In recent years, the worldwide epidemic of metabolic diseases, namely obesity, metabolic syndrome, diabetes and metabolic-associated fatty liver disease (MAFLD) has been strongly associated with constant exposure to endocrine-disruptive chemicals (EDCs), in particular, the ones able to disrupt various metabolic pathways. EDCs have a negative impact on several human tissues/systems, including metabolically active organs, such as the liver and pancreas. Among their deleterious effects, EDCs induce mitochondrial dysfunction and oxidative stress, which are also the major pathophysiological mechanisms underlying metabolic diseases. In this narrative review, we delve into the current literature on EDC toxicity effects on the liver and pancreatic tissues in terms of impaired mitochondrial function and redox homeostasis.

Background Objectives: The neoplastic process remains a major health problem facing humanity. Although there are currently different therapeutic options, they raise a multitude of shortcomings related to the toxic effects associated with their administration. Methotrexate (Met) and Cetuximab (Cet) are two basic chemotherapeutics used in cancer practice, but notwithstanding despite many years of use, the mechanisms by which the multitude of side-effects occur are not yet fully understood. Thus, the present study focused on the in vitro and in ovo evaluation of the associated toxic mechanisms on keratinocytes, keys cells in the wound healing process. Materials and Methods: The two chemotherapeutics were tested in eight different concentrations to evaluate keratinocytes viability, the anti-migratory effect, and the influence on the expression of markers involved in the production of cell apoptosis. In addition, the potential irritating effect on the vascular plexus were highlighted by applying the in ovo method, chick chorioallantoic membrane (HET-CAM). Results: The results revealed that Met induced decreased cell viability as well as increased expression of pro-apoptotic genes. In the vascular plexus of the chorioallantoic membrane, Met caused vascular irritation accompanied by capillary hemorrhage and vascular stasis. Conclusions: Summarizing, Cet presents a safer toxicological profile, compared to Met, based on the results obtained from both in vitro (cell viability, wound healing, RT-PCR assays), and in ovo (HET-CAM assay) techniques.

Colorectal cancer (CRC) represents one of the most serious health issues and the third most commonly diagnosed cancer worldwide. However, the treatment options for CRC are associated with adverse reactions, and in some cases, resistance can develop. Flavonoids have emerged as promising alternatives for CRC prevention and therapy due to their multitude of biological properties and ability to target distinct processes involved in CRC pathogenesis. Their innate disadvantageous properties (e.g., low solubility and stability, reduced bioavailability, and lack of tumor specificity) have delayed the potential inclusion of flavonoids in CRC treatment regimens but have hastened the design of nanopharmaceuticals comprising a flavonoid agent entrapped in a nanosized delivery platform that not only counteract these inconveniences but also provide an augmented therapeutic effect and an elevated safety profile by conferring a targeted action. Starting with a brief presentation of the pathological features of CRC and an overview of flavonoid classes, the present study comprehensively reviews the anti-CRC activity of different flavonoids from a mechanistic perspective while also portraying the latest discoveries made in the area of flavonoid-containing nanocarriers that have proved efficient in CRC management. This review concludes by showcasing future perspectives for the advancement of flavonoids and flavonoid-based nanopharmaceuticals in CRC research.

Traumatic brain injury (TBI) represents a significant public health issue, causing long-term disabilities and imposing considerable socioeconomic and healthcare challenges. While advancements in acute care have improved survival rates, the demand for effective neurorehabilitation is increasing. This narrative review explores the evidence on neurorehabilitation strategies for TBI, focusing on interventions targeting cognitive, motor, and psychological recovery. A total of 32 studies were included and categorized into six approaches: non-invasive brain stimulation, virtual reality (VR), computer-based training, telerehabilitation, robot-assisted therapy (RAT), and mixed approaches. Non-invasive brain stimulation techniques, such as transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS), showed variable effectiveness in improving cognitive outcomes. VR-based therapies enhanced attention and executive functions, while RAT, such as Lokomat and exoskeletons, improved gait symmetry and functional mobility. Computer-assisted programs demonstrated benefits in rehabilitating social cognition and executive functions. Telerehabilitation and telephone-based treatments provided short-term gains but lacked sustained effects. Overall, cognitive improvements were better described and represented, while several motor improvements lacked consistency. Despite the promising results, significant gaps remain, including heterogeneity in methodologies, small sample sizes, and limited long-term outcome data.

Cutaneous melanoma (CM) represents a severe skin cancer with a rising incidence at present and limited treatment options. 5-Fluorouracil (5-FU) is widely used, including for CM; however, the innate resistance of this cancer to conventional therapy remains problematic. Quercetin (QUE) is a flavonoid that can sensitize cancer cells to antitumor agents such as 5-FU. However, the potential sensitization capability of CM cells to 5-FU has scarcely been determined, and is investigated herein. Therefore, A375 CM cells were tested in terms of their cell viability, cell confluence, and morphological changes. Their nuclear and cytoskeletal aspects, clonogenic potential, and in ovo properties were also followed. The results showed that the 50% inhibitory concentrations (IC50s) of 5-FU and QUE determined by a cell proliferation assay were 11.56 and 11.08 µM, respectively. The addition of QUE (10 µM) to 5-FU (5–50 µM) increased the cytotoxic potential. A significant decline in cell viability (up to 43.51%), the loss of cell confluence, chromatin condensation and nuclear dysmorphology, tubulin and F-actin constriction, and a suppressed clonogenic ability were noted. The QUE + 5-FU association was non-irritating to the chorioallantoic membrane and showed an antiangiogenic effect in ovo. Thus, our results highlight that combining QUE with 5-FU can enhance the cytotoxic effect of 5-FU in A375 melanoma cells and present a safe profile in ovo.

Diabetes is a complex global healthcare burden involving multiple organ systems with its prevalence on the rise. SGLT2 inhibitors enhance glucose excretion. The objective of our literature review was to determine the association between cutaneous adverse drug reactions (CADRs) and the use of SGLT2 inhibitors. We collected data on CADRs related to the use of SGLT2 inhibitors from all available published articles and studied their details to understand the patterns of their association. PubMed, Cochrane, Google, and Embase were searched for relevant articles. A total of 37 papers were included and studied. Most articles were case reports followed by pharmacovigilance studies, case series, and reviews. The cutaneous findings ranged from benign eruptions to severe reactions. The available literature suggests a strong link between the use of SGLT2 inhibitors and Fournier’s gangrene/necrotizing fasciitis. T2DM patients using SGLT2 inhibitors have also developed fixed drug eruptions, drug-induced pruritus, and Sweet syndrome/acute febrile neutrophilic dermatosis, among other skin lesions. We found that SGLT2 inhibitors present a risk of developing CADRs. Raising awareness among healthcare providers regarding CADRs to SGLT2 inhibitors can reduce complications, minimize hospitalizations, and improve patient care in the vulnerable population of diabetes patients.