Bilal Azakir

Cedrus libani A. Rich is a coniferous tree native to the eastern Mediterranean region that is known for exhibiting pharmacological properties. In the present study, we investigated the anti-proliferative effect of C. libani leaf essential oil (EO) against H460 and HT-29, as well as evaluated its chemo-modulatory effect with cisplatin (CIS). The EO chemical profile was analyzed via GC-MS. Cell viability was assessed using MTT, while trypan blue exclusion and Annexin V/Propidium Iodide staining were employed to detect cell death. Colony biomass and wound closure were evaluated using crystal violet staining and a scratch assay, respectively. Nuclear morphology and reactive oxygen species (ROS) were assessed using DAPI staining and an NBT assay, respectively. EO and CIS individually reduced cell viability in a time- and concentration-dependent manner with combination treatments demonstrating synergistic/additive/antagonistic interactions depending on the combination ratio, cell line and time point. EO alone does not exhibit significant cell death, whereas CIS demonstrated significant apoptosis and necrosis. The combination (IC₅₀:IC₅₀) enhanced cell death, particularly in HT-29. Both EO and CIS reduced colony biomass and wound closure, with the combination showing higher inhibitory effect on colony biomass in both cell lines and enhanced wound closure inhibitory effect in HT-29 but reduced effect in H460. CIS and combination caused more notable nuclear alterations compared to EO alone, whereas an early increase in NBT reduction followed by a subsequent decrease was observed for individual treatments as well as the combination. This study provides insights into the antiproliferative and chemo-modulatory potential of C. libani leaf essential oil, although further studies are needed to elucidate the underlying molecular mechanisms.

Onions represent one of the most widely consumed vegetables within the Allium genus, generating a significant amount of waste. Onion waste is mainly composed of non-edible fractions, including roots, outer dry skins, and the outer fleshy scale. This study aimed to valorize red onion waste (ROW) and assess its total phenolic content and antioxidant activity using a water bath extraction method with distilled water as the extraction solvent. response surface methodology was employed to optimize the extraction parameters, namely temperature and time. The phenolic composition of freeze-dried ROW extract was analyzed using liquid chromatography–mass spectrometry analysis. The antibacterial activity was assessed using the disk diffusion and broth dilution methods against Gram-positive and Gram-negative bacteria, and the anticancer activity was tested against H460 lung, Caco-2 colon, and HT-29 colorectal cancer cell lines. The ideal extraction parameters were 1:40 g/mL, 98 °C for 27 min. The major detected compounds were isorhamnetin (55.32%), hyperoside (19.44%), and quercetin (13.65%). ROW extract showed antibacterial activity against Bacillus cereus, Staphylococcus aureus, Listeria monocytogenes, Escherichia coli, Pseudomonas aeruginosa, and Salmonella Typhimurium, with the highest activity observed against S. aureus. A cytotoxic effect against H460 and Caco-2 was shown by the ROW extract, with IC₅₀ values detected within the tested concentrations. The results suggest that ROW extract has potential for effective application as an antioxidant, antibacterial, and anticancer agent, demonstrating its potential for incorporation into functional foods and nutraceutical development.

(1) Background: Kiwifruit is a globally valued fruit. Its industrial processing produces a substantial amount of waste, particularly peels, which present an appealing potential source of bioactive compounds. This study focuses on optimizing the extraction of phenolics from kiwi peels using a water bath (WB) and infrared irradiation (IR) and assessing their biological activities. (2) Methods: Optimal conditions for polyphenol extraction from kiwifruit peels, in terms of temperature and time, were determined using Response Surface Methodology. Total phenolic content (TPC) was measured by the Folin–Ciocalteu method, and antioxidant activity was assessed utilizing the DPPH method. Antibacterial activities against Bacillus cereus, Staphylococcus aureus, Escherichia coli, and Salmonella Typhimurium were determined using the minimum inhibitory concentration (MIC). The lyophilized extract was tested for its anticancer effect on A549 lung cancer cell lines. The phytochemical profiles of the WB and IR extracts were analyzed through High-Performance Liquid Chromatography (HPLC). (3) Results: The optimal extraction conditions for the WB method were found to be 75 °C for 35 min, and 90 °C for 5 min for IR. The corresponding TPC obtained by IR was 21 mg GAE/g DM, which was 4.4 times higher than that obtained by WB (4.8 mg GAE/g DM). This indicates that IR was more efficient in extracting phenolics from kiwi peels. The antioxidant activity under the optimum conditions of WB and IR was 14 mg TE/g DM and 16 mg TE/g DM, respectively. Both the WB and IR extracts demonstrated antibacterial activity against B. cereus with an MIC value of 25 mg/mL. Additionally, the IR extract displayed an antibacterial effect against S. aureus, with an MIC value of 50 mg/mL. The WB and IR kiwi peel extracts were effective in significantly reducing A549 cell viability at 50 µg/mL and 100 µg/mL, respectively. Caffeic acid (0.54 ppm) and catechin (5.44 ppm) were the major polyphenols identified in WB and IR extracts, as determined by HPLC. (4) Conclusions: IR was more efficient in extracting phenolics from kiwi peels than WB. The findings also suggest that kiwi peel can be effectively utilized as an antioxidant, antibacterial, and anticancer agent.

