches. Data analyses were performed using Stata 15.4 software. RESULTS: From 2461 studies, 27 RCTs involving 1923 women were eligible. The pooled results showed that dietary pattern interventions during pregnancy reduced birth weight (WMD: -0.14 kg; 95% CI: -0.24, -0.00), hemoglobin A1 C (HbA1 C) (WMD: -0.19, 95% CI: -0.34, -0.05), and macrosomia incidence (RR 0.65 [95% CI 0.48, 0.88]). Low glycemic index (GI) diet reduced macrosomia incidence (RR 0.31 [95% CI 0.11, 0.93]) and fasting plasma glucose (FPG) levels (WMD: -0.10 mmol/L; 95% CI: -0.14, -0.05); a low carbohydrate (CHO) diet reduced large for gestational age (LGA) incidence (RR 0.33 [95% CI 0.13, 0.82]) and HbA1 C (WMD: -0.32; 95% CI: -0.51, -0.14); dietary approaches to stop hypertension (DASH) diet reduced birth weight (WMD:-0.59 kg; 95% CI: -0.64, -0.55), insulin use (RR 0.31 [95% CI 0.18, 0.56), macrosomia incidence (RR 0.12 [95% CI 0.03, 0.50]), and cesarean sections incidence (RR 0.57 [95% CI 0.40, 0.82]). CONCLUSION: Dietary patterns during pregnancy can improve certain birth outcomes and glycemic parameters. Due to limitations in the quality and number of included studies, the above findings still need to be validated by further randomized controlled trials with high quality and large samples.

Molecular detection of Bartonella species in wild small mammals in western Yunnan Province, China.

Background: Small mammals serve as the main reservoir for Bartonella and as a proxy indicator of the potential risk of Bartonella transmission from nature to humans. They offer a valuable early warning for human infection. Nevertheless, geographical variations in the impact of the host on the occurrence of Bartonella infection are underestimated. This study was designed to investigate the infection characteristics of Bartonella and explore its species diversity in wild small mammals in western Yunnan Province, China. Methods: Wild small mammals were captured from Yulong, Jianchuan, and Lianghe counties in western Yunnan Province between 2015 and 2016. Real-time quantitative PCR (qPCR) was used to detect Bartonella infection, and the Bartonella species were identified by phylogenetic analysis. The factors associated with Bartonella infection in small mammals were analyzed by the Chi-square Test. Results: The prevalence of Bartonella in small mammals was 47.85% (768/1605). Lianghe County had the highest Bartonella infection rate, with 56.27% of the samples tested positive, followed by a rate of 50.91% was tested in Yulong County, and 39.97% in Jianchuan County (p < 0.001). Bartonella was detected positive in a total 25 small mammal species, with infection rates ranging from 2.17% to 100%. Niviventer fulvescens had the highest Bartonella infection rate. In comparison with the dominant small mammal species, Eothenomys mileyus had the lowest Bartonella infection rate than that in Apodemus chevrieri, Rattus tanezumi, and Apodemus draco (p < 0.001). Male small mammals had a higher infection rate than females (p < 0.05). The prevalence of Bartonella in small mammals during the summer season was higher compared to the other three seasons (p < 0.001). Woodland landscape had the highest Bartonella infection rate (p < 0.001). Bartonella rochalimae, B. japonica, B. tribocorum, B. washoensis, B. sylvatica, and B. rattimassiliensis were obtained from infected small mammals. Conclusion: This study showed a high prevalence of Bartonella was detected with various Bartonella species in small mammals in Yulong, Jianchuan, and Lianghe counties of western Yunnan Province. These findings hold significant scientific clues, providing valuable reference points for further research of Bartonella natural foci in Yunnan or other analogues environments.

Huperzine A ameliorates cognitive deficits and oxidative stress in the hippocampus of rats exposed to acute hypobaric hypoxia.

