Effect of Sodium–Glucose Cotransporter 2 Inhibitors on Diabetic Ketoacidosis Among Patients With Type 2 Diabetes: A Meta-analysis of Randomized Controlled Trials

SCI(E)[email protected]

Pharmacokinetic studies and anticancer activity of curcumin-loaded nanostructured lipid carriers

In order to investigate the potential of nanostructured lipid carriers for efficient and targeted delivery of curcumin, the pharmacokinetic parameters of curcumin-loaded nanostructured lipid carriers (Cur-NLC) were evaluated in rats after a single intraperitoneal dose of Cur-NLC. In addition, the anticancer activity of Cur-NLC against human lung adenocarcinoma A549 cells was verified by a cellular uptake study, and a cytotoxicity and apoptosis assay. Bioavailability of Cur-NLC was better than that of native curcumin (p > 0.01), as seen from the area under the plasma concentration-time curve (AUC), maximum plasma concentration (Cmax), mean residence time (MRT) and total plasma clearance (CLz/F). Cur-NLC has a more obvious lung-targeting property in comparison with native curcumin. Cur-NLC showed higher anticancer activity in vitro against A549 cells than native curcumin (IC50 value of 5.66 vs. 9.81 mg L–1, respectively). Meanwhile, Cur-NLC treated A549 cells showed a higher apoptosis rate compared to that of native curcumin. These results indicate that NLC is a promising system for the delivery of curcumin in the treatment of lung adenocarcinoma

Curcumin-loaded nanostructured lipid carrier induced apoptosis in human HepG2 cells through activation of DR5/caspases-mediated extrinsic apoptosis pathway

Curcumin is a lipophilic anti-cancer compound extracted from turmeric. Our previous study demonstrated that the curcumin-loaded nanostructured lipid carrier (Cur-NLC) exhibits superior anti-cancer activity in inhibiting proliferation as well as inducing apoptosis of human HepG2 cells compared to native curcumin. This study aims to unveil the mechanisms underlying the pro-apoptotic effect of Cur-NLC on HepG2 cells. Evidence indicates that low expression of death receptors (DRs) on cancer cell membranes leads to attenuated apoptosis signaling. This study showed that Cur-NLC significantly increased total expression of DR5 protein while simultaneously upregulated cell membrane expression of DR5. Cur-NLC significantly increased caspase-8 and caspase-3 activities, accompanied by increased apoptosis. Furthermore, enhanced apoptosis was inhibited in the presence of a pan-caspase inhibitor, Z-VAD-FMK. Therefore, Cur-NLC induced activation of the extrinsic apoptosis pathway via modulating the DR5/caspase-8/-3 mediated apoptosis pathway in HepG2 cells, suggesting that Cur-NLC is a promising therapeutic agent or supplement for the treatment of hepatocellular carcinoma

Sodium-glucose co-transporter-2 inhibitors and risk of adverse renal outcomes among patients with type 2 diabetes: A network and cumulative meta-analysis of randomized controlled trials

Aim To compare the associations of individual sodium-glucose co-transporter-2 (SGLT2) inhibitors with adverse renal outcomes in patients with type 2 diabetes mellitus (T2DM). Methods PubMed, EMBASE, CENTRAL and ClinicalTrials.gov were searched for studies published up to May 24, 2016, without language or date restrictions. Randomized trials that reported at least 1 renal-related adverse outcome in patients with T2DM treated with SGLT2 inhibitors were included. Pairwise and network meta-analyses were carried out to calculate the odds ratios (ORs) with 95% confidence intervals (CIs), and a cumulative meta-analysis was performed to assess the robustness of evidence. Results In total, we extracted 1334 composite renal events among 39 741 patients from 58 trials, and 511 acute renal impairment/failure events among 36 716 patients from 53 trials. Dapagliflozin was significantly associated with a greater risk of composite renal events than placebo (OR 1.64, 95% CI 1.26-2.13). Empagliflozin seemed to confer a lower risk than placebo (OR 0.63, 95% CI 0.54-0.72), canagliflozin (OR 0.48, 95% CI 0.29-0.82) and dapagliflozin (OR 0.38, 95% CI 0.28-0.51). With regard to acute renal impairment/failure, only empagliflozin was significantly associated with a lower risk than placebo (OR 0.72, 95% CI 0.60-0.86). The cumulative meta-analysis indicated the robustness of our significant findings. Conclusions The present meta-analysis indicated that dapagliflozin may increase the risk of adverse renal events, while empagliflozin may have a protective effect among patients with T2DM. Further data from large well-conducted randomized controlled trials and a real-world setting are warranted

Micro-PIV visualization and numerical simulation of flow and heat transfer in three micro pin-fin heat sinks

