Compound probiotics regulate the NRF2 antioxidant pathway to inhibit aflatoxin B1-induced autophagy in mouse Sertoli TM4 cells.

This study investigated the effects of compound probiotics (CP) on AFB1-induced cytotoxicity in Sertoli TM4 cells. The L9 (3 × 3) orthogonal test was conducted to determine the optimal CP required for high AFB1 degradation in the artificial gastrointestinal fluid in vitro. The maximal AFB1 degradation rate was 40.55 % (P < 0.05) when the final viable count was 1.0 × 105 CFU/mL for Bacillus subtilis, Lactobacillus casein, and Saccharomyces cerevisiae. The effects of CP and the CP supernatant (CPS) on TM4 cell viability were evaluated to achieve the optimal protective conditions. When CPS4 (corresponding to CP viable counts of 1.0 × 104 CFU/mL) was added to the TM4 cells for 24 h, the cell viability reached 108.86 % (P < 0.05). AFB1 reduced TM4 cell viability in a concentration- and time-dependent manner at an AFB1 concentration ranging from 0 to 1.5 µM after 48-h AFB1 exposure. The optimal AFB1 concentration/times for low- and high damage models were 0.5 and 1.25 µM both for 24 h, which decreased viability to 76.04 % and 65.35 %, respectively. however, CPS4 added to low- and high-damage models increased the cell viability to 97.43 % and 75.12 %, respectively (P < 0.05). Transcriptome sequencing was performed based on the following designed groups: the control, 0.5 µM AFB1, 1.25 µM AFB1, CPS4, and CPS4+0.5 µM AFB1. The Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis was further performed to identify significantly enriched signaling pathways, which were subsequently verified. It was shown that AFB1 induced apoptosis by blocking the PI3K-AKT-mTOR pathway and upregulating autophagy proteins such as LC3B, Beclin1, and ATG5 while inhibiting autophagic flux. CPS4 promoted AFB1 degradation, activated the p62-NRF2 antioxidant, and inhibited ROS/TRPML1 pathways, thereby reducing ROS production and inflammation and ultimately alleviating AFB1-induced autophagy and apoptosis. These findings supports the potential of probiotics to protect the male reproductive system from toxin damage.

Vitamin D Deficiency and Increased Risk of Bladder Carcinoma: A Meta-Analysis.

BACKGROUND/AIMS: Vitamin D status in relation to bladder carcinoma risk was still inconsistent. This study was carried out to evaluate the relationship between vitamin D status and bladder carcinoma risk through a meta-analysis approach. METHODS: Pubmed, Web of Science, CNKI, and Embase were searched systemically to find eligible studies from the earliest available date to April 16, 2015. The search terms "vitamin D", "25-hydroxyvitamin D", "bladder cancer" or "bladder carcinoma" were used to retrieve relevant studies. The exposure of interest was intake of vitamin D or serum vitamin D levels, and the outcome of interest was bladder carcinoma incidence or mortality. The pooled risk ratio (RR) values and their 95%CIs were calculated through meta-analysis. RESULTS: Seven studies with a total of 62,141 participants met the inclusion criteria and were finally included into the meta-analysis. There was no heterogeneity among those included studies (I2 = 0%, P = 0.53). The pooled RR of bladder carcinoma for the lowest category versus the highest category of vitamin D was 1.34 (95% CI 1.17-1.53, P < 0.0001). Sensitivity analysis by omitting one study by turns showed all the pooled RRs were statistically significant. Meta-analysis of 5 studies reporting outcomes of serum vitamin D levels also showed that the low serum vitamin D level was associated with increased risk of bladder carcinoma (RR = 1.32, 95%CI 1.15-1.52, P = 0.0001). No obvious risk of publication bias was observed. CONCLUSION: Vitamin D deficiency is associated with increased risk of bladder carcinoma in present study.

AAV9-HGF cooperating with TGF-beta/Smad inhibitor attenuates silicosis fibrosis via inhibiting ferroptosis.

Silicosis is a devastating interstitial lung disease characterized by silicon nodules and diffuse pulmonary fibrosis. To date, inefficient therapy is still a challenge of this disease due to its complicated pathogenesis. Hepatocyte growth factor (HGF) which is highly expressed in hepatocyte with anti-fibrotic and anti-apoptotic function was downregulated in silicosis. In addition, the upregulation of transforming growth factor-beta (TGF-ß), another pathological molecular was observed to aggravate the severity and accelerate the progression of silicosis. Here AAV expressed HGF with targeting pulmonary capillaries and SB431542, the inhibitor of TGF-ß signal pathway, were simultaneously adopted to synergistically reduce silicosis fibrosis. In vivo result demonstrated that the cooperation of HGF with SB431542 showed strong anti-fibrosis effects on the silicosis mice via tracheal administration of silica, compared to the separate treatment. The high efficacy was mainly achieved by remarkably by reducing ferroptosis of lung tissue. In our point, the combination of AAV9-HGF with SB431542 provide an alternative to relieve silicosis fibrosis from the perspective of targeting pulmonary capillaries.

