Modification of bacterial cell membrane to accelerate decolorization of textile wastewater effluent using microbial fuel cells: role of gamma radiation

The aim of the present work was to increase bacterial adhesion on anode via inducing membrane modifications to enhance textile wastewater treatment in Microbial Fuel Cell (MFC). Real textile wastewater was used in mediator-less MFCs for bacterial enrichment. The enriched bacteria were pre-treated by exposure to 1 KGy gamma radiation and were tested in MFC setup. Bacterial cell membrane permeability and cell membrane charges were measured using noninvasive dielectric spectroscopy measurements. The results show that pre-treatment using gamma radiation resulted in biofilm formation and increased cell permeability and exopolysaccharide production; this was reflected in both MFC performance (average voltage 554.67 mV) and decolorization (96.42%) as compared to 392.77 mV and 60.76% decolorization for non-treated cells. At the end of MFC operation, cytotoxicity test was performed for treated wastewater using a dermal cell line, the results obtained show a decrease in toxicity from 24.8 to 0 (v/v%) when cells were exposed to gamma radiation. Fourier-transform infrared (FTIR) spectroscopy showed an increase in exopolysaccharides in bacterial consortium exposed to increasing doses of gamma radiation suggesting that gamma radiation increased exopolysaccharide production, providing transient media for electron transfer and contributing to accelerating MFC performance. Modification of bacterial membrane prior to MFC operation can be considered highly effective as a pre-treatment tool that accelerates MFC performance

Hepatitis C treatment: where are we now?

Chronic hepatitis C infection affects millions of people worldwide and confers significant morbidity and mortality. Effective treatment is needed to prevent disease progression and associated complications. Previous treatment options were limited to interferon and ribavirin regimens, which gave low cure rates and were associated with unpleasant side effects. The era of direct acting antiviral (DAA) therapies began with the development of the first-generation of NS3/4A protease inhibitors (PI) in 2011. They vastly improved outcomes for patients, particularly those with genotype 1 infection, the most prevalent genotype globally. Since then a multitude of DAAs have been licensed for use and outcomes for patients have improved further, with fewer side effects and cure rates approaching 100%. Recent regimens are interferon-free, and in many cases, ribavirin-free and involve a combination of DAA agents. This review summarises the treatment options currently available and discusses potential barriers that may delay the global eradication of hepatitis C

Analysis of endometrial biopsy reports from adult women with abnormal uterine bleeding, a cross-sectional descriptive study

Background: Abnormal uterine bleeding is a common complaint in most women of different ages that prompts seeking gynecologic care. This study aimed to analyze and age-classify the prevalence of endometrial pathologies in women with abnormal uterine bleeding.Methods: This is a cross-sectional and a descriptive study, conducted at the obstetrics and gynecology department of the American Mission Hospital in the Kingdom of Bahrain on 88 patients who presented with abnormal uterine bleeding between January 2019 and January 2020.Results: Eighty-eight women with abnormal uterine bleeding demonstrated a fluctuating pattern of twenty endometrial pathologies distributed among five age groups in the range of 30-71. The mean age of the study cohort was 44.9±7.65 years; 55% of which were reported in the 41-50 age group. Benign endometrial polyp was reported as the most common pathology, accounting for 47.8% of the cohort. Although benign endometrial polyp was significantly the highest overall finding in all three age groups younger than 60, disordered proliferative endometrium was the highest reported single pathology in the age group 41-50, (N=10, p≤0.0001).Conclusions: This study demonstrated that benign endometrial polyp was the most common finding in women with abnormal uterine bleeding. This information could be essential for patient guidance and awareness of the benefits of endometrial biopsy. Eventually, the prediction of the potential endometrial pathology in women with abnormal uterine bleeding is vital for early disease management

Design, synthesis, crystal structures and biological evaluation of some 1,3-thiazolidin-4-ones as dual CDK2/EGFR potent inhibitors with potential apoptotic antiproliferative effects

