Artificial Intelligence Readiness, Perceptions, and Educational Needs Among Dental Students: A Cross-Sectional Study.

OBJECTIVES: With Artificial Intelligence (AI) profoundly affecting education, ensuring that students in health disciplines are ready to embrace AI is essential for their future workforce integration. This study aims to explore dental students' readiness to use AI, perceptions about AI in health education and healthcare, and their AI-related educational needs. MATERIAL AND METHODS: A cross-sectional survey was conducted among dental students at the College of Dental Medicine, Qatar University. The survey assessed readiness for AI using the Medical Artificial Intelligence Readiness Scale (MAIRS). Students' perceptions of AI in healthcare and health education and their educational needs were also explored. RESULTS: A total of 94 students responded to the survey. AI readiness scores were average (3.3 ± 0.64 out of 5); while participants appeared more ready for the vision and ethics domains of MAIRS, they showed less readiness regarding cognition and ability. Participants scored average on AI perceptions (3.35 ± 0.45 out of 5), with concerns regarding AI risks and disadvantages. They expressed a high need for knowledge and skills related to AI use in healthcare (84%), AI for health-related research (81.9%), and AI in radiology and imaging procedures (79.8%). Student readiness had a significant correlation with AI perceptions and perceived level of AI knowledge. CONCLUSIONS: This is the first study in Qatar exploring dental students' AI readiness, perceptions, and educational needs regarding AI applications in education and healthcare. The perceived AI knowledge gaps could inform future curricular AI integration. Advancing AI skills and deepening AI comprehension can empower future dental professionals through anticipated advances in the AI-driven healthcare landscape.

Associations between perceived occupational stressors and symptoms severity of depression, anxiety and stress among academic faculty: First cross-sectional study from Qatar.

BACKGROUND: Mental health concerns among university faculty are on the rise, with reports of anxiety, depression, and occupational stress, impacting the higher education community. In Qatar, an assessment of faculty mental health has not been previously realized. The objectives of the current study were twofold: Firstly, to evaluate the extent of perceived occupational stress, depression, anxiety, and stress, and secondly, to assess the association among these mental health parameters. METHODS: A cross-sectional study was conducted among faculty using an online, self-administered, anonymous, voluntary survey. All faculty were included by sending the survey to their institutional emails. In addition to faculty demographics and general health status, the survey measured perceived stress due to academic job roles using the Faculty Stress Index (FSI) with its five distinct domains, and assessed faculty mental health using the Depression, Anxiety, and Stress Scale-21 items (DASS-21). Modified Poisson regression with robust variance was used to assess how FSI influences levels of depression, anxiety, and stress. RESULTS: A total of 112 faculty responded to the survey. The highest faculty self-perceptions of mental health conditions were for anxiety (63% at least moderate), followed by depression (30% at least moderate), and least for stress (26% at least moderate). The overall mean FSI score was 48.8 ± 29.4; time constraint and rewards and recognition domains scored highest (18.5 ± 11.4 and 13.3 ± 9.3 respectively) while the departmental influence domain scored least (4.8 ± 4.4). Increased risk of at least moderate levels of self-perceived depression and stress were significantly associated with higher FSI score (p˂0.001). Increased risk of at least moderate levels of depression were less likely among faculty aged 50 years and above (p = 0.034), while increased risk of at least moderate levels of anxiety were more likely among faculty from humanities colleges (p = 0.027). CONCLUSIONS: This is the first investigation of university faculty mental health in Qatar, indicating multifactorial perceived occupational stress, associated with higher perceived severity of mental health conditions. These baseline results establish links between specific occupational stressors for faculty and their mental well-being. As such, assessment of mental health conditions, controlling occupational stress, and developing tailored mental health interventions for faculty, are strategic to implement and foster well-being of academics. Further research into mental health of faculty and designing effective interventions that consider their specific stressors and associated factors are warranted.

Pharmacy faculty experiences with student academic entitlement: a multinational study from the Arab world.

