Renalase gene polymorphisms and plasma levels are associated with preeclampsia: a hospital-based study in the Chinese cohort.

Preeclampsia (PE) is one of the major contributors to maternal and fetal mortality worldwide. Many host-related biomolecules regulate the pathophysiology of PE. The current study aims to examine the role of the renalase in PE manifestations. A total of 384 Chinese women consisting of subjects with normotensive pregnancy (n = 105), women with PE (n = 121), and healthy women (n = 158) were included in the study. Serum renalase level was measured in all subjects by ELISA. Renalase gene polymorphisms (rs10887800, rs2576178, and rs2296545) were genotyped by PCR-RFLP. The pregnant women had elevated renalase levels compared to healthy controls and subjects with PE. Renalase level was negatively correlated with systolic and diastolic blood pressure. Interestingly, renalase was positively correlated with the glomerular filtration rate. Prevalence of homozygous mutant (GG) and minor allele (G) for rs10887800 and rs2576178 renalase gene polymorphisms were significantly higher in PE patients compared to normotensive pregnant women and healthy controls. Furthermore, an association of G-G-C haplotype with susceptibility to PE was also noticed. A low level of renalase may be associated with an increased risk of PE during pregnancy. Renalase gene polymorphisms (rs10887800 and rs2576178) are correlated with serum renalase and are associated with predisposition to PE development in the Chinese cohort.

Panax notoginseng preparations as adjuvant therapy for diabetic kidney disease: a systematic review and meta-analysis.

Context: Panax notoginseng (Burk.) F.H. Chen (Araliaceae) preparations (PNP) are traditional Chinese medicines used as adjuvant therapeutics for diabetic kidney disease (DKD).Objective: To systematically review the efficacy of PNP as adjunct DKD therapy, including their effects on kidney function, serum lipid levels and fasting blood glucose levels.Methods: The databases PubMed, Embase, Medline, Cochrane Library, CINAHL, China Biology Medicine disc, Wanfang, VIP and China National Knowledge Infrastructure were systematically searched from the date of their inception until May 2019. Panax notoginseng, Panax notoginseng saponins, Lulutong, Xueshuantong and Xuesaitong were the key terms searched. Randomized controlled trials (RCTs) comparing the combined use of PNP and conventional medicines (CM) versus CM for DKD were included. Data were pooled using random or fixed effect models depending on heterogeneity.Results: In total, 24 RCTs involving 1918 participants were analysed. Adjunct PNP with CM was associated with reduction of albuminuria (MD -26.89 mg, 95% CI: -33.35 to -20.42), proteinuria (MD -0.32 g/24 h, 95% CI: -0.36 to -0.27), serum creatinine (MD -4.52 µmol/L, 95% CI: -8.71 to -0.32), total cholesterol (MD -1.56 mmol/L, 95% CI: -2.33 to -0.78), triglycerides (TG) (MD -0.56 mmol/L, 95% CI: -0.80 to -0.31) and low-density lipoprotein cholesterol (MD -0.94 mmol/L, 95% CI: -1.49 to -0.40) compared with CM.Conclusions: This is the first meta-analysis investigating adjuvant PNP therapy for DKD. PNP apparently exerted beneficial effects on kidney function and improved the metabolism of serum lipids by CM. Further, well-conducted, high-quality trials on DKD patients are needed to provide high-quality evidence.

New insights into the function and mechanisms of piRNA PMLCPIR in promoting PM2.5-induced lung cancer.

