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.

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.

Investigating the Impact of IL6 on Insulin Secretion: Evidence from INS-1 Cells, Human Pancreatic Islets, and Serum Analysis.

Interleukin-6 (IL6) is a pleiotropic cytokine implicated in metabolic disorders and inflammation, yet its precise influence on insulin secretion and glucose metabolism remains uncertain. This study examined IL6 expression in pancreatic islets from individuals with/without diabetes, alongside a series of functional experiments, including siRNA silencing; IL6 treatment; and assessments of glucose uptake, cell viability, apoptosis, and expression of key ß-cell genes, which were conducted in both INS-1 cells and human islets to elucidate the effect of IL6 on insulin secretion. Serum levels of IL6 from Emirati patients with type 2 diabetes (T2D) were measured, and the effect of antidiabetic drugs on IL6 levels was studied. The results revealed that IL6 mRNA expression was higher in islets from diabetic and older donors compared to healthy or young donors. IL6 expression correlated negatively with PDX1, MAFB, and NEUROD1 and positively with SOX4, HES1, and FOXA1. Silencing IL6 in INS-1 cells reduced insulin secretion and glucose uptake independently of apoptosis or oxidative stress. Reduced expression of IL6 was associated with the downregulation of Ins, Pdx1, Neurod1, and Glut2 in INS-1 cells. In contrast, IL6 treatment enhanced insulin secretion in INS-1 cells and human islets and upregulated insulin expression. Serum IL6 levels were elevated in patients with T2D and associated with higher glucose, HbA1c, and triglycerides, regardless of glucose-lowering medications. This study provides a new understanding of the role of IL6 in ß-cell function and the pathophysiology of T2D. Our data highlight differences in the response to IL6 between INS-1 cells and human islets, suggesting the presence of species-specific variations across different experimental models. Further research is warranted to unravel the precise mechanisms underlying the observed effects of IL-6 on insulin secretion.

A roadmap beyond dispensing for educating and training community pharmacists on key mental health competencies: A mixed-methods national study.

BACKGROUND: Including pharmacists in collaborative mental healthcare models has yielded positive results. Establishing processes to enhance pharmacists' mental health care capabilities is crucial for addressing the increasing burden and improving access to mental health services. OBJECTIVES: This study evaluated community pharmacists' mental health competencies and analyzed associated factors using a rigorous international framework. Additionally, it sought to identify pharmacists' training needs and support requirements as the first stop in creating a roadmap for enhancing mental healthcare through community pharmacies. METHODS: A large-scale national study employing a mixed-methods approach was conducted with community pharmacists in United Arab Emirates. Semi-structured individual interviews and a cross-sectional survey were conducted. Pharmacists' core competencies were assessed using the Core Mental Health Competencies Framework for all Pharmacy Professionals. Generalized linear models were utilized to identify predictors of pharmacists' competency levels. Thematic analysis was used to analyze qualitative data. RESULTS: In total 650 community pharmacists completed the survey (93.7% response rate). Eight pharmacists participated in semi-structured interviews. Nearly two-thirds (63.7%) received general communication skills training, while training in motivational interviewing (44.7%), shared decision-making (37.2%), and mental illness stereotyping/stigma (23.9%) were less common. Pharmacists reported lower perceived competence in their relationship with multidisciplinary teams (M = 3.02, SD = 0.89), stigma recognition (M = 3.02, SD = 1.04), and identifying mental health crises and aiding in the person's safety (M = 3.01, SD = 1.05). Poor communication skills (p < 0.001) and working in pharmacies that do not stock psychotropic medications (p = 0.023) were associated with lower perceived competence. Qualitative analysis identified training needs in various domains, including attitudes, values, and beliefs about mental health; relationships with multidisciplinary teams; communication skills; pharmaceutical knowledge; and personal and service development. CONCLUSIONS: Mental health-related training is needed for community pharmacists. Addressing these needs through an intentional roadmap approach will enable pharmacists to better engage with patients with mental illness and increase access to care.

Assessing Students' Knowledge and Attitudes Regarding the Risks and Prevention of Consanguineous Marriage: A Cross-Sectional Online Survey.

Background: Several studies indicate a correlation between consanguinity and genetic disorders, congenital malformations, harm to reproductive health, and increased child mortality. Objective: To assess students' knowledge and attitudes about risks and prevention of consanguineous marriage. Methods: Demographic details of the participants and data on knowledge and attitudes concerning the risks and prevention of consanguineous marriage were obtained using an online self-administered questionnaire. The factors associated with good knowledge and attitude toward consanguineous marriage were investigated by logistic regression analysis. Results: A total of 667 participants enrolled in the study. The average knowledge score about consanguineous marriage risk and prevention was 78.6% with a 95% confidence interval (CI) [77.3, 79.8], and the average attitude was 79.7% with a 95% confidence interval (CI) [79, 80.6]. A better knowledge score was observed in older participants (OR 1.01; 95% CI 1.004-1.024), females (OR 1.69; 95% CI 1.48-1.94), participants with parental history of consanguinity (OR 1.33; 95% CI 1.17-1.52), participants with family history of consanguineous marriage (OR 5.18; 95% CI 2.19-7.10), and participants with family history of inherited disease (OR 1.52; 95% CI 1.25-1.86). Conclusion: In general, the overall level of knowledge and attitudes toward consanguineous marriage risk and prevention was good among university students. To efficiently control and manage the adverse health impacts associated with consanguineous marriage, there is an urgent need to develop and implement evidence-based counseling and screening programs for consanguineous marriage that would significantly reduce the number of at-risk marriages.

