The published data on the association between MCP-1 -2518A>G polymorphism and asthma susceptibility are inconclusive. Therefore, we performed a meta-analysis to estimate the impact of MCP-1 -2518A>G polymorphism on asthma susceptibility. PubMed, Web of Science, Wanfang, and China National Knowledge Infrastructure (CNKI) databases were used to identify eligible studies. The pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to calculate the strength of association. Sensitivity analysis was performed to evaluate the influence of individual studies on the estimates of overall effect, and funnel plots and Egger's test were used to assess publication bias. Eight publications with 1562 asthma patients and 1574 controls were finally identified. Overall, we found no significant association between MCP-1 -2518A>G polymorphism and asthma susceptibility in any of the genetic model comparisons. After stratified analysis by ethnicity, the results showed that a significant association with asthma risk was found in Caucasians in all the genetic models. However, a protective association was found in Africans under the dominant model. The present meta-analysis suggested that the MCP-1 -2518 A>G polymorphism is a risk factor for asthma in the Caucasian population, nevertheless it has a protective effect in the African population.

Although Taxol has improved the survival of cancer patients as a first-line chemotherapeutic agent, an increasing number of patients develop resistance to Taxol after prolonged treatment. The potential mechanisms of cancer cell resistance to Taxol are not completely clear. It has been reported that microRNAs (miRNAs) are involved in regulating the sensitivity of cancer cells to various chemotherapeutic agents. In this study, we aimed to explore the role of miR-129-5p in regulating the sensitivity of breast cancer cells to Taxol. Cell apoptosis and autophagy, and the sensitivity of MCF-7 cells to Taxol were assessed with a series of in vitro assays. Our results showed that the inhibition of autophagy increased the Taxol-induced apoptosis and the sensitivity of MCF-7 cells to Taxol. Up-regulation of miR-129-5p also inhibited autophagy and induced apoptosis. Furthermore, miR-129-5p overexpression increased the sensitivity of MCF-7 cells to Taxol. High mobility group box 1 (HMGB1), a target gene of miR-129-5p and a regulator of autophagy, was negatively regulated by miR-129-5p. We found that interference of HMGB1 enhanced the chemosensitivity of Taxol by inhibiting autophagy and inducing apoptosis in MCF-7 cells. Taken together, our findings suggested that miR-129-5p increased the chemosensitivity of MCF-7 cells to Taxol through suppressing autophagy and enhancing apoptosis by inhibiting HMGB1. Using miR-129-5p/HMGB1/autophagy-based therapeutic strategies may be a potential treatment for overcoming Taxol resistance in breast cancer.

To investigate the epidemiological data of hypertension in pregnant women, as well as to identify its possible associated events.

to synthesize the knowledge about the association of frailty syndrome and cognitive impairment in older adults.

To compare the amount of ultrasound energy and irrigation volume in conventional phacoemulsification cataract surgery versus femtosecond laser-assisted phacoemulsification at different nuclear-cortical cataract grades.

Microvesicles (MVs) were involved in the pathogenesis of many diseases, such as cardiovascular diseases and diabetes. Oxidative stress played a key role in the development and progression of diabetic nephropathy (DN). Our aim of the present study was to investigate whether high glucose (HG) could provoke MVs generation from podocytes and its potential mechanism. Mouse podocyte clone 5 (MPC-5) was stimulated by HG. The intracellular reactive oxygen species (ROS) of podocytes were measured by fluorescence microscopy with the probe of CM-H2DCFDA and MitoSOX™. Antioxidants N-Acetyl-l-cysteine (NAC) and α lipoic acid (α-LA) were used to treat podocytes after HG stimulation. The rate of podocyte apoptosis was evaluated with Annexin V-FITC by flow cytometry. NOX4 expression was examined and siRNA were performed to explore the mechanism of MVs generation. The quantities of MVs from MPC-5 cells was significantly increased (P<0.05) by 4.6-times after 30 mM glucose stimulation, accompanied with double increased apoptosis. Cellular ROS generation was increased by HG at the peak of 48 h stimulation. HG-induced MVs were significantly decreased by 52.9% after pretreatment by antioxidant NAC. Nevertheless, mitochondrial ROS in podocytes reached a peak at 4 h stimulation, but specific antioxidant α-LA had no effect on the production of MVs (P>0.05). Levels of NOX4 mRNA and protein expression were significantly up-regulated by HG (P<0.05). Podocyte-derived MVs by HG were eliminated by NOX4 siRNA. HG can provoke MVs generation from glomerular podocytes through ROS/NOX4 pathway, not from mitochondrial pathway.

