Lifestyle medicine as a modality for prevention and management of chronic diseases.

Lifestyle medicine is an approach that focuses on modifying unhealthy behaviors and promoting healthy ones to prevent and manage chronic diseases. This modality addresses multiple risk factors such as physical inactivity, unhealthy diet, tobacco use, and stress. Evidence shows that adopting a healthy lifestyle can significantly reduce the incidence and progression of chronic diseases such as cardiovascular diseases, diabetes, and cancer. The implementation of Lifestyle medicine requires a multidisciplinary approach involving healthcare providers, patients, and communities. Healthcare providers play a pivotal role in educating and motivating patients to adopt healthy behaviors, while communities can provide a supportive environment that fosters healthy lifestyles. The aim of this letter to editor is to summarize the evidence supporting the use of Lifestyle medicine in the prevention and management of chronic diseases.

An insight into the mechanisms of action of selected bioactive compounds against epigenetic targets of prostate cancer: implications on histones modifications.

Prostate cancer is a leading cause of morbidity and mortality among men globally. In this study, we employed an in silico approach to predict the possible mechanisms of action of selected novel compounds reported against prostate cancer epigenetic targets and their derivatives, exhausting through ADMET profiling, drug-likeness, and molecular docking analyses. The selected compounds: sulforaphane, silibinin, 3, 3'-diindolylmethane (DIM), and genistein largely conformed to ADMET and drug-likeness rules including Lipinski's. Docking studies revealed strong binding energy of sulforaphane with HDAC6 (- 4.2 kcal/ mol), DIM versus HDAC2 (- 5.2 kcal/mol), genistein versus HDAC6 (- 4.1 kcal/mol), and silibinin against HDAC1 (- 7.0 kcal/mol) coupled with improved binding affinities and biochemical stabilities after derivatization. Findings from this study may provide insight into the potential epigenetic reprogramming mechanisms of these compounds against prostate cancer and could pave the way toward more success in prostate cancer phytotherapy.

Free Radicals and Oxidative Stress: Signaling Mechanisms, Redox Basis for Human Diseases, and Cell Cycle Regulation.

Free radicals contain one or more unpaired electrons in their valence shell, thus making them unstable, short-lived, and highly reactive species. Excessive generation of these free radicals ultimately leads to oxidative stress causing oxidation and damage to significant macromolecules in the living system and essentially disrupting signal transduction pathways and antioxidants equilibrium. At lower concentrations, ROS serves as "second messengers," influencing many physiological processes in the cell. However, higher concentrations beyond cell capacity cause oxidative stress, contributing to human pathologies such as diabetes, cancer, Parkinson's disease, cardiovascular diseases, cataract, asthma, hypertension, atherosclerosis, arthritis, and Alzheimer's disease. Signaling pathways such as NF-κB, MAPKs, PI3K/Akt/ mTOR, and Keap1-Nrf2- ARE modulate the detrimental effects of oxidative stress by increasing the expression of cellular antioxidant defenses, phase II detoxification enzymes, and decreased production of ROS. Free radicals such as H2O2 are indeed needed for the advancement of the cell cycle as these molecules influence DNA, proteins, and enzymes in the cell cycle pathway. In the course of cell cycle progression, the cellular redox environment becomes more oxidized, moving from the G1 phase, becoming higher in G2/M and moderate in the S phase. Signals in the form of an increase in cellular pro-oxidant levels are required, and these signals are often terminated by a rise in the amount of antioxidants and MnSOD with a decrease in the level of cyclin D1 proteins. Therefore, understanding the mechanism of cell cycle redox regulation will help in the therapy of many diseases.

Comparative G-Protein-Coupled Estrogen Receptor (GPER) Systems in Diabetic and Cancer Conditions: A Review.

For many patients, diabetes Mellitus and Malignancy are frequently encountered comorbidities. Diabetes affects approximately 10.5% of the global population, while malignancy accounts for 29.4 million cases each year. These troubling statistics indicate that current treatment approaches for these diseases are insufficient. Alternative therapeutic strategies that consider unique signaling pathways in diabetic and malignancy patients could provide improved therapeutic outcomes. The G-protein-coupled estrogen receptor (GPER) is receiving attention for its role in disease pathogenesis and treatment outcomes. This review aims to critically examine GPER' s comparative role in diabetes mellitus and malignancy, identify research gaps that need to be filled, and highlight GPER's potential as a therapeutic target for diabetes and malignancy management. There is a scarcity of data on GPER expression patterns in diabetic models; however, for diabetes mellitus, altered expression of transport and signaling proteins has been linked to GPER signaling. In contrast, GPER expression in various malignancy types appears to be complex and debatable at the moment. Current data show inconclusive patterns of GPER expression in various malignancies, with some indicating upregulation and others demonstrating downregulation. Further research should be conducted to investigate GPER expression patterns and their relationship with signaling pathways in diabetes mellitus and various malignancies. We conclude that GPER has therapeutic potential for chronic diseases such as diabetes mellitus and malignancy.

