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.

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.

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.

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.

Lung cancer (LC) is one of the most common malignancies and the leading cause of death worldwide. LC is classified into two main histological subtypes: non-small-cell lung cancer (NSCLC), representing the 85% of all LC types, and small-cell lung cancer (SCLC), representing 15% of all lung neoplasm. The recent discovery and clinical approval of new therapeutic approaches has resulted in significant advancements in the management of NSCLC patients. This review aims to summarize the current and ongoing clinical trials that have led to the approval of immune checkpoint inhibitors (ICIs) and the emerging immunotherapy approaches for advanced NSCLC patients. Additionally, the current benefits and drawbacks of these therapeutic strategies will be explored. The treatment for NSCLC is evolving toward a more comprehensive approach that considers both the tumor immune history and genomic features. In this respect, we hope that the ongoing research will make it possible to treat each NSCLC patient individually in the near future.

Alzheimer’s disease (AD) is a neurodegenerative disorder classically characterized by two neuropathological hallmarks: β-amyloid plaques and tau tangles in the brain. However, the cellular and molecular mechanisms involved in AD are still elusive, which dampens the possibility of finding new and more effective therapeutic interventions. Current in vitro models are limited in modelling the complexity of AD pathogenesis. In this study, we aimed to characterize the AD expression signature upon a meta-analysis of multiple human datasets, including different cell populations from various brain regions, and compare cell-specific alterations in AD patients and in vitro models to highlight the appropriateness and the limitations of the currently available models in recapitulating AD pathology. The meta-analysis showed consistent enrichment of the Rho GTPases signaling pathway among different cell populations and in the models. The accuracy of in vitro models was higher for neurons and lowest for astrocytes. Our study underscores the particularly low fidelity in modelling down-regulated genes across all cell populations. The top enriched pathways arising from meta-analysis of human data differ from the enriched pathways arising from the overlap. We hope that our data will prove useful in indicating a starting point in the development of future, more complex, 3D in vitro models.