Hoganfoley8026

The antidepressant effect of curcumin-coated iron oxide nanoparticles (Cur-IONPs) was investigated in the current study using depression rat model induced by reserpine. IONPs were synthesized by curcumin as a reducing agent producing Cur-IONPs. Rats were divided into control, depression rat model, and depressed rats treated with Cur-IONPs. After treatment rat behavior was evaluated using forced swimming test (FST). Serotonin (5-HT), norepinephrine (NE), dopamine (DA), monoamine oxidase (MAO), acetylcholinesterase (AchE), Na+, K+, ATPase, lipid peroxidation (MDA), reduced glutathione (GSH), glutathione-s-transferase (GST) and nitric oxide (NO) were measured in the cortex and hippocampus. In depressed rats, FST showed increased immobilization time and reduced swimming time. This was associated with a significant decrease in 5-HT, NE, DA and GSH and a significant increase in MDA and NO levels and GST, MAO, AchE and Na+, K+, ATPase activities in the cortex and hippocampus. Treatment with Cur-NONPs for two weeks increased the swimming time reduced the immobility time, and elevated 5-HT, NE and DA levels. Cur-IONPs attenuated the oxidative stress induced by reserpine and restored the MAO, AchE and Na+, K+, ATPase. The present green method used curcumin in the IONPs synthesis and has several merits; obtaining nanoform of iron oxide, increasing the bioavailability of curcumin and reducing the oxidative stress induced by iron. The present antidepressant effect of Cur-IONPs could be attributed to the ability of Cur-IONPs to restore monoamine neurotransmitter levels by increasing their synthesis and reducing their metabolism. In addition, the antioxidant activity of curcumin prevented oxidative stress in the depressed rats.Mitochondrial ATP-sensitive potassium channels (mitoKATP) locate in the inner mitochondrial membrane and possess protective cellular properties. mitoKATP opening-induced cardioprotection (using the pharmacological agent diazoxide) is preventable by antagonists, such as glibenclamide. However, the mechanisms of action of these drugs and how mitoKATP respond to them are poorly understood. Here, we show data that reinforce the existence of a mitochondrial sulfonylurea receptor (mitoSUR) as part of the mitoKATP. We also show how diazoxide and glibenclamide compete for the same binding site in mitoSUR. A glibenclamide analog that lacks its cyclohexylurea portion (IMP-A) loses its ability to inhibit diazoxide-induced swelling. These results suggest that the cyclohexylureia portion of glibenclamide is indispensable for mitoKATP inhibition. Moreover, IMP-A did not suppress diazoxide-induced preconditioning (EC50 10.66 μM) in a rat model of a cardiac ischemia/reperfusion. Importantly, glibenclamide inhibited both diazoxide-induced cardioprotection (IC50 86 nM). We suggest that IMP-A must be used with caution since we found this drug possesses significant inhibitory effects on mitochondrial respiration. We characterized the binding of glibenclamide and diazoxide using a molecular simulation (docking) approach. Using the molecular structure of the ATP binding protein ABCB8 (pointed by others as the mitoSUR) we demonstrate that glibenclamide competitively inhibits diazoxide actions. This was reinforced (pharmacologically) in a competitive antagonism test. Taken together, these results bring valuable and novel insights into the pharmacological/biochemical aspects of mitokATP activation and cardioprotection. This study may lead to the discovery of novel therapeutic strategies that may impact ischemia-reperfusion injury.Escin is a natural mixture of triterpene saponins, exhibits anti-oedematous properties and promotes venous drainage by oral administration or injection. Upon clinical application of escin, adverse kidney reactions have been reported and the nephrotoxic mechanism responsible for this reaction remains elusive. In the present study, four isomeric escins (β-form escin Ia and escin Ib; α-form isoescin Ia and isoescin Ib) were found severely decreasing the cell viability of human kidney (HK-2) cells. A decline in HK-2 cell viability caused by sodium aescinate (a mixture of four isomers) was reduced after β-glucuronidase hydrolysis. Torin 1 manufacturer In addition, sodium aescinate concentration-dependently inhibited the expression level of heat shock proteins (HSPs) in the Madin-Darby Canine Kidney (MDCK) cells. Moreover, with molecular docking and molecular dynamics simulation, these four isomeric escins could directly bind to the ATP-binding domain of HSP70 and HSP90, thus competitively inhibiting the function of HSPs. Escin Ia is bound to HSPs with the lowest binding free energy, which is consistent with the observation that escin Ia most severely decreases HK-2 cell viability. Thus, we demonstrate a heretofore unknown molecular mechanism of escin-induced renal cytotoxicity as well as identify HSPs as potential targets for the renal cytotoxic effect of escin.Colorectal cancer (CRC) is the most fatal gastrointestinal tumor and it is urge to explore powerful drugs for the treatment. Diosgenin (DSG) as a new steroidal had been reported exerts anti-tumor activity in multiple cancers, including CRC. However, the potential mechanism of DSG suppresses CRC remains further to be revealed. Here, we reported that DSG inhibited proliferation of CRC cells in dose- and time-dependent manner, induced apoptosis by modulating p53 and Bcl-2 family proteins expression to mediate mitochondrial apoptosis pathway, suppressed migration and invasion by reducing MMP-9 (matrix metalloproteinase) and decreased aerobic glycolysis by mediating glucose transporter (GLUT) like GLUT3 and GLUT4, and pyruvate carboxylase PC downregulation. Intriguingly, mechanistic study suggests those phenotypes involved DSG inhibited cAMP/PKA/CREB pathway in CRC cells, and result to inhibit the phosphorylation of CREB to regulate the transcription of genes above-mentioned. Finally, nude mice xenograft tumor model further indicated that DSG could be a great agent to suppress the growth of CRC cells in vivo and have no obvious side effects. Taken together, we revealed a unique mechanism that DSG suppresses CRC cells through cAMP/PKA/CREB pathway and DSG is a promising candidate drug for CRC treatment.Exploration of long-term in vivo effects of nanomaterials, particularly those with potential biomedical applications, is quite important for better understanding and evaluating their biosafety. Selenium nanoparticles (SeNPs) has been considered as a good candidate in biomedical applications due to its high bioavailability, considerable biological activity, and low toxicity. However, its long-term biological effects and biosafety remain unknown. Our previous study demonstrated that 8-week supplementation with SeNPs (50 μg Se/kg/day) was safe and had an anti-atherosclerotic activity in apolipoprotein E-deficient (ApoE-/-) mice, a well-known animal model of atherosclerosis. As a chronic disease, atherosclerosis needs long-term drug therapy. The aim of this study is to investigate the long-term effects of SeNPs with different sizes on atherosclerotic lesions and their biosafety in ApoE-/- mice fed with a high fat diet. Unexpectedly, the results showed that 24-week administration of SeNPs even at a low dose (50 μg Se/kg/day) aggravated atherosclerotic lesions. Furthermore, SeNPs exacerbated oxidative stress by inhibiting the activities of antioxidant enzymes and the expression of antioxidant selenoenzymes. SeNPs also exacerbated hyperlipidaemia by inducing hepatic lipid metabolic disorder. In the meanwhile, SeNPs aggravated organ injury, especially liver and kidney injury. The above adverse effects of SeNPs were size dependent SeNPs with the size of 40.4 nm showed the highest adverse effects among the SeNPs with three sizes (23.1 nm, 40.4 nm, and 86.8 nm). In conclusion, the present work shows that long-term administration of low-dose SeNPs aggravated atherosclerotic lesions by enhancing oxidative stress and hyperlipidaemia in ApoE-/- mice, indicative of cardiovascular toxicity. Moreover, long-term administration of SeNPs led to injury to liver and kidney. These results offer novel insights for better understanding the biosafety of SeNPs and other biomedical nanomaterials.

