Assessment of elemental chemistry, spatial distribution, and potential risks of road-deposited dusts in Sharjah, United Arab Emirates.

Road dust is a major source of pollution in the environment, carrying different pollutants, including heavy metals and metalloids, from one location to another. This study assesses the concentrations of eight heavy metals and one metalloid (Zn, Pb, Mn, Fe, Cr, Cu, Cd, Ni, and As) in dust samples collected from sixty-eight streets of Sharjah, United Arab Emirates using ICP-OES, as well as investigates their effects on both the environment and humans. Mean concentrations of the elements in µg/g across the sites were 392 ± 46 (Zn), 68.28 ± 11.3 (Pb), 1437 ± 67 (Mn), 39,481 ± 4611 (Fe), 460 ± 31 (Cr), 150 ± 44 (Cu), 1.25 ± 0.65 (Cd), 856 ± 72 (Ni), and 0.97 ± 0.28 (As). The Cdeg and ERI calculated from the study were 54.79 and 573, respectively, suggesting varying pollution levels. The highest contributions were from Ni, Cd, Zn, Cu, Cr, and Pb, especially in areas with heavy traffic. The non-carcinogenic risk assessments were generally low for the three routes of exposure, except HQoral that was slightly higher for children. Similarly, none of the elements exhibited any carcinogenic risk except chromium. Overall, the cancer risk is considered low. In view of the limited studies from UAE in relation to the metal content of road-deposited dusts, the current study serves as novel knowledge, especially in the context of geographical areas with a higher occurrence of sandstorms and the presence of particulate matter. The study also adds to the global understanding of the contribution of street dust to environmental pollution and its implications for human health.

Ephedra alte extracts' GC-MS profiles and antimicrobial activity against multidrug-resistant pathogens (MRSA).

The extracts of E. alte offer promising potential as renewable resources for various chemical derivative products aimed at addressing antibiotic resistance. These extracts exhibited significant activity against methicillin-resistant Staphylococcus aureus (MRSA), a strain known for its resistance to multiple antibiotics. The extracts were found to be effective against several common antibiotics, including Imipenem, Ampicillin, Penicillin G, Oxacillin, and Amoxicillin-clavulanate. GC-MS analysis revealed that the phytoconstituents of E. alte extracts, obtained using both methanol and ethyl acetate, consist of a diverse range of 83 and 160 phytocompounds, respectively. These organic compounds serve as important biochemical precursors for the synthesis of vitamins E and K1, and exhibit antioxidant, antimicrobial, and anti-inflammatory properties in both plants and microorganisms. Notable compounds identified include fatty acids (such as palmitic acid, dodecanoic acid, sebacic acid, pentadecanoic acid, myristic acid, stearic acid, behenic acid, and linoelaidic acid), phytosterols (Campesterol, ß-sitosterol, Stigmast-5-ene), sugars (D-fructose, Fructofuranans), terpenoids (Phytol, citronellol), and phenolic acids (Protocatechoic acid, shikimic acid). The antimicrobial activity of all E. alte extracts was found to be superior to that of mupirocin and ciprofloxacin, as observed in susceptibility testing against MRSA ATCC 43300 and other pathogenic bacteria and fungi. It is likely that the combined action of the antimicrobial components within the E. alte extract bypasses the mechanisms employed by MRSA to protect itself from antibiotics. Further experiments are needed to investigate the individual effects of each pure compound and their potential synergistic interactions, which may enhance their overall performance.

Occurrence, spatial and seasonal variations of emerging contaminants in the aquatic environment of Sharjah, United Arab Emirates.

The occurrence, seasonal variations and spatial distribution of emerging contaminants (ECs) in wastewater effluents from wastewater treatment plant (WWTP) and UAE's receiving coastal aquatic environment (seawater and sediments) were evaluated in the present study. A total of 21, 23, and 22 contaminants in the effluents, seawater, and sediments, respectively, at concentrations ranging from low ng L-1 up to 1782 ng L-1 in effluents, from low ng/l up to 236.10 ng L-1 in seawater, and from low ng g-1 up to 60.15 ng g-1 in sediments were recorded. The study revealed that imidacloprid, thiabendazole, and acetaminophen were the most ubiquitous compounds in effluents, seawater, and sediments, respectively, since they were found in all samples collected with a detection frequency of 100%. The study also revealed that the higher concentrations of most contaminants were recorded in autumn. However, thiabendazole in effluents and seawater, acetamiprid in effluents, and sulphapyridine in seawater and sediments showed a higher load in winter. This study highlights the need for proper monitoring and management of ECs in wastewater effluents, seawater, and sediments, especially during the autumn and winter seasons, to minimize their impact on the marine ecosystem and public health.

