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Tungsten oxide sol, containing highly crystalline nanoparticles of orthorhombic WO3 and having good sedimentation stability, was synthesized using a facile, ultrasonic-assisted technique. An additional steric stabilizer, dextran, was proposed to enhance the stability of WO3 nanoparticles in biological media and to reduce their in vivo toxicity. The cytotoxicity of dextran-stabilized and nonstabilized WO3 sols was studied in vitro using dental pulp stem (DPS) cell lines and breast cancer (MCF-7) cell lines. Both tungsten oxide sols demonstrated low cytotoxicity and low genotoxicity for both stem cells and malignant cells and only slightly reduced their metabolic activity in the concentration range studied (from 0.2 to 200 μg/ml). The data obtained support possible theranostic applications of tungsten oxide colloidal solutions. [ABSTRACT FROM AUTHOR]

A growth trial was conducted to examine the effect of dietary digestible energy ( DE) content on methionine (Met) utilization and requirement in juvenile Nile tilapia ( Oreochromis niloticus). Ten iso-nitrogenous (288 g kg−1 protein) practical diets, with two DE levels (10.9 MJ kg−1; 12.4 MJ kg−1) and five methionine supplementation levels (0, 1, 2, 4 and 6 g kg−1), were hand-fed twice daily to triplicate groups of Nile tilapia (initial body weight 8.95 ± 0.06 g) for 8 weeks. Weight gain ( WG) and specific growth rate ( SGR) increased significantly with increasing dietary methionine concentration at the same DE content ( P < 0.001). At the same dietary methionine level, WG and SGR of fish fed high- DE diets were significantly higher than that of fish fed low- DE diets ( P = 0.0001), although no interaction was found between dietary DE and methionine supplementation. Based on quadratic regression analysis between dietary methionine concentration and weight gain, optimal methionine requirement for maximum growth, expressed as g Met required kg−1 diet (low- versus high- DE diets), increased as diet DE concentration increased (7.34 versus 9.90 g kg−1 diet, respectively; with cysteine 4.70 g kg−1 diet). The results indicated that diet DE content affects methionine utilization and requirement in juvenile Nile tilapia, fish fed high- DE diets required more methionine for maximum growth. [ABSTRACT FROM AUTHOR]

Polycyclic aromatic hydrocarbons ( PAHs) are among the most toxic air pollutants in China. However, because there are unsubstantial data on indoor and outdoor particulate PAHs, efforts in assessing inhalation exposure and cancer risk to PAHs are limited in China. This study measured 12 individual PAHs in indoor and outdoor environments at 36 homes during the non-heating period and heating period in 2009. Indoor PAH concentrations were comparable with outdoor environments in the non-heating period, but were lower in the heating period. The average indoor/outdoor ratios in both sampling periods were lower than 1, while the ratios in the non-heating period were higher than those in the heating period. Correlation analysis and coefficient of divergence also verified the difference between indoor and outdoor PAHs, which could be caused by high ventilation in the non-heating period. To support this conclusion, linear and robust regressions were used to estimate the infiltration factor to compare outdoor PAHs to indoor PAHs. The calculated infiltration factors obtained by the two models were similar in the non-heating period but varied greatly in the heating period, which may have been caused by the influence of ventilation. Potential sources were distinguished using a diagnostic ratio and a mixture of coal combustion and traffic emission, which are major sources of PAHs. [ABSTRACT FROM AUTHOR]