A series of novel thiazolidine-4-one derivatives was synthesized by reacting 1,4-disubstituted hydrazine carbothioamides with diethyl azodicarboxylate. The structures were confirmed by spectroscopic data as well as single-crystal X-ray analyses. The antiproliferative activity of the synthesized compounds was investigated against four human cancer cell lines using an MTT assay. Compounds 5d, 5e, and 5f revealed the most potent antiproliferative activity with GI$_{50}$ values ranging from 0.70 µM to 1.20 µM, compared to doxorubicin GI$_{50}$ value = 1.10 µM. Compounds 5d, 5e, and 5f were further investigated for their inhibitory activities against CDK2 and EGFR as potential targets for their molecular mechanism. Compounds 5e and 5f have showed potent inhibitory activity to CDK2 enzyme with IC$_{50}$ values of 18 and 14 nM, which is more potent than the reference dinaciclib (IC$_{50}$ = 20 nM). Moreover, compounds 5e and 5f were the most potent EGFR inhibitors, with IC$_{50}$ values of 93 and 87 nM, respectively, compared to the reference erlotinib (IC$_{50}$ = 70 nM). In addition, the most potent derivatives were tested for their apoptotic activity against caspases 3, 8, and 9, and the results showed that compounds 5d, 5e, and 5f revealed a greater increase in active caspases 3,8 and 9 than doxorubicin. Also, compounds 5d, 5e, and 5f elevated cytochrome C levels in the MCF-7 human breast cancer cell line by about 15.5, 15.8, and 16.5 times, respectively. Finally, a molecular docking study was performed to investigate the binding sites of these compounds within the active sites of CDK2 and EGFR targets, and the results confirmed that the most potent CDK2 and EGFR inhibitor 5h also have showed the highest docking score

Design, synthesis, crystal structures and biological evaluation of some 1,3-thiazolidin-4-ones as dual CDK2/EGFR potent inhibitors with potential apoptotic antiproliferative effects

A series of novel thiazolidine-4-one derivatives was synthesized by reacting 1,4disubstituted hydrazine carbothioamides with diethyl azodicarboxylate. The structures were confirmed by spectroscopic data as well as single-crystal X-ray analyses. The antiproliferative activity of the synthesized compounds was investigated against four human cancer cell lines using an MTT assay. Compounds 5d, 5e, and 5f revealed the most potent antiproliferative activity with GI50 values ranging from 0.70 mM to 1.20 mM, compared to doxorubicin GI50 value = 1.10 mM. Compounds 5d, 5e, and 5f were further investigated for their inhibitory activities against CDK2 and EGFR as potential targets for their molecular mechanism. Compounds 5e and 5f have showed potent inhibitory activity to CDK2 enzyme with IC50 values of 18 and 14 nM, which is more potent than the reference dinaciclib (IC50 = 20 nM). Moreover, compounds 5e and 5f were the most potent EGFR inhibitors, with IC50 values of 93 and 87 nM, respectively, compared to the reference erlotinib (IC50 = 70 nM). In addition, the most potent derivatives were tested for their apoptotic activity against caspases 3, 8, and 9, and the results showed that compounds 5d, 5e, and 5f revealed a greater increase in active caspases 3,8 and 9 than doxorubicin. Also, compounds 5d, 5e, and 5f elevated cytochrome C levels in the MCF-7 human breast cancer cell line by about 15.5, 15.8, and 16.5 times, respectively. Finally, a molecular docking study was performed to investigate the binding sites of these compounds within the active sites of CDK2 and EGFR targets, and the results confirmed that the most potent CDK2 and EGFR inhibitor 5h also have showed the highest docking (c) 2022 The Author(s). Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Peer reviewe

Synthesis of novel amidines via one-pot three component reactions: Selective topoisomerase I inhibitors with antiproliferative properties

Novel series of amidines were synthesized via the interaction between alicyclic amines, cyclic ketones, and a highly electrophilic 4-azidoquinolin-2(1H)-ones without any catalyst or additive. All the obtained products were elucidated based on NMR spectroscopy, mass spectrometry, and elemental analysis. The reaction conditions were optimized using cyclohexanone (2), piperidine (3a), and 4-azido-quinolin-2(1H)-one (1a) under an air atmosphere. The new compounds 4a-l and 5a-c were tested for antiproliferative activity against four cancer cell lines using doxorubicin as a reference drug. The most potent derivatives were compounds 4b, 4d, 4e, 4i, and 5c, with GI$_{50}$ ranging from 1.00 µM to 1.50 µM. Compound 5c was the most effective derivative against the four cancer cell lines, outperforming doxorubicin. The compounds 4b, 4d, 4e, 4i, and 5c were studied further as topoisomerase I and IIα inhibitors. The compounds tested showed selective inhibition of topo I over topo IIα. Finally, docking studies explain why these compounds prefer topo I over topo IIα

Modification of bacterial cell membrane to accelerate decolorization of textile wastewater effluent using microbial fuel cells: role of gamma radiation, salinity and endogenous biosurfactant induction

