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Papers by mohammed qudah

Research paper thumbnail of Metabolomics Analysis Revealed Significant Metabolic Changes in Brain Cancer Cells Treated with Paclitaxel and/or Etoposide

International Journal of Molecular Sciences

Cancer of the central nervous system (CNS) is ranked as the 19th most prevalent form of the disea... more 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 t...

Research paper thumbnail of Effect of metformin on irinotecan-induced cell cycle arrest in colorectal cancer cell lines HCT116 and SW480

International Journal of Health Sciences, 2021

Objectives: Metformin is widely used for the treatment of type 2 diabetes mellitus and found to h... more Objectives: Metformin is widely used for the treatment of type 2 diabetes mellitus and found to have a crucial rule in the induction of apoptosis in several cancer types including pancreatic cell carcinoma, epithelial ovarian cancer, breast cancer, and renal cell carcinoma. In this study, we propose to explore the potential role of metformin as an adjuvant of irinotecan to target colorectal cancer (CRC) cell lines, exploring the effects underlying the anticancer properties of metformin on CRC cell lines. Methods: HCT116 and SW480 cell lines were treated with metformin, irinotecan and their combination. The effect of metformin on cell viability was evaluated using MTT assay. Flow cytometry technique was used to analyze apoptosis and cell cycle progression. While, detection of protein expression was analyzed by Western blot. Results: Metformin was found to inhibit growth in both HCT1116 and SW480 cell lines. On combination with irinotecan, it has been revealed that metformin sensitize...

Research paper thumbnail of Amlodipine inhibits proliferation, invasion, and colony formation of breast cancer cells

Biomedical Reports

Calcium channel upregulation has been implicated in cancer cell proliferation and progression inc... more Calcium channel upregulation has been implicated in cancer cell proliferation and progression including in breast cancer. Fortunately, the function of calcium channels can be manipulated pharmacologically using calcium channel blockers (CCBs). Amlodipine, a dihydropyridine CCB, has been demonstrated to exert cytotoxic effects in several types of cancers. The present study evaluated the effects of amlodipine on proliferation, caspase activation, colony formation, and invasion of human breast cancer cells. Cell viability was assessed using a colorimetric MTT assay. An Apo-ONE ® caspase-3/7 assay was used to measure caspase-3/7 levels. Cell invasion was evaluated using Matrigel invasion chambers. The expression of phospho-(p-)ERK1/2, Bcl-2, and integrin β1 proteins were analyzed using western blotting. A one-way ANOVA with a post-hoc Tukey's multiple comparison tests was used for statistical analysis. Amlodipine significantly inhibited the growth of both MDA-MB-231 and MCF-7 human breast cancer cells in a dose-dependent manner and inhibited colony formation of MCF-7 cells, and this was accompanied by the downregulation of p-ERK1/2 in MDA-MB-231 cells. In addition, treatment with amlodipine resulted in increased caspase-3/7 levels in MDA-MB-231 cells, which was accompanied by the downregulation of the anti-apoptotic protein, Bcl-2. Moreover, amlodipine impaired the invasive abilities of MDA-MB-231 cells, and integrin β1 expression was concurrently downregulated. The present study illustrates the anticancer effects of amlodipine on breast cancer proliferation, colony formation, and invasion in vitro and highlights the potential value of amlodipine as an anticancer agent.

Research paper thumbnail of Insights into the Molecular Mechanisms Mediating Extravasation in Brain Metastasis of Breast Cancer, Melanoma, and Lung Cancer

Cancers

Brain metastasis is an incurable end-stage of systemic cancer associated with poor prognosis, and... more Brain metastasis is an incurable end-stage of systemic cancer associated with poor prognosis, and its incidence is increasing. Brain metastasis occurs through a multi-step cascade where cancer cells spread from the primary tumor site to the brain. The extravasation of tumor cells through the blood–brain barrier (BBB) is a critical step in brain metastasis. During extravasation, circulating cancer cells roll along the brain endothelium (BE), adhere to it, then induce alterations in the endothelial barrier to transmigrate through the BBB and enter the brain. Rolling and adhesion are generally mediated by selectins and adhesion molecules induced by inflammatory mediators, while alterations in the endothelial barrier are mediated by proteolytic enzymes, including matrix metalloproteinase, and the transmigration step mediated by factors, including chemokines. However, the molecular mechanisms mediating extravasation are not yet fully understood. A better understanding of these mechanisms...

Research paper thumbnail of COVID-19 Vaccines, Effectiveness, and Immune Responses

International Journal of Molecular Sciences

The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)... more The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has captivated the globe’s attention since its emergence in 2019. This highly infectious, spreadable, and dangerous pathogen has caused health, social, and economic crises. Therefore, a worldwide collaborative effort was made to find an efficient strategy to overcome and develop vaccines. The new vaccines provide an effective immune response that safeguards the community from the virus’ severity. WHO has approved nine vaccines for emergency use based on safety and efficacy data collected from various conducted clinical trials. Herein, we review the safety and effectiveness of the WHO-approved COVID-19 vaccines and associated immune responses, and their impact on improving the public’s health. Several immunological studies have demonstrated that vaccination dramatically enhances the immune response and reduces the likelihood of future infections in previously infected individuals. Howev...