Biosynthesized Silver Nanoparticles from Cyperus Conglomeratus Root Extract Inhibit Osteogenic Differentiation of Immortalized Mesenchymal Stromal Cells.

BACKGROUND: Silver nanoparticles (AgNPs) are a focus of huge interest in biological research, including stem cell research. AgNPs synthesized using Cyperus conglomeratus root extract have been previously reported but their effects on mesenchymal stromal cells have yet to be investigated. OBJECTIVES: The aim of this study is to investigate the effects of C. conglomeratus-derived AgNPs on adipogenesis and osteogenesis of mesenchymal stromal cells. METHODS: AgNPs were synthesized using C. conglomeratus root extract, and the phytochemicals involved in AgNPs synthesis were analyzed using gas chromatography-mass spectrometry (GC-MS). The cytotoxicity of the AgNPs was tested on telomerase-transformed immortalized human bone marrow-derived MSCs-hTERT (iMSC3) and human osteosarcoma cell line (MG-63) using MTT and apoptosis assays. The uptake of AgNPs by both cells was confirmed using inductively coupled plasma-optical emission spectrometry (ICP-OES). Furthermore, the effect of AgNPs on iMSC3 adipogenesis and osteogenesis was analyzed using stain quantification and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). RESULTS: The phytochemicals predominately identified in both the AgNPs and C. conglomeratus root extract were carbohydrates. The AgNP concentrations tested using MTT and apoptosis assays (0.5-64 µg/ml and 1,4 and 32 µg/ml, respectively) showed no significant cytotoxicity on iMSC3 and MG-63. The AgNPs were internalized in a concentration-dependent manner in both cell types. Additionally, the AgNPs exhibited a significant negative effect on osteogenesis but not on adipogenesis. CONCLUSION: C. conglomeratus-derived AgNPs had an impact on the differentiation capacity of iMSC3. Our results indicated that C. conglomeratus AgNPs and the associated phytochemicals could exhibit potential medical applications.

Exploring the effect of estrogen on Candida albicans hyphal cell wall glycans and ergosterol synthesis.

Increased levels of 17-ß estradiol (E2) due to pregnancy in young women or to hormonal replacement therapy in postmenopausal women have long been associated with an increased risk of yeast infections. Nevertheless, the effect underlying the role of E2 in Candida albicans infections is not well understood. To address this issue, functional, transcriptomic, and metabolomic analyses were performed on C. albicans cells subjected to temperature and serum induction in the presence or absence of E2. Increased filament formation was observed in E2 treated cells. Surprisingly, cells treated with a combination of E2 and serum showed decreased filament formation. Furthermore, the transcriptomic analysis revealed that serum and E2 treatment is associated with downregulated expression of genes involved in filamentation, including HWP1, ECE1, IHD1, MEP1, SOD5, and ALS3, in comparison with cells treated with serum or estrogen alone. Moreover, glucose transporter genes HGT20 and GCV2 were downregulated in cells receiving both serum and E2. Functional pathway enrichment analysis of the differentially expressed genes (DEGs) suggested major involvement of E2 signaling in several metabolic pathways and the biosynthesis of secondary metabolites. The metabolomic analysis determined differential secretion of 36 metabolites based on the different treatments' conditions, including structural carbohydrates and fatty acids important for hyphal cell wall formation such as arabinonic acid, organicsugar acids, oleic acid, octadecanoic acid, 2-keto-D-gluconic acid, palmitic acid, and steriacstearic acid with an intriguing negative correlation between D-turanose and ergosterol under E2 treatment. In conclusion, these findings suggest that E2 signaling impacts the expression of several genes and the secretion of several metabolites that help regulate C. albicans morphogenesis and virulence.

