Environmental or occupational exposure to pesticides is considered one of the main risk factors for the development of various diseases. Behind the development of pesticide-associated pathologies, there are both genetic and epigenetic alterations, where these latter are mainly represented by the alteration in the expression levels of microRNAs and by the change in the methylation status of the DNA. At present, no studies have comprehensively evaluated the genetic and epigenetic alterations induced by pesticides; therefore, the aim of the present study was to identify modifications in gene miRNA expression and DNA methylation useful for the prediction of pesticide exposure. For this purpose, an integrated analysis of gene expression, microRNA expression, and DNA methylation datasets obtained from the GEO DataSets database was performed to identify putative genes, microRNAs, and DNA methylation hotspots associated with pesticide exposure and responsible for the development of different diseases. In addition, DIANA-miRPath, STRING, and GO Panther prediction tools were used to establish the functional role of the putative biomarkers identified. The results obtained demonstrated that pesticides can modulate the expression levels of different genes and induce different epigenetic alterations in the expression levels of miRNAs and in the modulation of DNA methylation status.

Due to the key role of tumor necrosis factor-alpha (TNF-α) in the pathogenesis of immunoinflammatory diseases, TNF-α inhibitors have been successfully developed and used in the clinical treatment of autoimmune disorders. Currently, five anti-TNF-α drugs have been approved: infliximab, adalimumab, golimumab, certolizumab pegol and etanercept. Anti-TNF-α biosimilars are also available for clinical use. Here, we will review the historical development as well as the present and potential future applications of anti-TNF-α therapies, which have led to major improvements for patients with several autoimmune diseases, such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), Crohn’s disease (CD), ulcerative colitis (UC), psoriasis (PS) and chronic endogenous uveitis. Other therapeutic areas are under evaluation, including viral infections, e.g., COVID-19, as well as chronic neuropsychiatric disorders and certain forms of cancer. The search for biomarkers able to predict responsiveness to anti-TNF-α drugs is also discussed.

Pomegranate is an important source of several bioactive compounds with beneficial properties. As widely described in the literature, pomegranate can be considered as a functional food able to promote the maintenance of a good health status. The present review article summarizes the properties of pomegranate, such as antioxidant, anti-inflammatory, anti-aging, prebiotic and anticancer effects, as well as its protective role against metabolic disorders and cardiovascular diseases. Pomegranate and its phytocompounds can prevent the development of several chronic diseases. Additionally, pomegranate can be considered an adjunct for current therapeutic strategies able to improve the standard treatment efficacy and reduce side-effects. However, further studies are required in order to better clarify the mechanisms of action and the synergistic effects of the phytochemicals contained in pomegranate. According to the current data, pomegranate may be a promising avenue against the most common chronic diseases, including cancer. refer to the consumable portion of the pomegranate tree (2).Historically, the pomegranate tree dates back to the early bronze age (3500-2000 B.C.) with fossil findings (seeds, leaves and branches) mainly discovered in Central Asia, the Mediterranean area and the Middle East (3). Currently, it is planted in North and South America, the Middle East and Caucasus region, South and Central Asia, North and tropical Africa, as well as in the Mediterranean area, including Sicily (4).Of note, the pomegranate was considered a symbol of life, symbolizing prosperity and fertility in a number of ancient cultures and religions. For example, the Egyptians considered pomegranate as a symbol of life after death, while in the Bible's Old Testament, it symbolized good luck, abundance and fertility (1,5).However, pomegranate has been known also for its medical use. Indeed, as described in the literature, pomegranate and its derivatives (fruit, juice, pericarp, seeds and leaves) have a number of therapeutic and pharmacological properties (6), including prebiotic effects (7).These properties are due to the presence of numerous phytochemicals. Among the known phytocompounds, ellagitannins, gallotannins, anthocyanins, anthocyanidins, flavonoids, flavonones, flavonols, organic acids, fatty acids and lipids, phenolic acids, alkaloids and lignans have been isolated from pomegranate (8,9).Over the past few years, the attention of the scientific community on the beneficial effects of pomegranate and its

Lung cancer (LC) represents the second most diagnosed tumor and the malignancy with the highest mortality rate. In recent years, tremendous progress has been made in the treatment of this tumor thanks to the discovery, testing, and clinical approval of novel therapeutic approaches. Firstly, targeted therapies aimed at inhibiting specific mutated tyrosine kinases or downstream factors were approved in clinical practice. Secondly, immunotherapy inducing the reactivation of the immune system to efficiently eliminate LC cells has been approved. This review describes in depth both current and ongoing clinical studies, which allowed the approval of targeted therapies and immune-checkpoint inhibitors as standard of care for LC. Moreover, the present advantages and pitfalls of new therapeutic approaches will be discussed. Finally, the acquired importance of human microbiota as a novel source of LC biomarkers, as well as therapeutic targets to improve the efficacy of available therapies, was analyzed. Therapy against LC is increasingly becoming holistic, taking into consideration not only the genetic landscape of the tumor, but also the immune background and other individual variables, such as patient-specific gut microbial composition. On these bases, in the future, the research milestones reached will allow clinicians to treat LC patients with tailored approaches.