Academic Entitlement (AE) is the expectation by students to receive high grades or preferential treatment without significant effort. Exploring AE from faculty perspective has not been investigated in Arab colleges of pharmacy. The aim of this study was to explore experiences and perceptions towards student AE among pharmacy faculty in the Arab World. A cross-sectional, self-administered, anonymous, electronic survey was sent to pharmacy faculty across pharmacy colleges in Arab countries. The survey collected demographic data, an AE measure including 17 items reflecting seven AE components, and faculty perceptions and perceived reasons for AE. A total of 345 responses were collected. The AE level was moderate (46.05 ±7.29), and the highest scores among its components were for customer service expectation (62%) and responsibility avoidance (59%). In multiple linear regression, AE showed positive significant association with faculty in clinical pharmacy departments and those having fewer years of experience. Most common complaints heard by faculty from students were requests to turn in assignments late (90%), while the most common communication issues faculty faced with students were unprofessional verbal communication (58%) and unprofessional messages on social media (57%). Poor admission criteria (40%) and existence of multiple private colleges of pharmacy (37%) were the most common perceived reasons for AE by participating faculty. This study reveals moderate AE experienced by pharmacy faculty in the Arab World, as well as common complaints, communication issues, and AE reasons. In collaboration with other stakeholders, faculty play an important role in indicating expectations from students regarding AE, and research is warranted to check if such interventions reduce AE among pharmacy students.

The effect of novel nitrogen-based chalcone analogs on colorectal cancer cells: Insight into the molecular pathways.

In colorectal cancer (CRC), aberrations in KRAS are associated with aggressive tumorigenesis and an overall low survival rate because of chemoresistance and adverse effects. Ergo, complementary, and integrative medicines are being considered for CRC treatment. Among which is the use of natural chalcones that are known to exhibit anti-tumor activities in KRAS mutant CRC subtypes treatment regimens. Consequently, we examine the effect of two novel compounds (DK13 and DK14) having chalcones with nitrogen mustard moiety on CRC cell lines (HCT-116 and LoVo) with KRAS mutation. These compounds were synthesized in our lab and previously reported to exhibit potent activity against breast cancer cells. Our data revealed that DK13 and DK14 treatment suppress cell growth, disturb the progression of cell cycle, and trigger apoptosis in CRC cell lines. Besides, treatment with both compounds impedes cell invasion and colony formation in both cell lines as compared to 5-FU; this is accompanied by up and down regulations of E-cadherin and Vimentin, respectively. At the molecular level, both compounds deregulate the expression and phosphorylation of ß-catenin, Akt and mTOR, which are the main likely molecular mechanisms underlying these biological occurrences. Our findings present DK13 and DK14 as novel chemotherapies against CRC, through ß-catenin/Akt/mTOR signaling pathways.

Metformin increases 3-hydroxy medium chain fatty acids in patients with type 2 diabetes: a cross-sectional pharmacometabolomic study.

Background: Metformin is a drug with a long history of providing benefits in diabetes management and beyond. The mechanisms of action of metformin are complex, and continue to be actively debated and investigated. The aim of this study is to identify metabolic signatures associated with metformin treatment, which may explain the pleiotropic mechanisms by which metformin works, and could lead to an improved treatment and expanded use. Methods: This is a cross-sectional study, in which clinical and metabolomic data for 146 patients with type 2 diabetes were retrieved from Qatar Biobank. Patients were categorized into: Metformin-treated, treatment naïve, and non-metformin treated. Orthogonal partial least square discriminate analysis and linear models were used to analyze differences in the level of metabolites between the metformin treated group with each of the other two groups. Results: Patients on metformin therapy showed, among other metabolites, a significant increase in 3-hydroxyoctanoate and 3-hydroxydecanoate, which may have substantial effects on metabolism. Conclusions: This is the first study to report an association between 3-hydroxy medium chain fatty acids with metformin therapy in patients with type 2 diabetes. This opens up new directions towards repurposing metformin by comprehensively understanding the role of these metabolites.

Use of machine learning to assess factors affecting progression, retention, and graduation in first-year health professions students in Qatar: a longitudinal study.