SiO2-induced ferroptosis in macrophages promotes the development of pulmonary fibrosis in silicosis models.

Silicosis is a devastating disease that, without effective treatment, endangers the health of miners. Therefore, studies exploring the pathogenesis of SiO2-induced pulmonary fibrosis are necessary to develop treatments for silicosis. Although macrophages are known to play a pivotal role in SiO2-induced pulmonary fibrosis, the underlying mechanism remains unknown. Here, we explored whether ferroptosis was involved in SiO2-induced pulmonary fibrosis. To this end, C57BL/6 mice and mouse macrophage (RAW264.7) cells and mouse lung fibroblast (MLF) cells were subjected to iron content, cell viability, enzyme-linked immunosorbent assay, immunofluorescence staining, histological, western blotting, quantitative reverse transcription-PCR, reactive oxygen species, and lipid peroxidation analysis. In vivo, SiO2 was found to damage the lung alveolar structure, cause infiltration of inflammatory cells, and facilitate fibrosis. Additionally, it increased the iron concentration and lipid peroxidation as well as altered the expression of ferroptosis-related genes and the mitochondrial morphology in macrophages. In vitro, ferroptosis occurred in SiO2-treated RAW264.7 cells, which showed iron overload, lipid peroxidation, and gene alterations. Furthermore, ferrostatin-1 (Fer-1) attenuated ferroptosis in SiO2-treated RAW264.7 cells by inhibiting lipid peroxidation and cell death and regulating ferroptosis-related genes expression, in addition to attenuating the secretion of pro-fibrotic cytokines and fibrosis. Collectively, SiO2 induces ferroptosis in macrophages, which leads to the secretion of pro-fibrotic cytokines and fibrosis.

Endurance Training Counteracts the High-Fat Diet-Induced Profiling Changes of ω-3 Polyunsaturated Fatty Acids in Skeletal Muscle of Middle-Aged Rats.

PURPOSE: To investigate the effects of endurance training on the content of ω-3 polyunsaturated fatty acids (PUFAs) and their distribution among lipid classes in skeletal muscle in middle aged, high-fat diet fed rats. METHOD: Thirty 10-month old male Sprague Dawley (SD) rats were assigned to four groups. Two groups of rats remained sedentary and were fed chow diet (C group), or high-fat diet (H group), respectively. The other two groups of rats were subjected to endurance training while maintaining their chow diet (EC group), or high-fat diet (EH group). After 16 weeks endurance training and/or diet intervention, the content of ω-3 PUFAs and ω-3 PUFA-containing lipids in rat soleus muscle were analyzed by lipidomics. RESULTS: Rats fed a high-fat diet exhibited decreased overall amount of ω-3 PUFAs in soleus muscle, while endurance training preserved the total amount of ω-3 PUFAs. Both the endurance training and high-fat diet alone changed the profiles of ω-3 PUFAs in different lipid classes. Specifically, the amount of triacylglycerol (TG), lysophosphatidylcholine (LPC), phosphatidylcholine (PC), and phosphatidylglycerol (PG) containing ω-3 PUFAs in soleus muscle was increased by endurance training, but the amount of lysophosphatidylenthanol (LPE), lysophosphatidylinositol (LPI), lysophosphatidylserine (LPS), cardiolipin (CL), phosphatidic acid (PA), and phosphatidylinositol (PI) was decreased. The high-fat diet induced a decrease of ω-3 PUFAs in TG, LPE, LPS, CL, platelet activating factor (PAF), PC, phosphatidylethanolamine (PE), and phosphatidylserine (PS), and an increase in LPC, LPI, PA, and PG. In addition, the effects of the endurance training on ω-3 PUFAs in skeletal muscle was also evident in high-fat diets fed rats, which counteracts the profiling changes caused by high-fat diet feeding. CONCLUSION: The beneficial effects of endurance training on skeletal muscle may be achieved to some extent through recovering the content of ω-3 PUFAs that has been decreased by high-fat diet feeding.

Facile Synthesis of PtCu Alloy/Graphene Oxide Hybrids as Improved Electrocatalysts for Alkaline Fuel Cells.