Mass spectroscopy-based proteomics and metabolomics analysis of triple-positive breast cancer cells treated with tamoxifen and/or trastuzumab.

PURPOSE: HER2-enriched breast cancer with high levels of hormone receptor expression, known as "triple positive" breast cancer, may represent a new entity with a relatively favourable prognosis against which the combination of chemotherapy, HER-2 inhibition, and endocrine treatment may be considered overtreatment. We explored the effect of the anticancer drugs tamoxifen and trastuzumab, both separately and in combination, on the integrated proteomic and metabolic profile of "triple positive" breast cancer cells (BT-474). METHOD: We employed ultra-high-performance liquid chromatography-quadrupole time of flight mass spectrometry using a Bruker timsTOF to investigate changes in BT-474 cell line treated with either tamoxifen, trastuzumab or a combination. Differentially abundant metabolites were identified using the Bruker Human Metabolome Database metabolite library and proteins using the Uniprot proteome for Homo sapiens using MetaboScape and MaxQuant, respectively, for identification and quantitation. RESULTS: A total of 77 proteins and 85 metabolites were found to significantly differ in abundance in BT-474 treated cells with tamoxifen 5 µM/and or trastuzumab 2.5 µM. Findings suggest that by targeting important cellular signalling pathways which regulate cell growth, apoptosis, proliferation, and chemoresistance, these medicines have a considerable anti-growth effect in BT-474 cells. Pathways enriched for dysregulation include RNA splicing, neutrophil degranulation and activation, cellular redox homeostasis, mitochondrial transmembrane transport, ferroptosis and necroptosis, ABC transporters and central carbon metabolism. CONCLUSION: Our findings in protein and metabolite level research revealed that anti-cancer drug therapy had a significant impact on the key signalling pathways and molecular processes in triple positive BT-474 cell lines.

Multi-Omics Analysis Revealed a Significant Alteration of Critical Metabolic Pathways Due to Sorafenib-Resistance in Hep3B Cell Lines.

Hepatocellular carcinoma (HCC) is the second prominent cause of cancer-associated death worldwide. Usually, HCC is diagnosed in advanced stages, wherein sorafenib, a multiple target tyrosine kinase inhibitor, is used as the first line of treatment. Unfortunately, resistance to sorafenib is usually encountered within six months of treatment. Therefore, there is a critical need to identify the underlying reasons for drug resistance. In the present study, we investigated the proteomic and metabolomics alterations accompanying sorafenib resistance in hepatocellular carcinoma Hep3B cells by employing ultra-high-performance liquid chromatography quadrupole time of flight mass spectrometry (UHPLC-QTOF-MS). The Bruker Human Metabolome Database (HMDB) library was used to identify the differentially abundant metabolites through MetaboScape 4.0 software (Bruker). For protein annotation and identification, the Uniprot proteome for Homo sapiens (Human) database was utilized through MaxQuant. The results revealed that 27 metabolites and 18 proteins were significantly dysregulated due to sorafenib resistance in Hep3B cells compared to the parental phenotype. D-alanine, L-proline, o-tyrosine, succinic acid and phosphatidylcholine (PC, 16:0/16:0) were among the significantly altered metabolites. Ubiquitin carboxyl-terminal hydrolase isozyme L1, mitochondrial superoxide dismutase, UDP-glucose-6-dehydrogenase, sorbitol dehydrogenase and calpain small subunit 1 were among the significantly altered proteins. The findings revealed that resistant Hep3B cells demonstrated significant alterations in amino acid and nucleotide metabolic pathways, energy production pathways and other pathways related to cancer aggressiveness, such as migration, proliferation and drug-resistance. Joint pathway enrichment analysis unveiled unique pathways, including the antifolate resistance pathway and other important pathways that maintain cancer cells' survival, growth, and proliferation. Collectively, the results identified potential biomarkers for sorafenib-resistant HCC and gave insights into their role in chemotherapeutic drug resistance, cancer initiation, progression and aggressiveness, which may contribute to better prognosis and chemotherapeutic outcomes.

Assessment of Uptake, Accumulation and Degradation of Paracetamol in Spinach (Spinacia oleracea L.) under Controlled Laboratory Conditions.

