Toxic Effects of Trichloroethylene on Rat Neuroprogenitor Cells

Trichloroethylene (TCE) is a common volatile organic solvent which is considered as an ubiquitous environmental pollutant. It is claimed to be a developmental neurotoxicant. Our group evaluated previously its impact on three-dimensional neurospheres in vitro. The current work aims to investigate the neurotoxic effects of a lower concentration of TCE on the same system. To perform the experiment, neural progenitor cells were obtained from the brains of nine newborn rats. Afterward, these cells were cultured in both growth and differentiation media to get the neurospheres. Cell cultures were divided into two groups: group 1 (control), group 2 (exposed to 0.25 μM TCE). Neurospheres were photographed at different durations and assessment of the morphological changes such as proliferation and differentiation of neurospheres was done. In addition, cell viability, apoptosis, and necrosis were analyzed using flow cytometry to clarify the mechanism of involved cytotoxicity. The results revealed that TCE-treated neurospheres showed significantly decreased proliferation on days 7 and 14. These cells failed to show the neurogenic differentiation seen in the neurospheres of the control group. Furthermore, a highly significant decrease in viability and a significant increase in the number of apoptotic cells were observed in the treated cells in comparison to the control group. The present work confirmed that TCE, at very low doses relevant to daily life exposure in humans, caused neurotoxic effects in 3D neurosphere model through the affection of neural proliferation and differentiation as well as disturbance of cell viability and apoptosis

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Functionalization of magnetic chitosan microparticles – Comparison of trione and trithione grafting for enhanced silver sorption and application to metal recovery from waste X-ray photographic films

International audienceMagnetic chitosan microparticles (MC) are successfully functionalized by grafting two pyrimidine derivatives (bearing either trione, MC-PYO, or trithione groups, MC-PYS). The sorbents are characterized using SEM, TEM, BET, TGA, FTIR, titration, and elemental analysis. The study focuses on the comparison of the differential effects of functionalized groups on the sorption of silver. FTIR analysis shows the contributions of N-based, carbonyl, hydroxyl for silver binding onto MC-PYO, completed by sulfur contribution in the case of MC-PYS. Maximum sorption capacities at pH 6 reach 1.9 and 2.3 mmol Ag g-1 for MC-PYO and MC-PYS, respectively. The Langmuir and the Sips equations fit sorption isotherms. The reactive groups affect the thermodynamic characteristics: endothermic for MC-PYS against exothermic for MC-PYO. The affinity of S-based soft ligand in MC-PYS for soft metals makes the sorbent selective for Ag(I). On the opposite hand, for MC-PYO the O-based functional groups readily bind hard metals (HSAB principle), involving less selective for silver recovery (from multi-component solutions). QSAR method (quantitative structure-activity relationships) allows correlating preferentially sorption properties with the covalent index. Nitric acid solutions (0.3 M) are highly efficient for total desorption of silver from metal-loaded sorbents, but soft enough to maintain remarkable sorption and desorption performances for at least five cycles. The sorbents are successfully applied to Ag(I) recovery from acidic leachate of waste photographic films: metal removal is enhanced at pH 5.2; MC-PYS is more efficient and selective than MC-PYO at pH 2.2

In Vitro Anticancer Activity of Novel Ciprofloxacin Mannich Base in Lung Adenocarcinoma and High-Grade Serous Ovarian Cancer Cell Lines via Attenuating MAPK Signaling Pathway

