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.

Pomegranate peel: Bioactivities as antimicrobial and cytotoxic agents.

This is a comparative study to evaluate the effectiveness of six pomegranate peel extracts (PPEs) as antibacterial and antiproliferative agents. The Six PPEs were prepared using four solvent systems and each filtrate was concentrated to a gummy material to be used in the evaluation. The well-diffusion method was used to evaluate their antimicrobial activity against bacteria typically associated with food spoilage: Escherichia coli, Pseudomonas aeruginosa, Salmonella typhimurium, Listeria monocytogenes, Staphylococcus epidermidis, Staphylococcus aureus, and three Bacillus species. The 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTT) was used to evaluate the cytotoxicity against colorectal carcinoma cells (HCT116), prostate adenocarcinoma (PC3), ovarian cancer cells (SKOV-3), and fibroblasts (MRC-5). The antioxidant evaluation was done using the 2,2-diphenyl-1-picrylhydrazyl-hydrate (DPPH) assay. The pH of the water-containing extracts was acidic and almost the same over 6 weeks. The six PPEs inhibited the bacterial growth in a comparable level to standard antibiotics. The effectiveness of each extract was dependent on the bacterial strain, and the Listeria showed a remarkable inhibition when exposed to the aqueous extract prepared at room temperature (RT). The aqueous (RT) and methanol PPEs had a significant antioxidant scavenging capability and a remarkable cytotoxic activity against the PC3 with half maximal inhibitory concentration (IC50) of 0.1 µg/mL. The boiled aqueous extract exhibited antiproliferative activity against HCT116 with an IC50 of 21.45 µg/mL. The effect on SKOV-3 and fibroblasts was insignificant. With the exception of butanol, the antioxidant screening shows an inverse correlation between the polarity of the extraction solvent and the IC50 exhibited by the PPEs. The variation in the effectiveness of PPEs is suggested to be due to variable soluble bioactive compounds that may interact differently with different cells, though water-containing extracts are promising antibacterial agents. The findings clearly show that pomegranate peel possessed the potential to be an eco-friendly novel source for natural compounds that can be implemented in the food industry as a natural antimicrobial and natural food additive to prevent foodborne illnesses.

Unraveling the significance of PPP1R1A gene in pancreatic ß-cell function: A study in INS-1 cells and human pancreatic islets.

BACKGROUND AND AIMS: The protein phosphatase 1 regulatory inhibitor subunit 1A (PPP1R1A) has been linked with insulin secretion and diabetes mellitus. Yet, its full significance in pancreatic ß-cell function remains unclear. This study aims to elucidate the role of the PPP1R1A gene in ß-cell biology using human pancreatic islets and rat INS-1 (832/13) cells. RESULTS: Disruption of Ppp1r1a in INS-1 cells was associated with reduced insulin secretion and impaired glucose uptake; however, cell viability, ROS, apoptosis or proliferation were intact. A significant downregulation of crucial ß-cell function genes such as Ins1, Ins2, Pcsk1, Cpe, Pdx1, Mafa, Isl1, Glut2, Snap25, Vamp2, Syt5, Cacna1a, Cacna1d and Cacnb3, was observed upon Ppp1r1a disruption. Furthermore, silencing Pdx1 in INS-1 cells altered PPP1R1A expression, indicating that PPP1R1A is a target gene for PDX1. Treatment with rosiglitazone increased Ppp1r1a expression, while metformin and insulin showed no effect. RNA-seq analysis of human islets revealed high PPP1R1A expression, with α-cells showing the highest levels compared to other endocrine cells. Muscle tissues exhibited greater PPP1R1A expression than pancreatic islets, liver, or adipose tissues. Co-expression analysis revealed significant correlations between PPP1R1A and genes associated with insulin biosynthesis, exocytosis machinery, and intracellular calcium transport. Overexpression of PPP1R1A in human islets augmented insulin secretion and upregulated protein expression of Insulin, MAFA, PDX1, and GLUT1, while silencing of PPP1R1A reduced Insulin, MAFA, and GLUT1 protein levels. CONCLUSION: This study provides valuable insights into the role of PPP1R1A in regulating ß-cell function and glucose homeostasis. PPP1R1A presents a promising opportunity for future therapeutic interventions.