Bartter and Gitelman syndromes are rare inherited tubulopathies characterized by hypokalaemic, hypochloraemic metabolic alkalosis. They are caused by mutations in at least 7 genes involved in the reabsorption of sodium in the thick ascending limb (TAL) of the loop of Henle and/or the distal convoluted tubule (DCT). Different subtypes can be distinguished and various classifications have been proposed based on clinical symptoms and/or the underlying genetic cause. Yet, the clinical phenotype can show remarkable variability, leading to potential divergences between classifications. These problems mostly relate to uncertainties over the role of the basolateral chloride exit channel CLCNKB, expressed in both TAL and DCT and to what degree the closely related paralogue CLCNKA can compensate for the loss of CLCNKB function. Here, we review what is known about the physiology of the transport proteins involved in these disorders. We also review the various proposed classifications and explain why a gene-based classification constitutes a pragmatic solution.

Advanced age is associated with increased mortality in acute respiratory distress syndrome (ARDS) patients. Preclinical studies suggest that the host response to an injurious challenge is age-dependent. In ARDS patients, we investigated whether the association between age and mortality is mediated through age-related differences in the host response.

Norovirus is commonly associated with food and waterborne outbreaks. Genetic susceptibility to norovirus is largely dependent on presence of histo-blood group antigens (HBGA), specifically ABO, secretor, and Lewis phenotypes. The aim of the study was to determine the association between HBGAs to norovirus susceptibility during a large norovirus foodborne outbreak linked to genotype GII.6 in an office-based company in Stockholm, Sweden, 2015. A two-episode outbreak with symptoms of diarrhea and vomiting occurred in 2015. An online questionnaire was sent to all 1109 employees that had worked during the first outbreak episode. Food and water samples were collected from in-house restaurant and tested for bacterial and viral pathogens. In addition, fecal samples were collected from 8 employees that had diarrhea. To investigate genetic susceptibility during the outbreak, 98 saliva samples were analyzed for ABO, secretor, and Lewis phenotypes using ELISA. A total of 542 of 1109 (49%) employees reported gastrointestinal symptoms. All 8 fecal samples tested positive for GII norovirus, which was also detected in coleslaw collected from the in-house restaurant. Eating at the in-house restaurant was significantly associated with risk of symptom development. Nucleotide sequencing was successful for 5/8 fecal samples and all belonged to the GII.6 genotype. HBGA characterization showed a strong secretor association to norovirus-related symptoms (P = 0.014). No association between norovirus disease and ABO phenotypes was observed. The result of this study shows that non-secretors were significantly less likely to report symptoms in a large foodborne outbreak linked to the emerging GII.6 norovirus strain.

The purpose of this study was to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of BOS161721, a humanized immunoglobulin G1 triple mutation (M252Y/S254T/T256E) monoclonal antibody that inhibits interleukin-21 (IL-21) bioactivity. This randomized, single-center, double-blind, placebo-controlled study randomized healthy volunteers 3:1 to single ascending intravenous and subcutaneous doses of BOS161721 (range 1-240 mg) or placebo. BOS161721 and placebo groups had similar rates of adverse events, mostly mild; none led to study discontinuation. There were no clinically significant findings in physical examination, vital signs, or laboratory assessment. In the pooled BOS161721 population, four subjects (8.5%) tested antidrug antibody-positive predose, and seven (14.9%) postdose. Absolute CD4+ lymphocyte count remained normal throughout follow-up. BOS161721 administered subcutaneously was absorbed slowly, with a median time to maximum concentration (Tmax ) of 144 hours across doses (range 1-15 days) and a mean apparent terminal elimination half-life of 80-87 days for doses ≥ 30 mg. Area under the concentration-time curve from time zero to infinity (AUC0-inf ) and maximum observed concentration (Cmax ) were linear across doses > 10 mg. Subcutaneous bioavailability was 64%. Phosphorylated signal transducer and activator of transcription 3 (pSTAT3) decreased dose-dependently with threshold characteristics at doses of ≥ 10 mg. Downregulation in BATF, IL6, LAG3, and SOCS3 genes caused by IL-21 stimulation was reversed dose-dependently. BOS161721 was well-tolerated across doses, suppressed IL-21-induced pSTAT3 dose-dependently, and reversed downregulation of genes critical to tolerance induction and T-cell exhaustion induced by IL-21. Further clinical studies are ongoing in patients with systemic lupus erythematosus, in which IL-21 has a pathogenetic role.

