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.

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.

[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.

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 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.

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.

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.

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).

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.

Ezetimibe Protects Endothelial Cells against Oxidative Stress through Akt/GSK-3ß Pathway.

Ezetimibe was reported to pharmacologically defend against oxidative stress. This study was designed to investigate whether ezetimibe can protect against the oxidative stress induced by oxidized low-density lipoprotein (oxLDL) in vitro and the underlying mechanism. Human umbilical vein endothelial cells (HUVECs) were pretreated with ezetimibe and then exposed to oxLDL for 24 h. TUNEL assay and detectionfor the protein levels of cleaved caspase-3, Bcl-xl and Bcl-2 were employed to assess the oxLDL-induced endothelial apoptosis. Intracellular reactive oxygen species (ROS) generation was evaluated by measuring dichlorofluorescein (DCF) fluorescence. The activities of endothelial antioxidant enzymes [superoxide dismutase (SOD) and catalase] were tested via an enzymatic assay. The mitochondrial membrane potential (MMP) was monitored by flow cytometry using JC-1 staining. Phosphorylation levels of glycogen synthase kinase-3p (p-GSK-3P) and Akt (p-Akt), as well as total GSK-3p and Akt were determined by Western blotting. The results showed that ezetimibe treatment inhibited HUVECs apoptosis, intracellular ROS production, and enhanced antioxidant enzyme activities elicited by oxLDL. HUVECs exposed to oxLDL alone had reduced mitochondrial function, while ezetimibe pre-intervention could significantly rescue the MMP. Furthermore, the protein levels of p-GSK-3p and p-Akt in ezetimibe-pretreated HUVECs were markedly increased as compared with those in oxLDL-induced HUVECs. However, no significant effect on total GSK- 3P and Akt was found in ezetimibe-pretreated HUVECs. Taken together, it was concluded that ezetimibe protects against oxLDL-induced oxidative stress through restoring the MMP, which may be mediated by Akt-dependent GSK-3P phosphorylation.

Growth performance, organ-level ionic relations and organic osmoregulation of Elaeagnus angustifolia in response to salt stress.

Elaeagnus angustifolia is one of the most extensively afforested tree species in environment-harsh regions of northern China. Despite its exceptional tolerance to saline soil, the intrinsic adaptive physiology has not been revealed. In this study, we investigated the growth, organ-level ionic relations and organic osmoregulation of the seedlings hydroponically treated with 0, 100 and 200 mM NaCl for 30 days. We found that the growth characteristics and the whole-plant dry weight were not obviously stunted, but instead, were even slightly stimulated by the treatment of 100 mM NaCl. In contrast, these traits were significantly inhibited by 200 mM NaCl treatment. Interestingly, as compared with the control (0 mM NaCl), both 100 and 200 mM NaCl treatments had a promotional effect on root growth as evidenced by 26.3% and 2.4% increases in root dry weight, respectively. Roots had the highest Na+ and Cl- concentrations and obviously served as the sink for the net increased Na+ and Cl-, while, stems might maintain the capacity of effective Na+ constraint, resulting in reduced Na+ transport to the leaves. K+, Ca2+ and Mg2+ concentrations in three plant organs of NaCl-treated seedlings presented a substantial decline, eventually leading to an enormously drop of K+/Na+ ratio. As the salt concentration increased, proline and soluble protein contents continuously exhibited a prominent and a relatively tardy accumulation, respectively, whereas soluble sugar firstly fell to a significant level and then regained to a level that is close to that of the control. Taken together, our results provided quantitative measures that revealed some robust adaptive physiological mechanisms underpinning E. angustifolia's moderately high salt tolerance, and those mechanisms comprise scalable capacity for root Na+ and Cl- storage, effectively constrained transportation of Na+ from stems to leaves, root compensatory growth, as well as an immediate and prominent leaf proline accumulation.

Wide Distribution and Genetic Diversity of Babesia microti in Small Mammals from Yunnan Province, Southwestern China.