The occurrence and persistence of pharmaceuticals in the food chain, particularly edible crops, can adversely affect human and environmental health. In this study, the impacts of the absorption, translocation, accumulation, and degradation of paracetamol in different organs of the leafy vegetable crop spinach (Spinacia oleracea) were assessed under controlled laboratory conditions. Spinach plants were exposed to 50 mg/L, 100 mg/L, and 200 mg/L paracetamol in 20% Hoagland solution at the vegetative phase in a hydroponic system. Exposed plants exhibited pronounced phytotoxic effects during the eight days trial period, with highly significant reductions seen in the plants' morphological parameters. The increasing paracetamol stress levels adversely affected the plants' photosynthetic machinery, altering the chlorophyll fluorescence parameters (Fv/Fm and PSII), photosynthetic pigments (Chl a, Chl b and carotenoid contents), and composition of essential nutrients and elements. The LC-MS results indicated that the spinach organs receiving various paracetamol levels on day four exhibited significant uptake and translocation of the drug from roots to aerial parts, while degradation of the drug was observed after eight days. The VITEK® 2 system identified several bacterial strains (e.g., members of Burkhulderia, Sphingomonas, Pseudomonas, Staphylococcus, Stenotrophomonas and Kocuria) isolated from spinach shoots and roots. These microbes have the potential to biodegrade paracetamol and other organic micro-pollutants. Our findings provide novel insights to mitigate the risks associated with pharmaceutical pollution in the environment and explore the bioremediation potential of edible crops and their associated microbial consortium to remove these pollutants effectively.

Identification of Insulin Resistance Biomarkers in Metabolic Syndrome Detected by UHPLC-ESI-QTOF-MS.

Metabolic syndrome (MetS) is a disorder characterized by a group of factors that can increase the risk of chronic diseases, including cardiovascular diseases and type 2 diabetes mellitus (T2D). Metabolomics has provided new insight into disease diagnosis and biomarker identification. This cross-sectional investigation used an untargeted metabolomics-based technique to uncover metabolomic alterations and their relationship to pathways in normoglycemic and prediabetic MetS participants to improve disease diagnosis. Plasma samples were collected from drug-naive prediabetic MetS patients (n = 26), normoglycemic MetS patients (n = 30), and healthy (normoglycemic lean) subjects (n = 30) who met the inclusion criteria for the study. The plasma samples were analyzed using highly sensitive ultra-high-performance liquid chromatography electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-ESI-QTOF-MS). One-way ANOVA analysis revealed that 59 metabolites differed significantly among the three groups (p < 0.05). Glutamine, 5-hydroxy-L-tryptophan, L-sorbose, and hippurate were highly associated with MetS. However, 9-methyluric acid, sphinganine, and threonic acid were highly associated with prediabetes/MetS. Metabolic pathway analysis showed that arginine biosynthesis and glutathione metabolism were associated with MetS/prediabetes, while phenylalanine, D-glutamine and D-glutamate, and lysine degradation were highly impacted in MetS. The current study sheds light on the potential diagnostic value of some metabolites in metabolic syndrome and the role of their alteration on some of the metabolic pathways. More studies are needed in larger cohorts in order to verify the implication of the above metabolites on MetS and their diagnostic value.

Untargeted Metabolomics of Breast Cancer Cells MCF-7 and SkBr3 Treated With Tamoxifen/Trastuzumab.

BACKGROUND/AIM: Trastuzumab and tamoxifen are two of the most widely prescribed anti-cancer drugs for breast cancer (BC). To date, few studies have explored the impact of anticancer drugs on metabolic pathways in BC. Metabolomics is an emerging technology that can identify new biomarkers for tracking therapy response and novel therapeutic targets. MATERIALS AND METHODS: We employed ultra-high-performance liquid chromatography-quadrupole time of flight mass spectrometry (UHPLC-QTOF-MS) to investigate changes in MCF-7 and SkBr3 cell lines treated with either tamoxifen, trastuzumab or a combination of both. The Bruker Human Metabolome Database (HMDB) metabolite library was used to match spectra and the MetaboScape software to assign each feature with a putative metabolite name or molecular formula for metabolite annotation. RESULTS: A total of 98 metabolites were found to significantly differ in abundance in MCF-7 and SkBr3 treated cells. Moreover, the metabolic profile of the combination medication is similar to that of tamoxifen alone, according to functional enrichment analysis. CONCLUSION: Tamoxifen/trastuzumab treatment had a significant effect on pathways essential for the control of energy-production, which have previously been linked to cancer progression, and aggressiveness.