INTRODUCTION: Extensive studies have established the correlation between long-term PM2.5 exposure and lung cancer, yet the mechanisms underlying this association remain poorly understood. PIWI-interacting RNAs (piRNAs), a novel category of small non-coding RNAs, serve important roles in various diseases. However, their biological function and mechanism in PM2.5-induced lung cancer have not been thoroughly investigated. OBJECTIVES: We aimed to explore the oncogenic role of piRNA in lung cancer induced by PM2.5 exposure, as well as the underlying mechanisms. METHODS: We conducted a PM2.5-induced human lung epithelial cell malignant transformation model. Human samples were used to further verify the finding. In vitro proliferation, migration, and invasion assays were performed to study the function of piRNA. RNA-sequencing was used to elucidate the the mechanisms of how piRNA mediates cell functions. PiRNA pull-down and computational docking analysis were conducted to identify proteins that binding to piRNA. In vivo experiments were used to explore whether inhibition of PMLCPIR could have a therapeutic effect on lung cancer. RESULTS: We identified a new up-regulated piRNA, termed PM2.5-induced lung cancer up-regulation piRNA (PMLCPIR), which promotes the proliferation of PM2.5-transformed cells and lung cancer cells. RNA sequencing revealed ITGB1 as a downstream target of PMLCPIR. Importantly, PMLCPIR binds to nucleolin (NCL) and increases the expression of its target gene, ITGB1, thereby activating PI3K/AKT signaling. The inhibition of PMLCPIR could promote apoptosis in lung cancer cells and enhance their chemosensitivity to anti-tumor drugs. CONCLUSION: We systematically identified the alterations of piRNA expression profiles in the PM2.5-induced malignant transformation model. Then, PMLCPIR was recognized as a novel oncogenic piRNA in PM2.5-induced lung cancer. Mechanically, PMLCPIR binds to NCL, enhancing ITGB1 expression and activating the ontogenetic PI3K/AKT signaling, potentially contributing to lung cancer progression. This study provides novel insights into the revelation of a new epigenetic regulator in PM2.5-induced lung cancer.

Carbapenems versus alternative ß-lactams monotherapy or in combination for febrile neutropenia: Systematic review and meta-analysis of randomized controlled trial.

BACKGROUND: Febrile neutropenia (FN) in cancer patients can be life threatening and require the timely antimicrobial agents treatment. METHODS: To compare the effectiveness and safety of carbapenems versus ß-lactams for FN. PubMed, Medline (Ovid SP), Cochrane CENTRAL, and Embase were searched up to March 2019. FN in patients due to undergoing chemotherapy and treated with carbapenems and ß-lactams were included. Odds ratio (OR) and 95% confidence interval (CI) were estimated. RESULTS: Fifty randomized controlled trials (RCTs) studies involving 10,995 participants were included. Carbapenems were more likely to experience treatment success without modification (OR = 1.34, 95% CI = 1.24-1.46) compared with ß-lactams. Meropenem (OR = 1.36, 95% CI = 1.18-1.56; OR = 1.24, 95% CI = 1.01-1.53), imipenem/cilastatin (OR = 1.40, 95% CI = 1.19-1.65; OR = 1.31, 95% CI = 1.04-1.67) showed higher effectiveness from that by ß-lactams monotherapy or in combination with aminoglycoside, respectively. Carbapenems-aminoglycoside combination therapy does not provide an advantage over carbapenems alone. Meropenem showed similar risk of adverse events (AEs) versus ß-lactams. Imipenem/cilastatin was related to higher risk of AEs compared with ß-lactams. There was no significant difference between carbapenems and ß-lactams monotherapy or in combination. CONCLUSION: Meropenem and imipenem/cilastatin monotherapy appears to be available treatment for FN compared with ß-lactams. Imipenem/cilastatin was related to higher risk of AEs. Balancing the evidence for drug efficacy and side effects, meropenem monotherapy appears to be available treatment for FN. Individual centers should select the best matching therapy regimens according to local epidemiology and susceptibility patterns.

Carbapenems vs alternative antibiotics for the treatment of complicated urinary tract infection: A systematic review and network meta-analysis.

BACKGROUND: Complicated urinary tract infections (cUTI) are universal reasons for hospitalization, and highly likely to develop into sepsis or septic shock. Carbapenem antibiotics with potentially higher efficacy or with fewer and milder side effects have increased in popularity, but evidence is limited by a scarcity of randomized controlled trials (RCTs) comparing different carbapenem antibiotics for cUTI. Network meta-analysis is a useful tool to compare multiple treatments when there is limited or no direct evidence available. OBJECTIVE: The aim of this study is to compare the efficacy and safety of different carbapenems with alternative antibiotics for the treatment of cUTI. METHODS: Pubmed, Medline, CENTRAL, and Embase were searched in November 2018. Studies of cUTI patients receiving carbapenem were included. We performed network meta-analysis to estimate the risk ratio (RR) and 95% credible interval (CrI) from both direct and indirect evidence; traditional meta-analysis was also performed. Primary outcomes were clinical and microbiological treatment success. RESULTS: A total of 19 studies and 7380 patients were included in the analysis. Doripenem (DOPM) was associated with lower clinical treatment success rates than other carbapenems. Although the efficacy of other carbapenems by RRs with 95% CrIs did not show statistical differences, the cumulative rank probability indicated that meropenem/vaborbactam (MV), ertapenem (ETPM), and biapenem (BAPM) had higher clinical and microbiological treatment success rates; imipenem/cilastatin (IC) and MV showed higher risk of adverse events (AEs). CONCLUSIONS: MV was associated with higher treatment success rates for cUTI, especially for cUTI caused by carbapenem-resistant uropathogens, but also with higher risk of AEs. Our findings suggest MV as a first-choice treatment of carbapenem-resistant cUTI. ETPM, BAPM, and meropenem (MEPM) is another reasonable choice for cUTI empiric therapy.