Unlocking the Therapeutic Potential of BCL-2 Associated Protein Family: Exploring BCL-2 Inhibitors in Cancer Therapy.

Apoptosis, programmed cell death pathway, is a vital physiological mechanism that ensures cellular homeostasis and overall cellular well-being. In the context of cancer, where evasion of apoptosis is a hallmark, the overexpression of anti-apoptotic proteins like Bcl2, Bcl-xL and Mcl-1 has been documented. Consequently, these proteins have emerged as promising targets for therapeutic interventions. The BCL-2 protein family is central to apoptosis and plays a significant importance in determining cellular fate serving as a critical determinant in this biological process. This review offers a comprehensive exploration of the BCL-2 protein family, emphasizing its dual nature. Specifically, certain members of this family promote cell survival (known as anti-apoptotic proteins), while others are involved in facilitating cell death (referred to as pro-apoptotic and BH3-only proteins). The potential of directly targeting these proteins is examined, particularly due to their involvement in conferring resistance to traditional cancer therapies. The effectiveness of such targeting strategies is also discussed, considering the tumor's propensity for anti-apoptotic pathways. Furthermore, the review highlights emerging research on combination therapies, where BCL-2 inhibitors are used synergistically with other treatments to enhance therapeutic outcomes. By understanding and manipulating the BCL-2 family and its associated pathways, we open doors to innovative and more effective cancer treatments, offering hope for resistant and aggressive cases.

Liposome-Based Drug Delivery Systems in Cancer Research: An Analysis of Global Landscape Efforts and Achievements.

Lipid-bilayer-based liposomes are gaining attention in scientific research for their versatile role in drug delivery. With their amphiphilic design, liposomes efficiently encapsulate and deliver drugs to targeted sites, offering controlled release. These artificial structures hold great promise in advancing cancer therapy methodologies. Bibliometric research analyzes systematic literary data statistically. This study used bibliometric indicators to examine, map, and evaluate the applications of liposomes in cancer therapy. A Scopus search was conducted to identify all English-language peer-reviewed scientific publications on the applications of liposomes in cancer therapy within the past twenty years. Bibliometric indicators were calculated using VOSviewer and Biblioshiny. We produced thematic, conceptual, and visualization charts. A total of 14,873 published documents were obtained. The procedure of keyword mapping has effectively identified the main areas of research concentration and prevailing trends within this specific field of study. The significant clusters discovered through theme and hotspot analyses encompassed many topics such as the use of multiple strategies in chemotherapy and different forms of cancer, the study of pharmacokinetics and nanomedicine, as well as the investigation of targeted drug delivery, cytotoxicity, and gene delivery. Liposomes were employed as drug delivery systems so as to selectively target cancer cells and improve the bioavailability of anticancer drugs. The work showcased the capacity to tailor these liposomes for accurate drug delivery by including potent anticancer medications. Our findings not only bring attention to the latest progress in utilizing liposomes for cancer treatment but also underscore the vital need for ongoing research, collaborative efforts, and the effective translation of these breakthroughs into tangible clinical applications, emphasizing the dynamic and evolving nature of cancer therapeutics.

Exploring the Global Landscape of Self-Medication Among Students: Trends, Risks, and Recommendations for Safe and Responsible Practices

Objective: This study aimed to provide a comprehensive overview of self-medication practices among students by conducting a bibliometric analysis of the available scientific literature. This research highlights the importance of promoting safe and responsible healthcare behaviors among students. Methods: A systematic search was conducted in the Scopus database to retrieve all peer-reviewed English articles and reviews published from 1968 onwards. The retrieved documents were analyzed to identify publication trends, citation counts, top journals, geographical distribution, and emerging research themes. Results: The findings indicate a significant increase in published literature about student self-medication over the past fifteen years. However, it was observed that the citation count for these documents was lower than expected, suggesting a need for increased attention toward this critical topic. The analysis also identified several hot topics in student self-medication, including the misuse of over-the-counter medications, dietary supplements, and psychoactive substances. The inappropriate use of antibiotics and the self-medication of mental health issues, such as anxiety and depression, were also identified as significant problems. Conclusions and recommendations: Self-medication among students is a complex and critical issue that requires immediate attention. This study highlights the urgent need for greater awareness and education regarding responsible self-medication practices among students. New policies, interventions, and strategies should be developed to address malpractices, misconceptions, and harmful practices related to self-medication. Educational institutions and health authorities should play a crucial role in providing students with mental health resources and support services... (AU)

Targeting Hypoxia-Inducible Factor-1 (HIF-1) in Cancer: Emerging Therapeutic Strategies and Pathway Regulation.

