Simple microfluidic devices for in situ detection of water contamination: a state-of-art review.

Water security is an important global issue that is pivotal in the pursuit of sustainable resources for future generations. It is a multifaceted concept that combines water availability with the quality of the water's chemical, biological, and physical characteristics to ensure its suitability and safety. Water quality is a focal aspect of water security. Quality index data are determined and provided via laboratory testing using expensive instrumentation with high maintenance costs and expertise. Due to increased practices in this sector that can compromise water quality, innovative technologies such as microfluidics are necessary to accelerate the timeline of test procedures. Microfluidic technology demonstrates sophisticated functionality in various applications due to the chip's miniaturization system that can control the movement of fluids in tiny amounts and be used for onsite testing when integrated with smart applications. This review aims to highlight the basics of microfluidic technology starting from the component system to the properties of the chip's fabricated materials. The published research on developing microfluidic sensor devices for monitoring chemical and biological contaminants in water is summarized to understand the obstacles and challenges and explore future opportunities for advancement in water quality monitoring.

Design, Synthesis, and Potent Anticancer Activity of Novel Indole-Based Bcl-2 Inhibitors.

The Bcl-2 family plays a crucial role in regulating cell apoptosis, making it an attractive target for cancer therapy. In this study, a series of indole-based compounds, U1-6, were designed, synthesized, and evaluated for their anticancer activity against Bcl-2-expressing cancer cell lines. The binding affinity, safety profile, cell cycle arrest, and apoptosis effects of the compounds were tested. The designed compounds exhibited potent inhibitory activity at sub-micromolar IC50 concentrations against MCF-7, MDA-MB-231, and A549 cell lines. Notably, U2 and U3 demonstrated the highest activity, particularly against MCF-7 cells. Respectively, both U2 and U3 showed potential BCL-2 inhibition activity with IC50 values of 1.2 ± 0.02 and 11.10 ± 0.07 µM using an ELISA binding assay compared with 0.62 ± 0.01 µM for gossypol, employed as a positive control. Molecular docking analysis suggested stable interactions of compound U2 at the Bcl-2 binding site through hydrogen bonding, pi-pi stacking, and hydrophobic interactions. Furthermore, U2 demonstrated significant induction of apoptosis and cell cycle arrest at the G1/S phase. Importantly, U2 displayed a favourable safety profile on HDF human dermal normal fibroblast cells at 10-fold greater IC50 values compared with MDA-MB-231 cells. These findings underscore the therapeutic potential of compound U2 as a Bcl-2 inhibitor and provide insights into its molecular mechanisms of action.

In silico and POM analysis for potential antimicrobial agents of thymidine analogs by using molecular docking, molecular dynamics and ADMET profiling.

Nucleoside analogs are an important, well-established class of clinically useful medicinal agents that exhibit potent antimicrobial activity. Thus, we designed to explore the synthesis and spectral characterization of 5'-O-(myristoyl)thymidine esters (2-6) for in vitro antimicrobial, molecular docking, molecular dynamics, SAR, and POM analyses. An unimolar myristoylation of thymidine under controlled conditions furnished the 5'-O-(myristoyl)thymidine and it was further converted into four 3'-O-(acyl)-5'-O-(myristoyl)thymidine analogs. The chemical structures of the synthesized analogs were ascertained by analyzing their physicochemical, elemental, and spectroscopic data. In vitro antimicrobial tests along with PASS, prediction indicated expectant antibacterial functionality of these thymidine esters compared to the antifungal activities. In support of this observation, their molecular docking studies have been performed against lanosterol 14α-demethylase (CYP51A1) and Aspergillus flavus (1R51) and significant binding affinities and non-bonding interactions were observed. The stability of the protein-ligand complexes was monitored by a 100 ns MD simulation and found the stable conformation and binding mode in a stimulating environment of thymidine esters. Pharmacokinetic predictions were studied to assess their ADMET properties and showed promising results in silico. SAR investigation indicated that acyl chains, lauroyl (C-12) and myristoyl (C-14), combined with deoxyribose, were most effective against the tested bacterial and fungal pathogens. The POM analyses provide the structural features responsible for their combined antibacterial/antifungal activity and provide guidelines for further modifications, with the aim of improving each activity and selectivity of designed drugs targeting potentially drug-resistant microorganisms. It also opens avenues for the development of newer antimicrobial agents targeting bacterial and fungal pathogens.