BACKGROUND: Across higher education, student retention, progression, and graduation are considered essential elements of students' academic success. However, there is scarce literature analyzing these attributes across health professions education. The current study aims to explore rates of student retention, progression, and graduation across five colleges of the Health Cluster at Qatar University, and identify predictive factors. METHODS: Secondary longitudinal data for students enrolled at the Health Cluster between 2015 and 2021 were subject to descriptive statistics to obtain retention, progression and graduation rates. The importance of student demographic and academic variables in predicting retention, progression, or graduation was determined by a predictive model using XGBoost, after preparation and feature engineering. A predictive model was constructed, in which weak decision tree models were combined to capture the relationships between the initial predictors and student outcomes. A feature importance score for each predictor was estimated; features that had higher scores were indicative of higher influence on student retention, progression, or graduation. RESULTS: A total of 88% of the studied cohorts were female Qatari students. The rates of retention and progression across the studied period showed variable distribution, and the majority of students graduated from health colleges within a timeframe of 4-7 years. The first academic year performance, followed by high school GPA, were factors that respectively ranked first and second in importance in predicting retention, progression, and graduation of health majors students. The health college ranked third in importance affecting retention and graduation and fifth regarding progression. The remaining factors including nationality, gender, and whether students were enrolled in a common first year experience for all colleges, had lower predictive importance. CONCLUSIONS: Student retention, progression, and graduation at Qatar University Health Cluster is complex and multifactorial. First year performance and secondary education before college are important in predicting progress in health majors after the first year of university study. Efforts to increase retention, progression, and graduation rates should include academic advising, student support, engagement and communication. Machine learning-based predictive algorithms remain a useful tool that can be precisely leveraged to identify key variables affecting health professions students' performance.

Association between metabolically healthy obesity and metastasis in lung cancer patients - a systematic review and meta-analysis.

Background: Many clinical trials have looked at the relationship between obesity and lung cancer (LC), however, there is scarcity of literature specifically addressing the association between metabolically healthy obesity and metastasis in LC patients. To address this gap in the body of evidence, the study was conducted to observe the association between metabolically healthy obesity and metastasis in LC patients. Methods: We conducted a pre-registered systematic review by searching six major online databases to identify studies relevant related to our investigation, in adherence with the PRISMA guidelines. A proper data extraction protocol was further established to synthesize the findings from the selected papers through a meta-analysis. Results: Eleven (11) studies met the requisite selection criterion and were included in the study. A random-effect model was used. Obesity was found to have a significant impact on readmission in LC patients. The combined analysis showed a significant effect size of 0.08 (95% CI 0.07 to 0.08), indicating a noticeable impact of obesity. It was also assessed that obese individuals had a 34% reduced risk of LC compared to normal weight individuals. Obesity was associated with a lower risk of surgical complications with a pooled risk ratio of 0.13 (95% CI 0.12 to 0.14). A statistically significant decreased risk of LC (pooled RR = 0.72, 95% CI: 0.68 to 0.77) was also observed in the obese individuals. Conclusion: The analysis reveals that obesity is associated with a noticeable increase in readmissions, although the impact on LC risk itself is negligible. Moreover, obesity appears to have a beneficial effect by reducing the risk of surgical complications. These results highlight the complex relationship between the two aforementioned factors, emphasizing the importance of considering obesity as a significant factor in patient management and healthcare decision-making. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023427612.

Enhancing Cardiovascular Health and Functional Recovery in Stroke Survivors: A Randomized Controlled Trial of Stroke-Specific and Cardiac Rehabilitation Protocols for Optimized Rehabilitation.

BACKGROUND: Stroke is a major contributor to disability and mortality globally. It leads to physical impairments, including weakness and cardiovascular deconditioning, posing significant challenges to stroke survivors' quality of life. Exercise-based cardiac rehabilitation has shown promise as a rehabilitation strategy. This study aims to assess and compare the impacts of stroke-specific rehabilitation and individualized cardiac rehabilitation exercises on various health parameters in stroke patients. METHODS: A randomized controlled trial was conducted, involving 38 stroke patients aged 40-75 years. Group A received stroke-specific rehabilitation, which consisted of a combination of range of motion exercises, strength training for the paralyzed side, balance and coordination training, gait training, functional mobility exercises, neuromuscular reeducation, and breathing exercises. This program was conducted five days per week for 12 weeks. Group B received individually designed cardiac rehabilitation exercises, in addition to stroke-specific rehabilitation. They engaged in this exercise for at least 30-45 min per day, four days per week, and incorporated two days of resistive training over a 12-week period. Baseline and post-intervention assessments included measures of cardiac autonomic function, balance (Berg Balance Scale), mobility (Timed Up and Go Test), cardiovascular fitness indicators, respiratory parameters, exercise efficiency, and perceived exertion. RESULTS: Group B receiving individualized cardio rehab showed significant improvements in balance and mobility compared to Group A receiving conventional stroke-specific rehab. Moreover, Group B exhibited enhanced cardiovascular fitness, respiratory performance, exercise efficiency, and autonomic function post-intervention. Notably, Group A displayed no significant improvements in these parameters. CONCLUSIONS: Individualized cardiac rehabilitation exercises demonstrated favorable outcomes in improving certain health parameters, highlighting the potential benefits of individualized rehabilitation strategies for stroke patients.