Hypoxia-inducible factor-1 (HIF-1) is a key regulator for balancing oxygen in the cells. It is a transcription factor that regulates the expression of target genes involved in oxygen homeostasis in response to hypoxia. Recently, research has demonstrated the multiple roles of HIF-1 in the pathophysiology of various diseases, including cancer. It is a crucial mediator of the hypoxic response and regulator of oxygen metabolism, thus contributing to tumor development and progression. Studies showed that the expression of the HIF-1α subunit is significantly upregulated in cancer cells and promotes tumor survival by multiple mechanisms. In addition, HIF-1 has potential contributing roles in cancer progression, including cell division, survival, proliferation, angiogenesis, and metastasis. Moreover, HIF-1 has a role in regulating cellular metabolic pathways, particularly the anaerobic metabolism of glucose. Given its significant and potential roles in cancer development and progression, it has been an intriguing therapeutic target for cancer research. Several compounds targeting HIF-1-associated processes are now being used to treat different types of cancer. This review outlines emerging therapeutic strategies that target HIF-1 as well as the relevance and regulation of the HIF-1 pathways in cancer. Moreover, it addresses the employment of nanotechnology in developing these promising strategies.

Potential of CDC25 phosphatases in cancer research and treatment: key to precision medicine.

The global burden of cancer continues to rise, underscoring the urgency of developing more effective and precisely targeted therapies. This comprehensive review explores the confluence of precision medicine and CDC25 phosphatases in the context of cancer research. Precision medicine, alternatively referred to as customized medicine, aims to customize medical interventions by taking into account the genetic, genomic, and epigenetic characteristics of individual patients. The identification of particular genetic and molecular drivers driving cancer helps both diagnostic accuracy and treatment selection. Precision medicine utilizes sophisticated technology such as genome sequencing and bioinformatics to elucidate genetic differences that underlie the proliferation of cancer cells, hence facilitating the development of customized therapeutic interventions. CDC25 phosphatases, which play a crucial role in governing the progression of the cell cycle, have garnered significant attention as potential targets for cancer treatment. The dysregulation of CDC25 is a characteristic feature observed in various types of malignancies, hence classifying them as proto-oncogenes. The proteins in question, which operate as phosphatases, play a role in the activation of Cyclin-dependent kinases (CDKs), so promoting the advancement of the cell cycle. CDC25 inhibitors demonstrate potential as therapeutic drugs for cancer treatment by specifically blocking the activity of CDKs and modulating the cell cycle in malignant cells. In brief, precision medicine presents a potentially fruitful option for augmenting cancer research, diagnosis, and treatment, with an emphasis on individualized care predicated upon patients' genetic and molecular profiles. The review highlights the significance of CDC25 phosphatases in the advancement of cancer and identifies them as promising candidates for therapeutic intervention. This statement underscores the significance of doing thorough molecular profiling in order to uncover the complex molecular characteristics of cancer cells.

Association of proton pump inhibitor use with survival and adverse effects outcomes in patients with multiple myeloma: pooled analysis of three clinical trials.

Proton pump inhibitors (PPIs) are commonly used in cancer patients, but their impact on treatment outcomes in multiple myeloma (MM) patients remains unclear. This study investigated the association of PPI use with survival and adverse effects in MM patients across three randomized-control trials initiating daratumumab, lenalidomide, or bortezomib combination treatments. Cox proportional hazard analysis and logistic regression were employed to assess the associations with treatment outcomes, while adjusting for age, sex, weight, MM international staging system stage, ECOG-performance status, comorbidity count, and presence of gastrointestinal disorders. Pooled data involving 1804 patients revealed that 557 (32%) used PPIs at baseline. PPI use was independently associated with worse overall survival (adjusted HR [95% CI] 1.32 [1.08-1.62], P = 0.007) and grade ≥ 3 adverse events (adjusted OR [95% CI] 1.39 [1.03-1.88], P = 0.030). However, the association with progression-free survival did not reach statistical significance (adjusted HR [95% CI] 1.14 [0.97-1.33], P = 0.112). Findings were consistent across trials and treatment arms. PPI use was identified as a negative prognostic factor in MM patients, potentially enhancing clinical decisions regarding its use. Further research is needed to fully comprehend the impacts and safety of PPI use in MM patients.