Summary What is known and Objective: Prostate cancer is a major health threat for men. Thiazolidenediones (TZDs) are synthetic ligands of the peroxisome proliferator-activated receptor γ (PPARγ), and previous studies have shown that TZDs induce apoptosis of prostate cancer cells independently of PPARγ activation. However, the exact mechanism of these effects remains unknown. Our objective was to investigate the effects of TZDs on apoptosis and on the serine/threonine kinase pathway, Akt, and glycogen synthase kinase 3β (GSK3β). Methods: LNCaP cells, a type of prostate cancer cells (derived from left supraclavicular lymph node of human prostrate carcinoma), were cultured in DMEM medium, and cell viability was evaluated with a colorimetric assay using MTT level. The total and phosphorylated protein level of Akt and GSK3β were detected by Western blotting. Results and Discussion: The apoptosis-inducing effect of TZDs on prostate cancer cells involves the inhibition of Akt phosphorylation. Furthermore, TZDs induce inactivation of GSK3β, a multifunctional kinase that mediates essential events promoting prostate cancer development and acquisition of androgen independence. In addition, the GSK3β inhibitor lithium chloride sensitizes prostate cancer cells to TZDs cytotoxicity. What is new and Conclusion: Our data suggest that modulation of Akt-GSK3β pathway is involved in the cell death pathway engaged by TZDs in prostate cancer cells. This reveals another possible mechanism of TZDs on apoptosis in prostate cancer. Inhibition of the Akt-GSK3β cascade may be a useful approach in prostate cancer. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) are shown to alleviate renal injury of diabetic nephropathy (DN) in rats. However, the underlying mechanism of this beneficial effect is not fully understood. The aims of this study are to evaluate effects of umbilical cord-derived mesenchymal stem cells (UC-MSCs) on renal cell apoptosis in streptozotocin- (STZ-) induced diabetic rats and explore the underlying mechanisms. Characteristics of UC-MSCs were identified by flow cytometry and differentiation capability. Six weeks after DN induction by STZ injection in Sprague-Dawley rats, the DN rats received UC-MSCs once a week for consecutive two weeks. DN-related physical and biochemical parameters were measured at 2 weeks after UC-MSC infusion. Renal histological changes were also assessed. Moreover, the apoptosis of renal cells and expression of apoptosis-related proteins were evaluated. Compared with DN rats, rats treated with UC-MSCs showed suppressed increase in 24-hour urinary total protein, urinary albumin to creatinine ratio, serum creatinine, and blood urea nitrogen. UC-MSC treatment ameliorated pathological abnormalities in the kidney of DN rats as evidenced by H&E, PAS, and Masson Trichrome staining. Furthermore, UC-MSC treatment reduced apoptosis of renal cells in DN rats. UC-MSCs promoted expression of antiapoptosis protein Bcl-xl and suppressed expression of high mobility group protein B1 (HMGB1) in the kidney of DN rats. Most importantly, UC-MSCs suppressed upregulation of thioredoxin-interacting protein (TXNIP), downregulation of thioredoxin 1 (TRX1), and activation of apoptosis signal-regulating kinase 1 (ASK1) and P38 MAPK in the kidney of DN rats. Our results suggest that UC-MSCs could alleviate nephrocyte injury and albuminuria of DN rats through their antiapoptotic property. The protective effects of UC-MSCs may be mediated by inhibiting TXNIP upregulation in part., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2020 Lian Chen et al.)

Calpain, calcineurin (CaN), and nuclear factor of activated T cell (NFAT) play a key role in the development of atrial fibrillation. Patients with valvular heart disease (VHD) are prone to develop atrial fibrillation (AF). Thus, our current study was aimed at investigating whether activation of calpain-CaN-NFAT pathway is associated with the incidence of AF in the patients with VHD and diabetes. The expressions of calpain 2 and alpha- and beta-isoforms of CaN catalytic subunit (CnA) as well as NFAT-c3 and NFAT-c4 were quantified by quantitative reverse transcription-polymerase chain reaction in atrial tissues from 77 hospitalized patients with VHD and diabetes. The relevant protein content was measured by Western blot and calpain 2 in human atrium was localized by immunohistochemistry. We found that the expressions of calpain 2, CnA alpha and CnA beta, and NFAT-c3 but not NFAT-c4 were significantly elevated in the samples from patients with AF compared to those with sinus rhythm (SR). Elevated protein levels of calpain 2 and CnA were observed in patients with AF, and so was the enhanced localization of calpain 2. We thereby concluded that CaN together with its upstream molecule, calpain 2, and its downstream effector, NFAT-c3, might contribute to the development of AF in patients with VHD and diabetes.

Objective: Glucagon-like peptide-1 (GLP-1) analogues (e.g., exenatide) increase insulin secretion in diabetes but less is known about their effects on glucose production or insulin-stimulated glucose uptake in peripheral tissues., Methods: Four groups of Sprague-Dawley rats were studied: nondiabetic (control, C); nondiabetic + exenatide (C + E); diabetic (D); diabetic + exenatide (D + E) with diabetes induced by streptozotocin and high fat diet. Infusion of 3-(3)H-glucose and U-(13)C-glycerol was used to measure basal rates of appearance (Ra) of glucose and glycerol and gluconeogenesis from glycerol (GNG). During hyperinsulinemic-euglycemic clamp, glucose uptake into gastrocnemius muscles was measured with 2-deoxy-D-(14)C-glucose., Results: In the diabetic rats, exenatide reduced the basal Ra of glucose (P < 0.01) and glycerol (P < 0.01) and GNG (P < 0.001). During the clamp, Ra of glucose was also reduced, whereas the rate of disappearance of glucose increased and there was increased glucose uptake into muscle (P < 0.01) during the clamp. In the nondiabetic rats, exenatide had no effect., Conclusion: In addition to its known effects on insulin secretion, administration of the GLP-1 analogue, exenatide, is associated with increased inhibition of gluconeogenesis and improved glucose uptake into muscle in diabetic rats, implying improved hepatic and peripheral insulin sensitivity.