RESUMEN
BACKGROUND: Adipose-derived stem cells (ADSC) are multipotent cells implicated in tissue homeostasis. Obesity represents a chronic inflammatory disease associated with metabolic dysfunction and age-related mechanisms, with progressive accumulation of senescent cells and compromised ADSC function. In this study, we aimed to explore mechanisms associated with the inflammatory environment present in obesity in modulating ADSC to a senescent phenotype. We evaluated phenotypic and functional alterations through 18 days of treatment. ADSC were cultivated with a conditioned medium supplemented with a pool of plasma from eutrophic individuals (PE, n = 15) or with obesity (PO, n = 14), and compared to the control. RESULTS: Our results showed that PO-treated ADSC exhibited decreased proliferative capacity with G2/M cycle arrest and CDKN1A (p21WAF1/Cip1) up-regulation. We also observed increased senescence-associated ß-galactosidase (SA-ß-gal) activity, which was positively correlated with TRF1 protein expression. After 18 days, ADSC treated with PO showed augmented CDKN2A (p16INK4A) expression, which was accompanied by a cumulative nuclear enlargement. After 10 days, ADSC treated with PO showed an increase in NF-κB phosphorylation, while PE and PO showed an increase in p38MAPK activation. PE and PO treatment also induced an increase in senescence-associated secretory phenotype (SASP) cytokines IL-6 and IL-8. PO-treated cells exhibited decreased metabolic activity, reduced oxygen consumption related to basal respiration, increased mitochondrial depolarization and biomass, and mitochondrial network remodeling, with no superoxide overproduction. Finally, we observed an accumulation of lipid droplets in PO-treated ADSC, implying an adaptive cellular mechanism induced by the obesogenic stimuli. CONCLUSIONS: Taken together, our data suggest that the inflammatory environment observed in obesity induces a senescent phenotype associated with p38MAPK/NF-κB axis, which stimulates and amplifies the SASP and is associated with impaired mitochondrial homeostasis.
RESUMEN
This paper describes the relationship between the landscape and the socio-economic and political characteristics of a highly biodiverse Andean region of Colombia, which is now recovering from the socio-ecological impact of protracted armed conflict. We quantify the current spatial relationship between nature and society, and we include legacy effects from the most recent period of armed conflict and its consequences of forced displacement and land use disruption. The procedure followed provides a quantitative model where a minimum number of socio-economic and political variables explain the variation in land cover. The results represent the relationship between land use intensity and the main socio-economic and political indicators, highlighting a close interaction between landscape configuration, socio-economic structure of local populations, coercive conservation and armed conflict. A simulated post-conflict landscape shows a clear transition gradient towards agrarian expansion and intensification, also in systems where naturalness is a relevant feature. The peace process in Colombia offers opportunities for new schemes of land planning and management, including natural resource governance and policy reforms to improve welfare and resilience of local communities. The results allow to define options for future planning given the possible consequences of socio-political legacy effects yet to fully play out across Colombia.
RESUMEN
OBJECTIVE: The diagnosis of oral lesions is often challenging for primary healthcare providers, which explains the high number of referrals to specialist care. This favors increases in waiting lines and delays in diagnosis, contributing to high mortality rates from oral cancer. This study aimed to summarize the experience of the EstomatoNet, a telediagnosis program catering to primary care dentists and physicians from southern Brazil. STUDY DESIGN: This exploratory study included all queries received by EstomatoNet from June 2015 to December 2016. Health providers (71 dentists and 18 physicians from primary care) submitted requests including clinical information and photographs of oral lesions by means of a cloud-based platform. Specialized oral medicine teleconsultants received the data, conveyed a diagnostic hypothesis, and conveyed management recommendations. RESULTS: Actinic cheilitis (n = 41, 15.8%), squamous cell carcinoma (n = 22, 8.5%), and inflammatory hyperplasia (21, 8.1%) were the most frequent diagnoses. Teleconsultants recommended referral to specialists in 42.9% of the cases, total biopsy in 23.6%, and follow-up in 16.2%. After the EstomatoNet use, the intention to refer the patients to face-to-face consultation reduced from 96.9% to 35.1%. CONCLUSION: Telediagnosis for oral lesions is feasible and has potential to improve the quality of primary health care by bridging the gap between primary and specialized health care.
Asunto(s)
Odontología/métodos , Enfermedades de la Boca/diagnóstico por imagen , Atención Primaria de Salud/métodos , Telemedicina , Adulto , Anciano , Actitud del Personal de Salud , Brasil , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fotograbar , Derivación y Consulta/estadística & datos numéricos , Adulto JovenRESUMEN
It is generally accepted that mitochondria are able to proliferate even in postmitotic cells due to their natural turnover and also to satisfy increased cell energy requirements. However, no detailed studies are available, particularly with respect to specific cell types. Since [3H]-thymidine is incorporated not only into nuclear (n) DNA but also into the DNA of cytoplasmic mitochondria, an autoradiographic approach was developed at the light microscopy level in order to study basic questions of mitochondrial (mt) proliferation in organs of rodents in situ via the cytoplasmic incorporation of [3H]-thymidine injected into the animals 1 h before sacrifice. Experiments carried out on mice after X-irradiation showed that cytoplasmic labeling was not due to a process such as unscheduled nuclear DNA synthesis (nUDS). Furthermore, half-lives of mitochondria between 8-23 days were deduced specifically in relation to cell types. The phase of mtDNA synthesis was about 75 min. Finally, mt proliferation was measured in brain cells of mice as a function of age. While all neurons showed a decreasing extent of mtDNA synthesis during old age, nUDS decreased only in distinct cell types of the cortex and hippocampus. We conclude that the leading theories explaining the phenomenon of aging are closely related, i.e., aging is due to a decreasing capacity of nDNA repair, which leads to unrepaired nDNA damage, or to an accumulation of mitochondria with damaged mtDNA, which leads to a deficit of cellular energy production.