Carbapenems vs tigecycline for the treatment of complicated intra-abdominal infections: A Bayesian network meta-analysis of randomized clinical trials.

BACKGROUND: Complicated intra-abdominal infections (cIAIs) are common in clinical practice, caused by a mixture of aerobic and anaerobic bacteria, increase the risk of mortality. Carbapenems and tigecycline (TGC) are recommended for antimicrobial therapies for cIAIs. OBJECTIVE: To compare the effectiveness and safety of different carbapenems vs TGC for the treatment of cIAIs. METHODS: PubMed, Embase, Medline (via Ovid SP) and Cochrane library databases were systematically searched. We included randomized controlled trials (RCTs) comparing different carbapenems vs TGC for the treatment of cIAIs. The pooled odds ratio (OR) with 95% credible interval (CrI) was calculated by Markov chain Monte Carlo methods. We estimated summary ORs using pairwise and network meta-analysis with random effects. RESULTS: Fifteen studies involving 6745 participants were included in the analysis. Five different carbapenems and TGC were ultimately evaluated in this study. Although, the efficacy of carbapenems and TGC by ORs with corresponding 95% CrIs had not yet reached statistical differences, the cumulative rank probability indicated that clinical treatment success from best to worst was doripenem (DOPM), meropenem (MEPM), imipenem/cilastatin (IC), biapenem (BAPM), TGC and imipenem/cilastatin/relebactam (ICRB); microbiological treatment success from best to worst was DOPM, MEPM, IC, BAPM, ICRB and TGC. As for the risk of adverse events (AEs), TGC showed higher risk of AEs compared with IC (OR = 1.53, 95% CrI = 1.02-2.41), the remain antibiotic agents from lower to higher was MEPM, IC, BAPM, DOPM, ICRB and TGC. The risk of mortality from lower to higher was BAPM, DOPM, MEPM, IC, TGC and ICRB. CONCLUSION: No differences in clinical and microbiological outcomes were observed between different carbapenems and TGC. Balancing the evidence for drug efficacy and side effects, DOPM appears to be the best available treatment for cIAIs. Therefore, it is reasonable to consider that DOPM is one of the best carbapenem monotherapy for cIAIs. MEPM and IC was also associated with higher rates of clinical and microbiological treatment success following DOPM. Empiric antimicrobial treatment of patients with cIAIs should be selected in light of the local bacterial epidemiology and patterns of resistance.

Carbapenems vs ß-Lactam Monotherapy or Combination Therapy for the Treatment of Complicated Intra-abdominal Infections: Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Complicated intra-abdominal infections (cIAIs) result in significant morbidity, mortality, and cost. Carbapenem-resistant sepsis has increased dramatically in the last decade, resulting in infections that are difficult to treat and associated with high mortality rates. To prevent further antibacterial resistance, it is necessary to use carbapenem selectively. The objective of this study was to compare the effectiveness and safety of carbapenems vs alternative ß-lactam monotherapy or combination therapy for the treatment of cIAIs. METHODS: The PubMed, Embase, Medline (via Ovid SP), and Cochrane library databases were systematically searched. We included randomized controlled trials (RCTs) comparing carbapenems vs alternative ß-lactam monotherapy or combination therapy for the treatment of cIAIs. RESULTS: Twenty-two studies involving 7720 participants were included in the analysis. There were no differences in clinical treatment success (odds ratio [OR], 0.86; 95% confidence interval [CI], 0.71-1.05; I 2 = 35%), microbiological treatment success (OR, 0.88; 95% CI, 0.71-1.09; I 2 = 25%), adverse events (OR, 0.98; 95% CI, 0.87-1.09; I 2 = 17%), or mortality (OR, 0.96; 95% CI, 0.68-1.35; I 2 = 7%). Patients.treated with imipenem were more likely to experience clinical or microbiological failure than those treated with alternative ß-lactam monotherapy or combination therapy. CONCLUSIONS: No differences in clinical outcomes were observed between carbapenems and noncarbapenem ß-lactams in cIAIs. Patients treated with imipenem were more likely to experience clinical or microbiological failure than those treated with alternative ß-lactam monotherapy or combination therapy.