Morphology-controllable preparation of Pt-based nanoalloys supporting on carbonaceous materials is a potential strategy to enhance the catalytic properties for oxygen reduction reaction (ORR) and ethanol oxidation reaction (EOR); they are recognized as irreplaceable electrode reactions in proton-exchange membrane ethanol fuel cells. Herein, we exhibit a facile, one-step synthesis method to directly prepare composition-tunable PtCu alloy/graphene oxide (GO) hybrids. The structure of the as-synthesized PtCu alloy/GO hybrids has been analyzed using transmission electron microscopy, high resolution transmission electron microscopy, energy-dispersive X-ray, X-ray diffraction, inductively coupled plasma, and X-ray photoelectron spectroscopy. In the PtCu alloy/GO hybrids, the PtCu alloy nanoparticles well disperse on GO, and the size is below 5.0 nm. The catalysis for ORR and EOR of the as-synthesized PtCu/GO hybrids has been evaluated in alkaline solution. Compared to commercial Pt/C, the PtCu/GO hybrids exhibit much higher mass activity and stability. The mass activities toward ORR/EOR on Pt75.4Cu24.6/GO hybrids are 5.3/2.36 times higher than the commercial Pt/C. This study proves that the as-synthesized PtCu/GO hybrids can be used as improved catalysts for ORR and EOR in alkaline medium.

Composition-driven shape evolution to Cu-rich PtCu octahedral alloy nanocrystals as superior bifunctional catalysts for methanol oxidation and oxygen reduction reaction.

Synergetic effects between Pt and a cheap metal, downshift of the d-band center of Pt and the shape can boost the catalytic performance of Pt-based nanocrystals. Therefore, tailoring the shape and composition within the nanoscale is the key to designing a robust electrocatalyst in electrochemical energy conversion. Here, Cu-rich PtCu octahedral alloys achieved by a composition-driven shape evolution route have been used as outstanding bifunctional electrocatalysts for both methanol oxidation (MOR) and oxygen reduction reaction (ORR) in an acid medium. When benchmarked against commercial Pt black or Pt/C, for MOR, the specific activity/mass activity on Pt34.5Cu65.5 octahedra is 4.74/7.53 times higher than that on commercial Pt black; for ORR, the specific activity/mass activity on Pt34.5Cu65.5 octahedra is 7.7/4.2 times higher than that on commercial Pt/C. After a current-time test for 3600 s, the remaining mass activity on Pt34.5Cu65.5 octahedra is 35.5 times higher than that on commercial Pt black for MOR. After undergoing 5000 cycles for ORR, the remaining mass activity on Pt34.5Cu65.5 octahedra is 4.2 times higher than that on commercial Pt/C.

Monodispersed sub-5.0 nm PtCu nanoalloys as enhanced bifunctional electrocatalysts for oxygen reduction reaction and ethanol oxidation reaction.

The development of effective electrocatalysts with enhanced activity and stability for both the anode and the cathode reaction in fuel cells still remains a challenge. Here, we report a one-pot route to prepare monodispersed, uniform sub-5.0 nm PtCu alloy polyhedra with a narrow size distribution. These PtCu alloy polyhedra exhibit enhanced electrocatalytic activity for both cathode and anode reactions as compared to the commercial Pt/C catalyst under alkaline conditions. The specific activity and mass activity on Pt68Cu32 nanoalloys are 15 and 2.8 times that on Pt/C catalyst toward oxygen reduction reaction (ORR), respectively. And the peak current density and mass activity on Pt68Cu32 nanoalloys are 11.8 and 2.12 times that on Pt/C catalyst toward ethanol oxidation reaction (EOR), respectively. Furthermore, the as-synthesized Pt68Cu32 nanoalloys have much higher stability than commercial Pt/C black for both ORR and EOR. These experimental results show an effective approach to the development of monodispersed, sub-5.0 nm PtCu nanoalloys as bifunctional electrocatalysts for both the cathode and the anode reaction in fuel cells.

Sorafenib improves the postoperative effect of early stage renal cell carcinoma.

Sorafenib was examined to determine whether it improves postoperative effects during early stage renal cell carcinoma (RCC). A total of 133 patients with early renal clear cell carcinoma (T1-2N0M0) with surgical indications were continuously selected. The patients were divided into 3 groups according to different treatments, including the surgery alone group (40 cases), surgery combined with cytokine group (45 cases) and surgery combined with sorafenib group (48 cases), to make a comparison of their clinical effects. The surgery combined with sorafenib group significantly reduced the recurrence rate and increased the survival rate (P<0.05). Its median survival period was >30 months and the other 2 groups were 27 months (P<0.05). In the subsequent 3 months patients were followed up and it was found that the creatinine levels were significantly elevated and hemoglobin levels were significantly decreased. The sorafenib group had significantly lower creatinine levels and higher hemoglobin levels than the other 2 groups (P<0.05). In the 3-month follow-up, vascular endothelial growth factor (VEGF) levels were significantly reduced and tumor necrosis factor (TNF)-α levels were elevated, although the sorafenib group had significantly decreased VEGF levels and a higher TNF-α level than the other 2 groups (P<0.05). The adverse reaction rate was significantly lower than that of the surgery combined with cytokines group (P<0.05). In conclusion, sorafenib improves the early RCC postoperative survival rate and prolongs the survival time while reducing the recurrence rate. It does not increase adverse reactions, and improves renal function, by decreasing the level of VEGF, and improving the level of TNF-α.