Simvastatin mitigates streptozotocin-induced type 1 diabetes in mice through downregulation of ADAM10 and ADAM17.

BACKGROUND: T cell mediates immune response in type 1 diabetes mellitus (T1DM) through its trafficking into pancreatic islets. The role of A Disintigrin And Metalloproteinase 10 (ADAM10) and 17 (ADAM17) in pancreatic T-cells recruitment into the pancreatic islets during T1DM is not known. AIM: Explore the role of ADAM10 and ADAM17 in the processing of CXCL16 in T1DM and possible protective effect of simvastatin (SIM) in streptozotocin (STZ)-induced T1DM. MAIN METHODS: Balb/c mice were classified into 4 groups, 10 each. Control group received buffer while SIM group received 50 mg/kg, i.p daily for 12 days starting from day 4 of the experiment. Diabetic group; received STZ (55 mg/kg, i.p.) for 5 consecutive days starting from day 1 of the experiment. SIM + STZ group; received SIM (50 mg/kg, i.p.) daily for 12 days and STZ (55 mg/kg, i.p.) for 5 consecutive days. Biochemical, inflammatory and apoptotic markers as well as expression of CXCL16, ADAM10, NF-κB and pancreatic T-cells expression were analyzed. KEY FINDINGS: Significant increase in biochemical, inflammatory, apoptotic parameters, expression of ADAM10, ADAM17, CXCL16, NF-κB, and infiltrated T-cells to the pancreatic islets were found in STZ group. SIM treatment in the presence of STZ improved biochemical and inflammatory parameters as well as it reduced the expression of CXCL16, ADAM10, ADAM17, NF-κΒ, T-cells migration and apoptosis in the pancreatic islets. SIGNIFICANCE: SIM mitigated pancreatic ß-cell death induced by STZ through down regulation of ADAM10, ADAM17and CXCL16. Therefore, ADAM10/ADAM17 and CXCL16 may serve as novel therapeutic targets for T1DM.

Effect of inhaled anaesthetics gases on cytokines and oxidative stress alterations for the staff health status in hospitals.

OBJECTIVES: The present study aimed to evaluate the effects of waste anaesthetic gases on cytokines and oxidative stress of hospital health team members following exposure to waste anaesthetic gases (WAGs). SUBJECTS AND METHODS: In total, 180 participants took part in this study; 60 of these were healthy male controls and the 120 participants in the intervention group were staff who work in the operating room. This latter group comprises six occupational subgroups (1) surgeons, (2) surgical assistants, (3) anaesthesiologists (4) anaesthesiology assistants, (5) nurses and (6) janitors. The following parameters were assessed: catalase (CAT), glutathione peroxidase (GSHpx) and superoxide dismutase (SOD) activities, plasma fluoride, serum interferon gamma (IFN-γ), serum interleukin 2 (IL2), serum interleukin 4 (IL4) and plasma thiobarbituric acid reactive substances (TBARS). RESULTS: Anaesthesiologists and their assistants exhibited the highest levels of plasma fluoride, serum IFN-γ and IL 2, exceeding the levels in detected in all the other occupational subgroups. Furthermore, the serum levels of IL4 were significantly raised in anaesthesiologists and the difference between this group and other groups was statistically significant. However, compared with the other subgroups, surgeons exhibited elevated plasma TBARS and reduced CAT, GSHpx and SOD; these variances were also statistically significant. CONCLUSION AND RECOMMENDATIONS: The findings of this study indicate that operating room staff exposed to WAGs are vulnerable to experiencing immunotoxicity as the WAGs are considered to initiate oxidative stress and increase the levels of cytokines in serum. Thus, an education programme is warranted to inform staff working in environments where they may be subjected to WAGs on the effects that the gases can have upon their health and how to minimise their exposure to WAGs. An ongoing effort is also needed to ensure anaesthesia safety standards are maintained at all times. The findings of this study may provide a springboard for future research into occupational exposure to WAGs and their wider effect upon health.

Silver Citrate Nanoparticles Inhibit PMA-Induced TNFα Expression via Deactivation of NF-κB Activity in Human Cancer Cell-Lines, MCF-7.

BACKGROUND: The nuclear factor kappa-B (NF-κB) is a major transcription factor responsible for the production of numerous inflammatory mediators, including the tumor necrosis factor (TNFα), which has a lethal association with cancer's onset. The silver nanoparticles (AgNPs) are widely used in cancer treatment and several other biomedical applications. OBJECTIVE: The study aimed to determine the effects of silver citrate nanoparticles (AgNPs-CIT) on NF-κB activation together with TNFα mRNA/protein expressions in the phorbol myristate acetate (PMA)-stimulated MCF-7 human breast cancer cell-lines. METHODS: The AgNPs-CIT were synthesized by the reduction method, and the prepared AgNPs-CIT were characterized for their shape, absorption in UV-VIS electromagnetic radiations, size distribution, ζ-potential, and antioxidant activity. The MCF-7 cell-lines were pretreated with AgNPs-CIT and stimulated with PMA. The TNFα mRNA expressions were determined by real-time PCR, whereas the protein production was determined by the ELISA. The NF-κB activity was distinctly observed by highly-specific DNA-based ELISA, and by NF-κB-specific inhibitor, Bay 11-7082. RESULTS: The prepared AgNPs-CIT were spherical and have an absorption wavelength range of 381-452 nm wherein the particles size ranged between 19.2±0.1 to 220.77±0.12 nm with the charge range -9.99±0.8 to -34.63±0.1 mV. The prepared AgNPs-CIT showed comparative antioxidant activity at >40% inhibitions level of the DPPH radicals. The AgNPs-CIT were found to be non-toxic to MCF-7 cell-lines and inhibited PMA-induced activation of the NF-κBp65, and also the mRNA/protein expression of TNFα. CONCLUSION: This is the first report that showed AgNPs-CIT inhibited TNFα expression via deactivation of the NF-κB signaling event in stimulated breast cancer cells. The results have important implications for the development of novel therapeutic strategies for the prevention/treatment of cancers and/or inflammatory disorders.