Research paper thumbnail of Knowledge and attitudes of pharmacists towards colorectal cancer health education in Jordan: A cross‐sectional study

International Journal of Clinical Practice, 2021

The purpose of this study was to assess pharmacists’ knowledge and attitude towards early detecti... more The purpose of this study was to assess pharmacists’ knowledge and attitude towards early detection of colorectal cancer (CRC) in Jordan and to explore potential predictor variables of such knowledge and attitude.

Research paper thumbnail of Impaired Awareness of Hypoglycaemia in Insulin-treated Type 2 Diabetes Mellitus

Current Diabetes Reviews, 2019

Background: Patients with Type 2 Diabetes Mellitus (T2DM) may develop hypoglycemia as an adverse ... more Background: Patients with Type 2 Diabetes Mellitus (T2DM) may develop hypoglycemia as an adverse effect of insulin therapy. Hypoglycemia has dangerous consequences that result from neuroglycopenia and hypersecretion of counter-regulatory hormones. Patients who recognize early symptoms of hypoglycemia can initiate self-treatment and rectify the situation. Impaired Awareness of Hypoglycemia (IAH) predisposes patients to severe hypoglycemia and unconsciousness. Objective: To assess the prevalence of IAH, the intensity of hypoglycaemic symptoms, the frequency of severe hypoglycemia and factors associated with IAH in patients with insulin-treated T2DM. Methods: This is a cross-sectional study that used Clarke's and Gold's surveys to assess IAH and Edinburgh survey to assess the intensity of hypoglycemic symptoms in patients with insulin-treated T2DM (n= 388). The frequency of hypoglycemia and other data were collected by self-reporting or from medical records. Results: The preval...

Research paper thumbnail of Vitamin C prevents memory impairment induced by waterpipe smoke: role of oxidative stress

Inhalation Toxicology, 2018

Waterpipe tobacco smoking (WTS) was previously shown to be associated with memory deficits, which... more Waterpipe tobacco smoking (WTS) was previously shown to be associated with memory deficits, which were related to oxidative stress. Vitamin C (VitC) has established antioxidant properties against memory deficits associated with several diseases and conditions. In this study, the potential protective effect of VitC on memory impairment induced by WTS exposure was evaluated in a rat model. VitC was administered to animals via oral gavage (100 mg/kg/day, 6 days a week for 4 weeks). At the same period, animals were exposed to WTS for one hour/day, 6 days a week for 4 weeks. Using radial arm water maze (RAWM), behavioral tests were conducted to evaluate the spatial learning and memory. In addition, hippocampal levels of oxidative stress biomarkers were analyzed. WTS exposure impaired both short-and long-term memory (p < .05). On the other hand, VitC protected memory impairment induced by WTS (p < .05). Moreover, VitC prevented the reduction in hippocampus ratio of GSH/GSSG (p < .05) induced by WTS. Furthermore, WTS reduced hippocampus activity of glutathione peroxidase (GPx) and catalase, which were also normalized by VitC treatment. However, thiobarbituric acid reactive substance (TBARS) levels were not changed by WTS and/or by VitC (p > .05). In conclusion, WTS resulted in inducing memory impairment, which was prevented by VitC administration. This could be related to preserving hippocampus antioxidant mechanisms by VitC during WTS exposure.

Research paper thumbnail of Analysis and mapping of global scientific research on human monkeypox over the past 20 years

Veterinary World

Background and Aim: Human monkeypox is an emerging global threat. Hundreds of publications were d... more 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 s...

Research paper thumbnail of Skin Cancer Metabolic Profile Assessed by Different Analytical Platforms

International Journal of Molecular Sciences

Skin cancer, including malignant melanoma (MM) and keratinocyte carcinoma (KC), historically name... more 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...

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

International Journal of Molecular Sciences

Untargeted multi-omics analysis of plasma is an emerging tool for the identification of novel bio... more 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 spec...