Understanding and Fostering Mental Health and Well-Being among University Faculty: A Narrative Review.

In recent years, there has been increasing recognition of mental health concerns in academia, with stress, burnout, anxiety, and depression being reported among faculty members. The demanding work environment, the need to balance personal and professional duties, and the constant pressure of productivity while navigating multiple tasks of teaching, research, mentorship, professional development, and service all impact the mental health and overall well-being of faculty. Higher education institutions have structurally changed as has the research landscape. These changes as well as faculty-specific and student-specific factors coupled to the effect of the COVID-19 pandemic have led to profound effects on the mental health of academics. This paper is a narrative review of the pertinent literature describing faculty mental health and well-being. It summarizes the available evidence on factors influencing faculty mental health and shows the prevalence of anxiety, depression, stress, and burnout among faculty from various academic fields and along the whole academic ladder. Using a suggested framework that collates the efforts of leaders and faculty, the paper concludes by exploring strategies that promote work-life balance among academics and suggesting effective interventions to improve their mental health outcomes.

Does Kidney Transplantation Help Young Patients on Dialysis With Erectile Dysfunction? A Single-center Study.

OBJECTIVE: to investigate the effects of a successful KT on EF in male patients with ESRD. MATERIALS AND METHODS: A single-center cross-sectional prospective study to assess the erectile dysfunction in male patients one month before and one year after KT. We adopted a validated, self-administered translated International Index of Erectile Function (IIEF-15) questionnaire. A sub-analysis was performed by categorizing the cohort into 2 age groups: <50 and ≥50 yr. RESULTS: Between September 2017 and February 2021, 68 ESRD patients underwent kidney transplantation (KT), with a mean age of 48.9 ± 12.9 years. Thirty-one patients were below 50 years (Group I). The median hemodialysis duration was 12 months. Sixty-three patients (92.6%) had ED. The mean total IIEF-15 score before and after was 46.8/75 ±12.7 and 55.5 ±13, respectively (P <.001). Forty-six patients (67.6%) reported improved erectile function, 22 (32.4%) did not demonstrate any change, and no patient reported deterioration. Moreover, after KT, sexual desire, orgasm, and overall patient satisfaction improved significantly. Before KT, 83.8% and 100% of groups I and II patients had ED, which dropped to 22.6% and 86.5%, respectively, after KT. IIEF-15 scores improved in both groups. However, the improvement in ED was observed significantly in young patients with mild ED. CONCLUSION: KT positively impacts sexual function and improves erectile dysfunction, especially among young patients. The duration of dialysis before kidney transplantation had no impact on ED improvement after transplantation. The positive effect of transplantation on ED could encourage ESRD patients to undergo KT.

Assessment of lung cancer risk factors and mortality in Qatar: A case series study.

BACKGROUND: The global burden of cancer has exponentially increased over the last few years. In 2018 alone, approximately more than half of the 18.1 million individuals who had cancer succumbed to it. Lung cancer cases and fatalities are particularly on the rise. Therefore, exploring the factors surrounding lung cancer mortality is of utmost importance. AIMS: We investigate the clinicopathological and epidemiological characteristics of patients with lung cancer undergoing treatments, and their 5-year survival rates from a case series study in Qatar. METHODS AND RESULTS: All patients' data (between January 2010 and December 2014) in this case series study were retrieved from Al-Amal Hospital database. Kaplan-Meier survival plots, life tables and Cox regression were utilized for the statistical analysis. A total of 229 lung cancer patients were included in this study; of which 23.6% are Qatari (40 males and 14 females) and 76.4% non-Qatari (133 males and 42 females). Approximately 57.6% of our patients received at least one type of treatment. We observe a 5-year survival rate of 9.4% in our patient cohort. We also observe other predictive factors, such as distant metastasis (adjusted hazards ratio, HR = 2.414, 95% CI: 1.035-5.632), smoking status (adjusted HR = 3.909, 95% CI: 1.664-9.180) and the treatment history (adjusted HR = 0.432, 95% CI: 0.270-0.691), to be significant. CONCLUSION: Lung cancer is a prevalent health condition in Qatar, particularly owing to the rising use of tobacco in the country. The survival rate for lung cancer patients in this country is lower, compared to the global average. Moreover, several factors such as distant metastasis, smoking status, and treatment history are associated with lung cancer survival in Qatar.

