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The rubric of immune-related (ir) diabetes mellitus (DM) (irDM) encompasses various hyperglycemic disorders related to immune checkpoint inhibitors (ICPis). Beyond sharing similarities with conventional DM, irDM is a distinct, yet important, entity. The present narrative review provides a comprehensive overview of the literature regarding irDM published in major databases from January 2018 until January 2023. Initially considered rare, irDM is increasingly being reported. To advance the knowledge of irDM, the present review suggests a concerted vision comprising two intertwined aspects: a scientific-centered and a patient-centered view. The scientific-centered aspect addresses the pathophysiology of irDM, integrating: (i) ICPi-induced pancreatic islet autoimmunity in genetically predisposed patients; (ii) altered gut microbiome; (iii) involvement of exocrine pancreas; (iv) immune-related acquired generalized lipodystrophy. The patient-centered aspect is both nurtured by and nurturing the four pillars of the scientific-centered aspect: awareness, diagnosis, treatment, and monitoring of irDM. The path forward is a multidisciplinary initiative towards: (i) improved characterization of the epidemiological, clinical, and immunological profile of irDM; (ii) standardization of reporting, management, and surveillance protocols for irDM leveraging global registries; (iii) patient stratification according to personalized risk for irDM; (iv) new treatments for irDM; and (v) uncoupling ICPi efficacy from immunotoxicity.

Isothiocyanates are biologically active secondary metabolites liberated via enzymatic hydrolysis of their sulfur enriched precursors, glucosinolates, upon tissue plant disruption. The importance of this class of compounds lies in their capacity to induce anti-cancer, anti-microbial, anti-inflammatory, neuroprotective, and other bioactive properties. As such, their isolation from natural sources is of utmost importance. In this review article, an extensive examination of the various parameters (hydrolysis, extraction, and quantification) affecting the isolation of isothiocyanates from naturally-derived sources is presented. Overall, the effective isolation/extraction and quantification of isothiocyanate is strongly associated with their chemical and physicochemical properties, such as polarity-solubility as well as thermal and acidic stability. Furthermore, the successful activation of myrosinase appears to be a major factor affecting the conversion of glucosinolates into active isothiocyanates.

Simple Summary Leveraging lessons learned from the coronavirus disease 2019 (COVID-19) pandemic, resilient health systems focus on the preservation of the continuum of care of chronic diseases, especially of cancer, beyond addressing emergency health requirements. Obesity has a detrimental impact on COVID-19 and affects the epidemic of thyroid cancer (TC). TC, especially differentiated TC (DTC), is a notable paradigm of obesity-related cancers. Thus, obesity–COVID-19–(D)TC interplay can be a constant threat to public health. The present review dissects the COVID-19–(D)TC association in the setting of obesity and beyond, highlighting: (i) the interrelationship between immunity, inflammation, obesity, oxidative stress, and cancer underlying this association; (ii) the challenging management of (D)TC in the COVID-19 era; (iii) the impact of COVID-19 on (D)TC and vice versa; and (iv) the oncogenic potential of SARS-CoV-2. Future perspectives for understanding and harnessing the COVID-19–(D)TC association to inform decision-making are underlined. Abstract Background: Conceived of as the “silver lining” of the dark cloud of the coronavirus disease 2019 (COVID-19) pandemic, lessons taught by this catastrophe should be leveraged by medical authorities and policy makers to optimize health care globally. A major lesson is that resilient health systems should absorb sudden shocks incited by overwhelming health emergencies without compromising the continuum of care of chronic diseases, especially of cancer. Methods: The present review dissects the association between COVID-19 and thyroid cancer (TC), especially with differentiated TC (DTC), focusing on available data, knowledge gaps, current challenges, and future perspectives. Results: Obesity has been incriminated in terms of both COVID-19 severity and a rising incidence of TC, especially of DTC. The current conceptualization of the pathophysiological landscape of COVID-19–(D)TC association implicates an interplay between obesity, inflammation, immunity, and oxidative stress. Whether COVID-19 could aggravate the health burden posed by (D)TC or vice versa has yet to be clarified. Improved understanding and harnessing of the pathophysiological landscape of the COVID-19–(D)TC association will empower a mechanism-guided, safe, evidence-based, and risk-stratified management of (D)TC in the COVID-19 era and beyond. Conclusion: A multidisciplinary patient-centered decision-making will ensure high-quality (D)TC care for patients, with or without COVID-19.