Novel drugs are desperately needed in order to combat a significant challenge due to chemo-therapeutic resistance and bad prognosis. This research aimed to assess the anticancer activity of a newly synthesized ciprofloxacin Mannich base (CMB) on ovarian cancer (OVCAR-3) and lung cancer (A-549) cell lines and to investigate probable involved molecular mechanisms. The cytotoxic and pro-apoptotic impact of CMB on both cell lines was investigated using MTT assay, Annexin V assay, and cell cycle analysis, as well as caspase-3 activation. Western blotting was carried out to evaluate downstream targets of the MAPK pathway, while qRT PCR was used to evaluate the gene expression pattern of the p53/Bax/Bcl2 pathway. CMB treatment showed significantly reduced cell proliferation in both OVCAR-3 and A-549 cells with half maximum inhibitory concentration (IC50) = 11.60 and 16.22 µg/mL, respectively. CMB also induced apoptosis, S phase cell cycle arrest, and up-regulated expression of p53, p21, and Bax while down-regulated Bcl2 expression. CMB also halted cell proliferation by deactivating the MAPK pathway. In conclusion, CMB may be regarded as a potential antiproliferative agent for lung and ovarian cancers due to anti-proliferative and pro-apoptotic actions via inhibition of the MAPK pathway and p53/Bax/Bcl2

In Vitro Anticancer Activity of Novel Ciprofloxacin Mannich Base in Lung Adenocarcinoma and High-Grade Serous Ovarian Cancer Cell Lines via Attenuating MAPK Signaling Pathway

Novel drugs are desperately needed in order to combat a significant challenge due to chemo-therapeutic resistance and bad prognosis. This research aimed to assess the anticancer activity of a newly synthesized ciprofloxacin Mannich base (CMB) on ovarian cancer (OVCAR-3) and lung cancer (A-549) cell lines and to investigate probable involved molecular mechanisms. The cytotoxic and pro-apoptotic impact of CMB on both cell lines was investigated using MTT assay, Annexin V assay, and cell cycle analysis, as well as caspase-3 activation. Western blotting was carried out to evaluate downstream targets of the MAPK pathway, while qRT PCR was used to evaluate the gene expression pattern of the p53/Bax/Bcl2 pathway. CMB treatment showed significantly reduced cell proliferation in both OVCAR-3 and A-549 cells with half maximum inhibitory concentration (IC50) = 11.60 and 16.22 µg/mL, respectively. CMB also induced apoptosis, S phase cell cycle arrest, and up-regulated expression of p53, p21, and Bax while down-regulated Bcl2 expression. CMB also halted cell proliferation by deactivating the MAPK pathway. In conclusion, CMB may be regarded as a potential antiproliferative agent for lung and ovarian cancers due to anti-proliferative and pro-apoptotic actions via inhibition of the MAPK pathway and p53/Bax/Bcl2

A New EGFR Inhibitor from <i>Ficus benghalensis</i> Exerted Potential Anti-Inflammatory Activity via Akt/PI3K Pathway Inhibition

Inflammation is a critical defensive mechanism mainly arising due to the production of prostaglandins via cyclooxygenase enzymes. This study aimed to examine the anti-inflammatory activity of fatty acid glucoside (FAG), which is isolated from Ficus benghalensis against lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The cytotoxic activity of the FAG on RAW 264.7 macrophages was evaluated with an MTT assay. The levels of PGE2 and NO and the activity of iNOS, COX-1, and COX-2 enzymes in LPS-stimulated RAW 264.7 cells were evaluated. The gene expression of IL-6, TNF-α, and PGE2 was investigated by qRT-PCR. The expression of epidermal growth factor receptor (EGFR), Akt, and PI3K proteins was examined using Western blotting analysis. Furthermore, molecular docking of the new FAG against EGFR was investigated. A non-cytotoxic concentration of FAG increased NO release and iNOS activity, inhibited COX-1 and COX-2 activities, and reduced PGE2 levels in LPS-stimulated RAW 264.7 cells. It diminished the expression of TNF-α, IL-6, PGE2, EGFR, Akt, and PI3K. Furthermore, the molecular docking study proposed the potential direct binding of FAG with EGFR with a high affinity. This study showed that FAG is a natural EGFR inhibitor, NO-releasing, and COX-inhibiting anti-inflammatory agent via EGFR/Akt/PI3K pathway inhibition