Research paper thumbnail of Prediction of hidden patterns in rheumatoid arthritis patients records using data mining

Multimedia Tools and Applications

Research paper thumbnail of Early Detection of Prostate Cancer: Self-Reported Knowledge and Attitude of Physicians in Jordan

INQUIRY: The Journal of Health Care Organization, Provision, and Financing

Prostate cancer (PC) screening aims to detect PC in early stages, amenable to curative treatment ... more Prostate cancer (PC) screening aims to detect PC in early stages, amenable to curative treatment and reduction in disease morbidity and mortality. However, PC screening may be associated with overdiagnosis and complications of unnecessary treatment for indolent disease. Therefore, careful patient selection for PC screening is critical to avoid overestimation and missed diagnosis. The aim of this study was to assess physicians’ knowledge and attitude towards early detection of PC in Jordan and whether their knowledge is an important predictor of their attitude. An electronic, self-reported questionnaire was used to collect data on demographics, knowledge, and attitude of physicians regarding early detection of PC. The participants’ responses were analyzed using descriptive statistics and multiple linear regression. Around 296 physicians agreed to participate in this study. Most respondents were males (75.7%), residents (34%), practiced medicine more than 15 years (29%) and graduated ...

Research paper thumbnail of Calcium-Sensing Receptor Antagonist NPS-2143 Inhibits Breast Cancer cell Proliferation, Migration and Invasion via Downregulation of p-ERK1/2, Bcl-2 and Integrin β1 and Induces Caspase 3/7 Activation

Advanced Pharmaceutical Bulletin, 2021

Purpose: Calcium-sensing receptor (CaSR) has been associated with breast cancer metastasis to the... more Purpose: Calcium-sensing receptor (CaSR) has been associated with breast cancer metastasis to the bone. Targeting chemoattractant factors, such as calcium, that are released in response to bone resorption could prevent metastasis and induce apoptosis of cancer cells. In the present study, we investigated the potential caspase 3/7 activation following treatment with a CaSR antagonist, NPS-2143, in breast cancer cells. In addition, the effects of NPS-2143 on breast cancer cell proliferation, migration and invasion were assessed. Methods: Colorimetric MTT assay was used to evaluate cell viability. Apo-one homogeneous caspase-3/7 assay was used to measure caspase 3/7 activities in breast cancer cells. Cell migration and invasion were assessed using scratch wound assay and matrigel invasion chambers, respectively. The protein expressions of p-ERK1/2, integrin β1 and Bcl-2 were evaluated using western blotting. Results: Our study revealed that NPS-2143 significantly reduced cell prolifera...

Research paper thumbnail of Lead optimization and biological evaluation of diazenylbenzenesulfonamides inhibitors against glyoxalase-I enzyme as potential anticancer agents

Bioorganic Chemistry, 2022

In a previous report, we described the discovery of (E)-5-((8-hydroxyquinolin-5-yl)diazenyl)-2-me... more In a previous report, we described the discovery of (E)-5-((8-hydroxyquinolin-5-yl)diazenyl)-2-methylbenzenesulfonamide as a potent inhibitor of GLO-I enzyme with IC50 of 1.28 ± 0.12 μM. Herein, lead optimization of this compound was achieved through targeting the central zinc atom and hydrophilic amino acid residues in the active site of the enzyme. Among the synthesized compounds, compound TS010 showed the most potent inhibitory activity with IC50 of 0.57 ± 0.04 μM. Compound TS013 also showed comparable activity to that of the lead compound with IC50 of 1.14 ± 0.03 μM. Molecular docking studies disclosed the binding mode of the compounds inside the active side of GLO-I enzyme.

Research paper thumbnail of An audit on pharmacists' knowledge and experience in pediatric care

Aims of the study: The aim of this study was to determine pharmacists' perceived knowledge and ex... more Aims of the study: The aim of this study was to determine pharmacists' perceived knowledge and expertise required to deliver pharmaceutical care services to pediatric patients. Methods used to conduct the study: Once ethical approval was obtained; a questionnaire was posted on local pharmacy groups. The questionnaire is composed of four domains: (1) Demographics (2) Perceived knowledge of pediatric treatment and dosing (3) Real life pediatric cases (4) Future aspirations to enhance pediatric pharmacy. Results of the study: Two-hundred questionnaires where complete and submitted online. Most participants (62.5%) practiced in a community setting. Most respondents (40%) reported that 41%-60% of their patients were pediatrics. In general, respondents had a good perception of their knowledge and expertise to deliver pharmaceutical care services to pediatric patients. However, most respondents had a low knowledge score when faced with real-life pediatric cases. On a scale of seven most respondents obtained the score of two (32.0%). Conclusions drawn from the study and clinical implications: The present study sheds the light on an alarming lack of knowledge in pediatric knowledge amongst pharmacies in Jordan. Further training and educational programs should be implemented to address this gap in knowledge and its reflections on practice.