Metabolic conversion of ß-pinene to ß-ionone in rats.

Exposure to or ingestion of turpentine can alter the scent of urine, conferring it a flowery, violet-like scent. Turpentine's effect on urine was initially noticed after its use either as medicine or as a preservative in winemaking. Regardless of the source of exposure, the phenomenon requires metabolic conversion of turpentine component(s) to ionone, the molecule mainly responsible for the scent of violets.The purpose of this study was to identify the presence of ionone in the urine of rats that received ß-pinene, and thus to demonstrate that the postulated conversion occurs.We treated rats intraperitoneally with normal saline (negative control), ß-ionone (positive control), low-dose ß-pinene (1/3 of LD50), and high-dose ß-pinene (1/2 of LD50). Urine samples were collected up to 72 h after administration of the compounds, followed by gas chromatography/mass spectrometry identification of the presence of ionone.ß-Ionone was found in the urine of rats exposed to both low and high doses of ß-pinene. In contrast, α-ionone appears unlikely to have been formed in rats exposed to either low or high doses of ß-pinene. ß-pinene was converted to ß-ionone, followed by partial excretion in the urine of rats. ß-Ionone is a minor metabolite of ß-pinene.

Candida albicans PPG1, a serine/threonine phosphatase, plays a vital role in central carbon metabolisms under filament-inducing conditions: A multi-omics approach.

Candida albicans is the leading cause of life-threatening bloodstream candidiasis, especially among immunocompromised patients. The reversible morphological transition from yeast to hyphal filaments in response to host environmental cues facilitates C. albicans tissue invasion, immune evasion, and dissemination. Hence, it is widely considered that filamentation represents one of the major virulence properties in C. albicans. We have previously characterized Ppg1, a PP2A-type protein phosphatase that controls filament extension and virulence in C. albicans. This study conducted RNA sequencing analysis of samples obtained from C. albicans wild type and ppg1Δ/Δ strains grown under filament-inducing conditions. Overall, ppg1Δ/Δ strain showed 1448 upregulated and 710 downregulated genes, representing approximately one-third of the entire annotated C. albicans genome. Transcriptomic analysis identified significant downregulation of well-characterized genes linked to filamentation and virulence, such as ALS3, HWP1, ECE1, and RBT1. Expression analysis showed that essential genes involved in C. albicans central carbon metabolisms, including GDH3, GPD1, GPD2, RHR2, INO1, AAH1, and MET14 were among the top upregulated genes. Subsequent metabolomics analysis of C. albicans ppg1Δ/Δ strain revealed a negative enrichment of metabolites with carboxylic acid substituents and a positive enrichment of metabolites with pyranose substituents. Altogether, Ppg1 in vitro analysis revealed a link between metabolites substituents and filament formation controlled by a phosphatase to regulate morphogenesis and virulence.

Assessment of sulfamethoxazole removal by nanoscale zerovalent iron.

Removal of pharmaceutical compounds, such as sulfamethoxazole (SMX) from the aquatic environments, is critical in order to mitigate their adverse environmental and human health effects. In this study, the effectiveness of nanoscale zerovalent iron (nZVI) particles for the removal of SMX was investigated under varying conditions of initial solution pH (3, 5, 7 and 11) and nZVI to SMX mass ratios (1:1, 5:1, 10:1, 13:1, 25:1). Batch kinetic studies, which were well represented using both pseudo-first-order and pseudo-second-order kinetic models (R2 > 0.98), showed that both solution pH and mass ratios strongly influenced SMX removal. At a fixed mass ratio of 10:1, removal efficiencies were higher in acidic conditions (83% to 91%) compared to neutral (29%) and alkaline (6%) conditions. A similar trend was observed for removal rates and removal amounts. For mass ratios between 1:1 and 10:1, an optimum pH existed (pH 5) wherein highest removal efficiencies were attained. Increasing the mass ratio above 10:1 resulted in virtually complete removal efficiencies at pH 3 and 5, and 70% at pH 7. Analysis of SMX speciation and zeta potential of nZVI particles provided insights into the role of pH on the efficiencies, rates and extents of SMX removal. Total organic carbon analysis and mass spectrometry measurements of SMX solution before and after exposure to nZVI particles suggested the transformation of SMX via redox reactions, which are likely the dominant process compared to adsorption. Five transformation products were observed at m/z 156 (TP1), 192 (TP2), 256 (TP3), 294 (TP4) and 296 (TP5). TP1, TP2 and TP3 were further identified using ion fragment analysis. Overall, results from this study indicate a strong potential for SMX removal by nZVI particles, and could be useful towards identifying reaction conditions for optimum SMX transformation.