A novel series of 5´-O-(myristoyl)thymidine derivatives were synthesized and characterized by FTIR, ¹H-NMR, 2D-NMR, ¹³C-NMR, mass and physicochemical studies.In vitro antimicrobial susceptibility revealed that alkyl chain and aromatic substituents can improve the antimicrobial efficacy of the thymidine structure which was also supported by PASS enumeration.Molecular docking study against lanosterol 14α-demethylase (CYP51A1) and Aspergillus flavus (1R51) exhibited a promising binding score and interaction in the catalytic active site.A 100ns MD simulation revealed the stable conformation and binding pattern in a stimulating environment of thymidine derivatives.ADMET analysis revealed that most of the compounds are non-toxic and most of them have an inhibitory property to the CYP1A2 and CYP3A4In silico and POM analyses provide substantial ideas about the structural features responsible for their combined antibacterial/antifungal agents and provide guidelines for further modifications.

Exploring Antimicrobial Features for New Imidazo[4,5-b]pyridine Derivatives Based on Experimental and Theoretical Study.

5-bromopyridine-2,3-diamine reacted with benzaldehyde to afford the corresponding 6-Bromo-2-phenyl-3H-imidazo[4,5-b]pyridine (1). The reaction of the latter compound (1) with a series of halogenated derivatives under conditions of phase transfer catalysis solid-liquid (CTP) allows the isolation of the expected regioisomers compounds (2-8). The alkylation reaction of (1) gives, each time, two regioisomers, N3 and N4; in the case of ethyl bromoactate, the reaction gives, at the same time, the three N1, N3 and N4 regioisomers. The structures of synthesized compounds were elucidated on the basis of different spectral data (1H NMR, 13C NMR), X-Ray diffraction and theoretical study using the DFT method, and confirmed for each compound. Hirshfeld surface analysis was used to determine the intermolecular interactions responsible for the stabilization of the molecule. Density functional theory was used to optimize the compounds, and the HOMO-LUMO energy gap was calculated, which was used to examine the inter/intra molecular charge transfer. The molecular electrostatic potential map was calculated to investigate the reactive sites that were present in the molecule. In order to determine the potential mode of interactions with DHFR active sites, the three N1, N3 and N4 regioisomers were further subjected to molecular docking study. The results confirmed that these analogs adopted numerous important interactions, with the amino acid of the enzyme being targeted. Thus, the most docking efficient molecules, 2 and 4, were tested in vitro for their antibacterial activity against Gram-positive bacteria (Bacillus cereus) and Gram-negative bacteria (Escherichia coli). Gram-positive bacteria were more sensitive to the action of these compounds compared to the Gram-negative, which were much more resistant.

Phenolic Contents and Antioxidant Activity of Citrullus colocynthis Fruits, Growing in the Hot Arid Desert of the UAE, Influenced by the Fruit Parts, Accessions, and Seasons of Fruit Collection.

Citrullus colocynthis (Cucurbitaceae) is an important medicinal plant traditionally used in the United Arab Emirates (UAE). In a recent study, it has been reported that different individuals of the same population of C. colocynthis, growing in the hot arid desert of the UAE, exhibited variations in their fruit size, color, and stripe pattern. In addition, these plants differed genetically, and their seeds showed variation in size, color, and germination behavior (hereinafter, these individuals are referred to as accessions). In the present study, the total phenolic content (TPC) and antioxidant activity of different fruit parts (rinds, pulps, and seeds) of three different accessions with significant genetic variations, from a single C. colocynthis population, were assessed in response to different seasonal environments. Green fruits were collected in summer and winter from three accessions growing in the botanic garden of the University of Sharjah, UAE. Methanolic extracts from different fruit parts were prepared. The TPC was qualitatively determined by a Folin-Ciocalteu assay, while the antioxidant capacity was analyzed using the 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) radical scavenging ability. The metabolic profiling of the antioxidant metabolites was determined using a gas chromatograph coupled to mass spectrometry (GC-MS), associated with a literature search. The results showed that the TPC and the DPPH free radical scavenging activity varied between seasons, accessions, and fruit parts. The highest phenolics were in rinds, but the highest antioxidant activities were in seeds during the summer, reflecting the role of these compounds in protecting the developed seeds from harsh environmental conditions. The metabolomic analysis revealed the presence of 28 metabolites with significant antioxidant activities relevant to fruit parts and season. Collectively, the formation of phenolics and antioxidant activity in different fruit parts is environmentally and genetically dependent.

