Expression and biological significance of c-FLIP in human hepatocellular carcinomas

<p>Abstract</p> <p>Background</p> <p>c-FLIP can be considered as a tumor-progression factor in regard to its anti-apoptotic functions. In the present study, we intended to investigate the expression of c-FLIP in human HCC tissues, and its relation with drug-induced cell apoptosis through the specific inhibition of c-FLIP expression by siRNA in 7721 cells.</p> <p>Methods</p> <p>c-FLIP expression was quantified immunohistochemically in HCC tissues(eighty-six cases), and corresponding noncancerous tissues (fifty-seven cases). Patients with HCC were followed up for cancer recurrence. Then, the c-FLIP gene was silenced with specific siRNA in 7721 HCC cells. c-FLIP expression was detected by RT-PCR, Western Blot and immunocytochemical staining. The cellular viability and cell apoptosis were assayed <it>in vitro </it>with cells treated with doxorubicin.</p> <p>Results</p> <p>Positive immunostaining was detected for c-FLIP in 83.72% (72/86) human HCC tissues, 14.81% (4/27) hepatic cirrhosis, 11.11% (2/18) hepatic hemangioma tissues, and absent in normal hepatic tissues. The overexpression(more than 50%) of c-FLIP in HCC adversely affected the recurrence-free survival. Through c-FLIP gene silencing with siRNA, the expressions of c-FLIP mRNA and protein were remarkably down-regulated in 7721 HCC cells. And doxorubicin showed apparent inhibition on cell proliferations, and induced more apoptosis.</p> <p>Conclusion</p> <p>These results indicate that c-FLIP is frequently expressed in human HCCs, and its overexpression implied a lesser probability of recurrence-free survival. The specific silencing of c-FLIP gene can apparently up-regulate drug-induced HCC cell apoptosis, and may have therapeutic potential for the treatment of human HCC.</p

Hydrogen sulfide attenuates cardiac dysfunction in a rat model of heart failure: a mechanism through cardiac mitochondrial protection

HF (heart failure) after MI (myocardial infarction) is a major cause of morbidity and mortality worldwide. Recent studies have shown that hydrogen sulfide (H2S) has cardioprotective effects. Hence, we aimed to elucidate the potential effects of H2S on HF after MI in rats. The HF model after MI was made by ligating the left anterior descending coronary artery. HF groups and sham-operated groups of rats were treated with vehicle, sodium hydrosulfide (NaHS) or PAG (propagylglycine). Equal volumes of saline, 3.136 mg·kg−1·day−1 NaHS or 37.5 mg·kg−1·day−1 PAG, were intraperitoneally injected into rats for 6 weeks after operation. Survival, lung-to-body weight ratio and left ventricular haemodynamic parameters were measured. The protein and gene expression of Bcl-2, Bax, caspase 3 and cytochrome c were analysed by Western blotting and RT–PCR (reverse transcription–PCR). TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling) and EM (electron microscopy) were used to examine apoptosis of heart tissues. NaHS was found to improve the survival and lower the lung-to-body weight ratio. It increased the LVSP (left ventricular systolic pressure) and the maximum rate of pressure and decreased LVEDP (left ventricular end-diastolic pressure). Furthermore, NaHS promoted Bcl-2 protein and mRNA expression and demoted Bax, caspase 3 protein and mRNA expression in HF rats. We also showed that NaHS decreased the leakage of cytochrome c protein from the mitochondria to the cytoplasm. Histological observation by TUNEL and EM proved that NaHS inhibited cardiac apoptosis in HF hearts and improved mitochondrial derangements, but that PAG aggravated those indices. Hence, H2S has protective effects in HF rats

Function of TRP channels in monocytes/macrophages

The transient receptor potential channel (TRP channel) family is a kind of non- specific cation channel widely distributed in various tissues and organs of the human body, including the respiratory system, cardiovascular system, immune system, etc. It has been reported that various TRP channels are expressed in mammalian macrophages. TRP channels may be involved in various signaling pathways in the development of various systemic diseases through changes in intracellular concentrations of cations such as calcium and magnesium. These TRP channels may also intermingle with macrophage activation signals to jointly regulate the occurrence and development of diseases. Here, we summarize recent findings on the expression and function of TRP channels in macrophages and discuss their role as modulators of macrophage activation and function. As research on TRP channels in health and disease progresses, it is anticipated that positive or negative modulators of TRP channels for treating specific diseases may be promising therapeutic options for the prevention and/or treatment of disease