Acute exposure to high altitudes can cause neurological dysfunction due to decreased oxygen availability to the brain. In this study, the protective effects of Huperzine A on cognitive deficits along with oxidative and apoptotic damage, due to acute hypobaric hypoxia, were investigated in male Sprague-Dawley rats. Rats were exposed to simulated hypobaric hypoxia at 6,000 m in a specially fabricated animal decompression chamber while receiving daily Huperzine A orally at the dose of 0.05 or 0.1 mg/kg body weight. After exposure to hypobaric hypoxia for 5 days, rats were trained in a Morris Water Maze for 5 consecutive days. Subsequent trials revealed Huperzine A supplementation at a dose of 0.1 mg/kg body weight restored spatial memory significantly, as evident from decreased escape latency and path length to reach the hidden platform, and the increase in number of times of crossing the former platform location and time spent in the former platform quadrant. In addition, after exposure to hypobaric hypoxia, animals were sacrificed and biomarkers of oxidative damage, such as reactive oxygen species, lipid peroxidation, lactate dehydrogenase activity, reduced glutathione, oxidized glutathione and superoxide dismutase were studied in the hippocampus. Expression levels of pro-apoptotic proteins (Bax, caspase-3) and anti-apoptotic protein (Bcl-2) of hippocampal tissues were evaluated by Western blotting. There was a significant increase in oxidative stress along with increased expression of apoptotic proteins in hypoxia exposed rats, which was significantly improved by oral Huperzine A at 0.1 mg/kg body weight. These results suggest that supplementation with Huperzine A improves cognitive deficits, reduces oxidative stress and inhibits the apoptotic cascade induced by acute hypobaric hypoxia.

CD151 promotes proliferation and migration of PC3 cells via the formation of CD151-integrin α3/α6 complex.

Over-expression of CD151 was found to be associated with metastasis and poor prognosis of prostatic carcinoma. This study was designed to examine the mechanism by which CD151 promotes the proliferation and migration of prostatic cancer cells. The pAAV-CD151, pAAV-GFP and pAAV-CD151-AAA mutant plasmids were constructed and used to transiently transfect PC3 cells (a prostatic carcinoma 3 cell line) by the mediation of Fugene HD. Then, the cells were assigned to control group, pAAV-GFP group, pAAV-CD151 group, and pAAV-CD151-AAA group respectively. Cell proliferation was evaluated by using the 3-[4,5-dimet-hylthiazol-2-yl]-2,5, diphenyltetrazolium bromide (MTT) method. Cell migration assay was performed by using Boyden chambers. The formation of CD151-integrin α3/α6 complex was determined by the method of co-immunoprecipitation. The protein expression levels of CD151 and extracellular signal-regulated kinase (ERK) were measured by Western blotting. The results showed that transfection of pAAV-CD151 or pAAV-CD151-AAA mutant increased the expression of CD151 protein in PC3 cells. Co-immunoprecipitation showed that more CD151-integrin α3/α6 complex was formed in the pAAV-CD151 group than in the control group, the pAAV-GFP group and the pAAV-CD151-AAA mutant group. Furthermore, the proliferative and migrating capacity of PC3 cells was substantially increased in the pAAV-CD151 group but inhibited in the pAAV-CD151-AAA mutant group. CD151 transfection increased the expression of phospho-ERK. Taken together, it was concluded that CD151 promotes the proliferation and migration of PC3 cells through the formation of CD151-integrin complex and the activation of phosphorylated ERK.

Aqueous extract of Polygonatum sibiricum ameliorates glucose and lipid metabolism via PI3K/AKT signaling pathway in high-fat diet and streptozotocin-induced diabetic mice.

This study was aimed to investigate the protective effects and elucidate the mechanisms of aqueous extract of Polygonatum sibiricum (PSAE) on glucolipid metabolism during the development of type 2 diabetes (T2DM). C57BL/6J mice fed with 60% high-fat diet (HFD) combined with streptozotocin (STZ) injection to simulate the occurrence process of T2DM. PSAE was administered daily by oral gavage during the experiment. The results demonstrated the protective effects in mice supplied with PSAE on the indicators of glycolipid metabolism (body weight, fasting blood glucose, the area under the curve, hemoglobin A1c, serum total cholesterol, triglyceride, low-density lipoprotein cholesterol, and liver triglyceride) compared with the Model group mice. Furthermore, PSAE can ameliorate insulin resistance in mice liver by activating phosphoinositide-3-kinase/protein kinase B (PI3K/AKT) pathway signaling. Overall, our research suggested that PSAE can effectively regulate glucose and lipid metabolism during the development of T2DM as an alternative functional food. PRACTICAL APPLICATIONS: Diabetes is a chronic metabolic disease which is characterized by abnormal metabolism of glucose and lipoid and nowadays it has been one of the most representative chronic systemic progressive metabolic diseases. Polygonatum sibiricum is a traditional Chinese galenical and it also can be used as food ingredients. PSAE is the aqueous extract of Polygonatum sibiricum. 34% polysaccharides were detected in PSAE and it can effectively regulate glucose and lipid metabolism during the development of T2DM in mice. Thus, PSAE might be a promising functional food for regulation of glucolipid metabolism and the study also provides a theoretical basis for the development and application of food about Polygonatum sibiricum.