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.

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.

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.

The Global, Regional, and National Burden of Adult Lip, Oral, and Pharyngeal Cancer in 204 Countries and Territories: A Systematic Analysis for the Global Burden of Disease Study 2019.

Importance: Lip, oral, and pharyngeal cancers are important contributors to cancer burden worldwide, and a comprehensive evaluation of their burden globally, regionally, and nationally is crucial for effective policy planning. Objective: To analyze the total and risk-attributable burden of lip and oral cavity cancer (LOC) and other pharyngeal cancer (OPC) for 204 countries and territories and by Socio-demographic Index (SDI) using 2019 Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study estimates. Evidence Review: The incidence, mortality, and disability-adjusted life years (DALYs) due to LOC and OPC from 1990 to 2019 were estimated using GBD 2019 methods. The GBD 2019 comparative risk assessment framework was used to estimate the proportion of deaths and DALYs for LOC and OPC attributable to smoking, tobacco, and alcohol consumption in 2019. Findings: In 2019, 370 000 (95% uncertainty interval [UI], 338 000-401 000) cases and 199 000 (95% UI, 181 000-217 000) deaths for LOC and 167 000 (95% UI, 153 000-180 000) cases and 114 000 (95% UI, 103 000-126 000) deaths for OPC were estimated to occur globally, contributing 5.5 million (95% UI, 5.0-6.0 million) and 3.2 million (95% UI, 2.9-3.6 million) DALYs, respectively. From 1990 to 2019, low-middle and low SDI regions consistently showed the highest age-standardized mortality rates due to LOC and OPC, while the high SDI strata exhibited age-standardized incidence rates decreasing for LOC and increasing for OPC. Globally in 2019, smoking had the greatest contribution to risk-attributable OPC deaths for both sexes (55.8% [95% UI, 49.2%-62.0%] of all OPC deaths in male individuals and 17.4% [95% UI, 13.8%-21.2%] of all OPC deaths in female individuals). Smoking and alcohol both contributed to substantial LOC deaths globally among male individuals (42.3% [95% UI, 35.2%-48.6%] and 40.2% [95% UI, 33.3%-46.8%] of all risk-attributable cancer deaths, respectively), while chewing tobacco contributed to the greatest attributable LOC deaths among female individuals (27.6% [95% UI, 21.5%-33.8%]), driven by high risk-attributable burden in South and Southeast Asia. Conclusions and Relevance: In this systematic analysis, disparities in LOC and OPC burden existed across the SDI spectrum, and a considerable percentage of burden was attributable to tobacco and alcohol use. These estimates can contribute to an understanding of the distribution and disparities in LOC and OPC burden globally and support cancer control planning efforts.

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.

Disrupting of family with sequence similarity 105, member A (Fam105a) deteriorates pancreatic ß-cell physiology and insulin secretion in INS-1 cells.

The role of "Family with sequence similarity 105, member A" (FAM105A) in pancreatic ß-cell function in relation to type 2 diabetes mellitus (T2D) is not fully understood. To address this issue, various molecular and functional experiments were conducted on primary human islets and INS-1 cells. RNA-seq expression analysis showed that FAM105A is highly expressed in human islets and its expression is reduced in diabetic islets compared to healthy islets. FAM105A expression correlated negatively with HbA1c levels and body mass index (BMI). Co-expression analysis showed a significant correlation between FAM105A with PDX1, GCK, GLUT1 and INSR, but not the INS gene. Silencing of Fam105a impaired insulin release, content, glucose uptake, and mitochondria ATP content but did not affect cell viability, reactive oxygen species (ROS) or apoptosis levels. Silencing of Fam105a was associated with reduced Pdx1 and Glut2 expression at mRNA and protein levels. RNA-seq analysis of dysregulated genes in Fam105a-silenced cells showed an overall downregulation of gene expression in ß-cells and insulin secretion pathway. Disrupting Pdx1 did not affect Fam105a expression in INS-1 cells. Overall, the results suggest that FAM105A plays an important role in pancreatic ß-cells biology and may be involved in the development of T2D.

Airport-based pharmacies: Products, services and challenges essential for patients in a global travel landscape.