Research paper thumbnail of Impaired awareness of hypoglycemia in children and adolescents with type 1 diabetes mellitus in north of Jordan

BMC Endocrine Disorders, 2019

Background Hypoglycemia is a common complication of insulin therapy in patients with Type 1 Diabe... more Background Hypoglycemia is a common complication of insulin therapy in patients with Type 1 Diabetes Mellitus (DM). Awareness of hypoglycemic symptoms helps patients to recognize hypoglycemia and initiate self-treatment. Impaired Awareness of Hypoglycemia (IAH) exposes patients to severe hypoglycemia, which could be associated with seizures and unconsciousness. This study aimed to assess IAH, frequency of hypoglycemia, severe hypoglycemia and intensity of hypoglycemic symptoms among children and adolescents with Type 1 DM in North of Jordan. Methods Data were collected from 94 children and adolescents with Type 1 DM. Clarke’s and Edinburgh surveys were used to assess IAH and individual symptoms of hypoglycemia, respectively. Frequency of hypoglycemia and other related information were obtained by self-reporting or from medical records. Results 16.0% of participants were having IAH, 66.0% of participants reported recurrent hypoglycemia (>once/month) and 18.0% of participants devel...

Research paper thumbnail of Association of brain-derived neurotrophic factor and interleukin-6 serum levels with depressive and anxiety symptoms in hemodialysis patients

General Hospital Psychiatry, 2018

OBJECTIVE This study assessed the possible association of serum brain-derived neurotrophic factor... more OBJECTIVE This study assessed the possible association of serum brain-derived neurotrophic factor (BDNF) and interleukin-6 (IL-6) with depressive and anxiety symptoms in hemodialysis (HD) patients. METHOD An analytical cross-sectional study was conducted over 274 HD patients from March to October 2017. The Hospital Anxiety and Depression Scale (HADS) was utilized to evaluate depressive (HADS-D) and anxiety (HADS-A) symptoms. The HADS-D/A is a self-report instrument that has a maximum score of 21. Serum BDNF and IL-6 were measured using enzyme-linked immunosorbant assay (ELISA). RESULTS Serum IL-6 was significantly higher in patients with depressive symptoms compared to normal (20.47 ± 4.27 pg/mL for HADS-D ≥11 versus 9.26 ± 1.59 pg/mL for HADS-D <7, p = 0.014). Multivariable regression analysis revealed that IL-6, education level, hypertension, and dialysis duration were significant predictors of HADS-D. Also, gender, education level, hypertension, and the number of dialysis sessions/week were significant predictors of HADS-A. Significant positive correlation was shown between HADS-D and IL-6 (r = 0.1729, p = 0.004). CONCLUSION Collectively, HD patients with depressive symptoms showed higher levels of IL-6, supporting previous findings that the circulating inflammatory mediator IL-6 can be used as a biomarker for prediction of depressive symptoms in HD patients. Further longitudinal or interventional studies are needed to further validate this association.

Research paper thumbnail of Vitamin E protects human lymphocytes from genotoxicity induced by oxaliplatin

Drug and Chemical Toxicology, 2017

Abstract Oxaliplatin is a platinum-based anticancer drug that has been shown to be genotoxic to t... more Abstract Oxaliplatin is a platinum-based anticancer drug that has been shown to be genotoxic to the normal cells. Vitamin E is a potent antioxidant that may protect and enhance the repair of the damaged DNA. In this study, we aimed to evaluate the genotoxic effect of oxaliplatin on DNA by measuring the frequency of chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs) in cultured human lymphocytes. We also attempted to explore the potential protective effect of vitamin E on chromosomal damage induced by oxaliplatin. Results showed that oxaliplatin significantly increased the frequency of CAs (p < 0.001) and SCEs (p < 0.001) as compared to control. This chromosomal damage, caused by oxaliplatin, was significantly decreased by pretreatment of cells with vitamin E. Moreover, the results showed that oxaliplatin caused a significant reduction in the cell kinetic parameters, the mitotic index (MI) and the proliferative index (PI). However, vitamin E did not affect this reduction in the MI and PI. Therefore, we conclude that oxaliplatin is genotoxic, and vitamin E can prevent the chromosomal damage induced by oxaliplatin but it has no effect on oxaliplatin-induced cytotoxicity.

Research paper thumbnail of Crizotinib, a MET inhibitor, inhibits growth, migration, and invasion of breast cancer cells in vitro and synergizes with chemotherapeutic agents

OncoTargets and therapy, 2017

MET is a receptor tyrosine kinase known for its pleiotropic effects in tumorigenesis. Dysregulati... more MET is a receptor tyrosine kinase known for its pleiotropic effects in tumorigenesis. Dysregulations of MET expression and/or signaling have been reported and determined to be associated with inferior outcomes in breast cancer patients rendering MET a versatile candidate for targeted therapeutic intervention. Crizotinib is a multi-targeted small-molecule kinase inhibitor for MET, ALK, and ROS1 kinases. This study evaluated the anti-proliferative, cytotoxic, anti-migratory, and anti-invasive effects of crizotinib in breast cancer cells in vitro. Cell viability was assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) colorimetric assay. In vitro wound-healing assay was used to examine the effect of crizotinib on breast cancer cell migration. The expressions of Ki-67, MET, and phospho-MET receptors were characterized using immunofluorescence staining. Results showed that crizotinib has significant anti-proliferative activity on all mammary tumor cells with...