Lipid-based therapies against SARS-CoV-2 infection.

Viruses have evolved to manipulate host lipid metabolism to benefit their replication cycle. Enveloped viruses, including coronaviruses, use host lipids in various stages of the viral life cycle, particularly in the formation of replication compartments and envelopes. Host lipids are utilised by the virus in receptor binding, viral fusion and entry, as well as viral replication. Association of dyslipidaemia with the pathological development of Covid-19 raises the possibility that exploitation of host lipid metabolism might have therapeutic benefit against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this review, promising host lipid targets are discussed along with potential inhibitors. In addition, specific host lipids are involved in the inflammatory responses due to viral infection, so lipid supplementation represents another potential strategy to counteract the severity of viral infection. Furthermore, switching the lipid metabolism through a ketogenic diet is another potential way of limiting the effects of viral infection. Taken together, restricting the access of host lipids to the virus, either by using lipid inhibitors or supplementation with exogenous lipids, might significantly limit SARS-CoV-2 infection and/or severity.

SARS-CoV-2 spike protein: pathogenesis, vaccines, and potential therapies.

PURPOSE: COVID-19 pandemic has emerged as a result of infection by the deadly pathogenic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), causing enormous threats to humans. Coronaviruses are distinguished by a clove-like spike (S) protein, which plays a key role in viral pathogenesis, evolutions, and transmission. The objectives of this study are to investigate the distinctive structural features of SARS-CoV-2 S protein, its essential role in pathogenesis, and its use in the development of potential therapies and vaccines. METHODOLOGY: A literature review was conducted to summarize, analyze, and interpret the available scientific data related to SARS-CoV-2 S protein in terms of characteristics, vaccines development and potential therapies. RESULTS: The data indicate that S protein subunits and their variable conformational states significantly affect the virus pathogenesis, infectivity, and evolutionary mutation. A considerable number of potential natural and synthetic therapies were proposed based on S protein. Additionally, neutralizing antibodies were recently approved for emergency use. Furthermore, several vaccines utilizing the S protein were developed. CONCLUSION: A better understanding of S protein features, structure and mutations facilitate the recognition of the importance of SARS-CoV-2 S protein in viral infection, as well as the development of therapies and vaccines. The efficacy and safety of these therapeutic compounds and vaccines are still controversial. However, they may potentially reduce or prevent SARS-CoV-2 infection, leading to a significant reduction of the global health burden of this pandemic.

Promising anti-SARS-CoV-2 drugs by effective dual targeting against the viral and host proteases.

SARS-CoV-2 caused dramatic health, social and economic threats to the globe. With this threat, the expectation of future outbreak, and the shortage of anti-viral drugs, scientists were challenged to develop novel antivirals. The objective of this study is to develop novel anti-SARS-CoV-2 compounds with dual activity by targeting valuable less-mutated enzymes. Here, we have mapped the binding affinity of >500,000 compounds for potential activity against SARS-CoV-2 main protease (Mpro), papain protease (PLpro) and human furin protease. The enzyme inhibition activity of most promising hits was screened and tested in vitro on SARS-CoV-2 clinical isolate incubated with Vero cells. Computational modelling and toxicity of the compounds were validated. The results revealed that 16 compounds showed potential binding activity against Mpro, two of them showed binding affinity against PLpro and furin protease. Respectively, compounds 7 and 13 showed inhibition activity against Mpro at IC50 0.45 and 0.11 µM, against PLpro at IC50 0.085 and 0.063 µM, and against furin protease at IC50 0.29 µM. Computational modelling validated the binding affinity against all proteases. Compounds 7 and 13 showed significant inhibition activity against the virus at IC50 0.77 and 0.11 µM, respectively. Both compounds showed no toxicity on mammalian cells. The data obtained indicated that compounds 7 and 13 exhibited potent dual inhibition activity against SARS-CoV-2. The dual activity of both compounds can be of great promise not only during the current pandemic but also for future outbreaks since the compounds' targets are of limited mutation and critical importance to the viral infection.

