Metabolomics and Proteomics in Prostate Cancer Research: Overview, Analytical Techniques, Data Analysis, and Recent Clinical Applications.

Prostate cancer (PCa) is a significant global contributor to mortality, predominantly affecting males aged 65 and above. The field of omics has recently gained traction due to its capacity to provide profound insights into the biochemical mechanisms underlying conditions like prostate cancer. This involves the identification and quantification of low-molecular-weight metabolites and proteins acting as crucial biochemical signals for early detection, therapy assessment, and target identification. A spectrum of analytical methods is employed to discern and measure these molecules, revealing their altered biological pathways within diseased contexts. Metabolomics and proteomics generate refined data subjected to detailed statistical analysis through sophisticated software, yielding substantive insights. This review aims to underscore the major contributions of multi-omics to PCa research, covering its core principles, its role in tumor biology characterization, biomarker discovery, prognostic studies, various analytical technologies such as mass spectrometry and Nuclear Magnetic Resonance, data processing, and recent clinical applications made possible by an integrative "omics" approach. This approach seeks to address the challenges associated with current PCa treatments. Hence, our research endeavors to demonstrate the valuable applications of these potent tools in investigations, offering significant potential for understanding the complex biochemical environment of prostate cancer and advancing tailored therapeutic approaches for further development.

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.

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.

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.

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.

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.

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.

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.

Old leaves accumulate more heavy metals than other parts of the desert shrub Calotropis procera at a traffic-polluted site as assessed by two analytical techniques.

Calotropis procera is a perennial big shrub that has the potential to accumulate high concentrations of heavy metals. Metal sequestration in old organs has been considered as a mechanism for plant survival in polluted soils. The aim of the present study was to assess the role of the old leaves as a sink for HMs accumulation in C. procera. Two instruments were used: atomic absorption spectroscopy (AAS) and X-ray fluorescence (XRF) microscopy. Soil and plant samples were collected from around one of the worst congested traffic areas in the United Arab Emirates (UAE). Samples from roots, stem, and green and old leaves were prepared and analyzed by both instruments. Calotropis procera was able to concentrate Fe, Mn, Sr, and Zn in the roots, but their translocation to stem and green leaves was low. Old leaves had greater ability to accumulate significantly higher concentrations of different metals, especially Fe and Sr, than other parts of the plants, indicating that C. procera uses these metabolically less-active leaves as sinks for heavy metals. Fe and Sr attained higher bioconcentration and accumulation values, compared to Zn and Mn. There were significant positive correlations between XRF and AAS for all elements in the different organs.

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.

Native desert plants have the potential for phytoremediation of phytotoxic metals in urban cities: implications for cities sustainability in arid environments.

Arid regions can benefit from using native desert plants, which require minimal freshwater and can aid in remediating soil phytotoxic metals (PTMs) from traffic emissions. In this study, we assessed the ability of three native desert plants-Pennisetum divisum, Tetraena qatarensis, and Brassica tournefortii-to accumulate phytotoxic metals (PTMs) in their different plant organs, including leaves, stems, and roots/rhizomes. The PTMs were analyzed in soil and plant samples collected from Dubai, United Arab Emirates (UAE). The results indicated significantly higher levels of PTMs on the soil surface than the subsurface layer. Brassica exhibited the highest concentrations of Fe and Zn, measuring 566.7 and 262.8 mg kg-1, respectively, while Tetraena accumulated the highest concentration of Sr (1676.9 mg kg-1) in their stems. In contrast, Pennisetum recorded the lowest concentration of Sr (21.0 mg kg-1), while Tetraena exhibited the lowest concentrations of Fe and Zn (22.5 and 30.1 mg kg-1) in their leaves. The roots of Pennisetum, Brassica, and Tetraena demonstrated the potential to accumulate Zn from the soil, with concentration factors (CF) of 1.75, 1.09, and 1.09, respectively. Moreover, Brassica exhibited the highest CF for Sr, measuring 2.34. Pennisetum, however, could not translocate PTMs from its rhizomes to other plant organs, as indicated by a translocation factor (TF) of 1. In contrast, Brassica effectively translocated the studied PTMs from its roots to the stem and leaves (except for Sr in the leaves). Furthermore, Pennisetum exclusively absorbed Zn from the soil into its leaves and stems, with an enrichment factor (EF) greater than 1. Brassica showed the ability to uptake the studied PTMs in its stem and leaves (except for Fe), while Tetraena primarily absorbed Sr and Zn into its stems. Based on the CF and TF results, Pennisetum appears to be a suitable species for phytostabilization of both Fe and Zn, while Brassica is well-suited for Sr and Zn polluted soils. Tetraena shows potential for Zn phytoremediation. These findings suggest that these plants are suitable for PTMs phytoextraction. Furthermore, based on the EF results, these plants can efficiently sequester PTMs.

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.

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.

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.

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.

Dataset in the characterization of black spot Ehrenberg snapper and its proteins' denaturation inhibition by natural antioxidants.

The data represented in this paper describe techniques, methodologies and data obtained during the biochemical composition characterization of Blackspot Snapper (Ehrenberg's Snapper). Data analysis of protein, lipids, moisture, ash contents of Ehrenberg's snapper, total polyphenols, total flavonoids contents and the DPPH scavenging activities of Cinnamon (Cinnamomum verum J. Presl) bark (50 mg/50 g), cumin (Cuminum cyminum L.) (50 mg/50 g), turmeric (Turmerica longa L.) (50 mg/50 g), garlic (Allium sativum L.) (50 mg/50 g), ginger (Zingiber officinale Roscoe) (50 mg/50 g) and Vitamin C (25 mg/50 g) are represented. Data obtained from the Infrared spectroscopy (FTIR) analysis of the six spices and vitamin C treated and stored fillets at -25 °C, namely three vibrations, Amide A, NH stretching at 3300 cm-1; Amide I, C=O stretching 1600-1690 cm-1 and Amide II, CN stretching and NH bending at 1480-1575 cm-1. Differential scanning calorimetry (DSC) analysis data of three main denaturations; myosin, actin and sarcoplasmic proteins are presented.

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.

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.

The Effects of Storage on Quality and Nutritional Values of Ehrenberg's Snapper Muscles (Lutjanus Ehrenbergi): Evaluation of Natural Antioxidants Effect on the Denaturation of Proteins.

: Protein denaturation in frozen minced fillets (Ehrenberg's Snapper), stored at -25°C was studied; 50.0 mg biomass/50g mince fillets treated with cinnamon, cumin, turmeric, garlic, ginger and 25.0 mg of vitamin C were used to slow protein denaturation. FT-IR stretching vibration of Amide-A (νNH) at 3300 cm-1; Amide-I stretching (νC=O) between 1600-1690 cm-1 and Amide-II stretching (νCN) and bending (δNH) between 1480 and 1575cm-1 were used as marker peaks. Garlic was the most significant (P ≤0.01) in controlling the rate of protein denaturation when νNH was used as a marker peak. DSC analysis showed that turmeric presented the highest effect on delaying the denaturation of sarcoplasmic proteins with a ∆H0=73.7J/g followed by garlic-treated mince fillets ∆H0=70.1J/g. All spices used were efficient in stopping the denaturation of myosin with the highest ∆H0=769.3 J/g registered for cinnamon-treated mince fillets. Actin was less vulnerable to denaturation in comparison to myosin and sarcoplasmic proteins.

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.