BACKGROUND: Babesia, usually found in wild and domestic mammals worldwide, have recently been responsible for emerging malaria-like zoonosis in infected patients. Human B. microti infection has been identified in China, primarily in the Southwest along the Myanmar border but little direct surveillance of B. microti infection in rodents has been carried out here (Yunnan province). In this region, a diverse topographic range combined with tropical moisture sustains a high biodiversity of small mammals, which might play important role on Babesia transmission. METHODS: Small mammals were captured in 141 sample locations from 18 counties located Yunnan Province, and screened for B. microti-like parasites infection by a nested PCR to target 18S rRNA gene of Babesia, plus directly sequencing for positive samples. Univariate and multivariate forward stepwise logistic regression analysis was used to access the association between infections and some related risk factors. RESULTS: Infection with Babesia microti was confirmed in 2.4% (53/ 2204) of small mammals. Significant differences in prevalence rates of B. microti were observed based on variations in forest, agricultural, and residential landscapes. Furthermore, adult small mammals had higher prevalence rates than younger, pubertal mammals. The near full-length 18S rRNA gene revealed that there were two types of B. microti, Kobe and Otsu, which demonstrate the genetic diversity and regional distribution. CONCLUSIONS: There exists a wide distribution and genetic diversity of endemic B. microti in Southwestern China, warranting further investigations and monitoring of clinical disease in individuals presenting with Babesia like symptoms in these areas.

Prenatal levonorgestrel exposure induces autism-like behavior in offspring through ERß suppression in the amygdala.

BACKGROUND: Autism spectrum disorder (ASD) is characterized by impairments in social communication and restricted or repetitive behaviors or interests. ASD is now diagnosed in more than one out of 100 children and is biased towards males by a ratio of at least 4:1. Many possible explanations and potential causative factors have been reported, such as genetics, sex, and environmental factors, although the detailed mechanisms of ASD remain unclear. METHODS: The dams were exposed through oral contraceptives to either vehicle control (VEH) alone, levonorgestrel (LNG) alone, ethinyl estradiol (EE) alone, or a combination of LNG/EE for 21 days during their pregnancy. The subsequent 10-week-old offspring were used for autism-like behavior testing, and the limbic tissues were isolated for analysis. In another experimental group, 8-week-old male offspring were treated by infusion of ERß overexpression/knockdown lentivirus in the amygdala, and the offspring were analyzed after 2 weeks. RESULTS: We show that prenatal exposure of either LNG alone or a LNG/EE combination, but not EE alone, results in suppression of ERß (estrogen receptor ß) and its target genes in the amygdala with autism-like behavior in male offspring, while there is a much smaller effect on female offspring. However, we find that there is no effect on the hippocampus and hypothalamus. Further investigation shows that ERß suppression is due to LNG-mediated altered methylation on the ERß promoter and results in tissue damage with oxidative stress and the dysfunction of mitochondria and fatty acid metabolism, which subsequently triggers autism-like behavior. Overexpression of ERß in the amygdala completely restores LNG-induced ERß suppression and autism-like behaviors in offspring, while ERß knockdown mimics this effect, indicating that ERß expression in the amygdala plays an important role in autism-like behavior development. CONCLUSIONS: We conclude that prenatal levonorgestrel exposure induces autism-like behavior in offspring through ERß suppression in the amygdala. To our knowledge, this is the first time the potential effect of oral contraceptives on the contribution of autism-like behavior in offspring has been discovered.

1400W ameliorates acute hypobaric hypoxia/reoxygenation-induced cognitive deficits by suppressing the induction of inducible nitric oxide synthase in rat cerebral cortex microglia.

Nitric oxide (NO) is involved in neuronal modifications, and overproduction of NO contributes to memory deficits after acute hypobaric hypoxia-reoxygenation. This study investigated the ability of the iNOS inhibitor 1400W to counteract spatial memory deficits following acute hypobaric hypoxia-reoxygenation, and to affect expression of NOS, NO, 3-NT and MDA production, and apoptosis in rat cerebral cortex. We also used primary rat microglia to investigate the effect of 1400W on expression of NOS, NO, 3-NT and MDA production, and apoptosis. Acute hypobaric hypoxia-reoxygenation impaired spatial memory, and was accompanied by activated microglia, increased iNOS expression, NO, 3-NT and MDA production, and neuronal cell apoptosis in rat cerebral cortex one day post-reoxygenation. 1400W treatment inhibited iNOS expression without affecting nNOS or eNOS. 1400W also reduced NO, 3-NT and MDA production, and prevented neuronal cell apoptosis in cerebral cortex, in addition to reversing spatial memory impairment after acute hypobaric hypoxia-reoxygenation. Hypoxia-reoxygenation activated primary microglia, and increased iNOS and nNOS expression, NO, 3-NT, and MDA production, and apoptosis. Treatment with 1400W inhibited iNOS expression without affecting nNOS, reduced NO, 3-NT and MDA production, and prevented apoptosis in primary microglia. Based on the above findings, we concluded that the highly selective iNOS inhibitor 1400W inhibited iNOS induction in microglial cells, and reduced generation of NO, thereby mitigating oxidative stress and neuronal cell apoptosis in the rat cerebral cortex, and improving the spatial memory dysfunction caused by acute hypobaric hypoxia-reoxygenation.