Research paper thumbnail of Metabolomics Analysis Revealed Significant Metabolic Changes in Brain Cancer Cells Treated with Paclitaxel and/or Etoposide

International Journal of Molecular Sciences

Cancer of the central nervous system (CNS) is ranked as the 19th most prevalent form of the disea... more 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 t...

Research paper thumbnail of Effect of metformin on irinotecan-induced cell cycle arrest in colorectal cancer cell lines HCT116 and SW480

International Journal of Health Sciences, 2021

Objectives: Metformin is widely used for the treatment of type 2 diabetes mellitus and found to h... more Objectives: Metformin is widely used for the treatment of type 2 diabetes mellitus and found to have a crucial rule in the induction of apoptosis in several cancer types including pancreatic cell carcinoma, epithelial ovarian cancer, breast cancer, and renal cell carcinoma. In this study, we propose to explore the potential role of metformin as an adjuvant of irinotecan to target colorectal cancer (CRC) cell lines, exploring the effects underlying the anticancer properties of metformin on CRC cell lines. Methods: HCT116 and SW480 cell lines were treated with metformin, irinotecan and their combination. The effect of metformin on cell viability was evaluated using MTT assay. Flow cytometry technique was used to analyze apoptosis and cell cycle progression. While, detection of protein expression was analyzed by Western blot. Results: Metformin was found to inhibit growth in both HCT1116 and SW480 cell lines. On combination with irinotecan, it has been revealed that metformin sensitize...

Research paper thumbnail of Amlodipine inhibits proliferation, invasion, and colony formation of breast cancer cells

Biomedical Reports

Calcium channel upregulation has been implicated in cancer cell proliferation and progression inc... more Calcium channel upregulation has been implicated in cancer cell proliferation and progression including in breast cancer. Fortunately, the function of calcium channels can be manipulated pharmacologically using calcium channel blockers (CCBs). Amlodipine, a dihydropyridine CCB, has been demonstrated to exert cytotoxic effects in several types of cancers. The present study evaluated the effects of amlodipine on proliferation, caspase activation, colony formation, and invasion of human breast cancer cells. Cell viability was assessed using a colorimetric MTT assay. An Apo-ONE ® caspase-3/7 assay was used to measure caspase-3/7 levels. Cell invasion was evaluated using Matrigel invasion chambers. The expression of phospho-(p-)ERK1/2, Bcl-2, and integrin β1 proteins were analyzed using western blotting. A one-way ANOVA with a post-hoc Tukey's multiple comparison tests was used for statistical analysis. Amlodipine significantly inhibited the growth of both MDA-MB-231 and MCF-7 human breast cancer cells in a dose-dependent manner and inhibited colony formation of MCF-7 cells, and this was accompanied by the downregulation of p-ERK1/2 in MDA-MB-231 cells. In addition, treatment with amlodipine resulted in increased caspase-3/7 levels in MDA-MB-231 cells, which was accompanied by the downregulation of the anti-apoptotic protein, Bcl-2. Moreover, amlodipine impaired the invasive abilities of MDA-MB-231 cells, and integrin β1 expression was concurrently downregulated. The present study illustrates the anticancer effects of amlodipine on breast cancer proliferation, colony formation, and invasion in vitro and highlights the potential value of amlodipine as an anticancer agent.

Research paper thumbnail of Insights into the Molecular Mechanisms Mediating Extravasation in Brain Metastasis of Breast Cancer, Melanoma, and Lung Cancer

Cancers

Brain metastasis is an incurable end-stage of systemic cancer associated with poor prognosis, and... more Brain metastasis is an incurable end-stage of systemic cancer associated with poor prognosis, and its incidence is increasing. Brain metastasis occurs through a multi-step cascade where cancer cells spread from the primary tumor site to the brain. The extravasation of tumor cells through the blood–brain barrier (BBB) is a critical step in brain metastasis. During extravasation, circulating cancer cells roll along the brain endothelium (BE), adhere to it, then induce alterations in the endothelial barrier to transmigrate through the BBB and enter the brain. Rolling and adhesion are generally mediated by selectins and adhesion molecules induced by inflammatory mediators, while alterations in the endothelial barrier are mediated by proteolytic enzymes, including matrix metalloproteinase, and the transmigration step mediated by factors, including chemokines. However, the molecular mechanisms mediating extravasation are not yet fully understood. A better understanding of these mechanisms...

Research paper thumbnail of COVID-19 Vaccines, Effectiveness, and Immune Responses

International Journal of Molecular Sciences

The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)... more The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has captivated the globe’s attention since its emergence in 2019. This highly infectious, spreadable, and dangerous pathogen has caused health, social, and economic crises. Therefore, a worldwide collaborative effort was made to find an efficient strategy to overcome and develop vaccines. The new vaccines provide an effective immune response that safeguards the community from the virus’ severity. WHO has approved nine vaccines for emergency use based on safety and efficacy data collected from various conducted clinical trials. Herein, we review the safety and effectiveness of the WHO-approved COVID-19 vaccines and associated immune responses, and their impact on improving the public’s health. Several immunological studies have demonstrated that vaccination dramatically enhances the immune response and reduces the likelihood of future infections in previously infected individuals. Howev...