Adeno associated viral vector-delivered and hypoxia response element-regulated CD151 expression in ischemic rat heart.

AIM: The aim of this study was to improve the delivery efficacy and target specificity of the pro-angiogenic gene CD151 to the ischemic heart. METHODS: To achieve the inducible expression of adeno-associated viral (AAV)-delivered CD151 gene in only the ischemic myocardium, we generated an AAV construct in which CD151 expression can be controlled by the hypoxia response element (HRE) sequence from the human Enolase gene. The function of this vector was examined in rat H9C2 cardiac myoblasts and in ischemic rat myocardium. The expression of CD151 in the areas of ischemic myocardium was confirmed at the mRNA level by real-time PCR and on the protein level by Western blot, whereas the CD151 expression in the microvessels within the areas of ischemic myocardium was detected by immunohistochemistry. RESULTS: HRE significantly enhances the expression of CD151 under hypoxic conditions or in the ischemic myocardium, and forced CD151 expression increases the number of microvessels in the ischemic myocardium. CONCLUSION: The AAV-mediated, HRE regulated delivery of the CD151 gene shows higher expression in the ischemic myocardium and more efficiently targets CD151 to the hypoxic regions after myocardial infarction.

Adeno-associated viral vector mediated and cardiac-specific delivery of CD151 gene in ischemic rat hearts.

Our previous studies demonstrated that CD151 gene promoted neovascularization in ischemic heart model. To improve the delivery efficacy and target specificity of CD151 gene to ischemic heart, we generated an adeno-associated virus (AAV) vector in which CD151 expression was controlled by the myosin light chain (MLC-2v) promoter to achieve the cardiac-specific expression of CD151 gene in ischemic myocardium and to limit unwanted CD151 expression in extracardiac organs. The function of this vector was examined in rat ischemic myocardium model. The protein expression of CD151 in the ischemic myocardium areas, liver and kidney was confirmed by using Western blot, while the microvessels within ischemic myocardium areas were detected by using immunohistochemistry. The results showed that MLC-2v significantly enhanced the expression of CD151 in ischemic myocardium, but attenuated its expression in other organs. The forced CD151 expression could increase the number of microvessels in the ischemic myocardium. This study demonstrates the AAV-mediated and MLC-2v regulated CD151 gene is highly expressed in the ischemic myocardium and cardiac-specific delivery that is more efficiently targets CD151 to the ischemia myocardium after myocardial infarction.

Activation of the ERK signaling pathway is involved in CD151-induced angiogenic effects on the formation of CD151-integrin complexes.

AIM: To assess the roles of extracellular signal-regulated kinase (ERK), p38, and CD151-integrin complexes on proliferation, migration, and tube formation activities of CD151-induced human umbilical vein endothelial cells (HUVECs). METHODS: CD151, anti-CD151 and CD151-AAA mutant were inserted into recombinant adeno-associated virus (rAAV) vectors and used to transfect HUVECs. After transfection, the expression of CD151 was measured. Proliferation was assessed using the 3-[4,5-dimethylthiazol- 2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay. Cell migration was evaluated in Boyden transwell chambers using FBS as the chemotactic stimulus. The tube formation assay was performed on matrigel. The potential involvement of various signaling pathways was explored using selective inhibitors. RESULTS: CD151 gene delivery increased the expression of CD151 at both the mRNA and protein levels. Overexpression of CD151 promoted cell proliferation, migration and tube formation in vitro, and phosphorylation of ERK was also increased. Further, CD151-induced cell proliferation, migration, and tube formation were attenuated by the ERK inhibitor PD98059 (20 micromol/L) but not by a p38 inhibitor (SB203580, 20 micromol/L). Moreover, there was no significant difference in CD151 protein expression between the CD151 group and the CD151-AAA group, but the CD151-AAA mutant abrogated cellular proliferation, migration, and tube formation and decreased the phosphorylation of ERK. CONCLUSION: This study suggests that activation of the ERK signaling pathway may be involved in the angiogenic effects of CD151. Activation of ERK was dependent on the formation of CD151-integrin complexes. Therefore modulation of CD151 may be as a novel therapeutic strategy for regulating angiogenesis.

Effects of transfection of ICAP-1α and its mutants on adhesion and migration of 2H-11 cells.