Objective: This study aimed to determine the prevalence of medical student mistreatment in Lebanon, the framework of the incidents, and the extent of students’ knowledge on mistreatment characteristics.Methods: This is a cross-sectional study conducted using an online-based survey among medical students who have performed clinical rotations in Lebanon.Results: Out of 300 respondents, 48.7% reported being subjected to mistreatment during clinical practice, which was significantly associated with gender, type of university, and family income. The two most common sources of mistreatment were patients and their families/friends (77.4%), and attending physicians (52.7%), followed by residents (49.3%). Students mostly chose to be passive and pacifying. Additionally, 64.7% of students stated they were not trained about the ideal way to handle these incidents.Conclusion: This study showed that medical student mistreatment is highly prevalent in Lebanon. It also highlighted the lack of proper education on mistreatment characteristics and the necessity for investigating its effects.

(1) Background: Cumin seeds, extracted from the plant Cuminum cyminum, are abundant in phenolic compounds and have been extensively researched for their chemical makeup and biological effects. The objective of this research is to enhance the water extraction of polyphenols through the water bath (WB) technique and to evaluate the antiradical, antibacterial, and anticancer effects of the extract. (2) Methods: Response Surface Methodology was used to find the best parameters to extract polyphenols. Three experimental parameters, time, temperature, and solid-liquid ratio, were tested. The disc diffusion method has been used to determine the antimicrobial activities against Salmonella Typhimurium, Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, and Candida albicans. The antiradical activity was performed using the DPPH method, while total phenolic content was performed using Folin–Ciocalteu. High-Performance Liquid Chromatography (HPLC) was conducted to analyze the phytochemical profile of WB extracts. The anticancer activity of the lyophilized extract was assessed against three cancer cell lines (colon (HT29), lung (A549), and breast (MCF7) cancer cell lines).; (3) Results: The optimal conditions for water extraction were 130 min at 72 °C. The total phenolic compounds yield (14.7 mg GAE/g DM) and antioxidant activity (0.52 mg trolox eq./mL) were obtained using a 1:40 solid–liquid ratio. The primary polyphenols identified were the flavonoids rutin (0.1 ppm) and ellagic acid (3.78 ppm). The extract had no antibacterial or antifungal activities against the microorganisms tested. The extract showed anticancer activity of about 98% against MCF7 (breast cancer cell line), about 81% against HT29 (colon cancer cell line), and 85% against A549 (lung cancer cell line) at high doses. (4) Conclusions: Extraction time and a high solid–liquid ratio had a positive impact on polyphenol recovery and in maintaining their quantity and quality. Furthermore, the optimal aqueous extract exhibited strong antiradical activity reflected by the inhibition of free radicals in addition to a significant specificity against the tested cancer cell lines.

Date seeds, which are the main by-products of date fruit consumption, were shown to possess promising biological activities and health benefits with minimal human use. The present investigation analyzed and compared the phenolic content of six date seed varieties from four different origins (Khudari, Sakai, and Safawi from Saudi Arabia, Majdool from Jordan, Zahdi from Iraq, and Kabkab from Iran). The aqueous extracts were examined for possible antioxidant, antibacterial, and anti-tumor potential. Date seed oil was extracted, and fatty acid profiles were compared. The results revealed that date seeds are a rich source of polyphenols, which have been linked to biological activities. Furthermore, the phenolic content seemed highly dependent on the variety, where Kabkab had the highest TPC value (271.2 mg GAE/g DM) while Majdool had the lowest value (63.2 mg GAE/g DM). Antioxidant activities of all varieties were highly correlated with the total phenolic content. The antibacterial investigation demonstrated that the Sakai variety possessed the dominant activity, whereas Majdool showed no activity. The results further indicated the sensitivity of both Staphylococcus aureus and Bacillus cereus, with a stronger effect against B. cereus, while no effect was observed against Gram-negative strains (Salmonella Typhi and Escherichia coli). All varieties were able to decrease colon and lung cancer cell viability, especially Khudari and Sakai, with stronger effects against colon cancer cells. Analysis of date seed oil showed high oleic acid content, especially in Sakai. The findings suggest that date seeds are promising candidates for future pharmaceutical applications as nutraceuticals to help combat certain illnesses, as well as functional foods and natural additives that boost the nutritional value of food products, increase their shelf lives, and improve the overall health of consumers.