Substantial transition to clean household energy mix in rural China

The household energy mix has significant impacts on human health and climate, as it contributes greatly to many health- and climate-relevant air pollutants. Compared to the well-established urban energy statistical system, the rural household energy statistical system is incomplete and is often associated with high biases. Via a nationwide investigation, this study revealed high contributions to energy supply from coal and biomass fuels in the rural household energy sector, while electricity comprised ∼20%. Stacking (the use of multiple sources of energy) is significant, and the average number of energy types was 2.8 per household. Compared to 2012, the consumption of biomass and coals in 2017 decreased by 45% and 12%, respectively, while the gas consumption amount increased by 204%. Increased gas and decreased coal consumptions were mainly in cooking, while decreased biomass was in both cooking (41%) and heating (59%). The time-sharing fraction of electricity and gases (E&G) for daily cooking grew, reaching 69% in 2017, but for space heating, traditional solid fuels were still dominant, with the national average shared fraction of E&G being only 20%. The non-uniform spatial distribution and the non-linear increase in the fraction of E&G indicated challenges to achieving universal access to modern cooking energy by 2030, particularly in less-developed rural and mountainous areas. In some non-typical heating zones, the increased share of E&G for heating was significant and largely driven by income growth, but in typical heating zones, the time-sharing fraction was <5% and was not significantly increased, except in areas with policy intervention. The intervention policy not only led to dramatic increases in the clean energy fraction for heating but also accelerated the clean cooking transition. Higher income, higher education, younger age, less energy/stove stacking and smaller family size positively impacted the clean energy transition

Association of Adiponectin SNP+45 and SNP+276 with Type 2 Diabetes in Han Chinese Populations: A Meta-Analysis of 26 Case-Control Studies

Recently, many studies have reported that the SNP+45(T>G) and SNP+276(G>T) polymorphisms in the adiponectin gene are associated with type 2 diabetes (T2DM) in the Chinese Han population. However, the previous studies yielded many conflicting results. Thus, a meta-analysis of the association of the adiponectin gene with T2DM in the Chinese Han population is required. In the current study, we first determined the distribution of the adiponectin SNP+276 polymorphism in T2DM and nondiabetes (NDM) control groups. Our results suggested that the genotype and allele frequencies for SNP+276 did not differ significantly between the T2DM and NDM groups. Then, a meta-analysis of 23 case-control studies of SNP+45, with a total of 4161 T2DM patients and 3709 controls, and 11 case-control studies of SNP+276, with 2533 T2DM patients and 2212 controls, was performed. All subjects were Han Chinese. The fixed-effects model and random-effects model were applied for dichotomous outcomes to combine the results of the included studies. The results revealed a trend towards an increased risk of T2DM for the SNP+45G allele as compared with the SNP+45T allele (OR = 1.34; 95% CI, 1.11–1.62; P<0.01) in the Chinese Han population. However, there was no association between SNP+276 and T2DM (OR = 0.90; 95% CI, 0.73–1.10; P = 0.31). The results of our association study showed there was no association between the adiponectin SNP+276 polymorphism and T2DM in the Yunnan Han population. The meta-analysis results suggested that the SNP+45G allele might be a susceptibility allele for T2DM in the Chinese Han population. However, we did not observe an association between SNP+276 and T2DM

The therapeutic use of quercetin in ophthalmology: recent applications

Quercetin is a natural flavonol antioxidant found in various plant sources and food samples. It is well known for its notable curative effects on the treatment of ophthalmic diseases due to various biological activities, such as antioxidant, anti-inflammatory, and anti-fibrosis activities. This review will discuss the latest developments in therapeutic quercetin for the treatment of keratoconus, Graves’ orbitopathy, ocular surface, cataracts, glaucoma, retinoblastoma, and other retinal diseases

Dissipation, Bioconcentration and Dietary Risk Assessment of Thiamethoxam and Its Metabolites in <i>Agaricus bisporus</i> and Substrates under Different Application Methods

In order to acquire scientific evidence for the application of thiamethoxam (TMX) in Agaricus bisporus cultivation, residue and dissipation experiments for field trials were performed with the application of TMX in compost and casing soil, respectively. An effective QuEChERS method was established to analyze TMX and its two metabolites, clothianidin (CLO) and thiamethoxam-urea (TMX-urea), in compost, casing soil, and fruiting bodies. The results indicated that the TMX dissipation half-lives (t1/2) at dosages of 10 and 50 mg kg−1 were 19.74 d (day) and 28.87 d in compost and 33.54 d and 42.59 d in casing soil, individually. TMX, CLO, and TMX-urea were observed after TMX application in compost and casing soil. For TMX applied to the casing soil, only TMX residues were detected in fruiting bodies with bioconcentration factors (BCFs) of 0.0003~0.0009. In addition, both the chronic risk quotient (RQ) and acute risk quotient (HQ) values of TMX in fruiting bodies were far less than 1, which means the dietary health risks to humans were acceptable. However, in the TMX application to the compost, these analytes were not detected in the fruiting bodies. This suggested that the application of TMX in compost was safer than in casing soil during A. bisporus cultivation

Transient Temperature Field Model of Wear Land on the Flank of End Mills: A Focus on Time-Varying Heat Intensity and Time-Varying Heat Distribution Ratio

Modelling methods for the transient temperature field of wear land on the flank of end mills have been proposed to address the challenges of inaccurate prediction in the temperature field of end mills during the high-speed peripheral milling of Ti6Al4V that is a titanium alloy. A transient temperature rise model of wear land on the flank of end mills was constructed under the influence of heat sources in the primary shearing zone (PSZ), rake-chip zone (RCZ), flank-workpiece zone (FWZ), and dissipating heat source. Then the transient temperature field model of wear land on the flank of end mills was constructed. Finally, the transient temperature field model of wear land on the flank of end mills was constructed. Comparison of simulation result and experimental data verified the accuracy of the model. In sum, the proposed model may provide a temperature model support for future studies of flank wear rate in end mill modeling