SIRT1-mediated ERß suppression in the endothelium contributes to vascular aging.

SIRT1 has many important molecular functions in aging, and the estrogen receptors (ERs) have a vasculoprotective effect, although the detailed mechanism for the roles of SIRT1 and ERs in vascular aging remains unclear. We found that ERß expression in the endothelium was reduced in aging mice, and the expression of ERα and SIRT1 did not change, while SIRT1 activity declined. Further investigation showed that the ERß expression was regulated by SIRT1 through complexes of SIRT1-PPARγ/RXR-p300 that bind to a PPRE (PPAR response element) site on the ERß promoter, and the declined SIRT1 function in aging mice was due to compromised phosphorylation at S154. A single-mutant SIRT1-C152(D) restored the reduced ERß expression in the endothelium with minimized reactive oxygen species generation and DNA damage and increased mitochondrial function and fatty acid metabolism. In high-fat diet aging mice, the endothelium-specific delivery of ERß or SIRT1-C152(D) on the vascular wall reduced the circulating lipids with ameliorated vascular damage, including the restored vessel tension and blood pressure. We conclude that SIRT1-mediated ERß suppression in the endothelium contributes to vascular aging, and the modulation of SIRT1 phosphorylation through a single-mutant SIRT1-C152(D) restores this effect.

ERß expression in the endothelium ameliorates ischemia/reperfusion-mediated oxidative burst and vascular injury.

Estrogen and estrogen receptors (ERs) have been reported to play protective roles in ischemia/reperfusion (I/R)-mediated injury, but the detailed mechanism remains to be fully understood. Nitric oxide (NO) and reactive oxygen species (ROS) also play important roles in the I/R process; however, due to the lack of sensitive and reproducible in vivo monitoring systems, we still do not have direct evidence for the effect of NO and ROS in vivo. In this study, we have established reliable in vivo monitoring systems to measure the variations in circulating ROS and NO during the I/R. We found that during the first few minutes of post-ischemia reperfusion, an oxidative burst occurred concurrent with a rapid loss of NO. Expression of ERß in the endothelium reduced these effects that accompanied an attenuation in myocardial infarction and vascular damage. Further investigation showed that Tie2-driven lentivirus delivery of ERß to the vascular wall in rats increased the expression of its target genes in the endothelium, including ERRα, SOD2 and eNOS. These changes modulate ROS generation, DNA damage, and mitochondrial function in rat endothelial cells. We also found that ERß expression in the endothelium reduced ROS generation and restored mitochondrial function in cardiomyocytes; this may be due to ERß-mediated NO formation and its high diffusibility to cardiomyocytes. We conclude that ERß expression in the endothelium ameliorates ischemia/reperfusion-mediated oxidative burst and vascular injury.

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.

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.

[Factors related to household rodent abundance in rodent-borne disease foci in western Yunnan].

OBJECTIVE: To analyze the factors related to the household abundance of rodents in rodent-borne disease foci in the western part of Yunnan province. METHODS: From July 2011 to October 2012, 800 households (20 households in 1 village) were randomly selected in 40 natural villages of 10 counties in western Yunnan where rodent borne disease was endemic to conduct a study on relationship between rodent abundance and environmental factors. Five cages were placed in each household for 3 consecutive nights to capture rodents. The rodent species were identified based on their morphological characteristics. The data on potential factors related to rodent abundance were collected through questionnaires and field observation. A dataset was established by using EpiData software and the analysis was performed with hurdle regression model under R software. RESULTS: A total of 421 rodents were captured in 800 households, belonging to 9 species, 6 genera, 2 families, 2 orders. Rattus tanezumi was the predominant species (66.03%). The final hurdle regression model showed that the probability of capturing rodents in the households where family member had high education level and the garbage was placed outside declined by 50%-68% ;The probability of capturing rodents in the households of Dai and Yi ethnic groups increased by 2.16-2.87 times;The probability of capturing rodents in the households where rodents were observed or vegetables grown near houses increased by 1.54-1.59 times;In the households where many rodents were believed to exist, the probability of capturing rodents and the number of rodents captured increased by 1.59 and 1.84 times respectively. The number of rodents captured in the houses with cement or tile floor increased by 3.62 times. CONCLUSION: The household abundance of rodents in the area in western Yunnan, where the rodent-borne disease survey was conducted, seemed to be closely related to the social economy status, human intervention and ecological environment. To control the abundance of rodents effectively, it is necessary to take these factors into consideration.