Design, synthesis, and computational validation of novel compounds selectively targeting HER2-expressing breast cancer.

Human epidermal growth factor receptor (HER) is a family of multidomain proteins that plays important role in the regulation of several biological functions. HER2 is a member of HER that is highly presented in breast cancer cells. Here, we designed and synthesized a series of diaryl urea/thiourea compounds. The compounds were tested on HER2+ breast cancer cells including MCF-7 and SkBr3, compared to HER2- breast cancer cells including MDA-MB-231 and BT-549. Only compounds 12-14 at 10 µM showed selective anti-proliferative activity against MCF-7 and SkBr3 by 65-79%. Compounds 12-14 showed >80% inhibition of the intracellular kinase domain of HER2. The results obtained indicated that compounds 12-14 are selectively targeting HER2+ cells. The IC50 of compound 13 against MCF-7 and SkBR3 were 1.3 ± 0.009 and 0.73 ± 0.03 µM, respectively. Molecular docking and MD simulations (50 ns) were carried out, and their binding free energies were calculated. Compounds 12-14 formed strong hydrogen bond and pi-pi stacking interactions with the key residues Thr862 and Phe864. 3DQSAR model confirmed the role of 3-bromo substituent of pyridine ring and 4-chloro substituent of phenyl ring in the activity of the compounds. In conclusion, novel compounds, particularly 13 were developed selectively against HER2-expressing/overexpressing breast cancer cells including MCF7 and SkBr3.

Effective targeting of breast cancer cells (MCF7) via novel biogenic synthesis of gold nanoparticles using cancer-derived metabolites.

Biogenic synthesis of nanoparticles provides many advantages over synthetic nanoparticles including clean and non-toxic approaches. Nanoparticle-based application for the development of diagnostics and therapeutics is a promising field that requires further enrichment and investigation. The use of biological systems for the generation of gold nanoparticles (AuNPs) has been extensively studied. The search for a biocompatibility approach for the development of nanoparticles is of great interest since it can provide more targeting and less toxicity. Here, we reported a bio-reductive approach of gold to AuNPs using metabolites extracted from mammalian cells, which provided a simple and efficient way for the synthesis of nanomaterials. AuNPs were more efficiently synthesized by the metabolites extracted from breast cancer (MCF7) and normal fibroblasts (F180) cells when compared to metabolites extracted from cell-free supernatants. The metabolites involved in biogenic synthesis are mainly alcohols and acids. Spectroscopic characterization using UV-visible spectra, morphological characterization using electron microscopy and structural characterization using X-ray diffraction (XRD) confirmed the AuNPs synthesis from mammalian cells metabolites. AuNPs generated from MCF7 cells metabolites showed significant anticancer activities against MCF7 and low toxicity when compared to those generated from F180 cells metabolites. The results reflected the cytotoxic activities of the parent metabolites extracted from MCF7 versus those extracted from F180. Comparative metabolomics analysis indicated that MCF7-generated AuNPs harbored tetratetracontane, octacosane, and cyclotetradecane while those generated from F180 harbored a high percentage of stearic, palmitic, heptadecanoic acid. We related the variation in cytotoxic activities between cell types to the differences in AuNPs-harboring metabolites. The process used in this study to develop the nanoparticles is novel and should have useful future anticancer applications mainly because of proper specific targeting to cancer cells.

GC-MS based comparative metabolomic analysis of MCF-7 and MDA-MB-231 cancer cells treated with Tamoxifen and/or Paclitaxel.