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.

Phenolic Composition and Antimicrobial Activity of Different Emirati Date (Phoenix dactylifera L.) Pits: A Comparative Study.

The biochemical composition, secondary metabolites (phenolic compounds, flavonoids) and antimicrobial potential of different varieties of Emirati date (Phoenix dactylifera L.) pits were investigated. Total phenolic acids (TPC) and total flavonoid contents (TFC) of the different date pits were measured using a Folin-Ciocalteau reagent. Different organic solvents [(n-hexane; H2O: EtOH (1:1); ethyl acetate; acetone: Water (1:1); and methanol: Chloroform (1:1)] were compared to evaluate the phytotoxicity of Ajwa, Fard, Khalas, Khodari, Abu Maan, Lulu, and Mabroom date pits. The antimicrobial activity of the date pit extracts were evaluated by means of agar-well diffusion assay on Staphylococcus aureus (ATCC 29123), Escherichia coli (ATCC 25922) and Candida albicans (ATCC 66027). Minimum inhibitory concentrations (MICs) were measured following clinical laboratory standardization institute (CLSI) protocol. The biochemical analyses of date pits indicate that TPC were ranged from 7.80 mg of equivalent gallic acid/100 g dry weight in Ajwa to 4.65 mg in Mabroom. The TFC were ranged between 1.6-4.54 mg of equivalent catechin/100 g dry weight. Ajwa pit extract showed good quality traits (higher protein, lower ash content, and intermediate dietary fiber). The results indicate that the ethyl acetate extract of Khalas and Khodari inhibited S. aureus with an inhibition zone diameter of 20 mm and MIC of 10 mg/mL. Abu Mann pit extract inhibited the S. aureus and also decreased the population of E. coli. The diameter of inhibition zone was 15, 16, and 18 mm after treatment with Ajwa extracts, while the MICs were 7.5 and 5 mg/mL. The MeOH: CFM extract of Abu Mann and Ajwa was more potent against E. coli bacteria than any other extract. This work demonstrates that the Emirati date pits extract has antimicrobial (antibacterial, antifungal) potential and can be used as phytotoxic natural compounds.

Comparative metabolomics of MCF-7 breast cancer cells using different extraction solvents assessed by mass spectroscopy.

Metabolic profiling of cancer cells can play a vital role in revealing the molecular bases of cancer development and progression. In this study, gas chromatography coupled with mass spectrometry (GC-MS) was employed for the determination of signatures found in ER+/PR+ breast cancer cells derived from MCF-7 using different extraction solvents including: A, formic acid in water; B, ammonium hydroxide in water; C, ethyl acetate; D, methanol: water (1:1, v/v); and E, acetonitrile: water (1:1, v/v). The greatest extraction rate and diversity of metabolites occurs with extraction solvents A and E. Extraction solvent D showed moderate extraction efficiency, whereas extraction solvent B and C showed inferior metabolite diversity. Metabolite set enrichment analysis (MSEA) results showed energy production pathways to be key in MCF-7 cell lines. This study showed that mass spectrometry could identify key metabolites associated with cancers. The highest enriched pathways were related to energy production as well as Warburg effect pathways, which may shed light on how energy metabolism has been hijacked to encourage tumour progression and eventually metastasis in breast cancer.

Quick and Sensitive UPLC-ESI-MS/MS Method for Simultaneous Estimation of Sofosbuvir and Its Metabolite in Human Plasma.