This paper presents the experimental results of laminar flow behavior of water in circular micro pin-fin (C-MPF), square micro pin-fin (S-MPF) and diamond micro pin-fin (D-MPF) heat sinks using micro-PIV flow visualization technology at first. All three micro pin-fin heat sinks have a hydraulic diameter of 200 μm. Second, numerical simulation results of the fluid flow characteristics in these heat sinks with CFD are compared to the experimental results of fluid flow behaviors measured with the micro-PIV flow visualization. The normalized time averaged streamline patterns and instantaneous velocity contours in the three heat sinks were obtained for laminar flow of Reynolds number from 10 to 200. By comparison, the experimental results favorably agree with the simulated results of fluid flow. Of the three types of heat sinks, the vortexes occur the earliest in the D-MPF heat sink, which also present very complicated back flow. The strong vortexes and back flow effectively enhance the mixing of fluid and therefore lead to higher pressure drops in the D-MPF heat sink as compared to the other two types of heat sinks. The vortexes in the D-MPF heat sink are very much easily involved in the main flow than those in the other two types of heat sinks due to the high deceleration and pressurization zone. Finally, numerical simulation results of heat transfer at steady state in the three heat sinks are presented. The initial temperature of the working fluid and the ambient air is maintained at 293 K and a constant heat flux of qw = 400 kW/m2 is adopted in the central area at the bottom of the heat sink. The Reynolds number ranges from 40 to 300 for the fluid flow and heat transfer simulations. It shows that D-MPF heat sink has better heat transfer performance than the other two type heat sinks. The combined effects of the vortex in the main flow at the front side wall and the strong vortex intensity behind the D-MPF heat sink obtained in both experimental and numerical results may reasonably explain the better heat transfer enhancement behaviors as compared to those in the other two types of heat sinks. Further experiments on the heat transfer performance will be conducted to compare to the simulated results in the follow-up planned research

The life cycle of Thelohanellus kitauei (Myxozoa: Myxosporea) infecting common carp (Cyprinus carpio) involves aurantiactinomyxon in Branchiura sowerbyi

Thelohanellus kitauei is a freshwater myxosporean parasite causing intestinal giant cystic disease of common carp. To clarify the life cycle of T. kitauei, we investigated the oligochaete populations in China and Hungary. This study confirms two distinct aurantiactinomyxon morphotypes (Aurantiactinomyxon type 1 and Aurantiactinomyxon type 2) from Branchiura sowerbyi as developmental stages of the life cycle of T. kitauei. The morphological characteristics and DNA sequences of these two types are described here. Based on 18S rDNA sequence analysis, Aurantiactinomyxon type 1 (2048 bp) and Aurantiactinomyxon type 2 (2031 bp) share 99.2–99.4 %, 99.8–100 % similarity to the published sequences of T. kitauei, respectively. The 18S rDNA sequences of these two aurantiactinomyxon morphotypes share 99.4 % similarity, suggesting intraspecific variation within the taxon, possibly due to geographic origin. Phylogenetic analyses demonstrate the two aurantiactinomyxon types clustered with T. kitauei. Regardless, based on 18S rDNA synonymy, it is likely that Aurantiactinomyxon type 1 and 2 are conspecific with T. kitauei. This is the fourth elucidated two-host life cycle of Thelohanellus species and the first record of T. kitauei in Europe

New insights into fibrotic signaling in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) mostly occurs in the background of liver fibrosis, and activated hepatic stellate cells (HSCs) exist in HCC tissues and adjacent tissues. HSC activation is involved throughout the development of HCC precancerous lesions, which has gradually attracted the attention of related researchers. In addition, HCC can promote the activation of HSCs, which in turn accelerates the occurrence and development of HCC by promoting tumor angiogenesis. In this review, we reviewed 264 studies from PubMed and ScienceDirect to summarize and analyze current significant fibrotic signaling in HCC. As a result, we found 10 fibrotic signaling pathways that are closely related to the activation, proliferation, invasion, migration, and promotion of apoptosis of HCC cells. In addition, we found that crosstalk between various fibrotic signaling pathways of HCC, hypoxia-induced energy metabolic reprogramming of HCC cells, matrix stiffness and stemness of HCC cells, and ferroptosis of HCC cells and HSCs are the latest research hotspots. Furthermore, related drugs that have been found to target these 10 fibrotic signaling pathways of HCC are listed. Our study provides a new reference for developing anti-HCC drugs

CRISPR/Cas9-mediated targeted mutation of the E1 decreases photoperiod sensitivity, alters stem growth habits, and decreases branch number in soybean

The distribution of elite soybean (Glycine max) cultivars is limited due to their highly sensitive to photoperiod, which affects the flowering time and plant architecture. The recent emergence of CRISPR/Cas9 technology has uncovered new opportunities for genetic manipulation of soybean. The major maturity gene E1 of soybean plays a critical role in soybean photoperiod response. Here, we performed CRISPR/Cas9-mediated targeted mutation of E1 gene in soybean cultivar Tianlong1 carrying the dominant E1 to investigate its precise function in photoperiod regulation, especially in plant architecture regulation. Four types of mutations in the E1 coding region were generated. No off-target effects were observed, and homozygous trans-clean mutants without T-DNA were obtained. The photoperiod sensitivity of e1 mutants decreased relative to the wild type plants; however, e1 mutants still responded to photoperiod. Further analysis revealed that the homologs of E1, E1-La, and E1-Lb, were up-regulated in the e1 mutants, indicating a genetic compensation response of E1 and its homologs. The e1 mutants exhibited significant changes in the architecture, including initiation of terminal flowering, formation of determinate stems, and decreased branch numbers. To identify E1-regulated genes related to plant architecture, transcriptome deep sequencing (RNA-seq) was used to compare the gene expression profiles in the stem tip of the wild-type soybean cultivar and the e1 mutants. The expression of shoot identity gene Dt1 was significantly decreased, while Dt2 was significantly upregulated. Also, a set of MADS-box genes was up-regulated in the stem tip of e1 mutants which might contribute to the determinate stem growth habit

Uniqueness of positive solutions for the singular fractional differential equations involving integral boundary value conditions

© 2018, The Author(s). This paper is concerned with the uniqueness of positive solutions for a class of singular fractional differential equations with integral boundary conditions. The nonlinear term and boundary conditions of fractional differential equation contain the fractional order derivatives. The uniqueness of positive solutions is derived by the fixed point theorem of mixed monotone operator. An example is given to demonstrate the validity of our main results