RESUMO
Diabetes mellitus (DM) is a global public health concern. DM is importantly linked to the modern lifestyle. Lifestyle-based interventions currently represent a critical preventive and therapeutic approach for patients with DM. Increasing physical activity has proven multiple benefits to prevent this condition; however, there is still room for further progress in this field, especially in terms of the effect of exercise in patients with already established DM. This study intends to examine the economic relationship between physical activity and direct/indirect costs in patients with DM. We analyze a national representative sample (n = 1496) of the general population of Spain, using available data from the National Health Survey of 2017 (NHS 2017). Our results show that 63.7% of the sample engaged in some degree of physical activity, being more frequent in men (67.5%), younger individuals (80.0%), and those with higher educational levels (69.7%). Conversely, lower levels of physical activity were associated with female sex, older subjects, and various comorbidities. Our study estimates that 2151 per (51% in direct costs) patient may be saved if a minimum level of physical activity is implemented, primarily, due to a decrease in indirect costs (absenteeism and presenteeism). This study shows that physical activity will bring notable savings in terms of direct and indirect costs in patients with DM, particularly in some vulnerable groups.
RESUMO
BACKGROUND: Some membrane proteins can translocate into the nucleus, defined as nuclear localized membrane proteins (NLMPs), including receptor tyrosine kinases (RTKs). We previously showed that nuclear MET (nMET), a member of RTKs, mediates cancer stem-like cells self-renewal to promote cancer recurrence. However, it is unknown that nMET or mMET, which is the ancestor in the evolution of cancer cell survival and clearance. Here, we aim to study the NLMP functions in cell death, differentiation and survival. METHOD: We applied the systematic reanalysis of functional NLMP and clinical investigations of nMET from databases. In addition, we used soft agar assay, immunoblotting, flow cytometry, and immunofluorescence confocal microscopy for examinations of nMET functions including stem-like cell formation, cell signaling, cell cycle regulation, and co-localization with regulators of cell signaling. ShRNA, antibody of recognizing surface membrane MET based treatment were used to downregulate endogenous nMET to uncover its function. RESULTS: We predicted and demonstrated that nMET and nEGFR are most likely not ancestors. nMET overexpression induces both cell death and survival with drug resistance and stem cell-like characters. Moreover, the paradoxical function of nMET in both cell death and cell survival is explained by the fact that nMET induces stem cell-like cell growth, DNA damage repair, to evade the drug sensitization for survival of single cells while non-stem cell-like nMET expressing single cells may undergo clearance by cell death through cell cycle arrest induced by p21. CONCLUSION: Taken together, our data suggest a link between nuclear RTK and cancer cell evolutionary clearance via cell death, and drug resistance for survival through stemness selection. Targeting evolved nuclear RTKs in cancer stem cells would be a novel avenue for precision cancer therapy.