Malignant melanoma is one of the most aggressive types of skin cancer with an increasing incidence worldwide. Thus, the development of innovative therapeutic approaches is of great importance. Salvia fruticosa (SF) is known for its anticancer properties and in this context, we aimed to investigate its potential anti-melanoma activity in an in vitro model of human malignant melanoma. Cytotoxicity was assessed through a colorimetric-based sulforhodamine-B (SRB) assay in primary malignant melanoma (A375), non-malignant melanoma epidermoid carcinoma (A431) and non-tumorigenic melanocyte neighbouring keratinocyte (HaCaT) cells. Among eight (8) different fractions of S. fruticosa extracts (SF1-SF8) tested, SF3 was found to possess significant cytotoxic activity against A375 cells, while A431 and HaCaT cells remained relatively resistant or exerted no cytotoxicity, respectively. In addition, the total phenolic (Folin–Ciocalteu assay) and total flavonoid content of SF extracts was estimated, whereas the antioxidant capacity was measured via the inhibition of tert-butyl hydroperoxide-induced lipid peroxidation and protein oxidation levels. Finally, apoptotic cell death was assessed by utilizing a commercially available kit for the activation of caspases - 3, - 8 and - 9. In conclusion, the anti-melanoma properties of SF3 involve the induction of both extrinsic and intrinsic apoptotic pathway(s), as evidenced by the increased activity levels of caspases - 8, and - 9, respectively.

Malignant melanoma is one of the most deadly types of solid cancers, a property mainly attributed to its highly aggressive metastatic form. On the other hand, different classes of isothiocyanates, a class of phytochemicals, present in cruciferous vegetables have been characterized by considerable anti-cancer activity in both in vitro and in vivo experimental models. In the current study, we investigated the anti-cancer response of five isothiocyanates in an in vitro model of melanoma consisting of non-metastatic (A375, B16F-10) and metastatic (VMM1, Hs294T) malignant melanoma as well as non-melanoma epidermoid carcinoma (A431) and non-tumorigenic melanocyte-neighboring keratinocyte (HaCaT) cells. Our aim was to compare different endpoints of cytotoxicity (e.g., reactive oxygen species, intracellular glutathione content, cell cycle growth arrest, apoptosis and necrosis) descriptive of an anti-cancer response between non-metastatic and metastatic melanoma as well as non-melanoma epidermoid carcinoma and non-tumorigenic cells. Our results showed that exposure to isothiocyanates induced an increase in intracellular reactive oxygen species and glutathione contents between non-metastatic and metastatic melanoma cells. The distribution of cell cycle phases followed a similar pattern in a manner where non-metastatic and metastatic melanoma cells appeared to be growth arrested at the G2/M phase while elevated levels of metastatic melanoma cells were shown to be at sub G1 phase, an indicator of necrotic cell death. Finally, metastatic melanoma cells were more sensitive apoptosis and/or necrosis as higher levels were observed compared to non-melanoma epidermoid carcinoma and non-tumorigenic cells. In general, non-melanoma epidermoid carcinoma and non-tumorigenic cells were more resistant under any experimental exposure condition. Overall, our study provides further evidence for the potential development of isothiocyanates as promising anti-cancer agents against non-metastatic and metastatic melanoma cells, a property specific for these cells and not shared by non-melanoma epidermoid carcinoma or non-tumorigenic melanocyte cells.