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.

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.

(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.

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.

(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.

Objectives: Unwanted pregnancy is sometimes associated with unsafe abortion, which may lead to maternal death. Pregnancy after unprotected sexual intercourse can be avoided by using emergency contraception (EC). Our study aimed to assess the knowledge and attitudes of reproductive-aged Lebanese women towards EC use. Methods: A descriptive cross-sectional study was conducted by interviewing randomly selected women aged between 15 and 49 years from the five major Lebanese governates. A pre-tested, pre-structured questionnaire was applied composed of three parts: (1) personal information, (2) knowledge about EC methods and (3) attitude towards EC. Results: We found that 78% of participants had never heard of EC. Among those who had heard of EC, only 29.3% had good knowledge about it. Knowledge about EC was not, however, associated with participants’ sociodemographic characteristics (i.e., age, marital status, educational level and background, occupation and occupational field and area of residence). There was a positive attitude towards EC among 57.3% of participants. Attitudes were statistically associated with level of education, area of residence and whether the respondent had ever heard of EC. Conclusion: Most Lebanese women of childbearing age lack knowledge about EC. There is a need to raise public awareness of EC.