Molecular Mechanisms of Colon Cancer Progression and Metastasis: Recent Insights and Advancements.

Colorectal cancer (CRC), the third most common type of cancer, is the second leading cause of cancer-related mortality rates worldwide. Although modern research was able to shed light on the pathogenesis of CRC and provide enhanced screening strategies, the prevalence of CRC is still on the rise. Studies showed several cellular signaling pathways dysregulated in CRC, leading to the onset of malignant phenotypes. Therefore, analyzing signaling pathways involved in CRC metastasis is necessary to elucidate the underlying mechanism of CRC progression and pharmacotherapy. This review focused on target genes as well as various cellular signaling pathways including Wnt/ß-catenin, p53, TGF-ß/SMAD, NF-κB, Notch, VEGF, and JAKs/STAT3, which are associated with CRC progression and metastasis. Additionally, alternations in methylation patterns in relation with signaling pathways involved in regulating various cellular mechanisms such as cell cycle, transcription, apoptosis, and angiogenesis as well as invasion and metastasis were also reviewed. To date, understanding the genomic and epigenomic instability has identified candidate biomarkers that are validated for routine clinical use in CRC management. Nevertheless, better understanding of the onset and progression of CRC can aid in the development of early detection molecular markers and risk stratification methods to improve the clinical care of CRC patients.

High-Risk HPV Oncoproteins and PD-1/PD-L1 Interplay in Human Cervical Cancer: Recent Evidence and Future Directions.

Cervical cancer is the fourth most common malignancy in women worldwide and a leading cause of cancer-related mortality in developing countries. Important etiological factors in this cancer are high-risk human papillomaviruses (HPV), as roughly 96% of cervical cancer cases are positive for these oncoviruses. On the other hand, it has been recently pointed out that E6/E7 oncoproteins of high-risk HPV can upregulate the programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) axis. Likewise, several recent reports showed that checkpoint blockades targeting PD-1/PD-L1 pathways have achieved efficient clinical responses via suppressing cancer progression and improving survival in several types of human cancers including metastatic cervical cancer. In this review, we summarize recent advances in our understanding of the PD-1/PD-L1 signaling pathway and its interaction with high-risk HPV and their oncoproteins, which could have an important impact on the management of HPV-associated cancers including cervical.

Vitamin D Signaling in Inflammation and Cancer: Molecular Mechanisms and Therapeutic Implications.

Vitamin D and its active metabolites are important nutrients for human skeletal health. UV irradiation of skin converts 7-dehydrocholesterol into vitamin D3, which metabolized in the liver and kidneys into its active form, 1α,25-dihydroxyvitamin D3. Apart from its classical role in calcium and phosphate regulation, scientists have shown that the vitamin D receptor is expressed in almost all tissues of the body, hence it has numerous biological effects. These includes fetal and adult homeostatic functions in development and differentiation of metabolic, epidermal, endocrine, neurological and immunological systems of the body. Moreover, the expression of vitamin D receptor in the majority of immune cells and the ability of these cells to actively metabolize 25(OH)D3 into its active form 1,25(OH)2D3 reinforces the important role of vitamin D signaling in maintaining a healthy immune system. In addition, several studies have showed that vitamin D has important regulatory roles of mechanisms controlling proliferation, differentiation and growth. The administration of vitamin D analogues or the active metabolite of vitamin D activates apoptotic pathways, has antiproliferative effects and inhibits angiogenesis. This review aims to provide an up-to-date overview on the effects of vitamin D and its receptor (VDR) in regulating inflammation, different cell death modalities and cancer. It also aims to investigate the possible therapeutic benefits of vitamin D and its analogues as anticancer agents.

E-Cigarette Liquid Provokes Significant Embryotoxicity and Inhibits Angiogenesis.