A combined approach was investigated to accelerate Microbial Fuel Cell (MFC) performance and textile wastewater decolorization through modifying bacterial membrane. The aim was to increase both bacterial adhesion on anode and electron mediator release. Ten Gram-positive exoelectrogenic bacteria were isolated from the anodic biofilm after decolorization of real textile waste water in mediator-less MFC. The isolates were identified and characterized, to understand the nature of the bacteria involved. According to the battery of tests performed, three factors gamma radiation, salinity and induction of endogenous biosurfactant were involved membrane modification. Dielectric measurement, a non-invasive technique, was used to measure the cell membrane permeability and cell surface charge. Plackett-Burman experimental design was carried out to determine the key contributor among the three studied factors. Exposing the cells to 1 KGy gamma radiation led to 7.84- and 1.71- fold increase in total surface-charge and cell-permeability, respectively. Scanning Electron Microscope (SEM) images and surface-bound protein concentrations for the samples indicated that biofilm formation increased under the same conditions. These results have been reflected on the power density profiles and decolorization of textile wastewater. Modification of bacterial membrane prior to MFC operation can be considered highly effective as a pre-treatment tool that accelerates MFC performance

Decolorization of synthetic melanoidins-containing wastewater by a bacterial consortium

The presence of melanoidins in molasses wastewater leads to water pollution both due to its dark brown color and its COD contents. In this study, a bacterial consortium isolated from waterfall sediment was tested for its decolorization. The identification of culturable bacteria by 16S rDNA based approach showed that the consortium composed of Klebsiella oxytoca, Serratia mercescens, Citrobacter sp. and unknown bacterium. In the context of academic study, prevention on the difficulties of providing effluent as well as its variations in compositions, several synthetic media prepared with respect to color and COD contents based on analysis of molasses wastewater, i.e., Viandox sauce (13.5% v/v), caramel (30% w/v), beet molasses wastewater (41.5% v/v) and sugarcane molasses wastewater (20% v/v) were used for decolorization using consortium with color removal 9.5, 1.13, 8.02 and 17.5%, respectively, within 2 days. However, Viandox sauce was retained for further study. The effect of initial pH and Viandox concentration on decolorization and growth of bacterial consortium were further determined. The highest decolorization of 18.3% was achieved at pH 4 after 2 day of incubation. Experiments on fresh or used medium and used or fresh bacterial cells, led to conclusion that the limitation of decolorization was due to nutritional deficiency. The effect of aeration on decolorization was also carried out in 2 L laboratory-scale suspended cell bioreactor. The maximum decolorization was 19.3% with aeration at KLa = 2.5836 h-1 (0.1 vvm)

Effect of microneedles on transdermal permeation enhancement of amlodipine

The present study aimed to investigate the effect of microneedle (MN) geometry parameters like length, density, shape and type on transdermal permeation enhancement of amlodipine (AMLO). Two types of MN devices viz. AdminPatch® arrays (ADM) (0.6, 1.2 and 1.5 mm lengths) and laboratory-fabricated polymeric MNs (PM) of 0.6 mm length were employed. In the case of PMs, arrays were applied thrice at different places within a 1.77-cm2 skin area (PM-3) to maintain the MN density closer to 0.6 mm ADM. Scaling analyses were done using dimensionless parameters like concentration of AMLO (Ct/Cs), thickness (h/L) and surface area of the skin (Sa/L2). Microinjection moulding technique was employed to fabricate PM. Histological studies revealed that the PM, owing to their geometry/design, formed wider and deeper microconduits when compared to ADM of similar length. Approximately 6.84- and 6.11-fold increase in the cumulative amount (48 h) of AMLO permeated was observed with 1.5 mm ADM and PM-3 treatments respectively, when compared to passive permeation amounts. Good correlations (R2 > 0.89) were observed between different dimensionless parameters with scaling analyses. The enhancement in AMLO permeation was found to be in the order of 1.5 mm ADM ≥ PM-3 > 1.2 mm ADM > 0.6 mm ADM ≥PM-1 > passive. The study suggests that MN application enhances the AMLO transdermal permeation and the geometrical parameters of MNs play an important role in the degree of such enhancement

Expression of the retinoic acid catabolic enzyme CYP26B1 in the human brain to maintain signaling homeostasis

Date of Acceptance: 27/08/2015 Funding was provided by the Wellcome Trust grant WT081633MA-NCE and Biological Sciences Research Council Grant BB/K001043/1. Prof Fragoso is the recipient of a Post Doctoral Science without Borders grant from the Brazilian National Council for Scientific and Technological Development (CNPq, 237450/2012-7).Peer reviewedPublisher PD