Research paper thumbnail of Knowledge and attitudes of pharmacists towards colorectal cancer health education in Jordan: A cross‐sectional study

International Journal of Clinical Practice, 2021

The purpose of this study was to assess pharmacists’ knowledge and attitude towards early detecti... more The purpose of this study was to assess pharmacists’ knowledge and attitude towards early detection of colorectal cancer (CRC) in Jordan and to explore potential predictor variables of such knowledge and attitude.

Research paper thumbnail of Impaired Awareness of Hypoglycaemia in Insulin-treated Type 2 Diabetes Mellitus

Current Diabetes Reviews, 2019

Background: Patients with Type 2 Diabetes Mellitus (T2DM) may develop hypoglycemia as an adverse ... more Background: Patients with Type 2 Diabetes Mellitus (T2DM) may develop hypoglycemia as an adverse effect of insulin therapy. Hypoglycemia has dangerous consequences that result from neuroglycopenia and hypersecretion of counter-regulatory hormones. Patients who recognize early symptoms of hypoglycemia can initiate self-treatment and rectify the situation. Impaired Awareness of Hypoglycemia (IAH) predisposes patients to severe hypoglycemia and unconsciousness. Objective: To assess the prevalence of IAH, the intensity of hypoglycaemic symptoms, the frequency of severe hypoglycemia and factors associated with IAH in patients with insulin-treated T2DM. Methods: This is a cross-sectional study that used Clarke's and Gold's surveys to assess IAH and Edinburgh survey to assess the intensity of hypoglycemic symptoms in patients with insulin-treated T2DM (n= 388). The frequency of hypoglycemia and other data were collected by self-reporting or from medical records. Results: The preval...

Research paper thumbnail of Vitamin C prevents memory impairment induced by waterpipe smoke: role of oxidative stress

Inhalation Toxicology, 2018

Waterpipe tobacco smoking (WTS) was previously shown to be associated with memory deficits, which... more Waterpipe tobacco smoking (WTS) was previously shown to be associated with memory deficits, which were related to oxidative stress. Vitamin C (VitC) has established antioxidant properties against memory deficits associated with several diseases and conditions. In this study, the potential protective effect of VitC on memory impairment induced by WTS exposure was evaluated in a rat model. VitC was administered to animals via oral gavage (100 mg/kg/day, 6 days a week for 4 weeks). At the same period, animals were exposed to WTS for one hour/day, 6 days a week for 4 weeks. Using radial arm water maze (RAWM), behavioral tests were conducted to evaluate the spatial learning and memory. In addition, hippocampal levels of oxidative stress biomarkers were analyzed. WTS exposure impaired both short-and long-term memory (p < .05). On the other hand, VitC protected memory impairment induced by WTS (p < .05). Moreover, VitC prevented the reduction in hippocampus ratio of GSH/GSSG (p < .05) induced by WTS. Furthermore, WTS reduced hippocampus activity of glutathione peroxidase (GPx) and catalase, which were also normalized by VitC treatment. However, thiobarbituric acid reactive substance (TBARS) levels were not changed by WTS and/or by VitC (p > .05). In conclusion, WTS resulted in inducing memory impairment, which was prevented by VitC administration. This could be related to preserving hippocampus antioxidant mechanisms by VitC during WTS exposure.

Research paper thumbnail of Analysis and mapping of global scientific research on human monkeypox over the past 20 years

Veterinary World

Background and Aim: Human monkeypox is an emerging global threat. Hundreds of publications were d... more 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 s...

Research paper thumbnail of Skin Cancer Metabolic Profile Assessed by Different Analytical Platforms

International Journal of Molecular Sciences

Skin cancer, including malignant melanoma (MM) and keratinocyte carcinoma (KC), historically name... more 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...

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

International Journal of Molecular Sciences

Untargeted multi-omics analysis of plasma is an emerging tool for the identification of novel bio... more 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 spec...

Research paper thumbnail of Prediction of hidden patterns in rheumatoid arthritis patients records using data mining

Multimedia Tools and Applications

Research paper thumbnail of Early Detection of Prostate Cancer: Self-Reported Knowledge and Attitude of Physicians in Jordan

INQUIRY: The Journal of Health Care Organization, Provision, and Financing

Prostate cancer (PC) screening aims to detect PC in early stages, amenable to curative treatment ... more Prostate cancer (PC) screening aims to detect PC in early stages, amenable to curative treatment and reduction in disease morbidity and mortality. However, PC screening may be associated with overdiagnosis and complications of unnecessary treatment for indolent disease. Therefore, careful patient selection for PC screening is critical to avoid overestimation and missed diagnosis. The aim of this study was to assess physicians’ knowledge and attitude towards early detection of PC in Jordan and whether their knowledge is an important predictor of their attitude. An electronic, self-reported questionnaire was used to collect data on demographics, knowledge, and attitude of physicians regarding early detection of PC. The participants’ responses were analyzed using descriptive statistics and multiple linear regression. Around 296 physicians agreed to participate in this study. Most respondents were males (75.7%), residents (34%), practiced medicine more than 15 years (29%) and graduated ...