E-cigarette smoking (ECS) is a new method of tobacco smoking that is gaining popularity as it is thought to be a "healthy method" of tobacco consumption. The adverse outcomes of ECS on the respiratory and cardiovascular systems in humans have been recently demonstrated. Nevertheless, the effect of e-cigarette liquid (ECL) on the early stage of embryogenesis and angiogenesis has not been explored yet. Chicken embryo at 3 days of incubation and its chorioallantoic membrane (CAM) of 5 days were used to explore the outcome of ECL on the embryo. Real-time PCR was also employed to study the regulation of a set of key controller genes of embryogenesis as well as angiogenesis. Our study revealed that ECL exposure is associated with a high rate of mortality in embryos as around 70% of treated embryos, at 3 days of incubation, die after 5 days of exposure. Additionally, ECL inhibits angiogenesis of the CAM of 5 days of incubation by more than 30%. These effects could be explained by the upregulation of ATF-3, FOXA2, INHBA, MAPRE-2, and RIPK-1, as well as the downregulation of SERPINA-4 and VEGF-C genes, which are important key controller genes of embryogenesis as well as angiogenesis. Our data suggest clearly that ECS can have dramatic toxic outcomes on the early stage of embryogenesis as well as angiogenesis. Accordingly, we believe that further studies to assess the effects of ECS on human health are essential.

Association between Soft Drink Consumption and Aggressive Behaviour among a Quarter Million Adolescents from 64 Countries Based on the Global School-Based Student Health Survey (GSHS).

Soft drink consumption has become a significant public health concern that is associated with various adverse health outcomes. We aim to examine the association between soft drink consumption and aggressive behavior among adolescents. We used open access data from 79 studies in 64 countries, including 263,890 adolescents aged 12-18 years who completed the global school-based student health survey (GSHS). Self-reported data on past 30-day carbonated soft drink consumption (number of times per day) and past 12-month physical fighting were utilized for analysis. Of the 263,890 participants (48% boys) aged 12-18 years, the weighted mean frequency of soft drink consumption varied from 0.5 in Kiribati to 2.5 times/day in Surname, while the weighted prevalence of frequent aggressive behavior varied from to 2.7% in Laos to 49.2% in Tuvalu. We found that each increment of soft drink consumption (time/day) was associated with an 11% (95%CI 10-13%) increase of the likelihood of frequent physical fighting. This result remained significant after adjusting for various covariates. In this large pooled sample of multinational data, there is a significant positive association between soft drink consumption and aggressive behavior among adolescents. Reducing soft drink consumption may help reduce aggressive behavior, a major risk factor for violence.

Epstein-Barr Virus-Associated Malignancies: Roles of Viral Oncoproteins in Carcinogenesis.

The Epstein-Barr virus (EBV) is the first herpesvirus identified to be associated with human cancers known to infect the majority of the world population. EBV-associated malignancies are associated with a latent form of infection, and several of the EBV-encoded latent proteins are known to mediate cellular transformation. These include six nuclear antigens and three latent membrane proteins (LMPs). In lymphoid and epithelial tumors, viral latent gene expressions have distinct pattern. In both primary and metastatic tumors, the constant expression of latent membrane protein 2A (LMP2A) at the RNA level suggests that this protein is the key player in the EBV-associated tumorigenesis. While LMP2A contributing to the malignant transformation possibly by cooperating with the aberrant host genome. This can be done in part by dysregulating signaling pathways at multiple points, notably in the cell cycle and apoptotic pathways. Recent studies also have confirmed that LMP1 and LMP2 contribute to carcinoma progression and that this may reflect the combined effects of these proteins on activation of multiple signaling pathways. This review article aims to investigate the aforementioned EBV-encoded proteins that reveal established roles in tumor formation, with a greater emphasis on the oncogenic LMPs (LMP1 and LMP2A) and their roles in dysregulating signaling pathways. It also aims to provide a quick look on the six members of the EBV nuclear antigens and their roles in dysregulating apoptosis.

Screening Novel Molecular Targets of Metformin in Breast Cancer by Proteomic Approach.