Potential epigenetic modifications implicated in triple- to quadruple-negative breast cancer transition: a review.

Current research on triple-negative breast cancer (TNBC) has resulted in delineation into the quadruple-negative breast cancer (QNBC) subgroup. Epigenetic modifications such as DNA methylation, histone posttranslational modifications and associated changes in chromatin architecture have been implicated in breast cancer pathogenesis. Herein, the authors highlight genes with observed epigenetic modifications that are associated with more aggressive TNBC/QNBC pathogenesis and possible interventions. Advanced literature searches were done on PubMed/MEDLINE, Scopus and Google Scholar. The results suggest that nine epigenetically altered genes/differentially expressed proteins in addition to the downregulated androgen receptor are associated with TNBC aggressiveness and could be implicated in the TNBC to QNBC transition. Thus, restoring the normal expression of these genes via epigenetic reprogramming could be therapeutically beneficial to TNBC and QNBC patients.

When the androgen hormone receptor becomes inactive in triple-negative breast cancer (TNBC) patients, it results in another subtype of breast cancer called quadruple-negative breast cancer (QNBC). This is because these patients already lack the biological activities of three other important hormone receptors. The functions of these receptors are targeted by some drugs used in the management of breast cancers, so the lack of these receptors in TNBC and QNBC patients is thought to be linked with poor response to treatment. Some epigenetic modifications are involved in a more severe disease that is very difficult to control in TNBC patients and could facilitate its transition to the more aggressive QNBC subtype. Treatment response could be improved by restoring the normal function of the altered genes by reversing the observed epigenetic alterations.

Epigenetic modifications associated with genes implicated in cytokine storm: The potential biotherapeutic effects of vitamins and minerals in COVID-19.

Cytokine storm is a phrase used to refer to an abrupt upsurge in the circulating levels of various pro-inflammatory cytokines, causing increased stimulation and activity of immune cells during disease conditions. The binding of pattern recognition receptors to pathogen-associated molecular patterns during COVID-19 infection recruits response machinery involving the activation of transcription factors and proteins required for a robust immune response by host cells. These immune responses could be influenced by epigenetic modifications as evidenced by significant variations in COVID-19 pathophysiology and response to therapy observed among patients across the globe. Considering that circulating levels of interleukin 1, tumor necrosis factor-α, and interleukin 6 are significantly elevated during cytokine storm in COVID-19 patients, genetic and epigenetic variations in the expression and function of these proteins could enhance our understanding of the disease pathogenesis. Treatment options that repress the transcription of specific cytokine genes during COVID-19 infection could serve as possible targets to counteract cytokine storm in COVID-19. Therefore, the present article reviews the roles of cytokines and associated genes in the COVID-19 cytokine storm, identifies epigenetic modifications associated with the disease progression, and possible ameliorative effects of some vitamins and minerals obtained as epigenetic modifiers for the control of cytokine storm and disease severity in COVID-19 patients. PRACTICAL APPLICATIONS: COVID-19 causes mortality and morbidity that adversely affect global economies. Despite a global vaccination campaign, side effects associated with vaccination, misconceptions, and a number of other factors have affected the expected successes. Cytokine storm in COVID-19 patients contributes to the disease pathogenesis and response to therapy. Epigenetic variations in the expression of various cytokines could be implicated in the different outcomes observed in COVID-19 patients. Certain vitamins and minerals have been shown to interfere with the expression and activity of cytokines implicated in cytokine storm, thereby counteracting observed pathologies. This review examines cytokines implicated in cytokine storm in COVID-19, epigenetic modifications that contribute to increased expression of identified cytokines, specific foods rich in the identified vitamins and minerals, and suggests their possible ameliorative benefits. The article will be beneficial to both scientists and the general public who are interested in the role of vitamins and minerals in ameliorating COVID-19.

Biotherapeutic effect of cell-penetrating peptides against microbial agents: a review.

Selective permeability of biological membranes represents a significant barrier to the delivery of therapeutic substances into both microorganisms and mammalian cells, restricting the access of drugs into intracellular pathogens. Cell-penetrating peptides usually 5-30 amino acids with the characteristic ability to penetrate biological membranes have emerged as promising antimicrobial agents for treating infections as well as an effective delivery modality for biological conjugates such as nucleic acids, drugs, vaccines, nanoparticles, and therapeutic antibodies. However, several factors such as antimicrobial resistance and poor drug delivery of the existing medications justify the urgent need for developing a new class of antimicrobials. Herein, we review cell-penetrating peptides (CPPs) used to treat microbial infections. Although these peptides are biologically active for infections, effective transduction into membranes and cargo transport, serum stability, and half-life must be improved for optimum functions and development of next-generation antimicrobial agents.