Research paper thumbnail of Calcium-Sensing Receptor Antagonist NPS-2143 Inhibits Breast Cancer cell Proliferation, Migration and Invasion via Downregulation of p-ERK1/2, Bcl-2 and Integrin β1 and Induces Caspase 3/7 Activation

Advanced Pharmaceutical Bulletin, 2021

Purpose: Calcium-sensing receptor (CaSR) has been associated with breast cancer metastasis to the... more Purpose: Calcium-sensing receptor (CaSR) has been associated with breast cancer metastasis to the bone. Targeting chemoattractant factors, such as calcium, that are released in response to bone resorption could prevent metastasis and induce apoptosis of cancer cells. In the present study, we investigated the potential caspase 3/7 activation following treatment with a CaSR antagonist, NPS-2143, in breast cancer cells. In addition, the effects of NPS-2143 on breast cancer cell proliferation, migration and invasion were assessed. Methods: Colorimetric MTT assay was used to evaluate cell viability. Apo-one homogeneous caspase-3/7 assay was used to measure caspase 3/7 activities in breast cancer cells. Cell migration and invasion were assessed using scratch wound assay and matrigel invasion chambers, respectively. The protein expressions of p-ERK1/2, integrin β1 and Bcl-2 were evaluated using western blotting. Results: Our study revealed that NPS-2143 significantly reduced cell prolifera...

Research paper thumbnail of Lead optimization and biological evaluation of diazenylbenzenesulfonamides inhibitors against glyoxalase-I enzyme as potential anticancer agents

Bioorganic Chemistry, 2022

In a previous report, we described the discovery of (E)-5-((8-hydroxyquinolin-5-yl)diazenyl)-2-me... more In a previous report, we described the discovery of (E)-5-((8-hydroxyquinolin-5-yl)diazenyl)-2-methylbenzenesulfonamide as a potent inhibitor of GLO-I enzyme with IC50 of 1.28 ± 0.12 μM. Herein, lead optimization of this compound was achieved through targeting the central zinc atom and hydrophilic amino acid residues in the active site of the enzyme. Among the synthesized compounds, compound TS010 showed the most potent inhibitory activity with IC50 of 0.57 ± 0.04 μM. Compound TS013 also showed comparable activity to that of the lead compound with IC50 of 1.14 ± 0.03 μM. Molecular docking studies disclosed the binding mode of the compounds inside the active side of GLO-I enzyme.

Research paper thumbnail of An audit on pharmacists' knowledge and experience in pediatric care

Aims of the study: The aim of this study was to determine pharmacists' perceived knowledge and ex... more Aims of the study: The aim of this study was to determine pharmacists' perceived knowledge and expertise required to deliver pharmaceutical care services to pediatric patients. Methods used to conduct the study: Once ethical approval was obtained; a questionnaire was posted on local pharmacy groups. The questionnaire is composed of four domains: (1) Demographics (2) Perceived knowledge of pediatric treatment and dosing (3) Real life pediatric cases (4) Future aspirations to enhance pediatric pharmacy. Results of the study: Two-hundred questionnaires where complete and submitted online. Most participants (62.5%) practiced in a community setting. Most respondents (40%) reported that 41%-60% of their patients were pediatrics. In general, respondents had a good perception of their knowledge and expertise to deliver pharmaceutical care services to pediatric patients. However, most respondents had a low knowledge score when faced with real-life pediatric cases. On a scale of seven most respondents obtained the score of two (32.0%). Conclusions drawn from the study and clinical implications: The present study sheds the light on an alarming lack of knowledge in pediatric knowledge amongst pharmacies in Jordan. Further training and educational programs should be implemented to address this gap in knowledge and its reflections on practice.

