Reactive oxygen and nitrogen species (RONS) are generated through various endogenous and exogenous processes; however, they are neutralized by enzymatic and non-enzymatic antioxidants. An imbalance between the generation and neutralization of oxidants results in the progression to oxidative stress (OS), which in turn gives rise to various diseases, disorders and aging. The characteristics of aging include the progressive loss of function in tissues and organs. The theory of aging explains that age-related functional losses are due to accumulation of reactive oxygen species (ROS), their subsequent damages and tissue deformities. Moreover, the diseases and disorders caused by OS include cardiovascular diseases [CVDs], chronic obstructive pulmonary disease, chronic kidney disease, neurodegenerative diseases and cancer. OS, induced by ROS, is neutralized by different enzymatic and non-enzymatic antioxidants and prevents cells, tissues and organs from damage. However, prolonged OS decreases the content of antioxidant status of cells by reducing the activities of reductants and antioxidative enzymes and gives rise to different pathological conditions. Therefore, the aim of the present review is to discuss the mechanism of ROS-induced OS signaling and their age-associated complications mediated through their toxic manifestations in order to devise effective preventive and curative natural therapeutic remedies.

Flavonoids, a subclass of polyphenols, have been shown to be effective against several types of cancer, by decreasing proliferation and inducing apoptosis. Therefore, the aim of the present study was to assess the anti-carcinogenic potential of luteolin on HeLa human cervical cancer cells, through the use of a cell viability assay, DNA fragmentation assay, mitochondrial membrane potential assay, cell cycle analysis using Annexin/PI staining and flow cytometry, gene expression analysis and a protein profiling array. Luteolin treatment exhibited cytotoxicity towards HeLa cells in a dose- and time-dependent manner, and its anti-proliferative properties were confirmed by accumulation of luteolin-treated cells in sub-G 1 phases. Cytotoxicity induced by luteolin treatment resulted in apoptosis, which was mediated through depolarization of the mitochondrial membrane potential and DNA fragmentation. Furthermore, luteolin treatment increased the expression of various proapoptotic genes, including APAF1, BAX, BAD, BID, BOK, BAK1, TRADD, FADD, FAS , and Caspases 3 and 9 , whereas the expression of anti-apoptotic genes, including NAIP, MCL-1 and BCL-2 , was decreased. Cell cycle regulatory genes, including CCND1, 2 and 3, CCNE2, CDKN1A, CDKN2B, CDK4 and CDK2 , were decreased following treatment. Expression of TRAILR2/DR5, TRAILR1/DR4, Fas/TNFRSF6/CD95 and TNFR1/TNFRSF1A, as well as pro-apoptotic proteins, including BAD, BAX and Cytochrome C were consistently increased, and the expression of antiapoptotic proteins, HIF1α, BCL-X, MCL1 and BCL2, were found to be decreased following treatment. Expression of AKT1 and 2, ELK1, PIK3C2A, PIK3C2B, MAPK14, MAP3K5, MAPK3 and MAPK1 was significantly decreased at the transcriptional level. Expression of GSK3b (p-ser9), PRAS 40 (p-Ther246), BAD (p-ser112), PTEN (p-ser380), AKT (p-ser473), ERK2 (p-Y185/Y187), RISK2 (p-ser386), P70S6k (p-Thr421/ser424), PDK1(p-ser241), ERK1 (p-T202/Y204) and MTOR (p-ser2448) was downregulated and expression of P53 (p-ser241) and P27(p-Thr198) was upregulated by luteolin in a dose-dependent manner, indicating its anti-proliferative and apoptosis enabling properties, and this may have been mediated via inhibition of the AKT and the MAPK pathways.

Objective Healthy lifestyle and adequate reproductive health knowledge are prerequisites for maintenance of physical and mental well-being of women across the world. With increasing prevalence of metabolic disorders such as polycystic ovary syndrome (PCOS), it is important that sufficient awareness of these issues is generated, especially in conservative communities in Arab regions. The main objective of this study is to assess reproductive health (RH) knowledge and awareness of PCOS among female Emirati students and also to explore their lifestyle choices. Materials and Methods A total of 493 Emirati students were recruited based on convenience sampling and completed a survey containing questions related to demography, lifestyle preferences, RH knowledge, and PCOS awareness. Results Of the students, 13% self-reported being diagnosed with PCOS, with 3.5% also taking medication for the same, 6% reported having high androgen levels, 30.7% reported polymenorrhea, and 3.5% reported oligomenorrhea for frequency of menstrual cycle. Also, 12.4% students experienced abnormal bleeding (heavy/none) during menstruation and 24% reported excessive body hair. It was found that 4.3% of students were taking medication for hyperglycemia and 75% of students reported a family history of diabetes. Students displayed low reproductive health knowledge and poor awareness of PCOS. Lifestyle preferences indicated low physical activity and high indulgence in fast food. Conclusion Lifestyle choices adopted by Emirati University students may predispose them to disorders such as PCOS. Early detection and management of PCOS coupled with a dynamic awareness campaign for RH can help in improving fertility rates of Emirati women. The study identifies major gaps in knowledge and awareness of RH and PCOS in Emirati women that need to be addressed by creating a culturally congruent heathcare policy with emphasis on education and health promotion. Mandatory PA programs and increasing availability of healthy eating options in campus should be considered by all universities, particularly in Arab regions, for improving lifestyle and preventing metabolic disorders in young students.

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Background: Fisetin, a flavonol profusely found in vegetables and fruits, exhibited a myriad of properties in preclinical studies to impede cancer growth. Purpose: This study was proposed to delineate molecular mechanisms through analysing the modulated expression of various molecular targets in HeLa cells involved in proliferation, apoptosis and inflammation. Methods: MTT assay, flow cytometry, nuclear morphology, DNA fragmentation and Annexin–Pi were performed to evaluate the anti-cancer potential of fisetin. Furthermore, qPCR and proteome profiler were performed to analyse the expression of variety of gene related to cell death, cell proliferation, oxidative stress and inflammation and cancer pathways. Results: Fisetin demonstrated apoptotic inducing ability in HeLa cells, which was quite evident through nuclear morphology, DNA ladder pattern, decreased TMRE fluorescent intensity, cell cycle arrest at G2/M and increased early and late apoptosis. Furthermore, fisetin treatment modulated pro-apoptotic genes such as APAF1, Bad, Bax, Bid and BIK at both transcript and protein levels and anti-apoptotic gene Bcl-2, BIRC8, MCL-1, XIAP/BIRC4, Livin/BIRC7, clap-2/BIRC3, etc. at protein levels to mitigate cell proliferation and induce apoptosis. Interestingly, the aforementioned alterations consequently led to an elevated level of Caspase-3, Caspase-8 and Caspase-9, which was found to be consistent with the transcript and protein level expression. Moreover, fisetin downregulated the expression of AKT and MAPK pathways to avert proliferation and enhance apoptosis of cancer cells. Fisetin treatment also improves oxidative stress and alleviates inflammation by regulating JAK-STAT/NF-kB pathways. Conclusion: Together, these studies established that fisetin deters human cervical cancer cell proliferation, enhances apoptosis and ameliorates inflammation through regulating various signalling pathways that may be used as a therapeutic regime for better cancer management.