Polymorphisms of TGF-ß1 and TGF-ß3 in Chinese women with gestational diabetes mellitus.

BACKGROUND: Gestational diabetes mellitus (GDM) is a pregnancy-specific carbohydrate intolerance Which can cause a large number of perinatal and postpartum complications. The members of Transforming growth factor-ß (TGF-ß) superfamily play key roles in the homeostasis of pancreatic ß-cell and may involve in the development of GDM. This study aimed to explore the association between the polymorphisms of TGF-ß1, TGF-ß3 and the risk to GDM in Chinese women. METHODS: This study included 919 GDM patients (464 with preeclampsia and 455 without preeclampsia) and 1177 healthy pregnant women. TaqMan allelic discrimination real-Time PCR was used to genotype the TGF-ß1 (rs4803455) and TGF-ß3 (rs2284792 and rs3917201), The Hardy-Weinberg equilibrium (HWE) was evaluated by chi-square test. RESULTS: An increased frequency of TGF-ß3 rs2284792 AA and AG genotype carriers was founded in GDM patients (AA vs. AG + GG: χ2 = 6.314, P = 0.012, OR = 1.270, 95%CI 1.054-1.530; AG vs. GG + AA: χ2 = 8.545, P = 0.003, OR = 0.773, 95%CI 0.650-0.919). But there were no significant differences in the distribution of TGF-ß1 rs4803455 and TGF-ß3 rs3917201 between GDM and healthy women. In addition, no significant differences were found in allele and genotype frequencies among GDM patients with preeclampsia (PE). CONCLUSIONS: The AA and AG genotype of TGF-ß3 rs2284792 polymorphism may be significantly associated with increased risk of GDM in Chinese population.

Investigation heme oxygenase-1 polymorphism with the pathogenesis of preeclampsia.

Objectives: The involvement of oxidative stress in the pathophysiology of preeclampsia (PE) has been already suggested. In this present study, we aimed to investigate the association of the genetic frequency of heme oxygense-1 (HMOX1) polymorphism with PE in Chinese Han women.Methods: We researched the genetic distribution of rs2071746 polymorphism in HMOX1 by the TaqMan allelic discrimination real-time PCR between 1235 PE patients and 1720 healthy women.Results: We found there were't significant differences in the distribution of HMOX1 rs2071746 polymorphism in PE compared to the control group (rs2071746, genotype χ2 = 0.282, P = 0.869 and allele χ2 = 0.027, P = 0.869, OR = 1.009, 95% = 0.909-1.120).Conclusion: The rs2071746 polymorphism in HMOX1 might not be related to PE in Chinese women, although further investigations should be conducted to confirm our findings.

The rs9932581 and rs1049255 Polymorphisms in CYBA is not Associated with Preeclampsia in Chinese Han Women.

BACKGROUND/AIMS: Several lines of evidence have been reported that oxidative stress plays an important role in the pathogenesis of Preeclampsia (PE). Therefore, this research is aimed to investigate whether polymorphisms of CYBA are related to susceptibility to PE in Chinese Han women. METHODS: We studied the genetic frequency of the rs9932581 and 1049255 polymorphisms in CYBA in 1029 PE patients and 1400 controls of later pregnant women by the TaqMan allelic discrimination real-time PCR and a case-control model. RESULTS: Our research indicated that no significant differences were found for the genotypic or allelic frequencies at the two polymorphic sites in CYBA between PE patients and controls. To further study the relationship between the polymorphic sites and PE, we also found that there is no significant difference in the genetic distributions identified between the mild or severe PE and early or the late-onset PE and controls. CONCLUSION: The study demonstrated that the genetic variants of rs9932581 and rs1049255 in CYBA might not be associated with PE. However, investigations of genetic variability that influence on the disease outcome are needed in other large prospective populations or regions, so the complicated interconnection of genetic and environmental elements can be emulated for better understanding.

Vitamin E highly cross-linked polyethylene reduces mid-term wear in primary total hip replacement: a meta-analysis and systematic review of randomized clinical trials using radiostereometric analysis.