The role of airport pharmacies has grown in recent years to provide a range of services to travelers, including over-the-counter and prescription medicines, as well as advice on prevention of infectious and other diseases. Prevention, including protective equipment, is especially important during pandemics, as seen with the recent coronavirus disease-2019 (COVID-19) pandemic. In addition, offering vaccinations where appropriate. However, this is not universal, and there are currently no acknowledged guidelines for pharmacists operating within airports. In addition, research into their role as well as potential ways to improve this is lacking. This is a concern with community pharmacists playing a valuable role during the COVID-19 pandemic. Potential ways forward include greater research into their activities to enhance their role and address challenges. These include issues of brand names and language, as well as encouraging travel pharmacy in future university curricula. In addition, producing guidelines for their activities and monitoring their implementation. This can help build a greater role for their services, benefiting airport staff and travelers in the future.

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.

RhoA/ROCK inhibition attenuates endothelin-1-induced glomerulopathy in the rats.

Endothelin-1 (ET-1) contributes to the development of kidney diseases. However, the underlying molecular mechanism is largely undefined. Here we sought to investigate the potential role of ET-1 receptors, ETA and ETB in the regulation of increased glomerular permeability and underlying signaling pathways post-ET-1 infusion. Male Sprague-Dawley rats were infused with ET-1 (2 pmol/kg per minute, i.v.) for four weeks, and the effect on glomerular permeability to albumin (Palb) and albuminuria was measured. The selective ROCK-1/2 inhibitor, Y-27632, was administered to a separate group of rats to determine its effect on ET-1-induced Palb and albuminuria. The role of ETA and ETB receptors in regulating RhoA/ROCK activity was determined by incubating isolated glomeruli from normal rats with ET-1 and with selective ETA and ETB receptor antagonists. ET-1 infusion for four weeks significantly elevated Palb and albuminuria. Y-27632 significantly reduced the elevation of Palb and albuminuria. The activities of both RhoA and ROCK-1/2 were increased by ET-1 infusion. Selective ETB receptor antagonism had no effect on the elevated activity of both RhoA and ROCK-1/2 enzymes. Selective ETA receptor and combined ETA/ETB receptors blockade restored the activity of RhoA and ROCK-1/2 to normal levels. In addition, chronic ET-1 infusion increased the levels of glomerular inflammatory and fibrotic markers. These effects were all attenuated in rats following ROCK-1/2 inhibition. These observations suggest that ET-1 contributes to increased albuminuria, inflammation, and fibrosis by modulating the activity of the ETA-RhoA/ROCK-1/2 pathway. Selective ETA receptor blockade may represent a potential therapeutic strategy to limit glomerular injury and albuminuria in kidney disease.

The Effects of Medications and the Roles of Pharmacists on the Recovery of Patients with COVID-19 Infection: An Epidemiological Study from the United Arab Emirates.

Patients infected with coronavirus have new experiences and hence new needs from the healthcare sector. Acknowledging patients' experiences can exhibit promising outcomes in coronavirus management. Pharmacists are considered a vital pillar in managing patients' experiences during their infection. A cross-sectional study was conducted to assess the experiences of COVID-19-infected individuals and the roles of pharmacists in the United Arab Emirates. The survey was face- and content-validated after being developed. Three sections were included in the survey (demographics, experiences of infected individuals, and the roles of pharmacists). Data were analyzed using the Statistical Package for the Social Sciences. The study participants (n = 509) had a mean age of 34.50 (SD = 11.93). The most reported symptoms among participants were fatigue (81.5%), fever (76.8%), headache (76.6%), dry cough (74.1%), muscle or joint pain (70.7%), and sore throat (68.6%). Vitamin C was the most used supplement (88.6%), followed by pain relievers (78.2%). Female gender was the only factor associated with symptom severity. About 79.0% agreed that the pharmacist played an important and effective role during their infection. The most reported symptom was fatigue, with females reporting more severe symptoms. The role of the pharmacist proved to be vital during this pandemic.

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.

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.

Metabolomics Analysis Revealed Significant Metabolic Changes in Brain Cancer Cells Treated with Paclitaxel and/or Etoposide.

Cancer of the central nervous system (CNS) is ranked as the 19th most prevalent form of the disease in 2020. This study aims to identify candidate biomarkers and metabolic pathways affected by paclitaxel and etoposide, which serve as potential treatments for glioblastoma, and are linked to the pathogenesis of glioblastoma. We utilized an untargeted metabolomics approach using the highly sensitive ultra-high-performance liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-ESI-QTOF-MS) for identification. In this study, 92 and 94 metabolites in U87 and U373 cell lines were profiled, respectively. The produced metabolites were then analyzed utilizing t-tests, volcano plots, and enrichment analysis modules. Our analysis revealed distinct metabolites to be significantly dysregulated (nutriacholic acid, L-phenylalanine, L-arginine, guanosine, ADP, hypoxanthine, and guanine), and to a lesser extent, mevalonic acid in paclitaxel and/or etoposide treated cells. Furthermore, both urea and citric acid cycles, and metabolism of polyamines and amino acids (aspartate, arginine, and proline) were significantly enriched. These findings can be used to create a map that can be utilized to assess the antitumor effect of paclitaxel and/or etoposide within the studied cancer cells.