This study examined the effect of integrin cytoplasmic domain-associated protein 1α (ICAP-1α) and its mutatants T38A and I138A on the adhesion, migration and tube formation of 2H-11 cells. rAAV-ICAP-1α, rAAV-T38A and rAAV-I138A were constructed. After infection, the expression of ICAP-1α and p-ERK1/2, p-c-Jun protein was measured by Western blotting. Adhesion ability was evaluated by using MTT. Cell migration was determined by using Boyden chamber method. Tube formation test was conducted on Matrigel. The results showed that in ICAP-1α, T38A and I138A groups, ICAP-1α protein expression was increased. In T38A and I138A groups, phospho-ERK1/2, phospho-c-Jun protein expressions were significantly increased as compared with the control group and the GFP group. ICAP-1α group protein expression was obviously decreased when compared with the control group and the GFP group. Cell adhesion ratio was 0.1429±0.0080 in control group, 0.1434±0.0077 in GFP group and the ratio in T38A and I138A groups increased to 0.3210±0.0082 and 0.3250±0.0079, respectively. In ICAP-1α group, the ratio was decreased to 0.1005±0.0073. In T38A and I138A groups, the number of migrating 2H-11 cells was increased to 31.45±3.20 and 33.10±5.40 against 18.51±2.80 in control group and 20.47±3.12 in GFP group. In ICAP-1α group, the number was decreased to 12.06±1.72. The number of tube-like structures was increased to 20.41±2.54 in T38A and to 22.26±3.07 in I138A groups as compared to those of control group 12.45±1.84 and GFP group 13.63±2.71. In ICAP-1α group, the number of tube-like structures was decreased to 8.32±1.24. It was suggested that rAAV-T38A and rAAV-I138A transfection can substantially increase 2H-11 cell adhesion, migration and angiogenisis, while rAAV-ICAP-1α can greatly inhibit the effect. These effects might be correlated with ERK1/2 and c-Jun protein phosphorylation.

Key Role of CD151-integrin Complex in Lung Cancer Metastasis and Mechanisms Involved.

Tetraspanin CD151 was found to be upregulated in malignant cell types and has been identified as a tumor metastasis promoter. In this study, we aimed to examine the role of the CD151-integrin complex in lung cancer metastasis and the underlying mechanisms. CD151 QRD194-196 →AAA194-196 mutant was generated and used to transfect A549 human lung adenocarcinoma cells. We found that there was no significant difference in CD151 protein expression between CD151 and CD151-AAA mutant groups. In vitro, CD151-AAA mutant delivery abrogated the migration and invasion of A549 cells, which was promoted by CD151 gene transfer. Furthermore, CD151-AAA delivery failed to activate FAK and p130Cas signaling pathways. Western blot and immunohistochemical staining showed strong CD151 expression in lung cancerous tissues but not in adjacent normal tissues. Increased level of CD151 protein was observed in 20 of the patients and the positive rate of CD151 protein in specimens was 62.5% (20/32). In addition, CD151 was co-localized with α3 integrin at the cell-cell contact site in carcinoma tissues. These results suggested that the disruption of the CD151-α3 integrin complex may impair the metastasis-promoting effects and signaling events induced by CD151 in lung cancer. Our findings identified a key role for CD151-α3 integrin complex as a promoter in the lung cancer.

The relationship between fleas and small mammals in households of the Western Yunnan Province, China.

The Yunnan province has one of the most serious outbreaks of the plague epidemic in China. Small mammals and fleas are risk factors for the occurrence of plague in commensal plague foci. Understanding the relationship between fleas and small mammals will help control fleas and prevent the onset of the plague. Four hundred and twenty-one small mammals, belonging to 9 species, were captured. Of these, 170 small mammals (40.4%) were found infested with fleas. A total of 992 parasitic fleas (including 5 species) were collected. The number of Leptopsylla segnis and Xenopsylla cheopis accounted for 91.03% (903/992). The final multiple hurdle negative binomial regression model showed that when compared with Rattus tanezumi, the probability of flea infestation with Mus musculus as well as other host species decreased by 58% and 99%, respectively, while the number of flea infestations of the other host species increased by 4.71 folds. The probability of flea prevalence in adult hosts increased by 74%, while the number of fleas decreased by 76%. The number of flea infestations in small male mammals increased by 62%. The number of fleas in small mammals weighing more than 59 g has been multiplied by about 4. R. tanezumi is the predominant species in households in the west Yunnan province, while L.segnis and X. cheopis were dominant parasitic fleas. There is a strong relationship between the abundance of fleas and the characteristics of small mammals (e.g. Species, age, sex, and body weight).