Breast cancer cells MCF-7 and MDA-MB-231 were treated with Tamoxifen (5 µM) or Paclitaxel (1 µM) or with a combination of the two drugs. Herein, we have employed gas chromatography coupled with mass spectroscopy to identify metabolic changes occurring as response to different drug treatments. We report the identification of sixty-one metabolites and overall the two studied cell lines showed a distinct metabolomic profile from each other. Further data analysis indicates that a total of 30 metabolites were significantly differentially abundant in MCF-7 drug-treated cells, most of the metabolic changes occurred when cells were treated with either Tamoxifen (15) or Paclitaxel (25). On the other side, a total of 31 metabolites were significantly differentially abundant in MDA-MB-31 cells with drug treatment. Similarly, to MCF-7 most of the metabolic changes occurred when cells were treated with either Tamoxifen (19) or Paclitaxel (20). In conclusion, this report demonstrates that Tamoxifen and/or Paclitaxel treatment have a pronounced effect on the main metabolic pathways in both breast cancer (BC) cell lines (MCF-7 and MDA-MB231), which could be used as a foundation for future investigations to understand the possible effect of these drugs on different metabolic pathways. SIGNIFICANCE: Metabolic profiling of cancer cells is a promising tool in tumor diagnosis, biomarker discovery and drug treatment protocols, since cancer cells exhibit altered metabolism when compared to normal cells. Although numerous studies have reported the use of various OMICs applications to investigate breast cancer cells, very few of these have performed thorough screening of metabolites in such cells. Our investigation highlights the first study to characterize MCF7 and MDA-MB-231 cancer cells treated with Tamoxifen and/or Paclitaxel and to identify the affected metabolic pathways. Such findings might play an important role in revealing the molecular bases of the underlying mechanism of action of these two frontline anti-breast cancer drugs.

Green and cytocompatible carboxyl modified gold-lysozyme nanoantibacterial for combating multidrug-resistant superbugs.

The dissemination of multi-drug resistant (MDR) superbugs in hospital environments, communities and food animals and the very dynamic bacterial mutation frequency require the development of prolonged therapeutic strategies to gain mastery over antibiotic resistance. A AuNP-lysozyme nanoantibacterial was fabricated by the conjugation of AuNPs-C6H4-4-COOH with lysozyme via green reduction of aryldiazonium gold(iii) salt [HOOC-4-C6H4N[triple bond, length as m-dash]N]AuCl4. Results from molecular docking calculations aimed at revealing the binding mode of benzoic acid with the lysozyme structure clearly showed the lowest energy conformation with benzoic acid bound in the deep buried hydrophobic cavity of the protein active site through strong hydrogen bonding and hydrophobic interactions, thus validating the experimental outcomes of the current study which also exhibited the binding of -COOH functional groups in the interior of the protein structure. The superiority of the lysozyme bioconjugate against superbugs was demonstrated by the enhanced and broadened lysozyme antibacterial activities of 98-99% against extended spectrum beta lactamase (ESBL) producing Escherichia coli and imipenem-resistant Pseudomonas aeruginosa clinical isolates and a selection of Gram-negative and Gram-positive standard ATCC strains. Selective toxicity against bacteria was confirmed by the high viability of HeLa and fibroblast cell lines and the outstanding hemocompatibility at the minimum bacterial inhibitory concentrations (MICs). Turbidimetric enzyme kinetic assay showed the enhancement of the lysozyme hydrolytic activity by gold nanoparticles on the Micrococcus lysodeikticus bacterial substrate. Using gel electrophoresis, the induced cell wall breakdown was confirmed by detecting the leaked-out bacterial genomic DNA. The integrity and morphology changes of the E. coli bacteria were investigated using a scanning electron microscope after one hour of contact with the lysozyme-gold bioconjugate. The antibacterial functionalities showed little or no damage to healthy human cells and can be applied to wound dressings and medical devices.

Antibacterial, antifungal and antioxidant activity of total polyphenols of Withania frutescens.L.