White root rot (WRR) disease caused by Rosellinia necatrix is one of the most important threats affecting avocado orchards in temperate regions. The eradication of WRR is a difficult task and environmentally friendly control methods are needed to lessen its impact. Priming plants with a stressor (biotic or abiotic) can be a strategy to enhance plant defense/tolerance against future stress episodes but, despite the known underlying common mechanisms, few studies use abiotic-priming for improving tolerance to forthcoming biotic-stress and vice versa ('cross-factor priming'). To assess whether cross-factor priming can be a potential method for enhancing avocado tolerance to WRR disease, 'Dusa' avocado rootstocks, susceptible to R. necatrix, were subjected to two levels of water stress (mild-WS and severe-WS) and, after drought-recovery, inoculated with R. necatrix. Physiological response and expression of plant defense related genes after drought-priming as well as the disease progression were evaluated.

Artificial mutagenesis not only provides a new approach to increase the diversity of desirable traits for breeding new varieties but are also beneficial for characterizing the genetic basis of functional genes. In recent decades, many mutation genes have been identified which are responsible for phenotype changes in mutants in various species including Arabidopsis and rice. However, the mutation feature in induced mutants and the underlying mechanisms of various types of artificial mutagenesis remain unclear.

Some Gynura species have been reported to be natural anti-diabetic plants. Improvement of their traits towards application relies on hybridization. Clearly, phylogenetic relationships could optimize compatible hybridizations. For flowerings plants, chloroplast genomes have been used to solve many phylogenetic relationships. To date, the chloroplast genome sequences of 4 genera of the tribe Senecioneae have been uploaded to GenBank. The internal relationships within the genus Gynura and the relationship of the genus Gynura with other genera in the tribe Senecioneae need further research.

Migrants often face barriers to accessing healthcare. We examined disparities in access to and use of HIV-related health services between migrant and non-migrant people recently diagnosed with HIV living in the Netherlands, taken into account sexual orientation. Also, we examined differences in experiences in living with HIV between these groups.

Limb-girdle muscular dystrophies (LGMDs) are large group of heterogeneous genetic diseases, having a hallmark feature of muscle weakness. Pathogenic mutations in the gene encoding the giant skeletal muscle protein titin (TTN) are associated with several muscle disorders, including cardiomyopathy, recessive congenital myopathies and limb-girdle muscular dystrophy (LGMD) type10. The phenotypic spectrum of titinopathies is expanding, as next generation sequencing (NGS) technology makes screening of this large gene possible.

Sexually transmitted infections (STIs) is a global health problem with increased risk and morbidities during pregnancy. This study investigated the magnitude of viral STIs among pregnant women from three rural hospitals/clinics providing antenatal care in Mwanza region, Tanzania.

Neuroblastoma (NB) is a frequent pediatric tumor associated with poor prognosis. The disregulation of Bcl-2, an anti-apoptotic protein, is crucial for the tumoral development and chemoresistance. Autophagy is also implicated in tumor cell survival and chemoresistance. The aim of our study was to demonstrate therapeutic efficiency of GX 15-070, a pan-Bcl-2 family inhibitor, used alone and in combination with conventional drugs or with hydroxychloroquine (HCQ), an autophagy inhibitor.

Several studies have investigated motor and cognitive skills in infants as well as gross motor abilities in schoolchildren treated for congenital idiopathic clubfoot, mostly indicating specific impairments in those children. However, until now, little is known about the motor and cognitive abilities of preschool children treated for idiopathic clubfoot. Thus, it was the aim of this study to examine gross motor, fine motor and cognitive skills of 3-year-old-children treated for idiopathic clubfoot.

The Woman's Condom, a newly designed condom for women, has obtained market approval in China, but it remains relatively unfamiliar to the migrant population. The aim of this study is to evaluate the short-term acceptability of the Woman's Condom and influencing factors among internal migrants.

Uganda is among the 51 countries where cholera outbreaks are common with epidemics occurring predominantly along the western border with Democratic Republic of Congo (DRC), Kampala city slums, Busia district which is a border town with Western Kenya, Mbale district and the Karamoja Sub-region. This report summarizes findings from the epidemiologic investigation, which aimed at identifying the mode of transmission and antibiotic susceptibility patterns of the Vibrio cholerae isolated in Kasese district, Uganda.