Fat mass and obesity-associated (FTO) gene is essential for insulin secretion and ß-cell function: In vitro studies using INS-1 cells and human pancreatic islets.

AIMS: In this study, we investigated the role of the FTO gene in pancreatic ß-cell biology and its association with type 2 diabetes (T2D). To address this issue, human pancreatic islets and rat INS-1 (832/13) cells were used to perform gene silencing, overexpression, and functional analysis of FTO expression; levels of FTO were also measured in serum samples obtained from diabetic and obese individuals. RESULTS: The findings revealed that FTO expression was reduced in islets from hyperglycemic/diabetic donors compared to normal donors. This reduction correlated with decreased INS and GLUT1 expression and increased PDX1, GCK, and SNAP25 expression. Silencing of Fto in INS-1 cells impaired insulin release and mitochondrial ATP production and increased apoptosis in pro-apoptotic cytokine-treated cells. However, glucose uptake and reactive oxygen species production rates remained unaffected. Downregulation of key ß-cell genes was observed following Fto-silencing, while Glut2 and Gck were unaffected. RNA-seq analysis identified several dysregulated genes involved in metal ion binding, calcium ion binding, and protein serine/threonine kinase activity. Furthermore, our findings showed that Pdx1 or Mafa-silencing did not influence FTO protein expression. Overexpression of FTO in human islets promoted insulin secretion and upregulated INS, PDX1, MAFA, and GLUT1 expression. Serum FTO levels did not significantly differ between individuals with diabetes or obesity and their healthy counterparts. CONCLUSION: These findings suggest that FTO plays a crucial role in ß-cell survival, metabolism, and function and point to a potential therapeutic utility of FTO in T2D patients.

Exploring the Potential of Rosemary Derived Compounds (Rosmarinic and Carnosic Acids) as Cancer Therapeutics: Current Knowledge and Future Perspectives.

Cancer is a global health challenge with high morbidity and mortality rates. However, conventional cancer treatment methods often have severe side effects and limited success rates. In the last decade, extensive research has been conducted to develop safe, and efficient alternative treatments that do not have the limitations of existing anticancer medicines. Plant-derived compounds have shown promise in cancer treatment for their anti-carcinogenic and anti-proliferative properties. Rosmarinic acid (RA) and carnosic acid (CA) are potent polyphenolic compounds found in rosemary (Rosmarinus officinalis) extract. They have been extensively studied for their biological properties, which include anti-diabetic, anti-inflammatory, antioxidant, and anticancer activities. In addition, RA and CA have demonstrated effective anti-proliferative properties against various cancers, making them promising targets for extensive research to develop candidate or leading compounds for cancer treatment. This review discusses and summarizes the anti-tumor effect of RA and CA against various cancers and highlights the involved biochemical and mechanistic pathways.

Multi-Omics Profiling of Candida albicans Grown on Solid Versus Liquid Media.

Candida albicans is a common pathogenic fungus that presents a challenge to healthcare facilities. It can switch between a yeast cell form that diffuses through the bloodstream to colonize internal organs and a filamentous form that penetrates host mucosa. Understanding the pathogen's strategies for environmental adaptation and, ultimately, survival, is crucial. As a complementary study, herein, a multi-omics analysis was performed using high-resolution timsTOF MS to compare the proteomes and metabolomes of Wild Type (WT) Candida albicans (strain DK318) grown on agar plates versus liquid media. Proteomic analysis revealed a total of 1793 proteins and 15,013 peptides. Out of the 1403 identified proteins, 313 proteins were significantly differentially abundant with a p-value < 0.05. Of these, 156 and 157 proteins were significantly increased in liquid and solid media, respectively. Metabolomics analysis identified 192 metabolites in total. The majority (42/48) of the significantly altered metabolites (p-value 0.05 FDR, FC 1.5), mainly amino acids, were significantly higher in solid media, while only 2 metabolites were significantly higher in liquid media. The combined multi-omics analysis provides insight into adaptative morphological changes supporting Candida albicans' life cycle and identifies crucial virulence factors during biofilm formation and bloodstream infection.