Metformin is a commonly prescribed antihyperglycemic drug, and has been investigated in vivo and in vitro for its effect to improve the comorbidity of diabetes and various types of cancers. Several studies investigated the therapeutic mechanisms of metformin on cancer cells, but the exact mechanism of metformin's effect on the proteomic pathways of cancer cells is yet to be further investigated. The main objective of our research line is to discover safe and alternative therapeutic options for breast cancer, we aimed in this study to design a novel "bottom up proteomics workflow" in which proteins were first broken into peptides to reveal their identity, then the proteomes were precisely evaluated using spectrometry analysis. In our study, metformin suppressed cell proliferation and induced apoptosis in human breast carcinoma cell line MCF-7 with minimal toxicity to normal breast epithelial cells MCF-10. Metformin induced apoptosis by arresting cells in G1 phase as evaluated by flow cytometric analysis. Moreover, The G1 phase arrest for the MCF-7 has been confirmed by increased expression levels of p21 and reduction in cyclin D1 level. Additionally, metformin increased the expression levels of p53, Bax, Bad while it reduced expression levels of Akt, Bcl-2, and Mdm2. The study employed a serviceable strategy that investigates metformin-dependent changes in the proteome using a literature-derived network. The protein extracts of the treated and untreated cell lines were analyzed employing proteomic approaches; the findings conveyed a proposed mechanism of the effectual tactics of metformin on breast cancer cells. Metformin proposed an antibreast cancer effect through the examination of the proteomic pathways upon the MCF-7 and MCF-10A exposure to the drug. Our findings proposed prolific proteomic changes that revealed the therapeutic mechanisms of metformin on breast cancer cells upon their exposure. In conclusion, the reported proteomic pathways lead to increase the understanding of breast cancer prognosis and permit future studies to examine the effect of metformin on the proteomic pathways against other types of cancers. Finally, it suggests the possibility to develop further therapeutic generations of metformin with increased anticancer effect through targeting specific proteomes.

Novel quinuclidinone derivatives induced apoptosis in human breast cancer via targeting p53.

Small molecules that can target human cancers have been highly sought to increase the anticancer efficacy, the present work describes the design and synthesis of novel series of five quinuclidinone derivatives (2a-2e). Their anticancer activities were investigated against breast cancer cells MCF-7, MDA-MB-231 breast cancer cells harboring mutant p53 and normal breast counterpart MCF-12a. Derivative 2e reduced proliferation of MCF-7 and MCF-12a while it has no effect on MDA-MB-231. Derivative 2e induced apoptosis in MCF-7 cells which is further confirmed by TUNEL assay and it reduced the percentage of cell in G2/M phase as confirmed by increased expression of cyclin B and reduced expression of cyclin D1. Derivative 2e reduced expression levels of Mdm2, Akt and ERK1/2 by and increased expression level of p53. Moreover, the apoptosis induction by 2e was also inhibited by PFT-α as evidenced by non-significant induction of apoptosis after treatment of MCF-7 cells with both derivative 2e and PFT-α. In addition, docking study reveals that derivative 2e has a binding pattern close to the pattern observed in the structure of the lead fragment 5,6-dimethoxy-2-methylbenzothiazole bound to T-p53C-Y220C. The above findings demonstrate that derivative 2e induces apoptosis in MCF-7 cells via targeting p53 which merits further development.

Antitumor Activities of the Novel Isosteviol Derivative 10C Against Liver Cancer.

BACKGROUND/AIM: Hepatocellular carcinoma (HCC) is the most common type of liver cancer and the fifth most common primary malignancy with worldwide increasing incidence. The current study aimed to investigate the anticancer activities of novel isosteviol derivatives towards human HepG2 hepatocellular cancer cells and in an animal model of hepatocellular carcinoma. MATERIALS AND METHODS: Twelve isosteviol derivatives were screened for their anti-proliferative activities against HepG2 and IC50 was calculated for all designed derivatives. The impact of the potent isosteviol derivative 10C on HepG2 cells was further studied by MTT assay, Annexin V/PI staining, flow cytometry and western blotting. In vivo studies were performed to assess the anticancer effect of isosteviol derivative 10C on Diethyl Nitrosamine-induced liver cancer in female rats by evaluating the physiological processes. RESULTS: isosteviol derivative 10C induced growth inhibition with IC50 of 2 µM mainly through induction of apoptosis in HepG2 cells. Additionally, isosteviol derivative 10C induced G1 phase arrest, which was further confirmed by increased expression of cyclin dependent kinase inhibitor 1A (CDKN1A, p21). It also increased BAX, BID and PARP-1 and while it reduced pro-CASPASE-3 expression and phosphorylation levels of AKT in HepG2 cells. Furthermore, western blotting data showed that E-cadherin, ß-catenin, VEGF and COX-2 expressions were suppressed by isosteviol derivative 10C in HepG2 cells. The in vivo study demonstrated that dose-dependent treatment of isosteviol derivative 10C led to significant reduction in tumor size compared to the untreated group after the fourth injection with no significant effects on major physiological processes. CONCLUSION: Taken together, in vitro and in vivo studies revealed that isosteviol derivative 10C induced apoptosis in HepG2 cells, blocked angiogenic signaling and it did not induce any apparent toxicity towards the treated hosts which merits further investigation at clinical level.