Characterization of SMAD3 Gene Variants for Possible Roles in Ventricular Septal Defects and Other Congenital Heart Diseases.

BACKGROUND: Nodal/TGF signaling pathway has an important effect at early stages of differentiation of human embryonic stem cells in directing them to develop into different embryonic lineages. SMAD3 is a key intracellular messenger regulating factor in the Nodal/TGF signaling pathway, playing important roles in embryonic and, particularly, cardiovascular system development. The aim of this work was to find evidence on whether SMAD3 variations might be associated with ventricular septal defects (VSD) or other congenital heart diseases (CHD). METHODS: We sequenced the SMAD3 gene for 372 Chinese Han CHD patients including 176 VSD patients and evaluated SNP rs2289263, which is located before the 5'UTR sequence of the gene. The statistical analyses were conducted using Chi-Square Tests as implemented in SPSS (version 13.0). The Hardy-Weinberg equilibrium test of the population was carried out using the online software OEGE. RESULTS: Three heterozygous variants in SMAD3 gene, rs2289263, rs35874463 and rs17228212, were identified. Statistical analyses showed that the rs2289263 variant located before the 5'UTR sequence of SMAD3 gene was associated with the risk of VSD (P value=0.013 <0.05). CONCLUSIONS: The SNP rs2289263 in the SMAD3 gene is associated with VSD in Chinese Han populations.

Bacterial communities in pigmented biofilms formed on the sandstone bas-relief walls of the Bayon Temple, Angkor Thom, Cambodia.

The Bayon temple in Angkor Thom, Cambodia has shown serious deterioration and is subject to the formation of various pigmented biofilms. Because biofilms are damaging the bas-reliefs, low reliefs engraved on the surface of sandstone, information about the microbial community within them is indispensable to control biofilm colonization. PCR-denaturing gradient gel electrophoresis (DGGE) analysis of biofilm samples from the pigmented sandstone surfaces showed that the bacterial community members in the biofilms differed clearly from those in the air and had low sequence similarity to database sequences. Non-destructive sampling of biofilm revealed novel bacterial groups of predominantly Rubrobacter in salmon pink biofilm, Cyanobacteria in chrome green biofilm, Cyanobacteria and Chloroflexi in signal violet biofilm, Chloroflexi in black gray biofilm, and Deinococcus-Thermus, Cyanobacteria, and Rubrobacter in blue green biofilm. Serial peeling-off of a thick biofilm by layers with adhesive sheets revealed a stratified structure: the blue-green biofilm, around which there was serious deterioration, was very rich in Cyanobacteria near the surface and Chloroflexi in deep layer below. Nitrate ion concentrations were high in the blue-green biofilm. The characteristic distribution of bacteria at different biofilm depths provides valuable information on not only the biofilm formation process but also the sandstone weathering process in the tropics.

Enumeration of sulfur-oxidizing microorganisms on deteriorating stone of the angkor monuments, Cambodia.

Annual change in the density of sulfur-oxidizing microorganisms on sandstone was enumerated to know the effects on the deterioration of stone materials of the Angkor monuments in Cambodia. Samples were obtained from total 12 stations at the Angkor Wat, Bayon, and Phnom Krom temples between 1998 and 2007. Sulfur-oxidizing microorganisms enumerated in a mineral salts medium supplemented with elemental sulfur as the sole energy source had a density of 10(1)-10(5) MPN (g sample)(-1). The sulfur-oxidizing microorganisms of the samples collected at Angkor Wat have tended to decrease in density since 2002; on the other hand, relatively constant values have been recorded in the samples of Bayon and Phnom Krom. These results suggest that the sulfur-oxidizing microorganisms on the stone play an important role in the decay of the building blocks by excreting sulfuric acid.