Rosemarinic acid protects ß-cell from STZ-induced cell damage via modulating NF-κß pathway.

Rosmarinic acid (RA), a natural ester phenolic compound, is known to have antioxidant and anti-inflammatory properties. RA has also been reported to exhibit a hypoglycemic effect; however, the mechanisms underlying this effect have yet to be investigated. Therefore, the present study focused on the anti-diabetic effects and mechanism of RA in INS-1 cells using in vitro model. Streptozotocin (STZ) at a concentration of 3 mM was applied to INS-1 cells for 4 h to create a diabetic model. The cells were pretreated for 24 h with various concentrations (1 and 2.5 µM) of RA. The Cell viability, glucose-stimulated insulin secretion (GSIS), glucose uptake, lipid peroxidation, reactive oxygen species (ROS), apoptosis, and protein expression of Bcl-2, NF-κB, 1L-1ß, and PARP were assessed. Results showed that STZ-treated INS-1 cells exhibited reduced cell viability, insulin release, insulin content, glucose uptake, and elevated MDA and ROS levels. Cells pretreated with RA maintained the function and morphology of ß-cells against STZ-induced damage. Moreover, RA sustained high protein expression levels of Bcl-2 and low expression levels of NF-κB, IL-1ß, and PARP. In conclusion, RA preserved ß-cells function against STZ-induced damage by altering NF-κB and Bcl-2 pathways.

Potential anticancer properties of calotropis procera: An investigation on breast and colon cancer cells.

Calotropis procera is a perennial flowering plant of the Apocynaceae family, traditionally used in medicine to treat various ailments. Recent investigations have revealed its potential therapeutic activities such as anti-inflammatory, gastroprotective, analgesic, anti-obesity, and anti-diabetic properties. RP-HPLC qualitatively and quantitatively evaluated the phenolic acids and flavonoids in the ethanolic extract at two different wavelengths, 280 and 330 nm. In addition, total phenolic and flavonoid contents were measured via spectrophotometric determination in addition to the antioxidant activity. The antiproliferative effects of C. procera were investigated on two cancer cell lines: human colon (HCT-116) and breast (MCF-7) cancer. Several methods were utilised to analyse the effectiveness of the plant extract on the cytotoxicity, apoptosis, cell cycle progression, genes involved in the cell cycle, and protein expression profiles of HCT-116 and MCF-7 cells. These included the MTT assay, Annexin V-FITC/PI, analysis of the cell cycle, and Western blot. Results indicated that ferulic and caffeic acids were the major compounds at λmax 280 nm (1.374% and 0.561%, respectively), while the major compounds at λmax 325 nm were kaempferol and luteolin (1.036% and 0.512%, respectively). The ethanolic extract had significantly higher antioxidant activity (80 ± 2.3%) compared to ascorbic acid (90 ± 3.1%). C. procera extract exhibited dose-dependent cell growth inhibition, with an estimated IC50 of 50 µg/mL for MCF-7 and 55 µg/mL for HCT-116 cells at 24 h. Annexin V-FITC/PI confirmed the induction of apoptosis. Remarkably, cell cycle arrest occurred at the sub-G1 phase in MCF-7 cells, while in HCT-116 cells, it was observed at the G2-M phase. The sub-G1 arrest was associated with dysregulation of Akt, p-AKT, mTOR, and p-mTOR proteins, as confirmed by the Western blot analysis, while downregulation of CDK1, cyclin B1, and survivin caused G2-M arrest.

Berberine Inhibited Growth and Migration of Human Colon Cancer Cell Lines by Increasing Phosphatase and Tensin and Inhibiting Aquaporins 1, 3 and 5 Expressions.