Vitamin E incorporation into highly cross-linked polyethylene (HXLPE) has been introduced to improve wear resistance, and vitamin E incorporated HXLPE (VEPE) has been used in total hip arthroplasty.The aim of this meta-analysis was to investigate the wear properties of VEPE in clinical practice by synthesizing the data provided in randomized clinical trials.The effects on implant stability, functional outcomes and revision rate of VEPE were also compared with those of HXPLE or ultra-high molecular weight polyethylene (UHMWPE).Literature searches were conducted on 1 January 2020 using MEDLINE, EMBASE, Cochrane and ClinicalTrials.gov databases. Randomized controlled trials (RCTs) comparing the aforementioned parameters between VEPE and standard HXPLE/UHMWPE liners were included.Methodological quality and the bias of the included studies were analysed. Meta-analyses were performed using the Review Manager software.Nine RCTs met the eligibility criteria and were included. At early and mid-term follow-up, the vertical penetration and the total penetration of the femoral head were both significantly reduced in the VEPE group. The steady state wear rate of the VEPE group was also remarkably lower.However, at two-year follow-up, significantly increased cup migration was observed in the VEPE group. Moreover, the mid-term clinical outcomes of the VEPE group were worse, while the total revision rates between the two groups were not significantly different.The limited number of included studies may compromise our conclusion regarding clinical outcomes of the VEPE bearing surface. More RCTs with longer follow-up periods are needed to further investigate the effects of VEPE in total hip arthroplasty. Cite this article: EFORT Open Rev 2021;6:759-770. DOI: 10.1302/2058-5241.6.200072.

Fibroblast Growth Factor 2 Attenuates Renal Ischemia-Reperfusion Injury via Inhibition of Endoplasmic Reticulum Stress.

Acute kidney injury (AKI) is a serious clinical disease that is mainly caused by renal ischemia-reperfusion (I/R) injury, sepsis, and nephrotoxic drugs. The pathologic mechanism of AKI is very complex and may involve oxidative stress, inflammatory response, autophagy, apoptosis, and endoplasmic reticulum (ER) stress. The basic fibroblast growth factor (FGF2) is a canonic member of the FGF family that plays a crucial role in various cellular processes, including organ development, wound healing, and tissue regeneration. However, few studies have reported the potential therapeutic effect of FGF2 in the repair of renal ischemic injury in the past two decades. In the present study, we investigated the protective effect of FGF2 on renal I/R injury using Sprague-Dawley and NRK-52E cells. Our results showed that FGF2 significantly attenuates the apoptosis of kidney tissues after I/R injury through the inhibition of excessive ER stress. Moreover, FGF2 also alleviated the excessive ER stress and apoptosis in cultured NRK-52E cells injured by tert-Butyl hydroperoxide (TBHP). Significantly, phosphatidylinositol 3-kinase (PI3K)-selective inhibitor LY294002 and mitogen-activated protein kinase kinase (MEK)-selective inhibitor U0126 were utilized in the present study to examine the protective mechanism of FGF2. Our in vitro experimental results confirmed that both LY294002 and U0126 largely abolished the protective effect of FGF2. Taken together, the findings of the present study indicated that FGF2 attenuates I/R-induced renal epithelial apoptosis by suppressing excessive ER stress via the activation of the PI3K/AKT and MEK-ERK1/2 signaling pathways.

Effects of neoadjuvant chemotherapy on the quantitative expression of P-gp, LRP, MRP, GST-π in NSCLC and its clinical significance.