The role of autophagy in lung cancer cells exposed to waterpipe smoke (WPS) is not known. Because of the important role of autophagy in tumor resistance and progression, we investigated its relationship with WP smoking. We first showed that WPS activated autophagy, as reflected by LC3 processing, in lung cancer cell lines. The autophagy response in smokers with lung adenocarcinoma, as compared to non-smokers with lung adenocarcinoma, was investigated further using the TCGA lung adenocarcinoma bulk RNA-seq dataset with the available patient metadata on smoking status. The results, based on a machine learning classification model using Random Forest, indicate that smokers have an increase in autophagy-activating genes. Comparative analysis of lung adenocarcinoma molecular signatures in affected patients with a long-term active exposure to smoke compared to non-smoker patients indicates a higher tumor mutational burden, a higher CD8+ T-cell level and a lower dysfunction level in smokers. While the expression of the checkpoint genes tested—PD-1, PD-L1, PD-L2 and CTLA-4—remains unchanged between smokers and non-smokers, B7-1, B7-2, IDO1 and CD200R1 were found to be higher in non-smokers than smokers. Because multiple factors in the tumor microenvironment dictate the success of immunotherapy, in addition to the expression of immune checkpoint genes, our analysis explains why patients who are smokers with lung adenocarcinoma respond better to immunotherapy, even though there are no relative differences in immune checkpoint genes in the two groups. Therefore, targeting autophagy in lung adenocarcinoma patients, in combination with checkpoint inhibitor-targeted therapies or chemotherapy, should be considered in smoker patients with lung adenocarcinoma.

Programmed cell death or type I apoptosis has been extensively studied and its contribution to the pathogenesis of disease is well established. However, autophagy functions together with apoptosis to determine the overall fate of the cell. The cross talk between this active self-destruction process and apoptosis is quite complex and contradictory as well, but it is unquestionably decisive for cell survival or cell death. Autophagy can promote tumor suppression but also tumor growth by inducing cancer-cell development and proliferation. In this review, we will discuss how autophagy reprograms tumor cells in the context of tumor hypoxic stress. We will illustrate how autophagy acts as both a suppressor and a driver of tumorigenesis through tuning survival in a context dependent manner. We also shed light on the relationship between autophagy and immune response in this complex regulation. A better understanding of the autophagy mechanisms and pathways will undoubtedly ameliorate the design of therapeutics aimed at targeting autophagy for future cancer immunotherapies.

Background: Inadequate use of statistics in biomedical research might not only affect science but also harm human beings if applied in medical practice. Biostatistics is fundamental to improve understanding and appraising of evidence-based medicine (EBM); yet, it is still not well understood and appreciated by medical students. Therefore, early exposure of medical students and physicians-in-training to research tools including Biostatistics is of utmost importance. Objective: The aim of this study is to determine the perception of Biostatistics by medical students at a private medical school in Beirut, Lebanon, and to identify its best implementation time in the medical curriculum. Methods: This is a cross-sectional study based on a self-administered questionnaire distributed among medical students in their pre-clerkship years (first three years of a 6-year program) who undertook Biostatistics. The assessment of perception was based on the 5-point Likert scale anchored by Strongly disagree = 1 and Strongly agree = 5 including 36 questions distributed into four domains to assess the course value, difficulty, behavioral, and expectations. Results: 186 of 269 students responded to the questionnaire, yielding a response rate of 69.14%. Around 60% of students declared that the knowledge gained from biostatistics courses is useful to their future career, and almost 70% understood the main concepts of biostatistics. 57.7% of students perceived that lack of practicing exercises might contribute to making the course more difficult. The mean score of domains was higher in females but did not significantly differ within the three academic years. Only 35.1% of the students positively perceived the importance of biostatistics modules, mostly third-year students. Conclusion: Although the majority of medical students perceived biostatistics modules negatively, they were aware of the relevance of biostatistics to their medical career and real-life health issues.

Introduction: Patient compliance to physicians' advice is pivotal for successful management of disease and in improving health care outcome. Aim: To identify the factors that affect medical compliance to physicians' advice among Lebanese internet users. Materials and Methods: This descriptive cross-sectional study was conducted by interviewing randomly-selected adults Lebanese internet users who visited a physician at least once in the past three months. A pre-tested, pre-structured questionnaire was applied comprising of six parts: (1) personal information; (2) patient's compliance; (3) perceived information asymmetry; (4) patient-physician concordance; (5) internet health information quality; and (6) physician quality. Descriptive statistics were computed as means/standard deviations (+/- SD) for continuous variables and as frequencies for categorical variables. The independent sample t-test or ANOVA was used to compare means of scales between groups and Pearson's correlation was used to determine the degree of correlation between continuous variables. Results: The mean age of the participants was 28.54 +/- 12 and the majority had secondary school education (53%), unmarried (64.5%), had a non-medical educational background (64.6%). Results showed that the level of education, patient-physician concordance and communication, and physicians' empathy and competence were significantly associated with patient compliance with medical advice. Primary educated Lebanese patients exhibited the highest compliance score (29.80 +/- 3.53). Interestingly, perceived information asymmetry and internet health information quality had no significant impact on patients' compliance. Conclusion: This study demonstrated that patients' compliance is affected by the level of education, patient-physician concordance, physician's competence and empathy, and communication between the patients and the physicians themselves. Henceforth, it is recommended that physicians should focus on improving their communication and professional skills rather than worrying about patients acquiring health information through the internet.