Introduction: Berberine is a natural isoquinoline alkaloid with anti-cancer properties. Nevertheless, the underlying mechanism of its action in human colorectal cancer (CRC) has not been thoroughly elucidated. We investigated the anti-cancer effect of berberine on HT-29, SW-480 and HCT-116 human CRC cell lines. Methods: Cell proliferation, migration and invasion were studied by MTT assay, wound healing, transwell chambers and flow cytometry. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunostaining were used to evaluate the expression of aquaporins (AQPs) 1, 3 and 5 in colon cancer cell lines before and after treatment with berberine (10, 30 and 100 µM). RT-qPCR and Western blotting were used to further explore the PI3K/AKT signaling pathway and the molecular mechanisms underlying berberine-induced inhibition of cell proliferation. Results: We demonstrated that treatment of these CRC cell lines with berberine inhibited cell proliferation, migration and invasion through induction of apoptosis and necrosis. HT-29, SW-480 and HCT-116 stained positively for AQP 1, 3 and 5, and berberine treatment down-regulated the expression of all three types of AQPs. Berberine also modulated PI3K/AKT pathway activity through up-regulating PTEN and down-regulating PI3K, AKT and p-AKT expression as well as suppressing its downstream targets, mTOR and p-mTOR at the protein level. Discussion/Conclusions: These findings indicate that berberine inhibited growth, migration and invasion of these colon cancer cell lines via down-regulation of AQP 1, 3 and 5 expressions, up-regulating PTEN which inhibited the PI3K/AKT pathway at the gene and protein levels, and that AQP 1, 3 and 5 expression level can be used as prognostic biomarkers for colon cancer metastasis.

Analysis and mapping of global scientific research on human monkeypox over the past 20 years.

Background and Aim: Human monkeypox is an emerging global threat. Hundreds of publications were disseminated in the last few months. This study aimed to map, analyze, and evaluate the bibliometric indicators of the global monkeypox research output. Materials and Methods: All documents published in the past 20 years were retrieved using the Scopus database. Papers published in English and peer-reviewed journals were included. VOSviewer was used to create density and network visualization maps. Results: A total of 1725 published documents were retrieved. Of these, 53% were published in 2022. The average number of authors per document was 4.2. Authors from the USA were the most active and published about 42.1% of the total documents. International collaboration was evident between the USA and both UK and Congo. Keywords mapping identified the main research lines in this field that correlate monkeypox with public health, smallpox, vaccination, and antiviral treatment. Conclusion: This study analyzed and mapped the expanding field of monkeypox research across the world. The bibliometric analysis revealed that the United States has contributed greatly in terms of both individual researchers and academic institutions. There was less cooperation on a global scale than was anticipated. Fostering international cooperation is essential for countering this worldwide danger. Additional scientific research should be conducted to investigate the link between smallpox immunization and monkeypox epidemics.

Secondary Metabolites Profiling, Antimicrobial and Cytotoxic Properties of Commiphora gileadensis L. Leaves, Seeds, Callus, and Cell Suspension Extracts.

Commiphora gileadensis L. is an important endangered medicinal plant that belongs to the family Burseraceae. In this study, C. gileadensis callus culture was established successfully using mature leaves as explants cultured on Murashige and Skoog (MS) media supplemented with 24.50 µM of indole butyric acid (IBA) and 2.22 µM 6-Benzylaminopurine (BAP) (callus induction media). The obtained callus was maintained on MS medium supplemented with 16.11 µM naphthalene acetic acid (NAA) in combination with 6.66 µM BAP, which resulted in a substantial increase in callus fresh and dry weights. The cell suspension culture was established successfully using liquid callus induction media supplemented with 3.0 mg·L-1 proline. Thereafter, the chemical constituents of different C. gileadensis methanolic extracts (callus, cell suspension, leaves, and seeds) were profiled, and their cytotoxic and antimicrobial properties were investigated. The LC-MS GNPS analyses were applied for chemical profiling of the methanolic plant extracts, and several natural products were identified, including flavonols, flavanones, and flavonoids glycosides, with two unusual families that included puromycin, 10-hydroxycamptothecin, and justicidin B. The methanolic extracts have shown selective antimicrobial and cytotoxic properties against different microbes and cancer cell lines. For instance, leaf extract showed the highest zone of inhibition for Staphylococcus aureus, while cell suspension culture was effective against Staphylococcus epidermidis and Staphylococcus aureus. All extracts showed selective activity against A549 cell lines for the cytotoxicity assay, while the leaf extract had a broad cytotoxic effect against all tested cell lines. This study revealed that C. gileadensis callus and cell suspension cultures can be employed to increase the in vitro formation of biologically active compounds that may have cytotoxicity and antibacterial action against different cancer cell lines and bacterial species. Further studies are required to isolate and identify such constituents that corroborate the observed activities.

Evaluation of Two Simultaneous Metabolomic and Proteomic Extraction Protocols Assessed by Ultra-High-Performance Liquid Chromatography Tandem Mass Spectrometry.