- To evaluate exposure-response relationships between 1,3-butadiene and styrene and selected diseases among synthetic rubber polymer workers.

- 21,087 workers (16,579 men; 4508 women) were followed from 1943 through 2009 to determine mortality outcomes. Cox regression models estimated rate ratios (RRs) and 95% confidence intervals (CIs) by quartile of cumulative exposure to butadiene or styrene and exposure-response trends for cancers of the bladder, lung, kidney, esophagus and pancreas, and for all nonmalignant respiratory disease (NMRD), chronic obstructive pulmonary disease (COPD) and pneumonia.

- Bladder cancer RRs were 2.13 (95% CI=1.03 to 4.41) and 1.64 (95% CI=0.76 to 3.54) in the highest quartiles of cumulative exposure to butadiene and styrene, respectively, and exposure-response trends were positive for both monomers (butadiene, trend p=0.001; styrene, trend p=0.004). Further analyses indicated that the exposure-response effect of each monomer on bladder cancer was demonstrated clearly only in

- This study found a positive exposure-response relationship between monomer exposures and bladder cancer. The independent effects of butadiene and styrene on this cancer could not be delineated. In some analyses, monomer exposure was associated with lung cancer in women and with COPD in men, but inconsistent exposure-response trends and divergent results by sex do not support a causal interpretation of the isolated positive associations.

To assess the relationship between telemedicine utilization and sociodemographic factors among patients seeking eye care.

Comparative utilization analysis.

We reviewed the eye care utilization patterns of a stratified random sample of 1,720 patients who were seen at the University of Michigan Kellogg Eye Center during the height of the COVID-19 pandemic (April 30 to May 25, 2020). link2 The odds of having a video, phone or in-person visit compared to having a deferred visit. Associations between independent variables and visit type were determined using a multinomial logistic regression model.

Older patients had lower odds of having a video visit (p=0.007) and higher odds of having an in-person visit (p=0.023) compared to being deferred, and in the non-retina clinic sample, older patients still had a lower odds of a video visit (p-0.02). Non-white patients had lower odds of having an in-person visit (p<0.02) in the overall sample compared to being deferred, with a similar trend seen in the retina clinic.exacerbate disparities in eye care.Neonicotinoids (NEOs) are extensively applied in global agricultural production for pest control but have adverse effects on human health. In this study, the concentrations of six NEOs and three characteristic metabolites were investigated by collecting 200 serum samples from an elderly population in China. Results showed that the NEOs and their metabolites were widely detected (89%-98 %) in the serum samples from the osteoporosis (OP) (n = 120) and non-OP (n = 80) population, and their median concentrations ranged from 0.04 ng/mL to 5.99 ng/mL and 0.01 ng/mL to 2.02 ng/mL, respectively. N-desmethyl-acetamiprid (ACE-dm) was the most abundant NEOs in the serum samples. Gender-related differences were found in concentrations of most NEOs and their metabolites in serum, with males having higher target analytes than females. Significantly (p less then 0.05) positive correlations were observed among most NEO concentrations, suggesting that exposure source of these substances is common or related. link3 However, associations between the concentrations of characteristic metabolites and their corresponding NEOs were insignificant, probably because the exogenous intake are the primary sources of metabolites of NEOs instead of the internal biotransformation.