Research paper thumbnail of Impaired awareness of hypoglycemia in children and adolescents with type 1 diabetes mellitus in north of Jordan

BMC Endocrine Disorders, 2019

Background Hypoglycemia is a common complication of insulin therapy in patients with Type 1 Diabe... more Background Hypoglycemia is a common complication of insulin therapy in patients with Type 1 Diabetes Mellitus (DM). Awareness of hypoglycemic symptoms helps patients to recognize hypoglycemia and initiate self-treatment. Impaired Awareness of Hypoglycemia (IAH) exposes patients to severe hypoglycemia, which could be associated with seizures and unconsciousness. This study aimed to assess IAH, frequency of hypoglycemia, severe hypoglycemia and intensity of hypoglycemic symptoms among children and adolescents with Type 1 DM in North of Jordan. Methods Data were collected from 94 children and adolescents with Type 1 DM. Clarke’s and Edinburgh surveys were used to assess IAH and individual symptoms of hypoglycemia, respectively. Frequency of hypoglycemia and other related information were obtained by self-reporting or from medical records. Results 16.0% of participants were having IAH, 66.0% of participants reported recurrent hypoglycemia (>once/month) and 18.0% of participants devel...

Research paper thumbnail of Association of brain-derived neurotrophic factor and interleukin-6 serum levels with depressive and anxiety symptoms in hemodialysis patients

General Hospital Psychiatry, 2018

OBJECTIVE This study assessed the possible association of serum brain-derived neurotrophic factor... more OBJECTIVE This study assessed the possible association of serum brain-derived neurotrophic factor (BDNF) and interleukin-6 (IL-6) with depressive and anxiety symptoms in hemodialysis (HD) patients. METHOD An analytical cross-sectional study was conducted over 274 HD patients from March to October 2017. The Hospital Anxiety and Depression Scale (HADS) was utilized to evaluate depressive (HADS-D) and anxiety (HADS-A) symptoms. The HADS-D/A is a self-report instrument that has a maximum score of 21. Serum BDNF and IL-6 were measured using enzyme-linked immunosorbant assay (ELISA). RESULTS Serum IL-6 was significantly higher in patients with depressive symptoms compared to normal (20.47 ± 4.27 pg/mL for HADS-D ≥11 versus 9.26 ± 1.59 pg/mL for HADS-D <7, p = 0.014). Multivariable regression analysis revealed that IL-6, education level, hypertension, and dialysis duration were significant predictors of HADS-D. Also, gender, education level, hypertension, and the number of dialysis sessions/week were significant predictors of HADS-A. Significant positive correlation was shown between HADS-D and IL-6 (r = 0.1729, p = 0.004). CONCLUSION Collectively, HD patients with depressive symptoms showed higher levels of IL-6, supporting previous findings that the circulating inflammatory mediator IL-6 can be used as a biomarker for prediction of depressive symptoms in HD patients. Further longitudinal or interventional studies are needed to further validate this association.

Research paper thumbnail of Vitamin E protects human lymphocytes from genotoxicity induced by oxaliplatin

Drug and Chemical Toxicology, 2017

Abstract Oxaliplatin is a platinum-based anticancer drug that has been shown to be genotoxic to t... more Abstract Oxaliplatin is a platinum-based anticancer drug that has been shown to be genotoxic to the normal cells. Vitamin E is a potent antioxidant that may protect and enhance the repair of the damaged DNA. In this study, we aimed to evaluate the genotoxic effect of oxaliplatin on DNA by measuring the frequency of chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs) in cultured human lymphocytes. We also attempted to explore the potential protective effect of vitamin E on chromosomal damage induced by oxaliplatin. Results showed that oxaliplatin significantly increased the frequency of CAs (p < 0.001) and SCEs (p < 0.001) as compared to control. This chromosomal damage, caused by oxaliplatin, was significantly decreased by pretreatment of cells with vitamin E. Moreover, the results showed that oxaliplatin caused a significant reduction in the cell kinetic parameters, the mitotic index (MI) and the proliferative index (PI). However, vitamin E did not affect this reduction in the MI and PI. Therefore, we conclude that oxaliplatin is genotoxic, and vitamin E can prevent the chromosomal damage induced by oxaliplatin but it has no effect on oxaliplatin-induced cytotoxicity.

Research paper thumbnail of Crizotinib, a MET inhibitor, inhibits growth, migration, and invasion of breast cancer cells in vitro and synergizes with chemotherapeutic agents

OncoTargets and therapy, 2017

MET is a receptor tyrosine kinase known for its pleiotropic effects in tumorigenesis. Dysregulati... more MET is a receptor tyrosine kinase known for its pleiotropic effects in tumorigenesis. Dysregulations of MET expression and/or signaling have been reported and determined to be associated with inferior outcomes in breast cancer patients rendering MET a versatile candidate for targeted therapeutic intervention. Crizotinib is a multi-targeted small-molecule kinase inhibitor for MET, ALK, and ROS1 kinases. This study evaluated the anti-proliferative, cytotoxic, anti-migratory, and anti-invasive effects of crizotinib in breast cancer cells in vitro. Cell viability was assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) colorimetric assay. In vitro wound-healing assay was used to examine the effect of crizotinib on breast cancer cell migration. The expressions of Ki-67, MET, and phospho-MET receptors were characterized using immunofluorescence staining. Results showed that crizotinib has significant anti-proliferative activity on all mammary tumor cells with...