Untargeted multi-omics analysis of plasma is an emerging tool for the identification of novel biomarkers for evaluating disease prognosis, and for developing a better understanding of molecular mechanisms underlying human disease. The successful application of metabolomic and proteomic approaches relies on reproducibly quantifying a wide range of metabolites and proteins. Herein, we report the results of untargeted metabolomic and proteomic analyses from blood plasma samples following analyte extraction by two frequently-used solvent systems: chloroform/methanol and methanol-only. Whole blood samples were collected from participants (n = 6) at University Hospital Sharjah (UHS) hospital, then plasma was separated and extracted by two methods: (i) methanol precipitation and (ii) 4:3 methanol:chloroform extraction. The coverage and reproducibility of the two methods were assessed by ultra-high-performance liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-ESI-QTOF-MS). The study revealed that metabolite extraction by methanol-only showed greater reproducibility for both metabolomic and proteomic quantifications than did methanol/chloroform, while yielding similar peptide coverage. However, coverage of extracted metabolites was higher with the methanol/chloroform precipitation.

Mass spectrometry-based metabolomics approach and in vitro assays revealed promising role of 2,3-dihydroquinazolin-4(1H)-one derivatives against colorectal cancer cell lines.

Colorectal cancer (CRC) is the most frequent form of gastrointestinal cancer and one of the major causes of human mortality worldwide. Many of the current CRC therapies have limitations due to multidrug resistance and/or severe side effects. Quinazoline derivatives are promising lead compounds with a wide range of pharmacological actions. In this study, the effect of seven synthesized 2,3-dihydroquinazolin-4(1H)-one analogues as potential anticancer agents against two CRC cell lines (HCT116 and SW480) was investigated using cell viability proliferation, migration, adhesion and invasion assays. A liquid chromatography-mass spectrometry (LC-MS/MS) metabolomics approach was used to identify the underlying biochemical pathways disturbed in treated-HCT116 cells. Cell viability proliferation assay revealed that four compounds (C2, C3, C5, and C7) had IC50 < 10 µM with C5 displaying the most potent cytotoxic effect (IC50 1.4 and 0.3 µM against HCT116 and SW480, respectively). Additionally, the compounds showed suppression of wound closure after 72 h, and both C2 and C5 significantly decreased the number of adherent cells and suppressed HCT116 cells invasion. Metabolomics study revealed that C5 induced significant perturbations in the level of several metabolites including spermine, polyamines, glutamine, creatine and carnitine, and altered biochemical processes essential for cell proliferation and progression such as amino acids biosynthesis and metabolism, redox homeostasis, energy related processes (e.g., fatty acid oxidation, second Warburg like effect) and one-carbon metabolism. Our findings indicate that 2,3-dihydroquinazolin-4(1H)-one analogues, particularly C5, have promising anticancer properties, and shed light on the role of metabolomics in identifying new therapeutic targets and providing better understanding of the pathways altered in treated cancer cells.

Skin Cancer Metabolic Profile Assessed by Different Analytical Platforms.

Skin cancer, including malignant melanoma (MM) and keratinocyte carcinoma (KC), historically named non-melanoma skin cancers (NMSC), represents the most common type of cancer among the white skin population. Despite decades of clinical research, the incidence rate of melanoma is increasing globally. Therefore, a better understanding of disease pathogenesis and resistance mechanisms is considered vital to accomplish early diagnosis and satisfactory control. The "Omics" field has recently gained attention, as it can help in identifying and exploring metabolites and metabolic pathways that assist cancer cells in proliferation, which can be further utilized to improve the diagnosis and treatment of skin cancer. Although skin tissues contain diverse metabolic enzymes, it remains challenging to fully characterize these metabolites. Metabolomics is a powerful omics technique that allows us to measure and compare a vast array of metabolites in a biological sample. This technology enables us to study the dermal metabolic effects and get a clear explanation of the pathogenesis of skin diseases. The purpose of this literature review is to illustrate how metabolomics technology can be used to evaluate the metabolic profile of human skin cancer, using a variety of analytical platforms including gas chromatography-mass spectrometry (GC-MS), liquid chromatography-mass spectrometry (LC-MS), and nuclear magnetic resonance (NMR). Data collection has not been based on any analytical method.