Our objective in this work is evaluated the antibacterial, antifungal and antioxidant activity of the phytochymic compounds of the roots and leaves of a species Withania frutescens. In the first part, the phenolic compound is determinate by the Folin-Ciocalteau reaction, the richness of the roots in polyphenols (53.33 ±â€¯1.20 mg EGA/g Extract) is six times higher than that of the leaves. The antioxidant test is evaluated by four methods: DPPH test, reducing power test (FRAP), total antioxidant capacity (CAT) and the ß-carotene discoloration test. The IC-50 values of the DPPH test of the studied parts are of the order of 0.36 µg/ml and 6.63 µg/ml, which showed a lower anti-free radical activity than that of BHT (0.12 µg/ml). The results obtained by the FRAP method revealed a low reducing power of iron for two extracts (EC-50 of 0.45%) compared to Quercetine (EC-50 of 0.03%). The compounds of root and leaf extracts have a significant total antioxidant capacity, respectively 477.65 ±â€¯37.60 and 317.03 ±â€¯46.64 mg EAA/g Extract. In the ß-carotene discoloration test, extracts from the aerial and underground parts showed antioxidant activity of 57% followed by (36%), respectively. The evaluation of the antibacterial activity of in vitro extracts against microorganisms is carried out by two methods: disc diffusion and microdilution. The results show that the extracts exert an intermediate inhibitory effect (inhibition diameter between 8 and 15 mm, the smallest MIC obtained is 2.80 mg/ml) on all strains tested. The antifungal activity was estimated by determining the growth inhibition rate of the fungus tested. Indeed, the compounds studied exhibit a good antifungal effect since the minimum inhibitory concentration (MIC) of 4.5 mg/ml for root extract and 9 mg/ml for leaf extract.

Helicobacter pylori profile in asymptomatic farmers and non-farmers.

There is a positive correlation between Helicobacter pylori infection and chronic active gastritis, peptic ulcer and gastric cancer and maltoma. There is little information on H. pylori profiles in farmers and non-farmers in the literature. Our main objective was to study the H. pylori profiles in farmers and non-formers in the United Arab Emirates. A prospective study of 151 subjects - 76 farmers and 75 non-farmers - was undertaken by determining their IgG and IgA H. pylori antibody profiles in their serum samples. Data on lifestyle were obtained from them. Eligible subjects were those who had engaged in farming for at least five years and who had not received an anti-H. pylori treatment during the six months prior to admission into the study. Most of the farmers lived in less modern accommodation, were less educated, ate their vegetable products unwashed, did not have drinking water facilities, when compared to non-farmers. Helicobacter pylori serology by IgG and IgA was positive in 112 and 77 subjects respectively (p < 0.0001). The sensitivity values for IgG and IgA serology tests were 74.2 and 51.0% respectively (p < 0.001). There were 59 and 42 H. pylori-positive farmers by IgG and IgA H. pylori serology tests respectively (p < 0.001). Among the non-farmers, the corresponding figures were 53 and 25 (p < 0.01), and neither IgG nor IgA (p = 0.4), respectively. The H. pylori serology test was able to differentiate between farmers and non-farmers. When the discordant values between IgG and IgA tests were computed for each group of subjects, the difference was significant for both farmers and non-farmers (p < 0.001 in each case). There was no difference between the farmers and non-farmers in respect of their H. pylori profiles. The farmers have a lower standard of living than non-farmers.

Aerobiological studies and low allerginicity of date-palm pollen in the UAE.

Date-Palm trees (Phoenix dactylifera L.) are the most abundant crop in the United Arab Emirates (UAE). The aim of this work was to conduct aerobiological studies on Date-Palm pollens and correlate that to allergenicity. An aerobiological survey was performed at three Date-Palm farms. Radioallergosorbent test (RAST) and total IgE were performed on 477 airborne allergic patients. Small mass bioactive constituents were fractionated and isolated by HPLC. Aerobiological studies demonstrate the short distance traveled by the Date-Palm pollens. Pollen counts were about 800 counts/m3 within the Date-Palm farms and decreased by about 80% just 100 meters away from the farm area and almost diminished beyond 200 meters. Scanning electron micrograph of the pollen grain showed a uniform smooth texture with an oval shape. Out of 477 airborne allergic patients having high total IgE counts, only 2.3% gave positive RAST for Date-Palm pollen. HPLC chromatogram separated the non-protein content of Date-Palm pollen into four distinct peak fractions. The present study revealed that Date-Palm pollens have a low allergic effect on airborne allergic people. The short distance traveled by the pollen, the smooth texture, the short pollination period and low molecular weight biomolecule content may be the main factors behind the low allergenicity.