BACKGROUND: Neoadjuvant chemotherapy (NACT) plays an important role in systemic chemotherapy for non-small cell lung cancer (NSCLC). P-glycoprotein (P-gp), lung resistance related protein (LRP), multidrug resistance-associated protein (MRP) and glutathione S-transferase (GST-π) may be associated to drug resisitance to chemotherapy in NSCLC. The aim of this study is to investigate the expressions of P-gp, LRP, MRP and GST-π in samples from NSCLC patients before and after treatment with NACT, and their quantitative changes, so that to evaluate the influence of NACT on drug resistance to chemotherapy of NSCLC. METHODS: Total 92 specimens from 72 cases of NSCLC, including 52 samples of surgery excision from non-NACT-treated patients and 20 paired samples before and after NACT from the same patient, were studied. The expression of P-gp, LRP, MRP and GST-π was detected with tissue chip technique and immunohistochemistry. The quantitative analysis was carried out by computer image analysis system.. RESULTS: In the samples before NACT, the positive rate of P-gp, LRP, MRP, GST-π expression was 66.67% (48/72), 72.22% (52/72), 81.94% (59/72), 83.33% (60/72), respectively. The expressive intensity of P-gp, LRP and GST-π was significantly stronger in adenocarcinoma than that in squamous cell carcinoma (P < 0.05, P < 0.001, P < 0.001, respectively); there was no significant difference in the expression of MRP between adenocarcinoma and squamous cell carcinoma (P > 0.05). In samples after treatment with NACT, the expression of P-gp, GST-π demonstrated by average optical density (AOD) and integral optical density (IOD) were significantly higher (P < 0.05, P < 0.001 respectively) than that in biopsied samples taken before NACT; The change in expression of P-gp, GST-π was also showed difference by different histopathological types, differentiations, ages, sizes, clinical stages as well as lymph node metastasis or not (P < 0.05 or P < 0.001). There was no significant difference between samples taken before and after NACT (P > 0.05) in the expression of LRP and MRP demonstrated by both of AOD and IOD. CONCLUSIONS: The results suggest that drug resistance in adenocarcinoma is primarily stronger than that in squamous cell carcinoma. NACT may enhance acquired drug resistance of NSCLC through inducing the expression of drug resistance protein. The results indicate that acquired drug resistance must be considered with the application of NACT to NSCLC patient in clinic, especially to patient in stage I and II. Since NACT may lead to the enhancement of acquired drug resistance in stage I and II, this may dwindle the therapeutic effect of chemotherapy after surgery. Comparative examination of drug resistance proteins before and after NACT, combining with comprehensive consideration of chemical regimens of NACT, should be recommended during chemotherapy of NSCLC for both before and after surgery.

Developmental changes in the expression of voltage-gated potassium channels in the ductus arteriosus of the fetal rat.

Oxygen-sensitive, voltage-gated potassium channels (Kv) may contribute to the determination of the membrane potential in smooth muscle cells of the ductus arteriosus (DA), and thus to regulation of contractile tone in response to oxygen. Developmental changes in Kv during gestation may be related to closure of the DA after birth. This study investigated developmental changes in the expression of Kv in the DA and compared it with that of the pulmonary artery (PA) and the aorta (Ao). The DA, PA, and Ao were isolated from fetal rats at days 19 and 21 of gestation (term: 21.5 days). The expression of Kv1.2, Kv1.5, Kv2.1, and Kv3.1, putative oxygen-sensitive Kv channels that open in response to oxygen, was evaluated at both the mRNA and protein levels, using quantitative real-time polymerase chain reaction and immunohistochemistry. In the Kv family studied, Kv1.5 mRNA was expressed most abundantly in the DA, PA, and Ao in both day-19 and day-21 fetuses. Although the expression levels of Kv1.2, Kv1.5, Kv2.1, and Kv3.1 did not change much with development in the PA and Ao, in the DA they decreased with development. The decrease in the expression of Kv channels may enhance DA closure after birth by eliminating the opening of Kv channels when oxygen increases.

Analysis of voltage-gated potassium channel beta1 subunits in the porcine neonatal ductus arteriosus.

The voltage-gated potassium channels (Kv) are partially responsible for the contraction/relaxation of blood vessels in response to changes in the Po(2) level. The present study determined the expression of Kvbeta1 and four oxygen-sensitive Kvalpha subunits (Kv1.2, Kv1.5, Kv2.1, and Kv9.3) in the ductus arteriosus (DA), the aorta (Ao), and the pulmonary artery (PA) in porcine neonates immediately after birth. We cloned three Kvbeta1 transcript variants (Kvbeta1.2, Kvbeta1.3, and Kvbeta1.4), Kv1.2, Kv1.5, and Kv9.3 from piglets. Three Kvbeta1 transcripts, Kv1.2, Kv1.5, and Kv9.3, encode predicted proteins of 401, 408, 202, 499, 600, and 491 residues. These Kv showed a high degree of sequence conservation with the corresponding Kv in human. Northern and quantitative real-time PCR (qr-PCR) analyses showed that Kvbeta1.2 expression was high in the DA and Ao but low in the PA. Kv1.5 expression was high in the Ao and PA but low in the DA. Expression of Kvbeta1.3, Kvbeta1.4, Kv1.2, Kv2.1, and Kv9.3 was low in these blood vessels. The inactivation property of Kvbeta1.2 against Kv1.5 was confirmed using Xenopus laevis oocytes. Our findings suggest that the molecular basis for the differential electrophysiological characteristics including opposing response to oxygen in the DA and the PA are partially due to diversity in expression of Kv1.5 and Kvbeta1.2 subunits. The high expression of Kvbeta1.2 and relatively low expression of Kv1.5 in the DA might be partially responsible for the ductal closure after birth.