A simple, fast and highly sensitive RP-UPLC-MS/MS method was developed and validated for the simultaneous determination of sofosbuvir (SR) and its metabolite GS331007 in human plasma using ketotifen as an internal standard (IS). The separation was achieved on Acquity UPLC BEH C18 (50 × 2.1 mm, i.d. 1.7 µm, Waters, USA) column using acetonitrile:5 mM ammonium formate:0.1% formic acid (85:15:0.1% v/v/v) as a mobile phase at a flow rate of 0.35 mL/min in an isocratic elution. The Xevo TQD UPLC-MS/MS was operated under the multiple-reaction monitoring mode using positive electrospray ionization. Extraction with dichloromethane was used in the sample preparation. Method validation was performed as per the Food and Drug Administration (FDA) guidelines and the calibration curves of the proposed method were found to be linear in the range of 1-1000 ng/mL for SR and in the range of 10-1500 ng/mL for its metabolite (GS331007) with an elution time of 1.83 min. All validation parameters were within the acceptable range according to the bioanalytical methods validation guidelines. Furthermore, the obtained results of matrix effects indicate that ion suppression or enhancement from human plasma components was negligible under the optimized conditions. The proposed method can be applied in high-throughput analysis required for pharmacokinetic and bioequivalence studies in human samples.

Enantioseparation of Synthetic Cathinones Enantiomers with Tertiary Amine Structure in Urine and Plasma.

A sensitive and selective method for detection and quantitation of the enantiomers of 18 synthetic cathinones with tertiary amine structure using HPLC-UV-VIS has been developed. Two chiral columns, Astec Cellulose DMP and Amylose-based Chiralpak AS-H, have been examined separately. Mobile phase composed of hexane, isopropanol and triethylamine (99.0:1.0:0.1) was used under an isocratic elution mode. Three of these compounds were separated simultaneously after being spiked into urine and plasma samples. 2,3-Methylenedioxy pyrovalerone was used as an internal standard for the purpose of quantitation. The analytical method has been validated in terms of linearity, limits of detection (LOD), limits of quantitation (LOQ), recoveries and reproducibilities in urine and plasma matrices. The calibration curves exhibited correlation coefficients better than 0.99. It was found that the LODs of these cathinone derivatives in urine were in the range of 1.00-1.47 ppm; while in plasma, the LODs were in the range of 0.14-0.67 ppm. The LOQs in urine were in the range of 3.03-4.46 ppm and in plasma they were in the range of 0.42-2.04 ppm. The method recoveries in terms of percent error averaged 2.4% and 3.2% for the spiked plasma and urine samples, respectively; while interday and intraday reproducibilities reported at three different levels, 5, 100 and 200 ppm, in terms of coefficient of variance were in the range of (0.27-5.39)% in plasma and (0.47-3.12)% in urine which lies in the acceptable range.

Quantitative determination of doxorubicin in the exosomes of A549/MCF-7 cancer cells and human plasma using ultra performance liquid chromatography-tandem mass spectrometry.

In cancer therapy, exosomes efflux enhances resistance of cancer cells toward anticancer agents through mediating the transport of anticancer drugs outside the cells. In this study, a rapid, simple and highly sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the determination of Doxorubicin (DOX) in exosomes of cancer cells and human plasma using Ketotifen as an internal standard (IS). Plasma samples spiked with DOX and two cancer cell lines (A549 & MCF-7) were incubated with different concentrations of DOX and IS. The analytes were then extracted with methanol after protein precipitation and the chromatographic separation was carried out using a C18 column, with a mixture of acetonitrile-water- formic acid (85:15:0.1%, v/v/v) as mobile phase. Multiple reaction monitoring (MRM) was utilized to monitor the protonated precursor to product ion transitions of m/z 544.25 > 397.16 and m/z 310.08 > 96.97 for the quantification of DOX and IS, respectively. The method was linear over ranges of 1-1000 ng/mL for DOX in plasma and 2-1000 ng/mL for DOX in exosome samples. The lower limit of quantification of this method was 1 ng/mL, 2 ng/mL and 2 ng/mL in human plasma, A549 & MCF-7 cells respectively. Intra- and inter day precision of all quality control concentrations were less than 10.33% and the accuracy values ranged from -4.82 to 12.60%. The optimized UPLC-MS/MS method proved to be fast, specific, simple and highly sensitive and was successfully applied for the estimation of DOX in the exosomes of cancer cells and plasma.