Patrón de alimentación y riesgo de diabetes tipo 2 en adultos indígenas: revisión sistemática

Type 2 diabetes has become a serious public health problem, the eating pattern takes on an important role for the appearance of overweight and obesity, risk factors for developing diabetes, a phenomenon little explored in indigenous adults. Objective: To review the available scientific evidence on eating patterns and the risk of type 2 diabetes in indigenous adults. Methodology: Systematic review, the search was conducted from March to August 2023, in the databases EBSCO, SciELO, Elsevier, Google Scholar, Science Direct, and PubMed. A search strategy was designed with the MeSH and DeCS; risk, Type 2 Diabetes Mellitus, dietary pattern, indigenous and adult, critical reading used the Joanna Briggs Institute checklist. Results: We included 13 studies that addressed the variables of interest in indigenous population aged 18 to 85 years, published in English (n = 12), the sample ranged from 103 to 89,185 participants. Overall, it was revealed that indigenous individuals with a Western dietary pattern, characterized by a high consumption of red and processed meats, alcoholic beverages, refined cereals and sugary drinks, were at higher risk of developing TD2. Conclusions: The evidence is consistent, there is an association between the dietary pattern: consumption of ultra-processed foods, high in carbohydrates, fats and salt with the risk of developing Type 2 Diabetes in indigenous adults, multidisciplinary health interventions aimed at improving the diet based on healthy traditional diet of indigenous groups are required.: La diabetes tipo 2 se ha convertido en un grave problema de salud pública, el patrón de alimentación cobra un papel importante para la aparición de sobrepeso y obesidad, factores de riesgo para desarrollar diabetes, fenómeno poco explorado en adultos indígenas. Objetivo: Revisar la evidencia científica disponible sobre el patrón de alimentación y el riesgo de diabetes tipo 2 en adultos indígenas. Metodología: Revisión Sistemática, la búsqueda se realizó de marzo a agosto de 2023, en las bases de datos EBSCO, SciELO, Elsevier, Google académico, Science Direct, y PubMed. Se diseñó una estrategia de búsqueda con los MeSH y DeCS; riesgo, Diabetes Tipo 2, patrón de alimentación, indígenas y adultos, la lectura crítica se utilizó la lista de verificación de Joanna Briggs Institute. Resultados: Se incluyeron 13 estudios que abordaron las variables de interés en población indígena con edad entre 18 a 85 años, publicados en inglés (n = 12), la muestra osciló entre 103 y 89.185 participantes. En conjunto, se reveló que las personas indígenas con un patrón alimentario occidental, caracterizado por un alto consumo de carnes rojas y procesadas, bebidas alcohólicas, cereales refinados y bebidas azucaradas, tenían mayor riesgo de desarrollar DT2. Conclusiones: La evidencia es consistente, existe asociación entre el patrón de alimentación: consumo de alimentos ultraprocesados, altos en carbohidratos, grasas y sal con el riesgo de desarrollar Diabetes Tipo 2 en adultos indígenas, se requiere de intervenciones multidisciplinarias en salud encaminadas a mejorar la alimentación basada en dieta tradicional saludable de los grupos indígena

Autophagy activation by resveratrol reduces severity of experimental rheumatoid arthritis

Instituto de Salud Carlos III; RETIC‐RIER RD16/0012/0002Instituto de Salud Carlos III; PI12/02771Instituto de Salud carlos III; AGRUP2015/05Instituto de Salud Carlos III; AGRUP2018/0

Perlecan Maintains microvessel integrity in vivo and modulates their formation in vitro

Perlecan is a heparan sulfate proteoglycan assembled into the vascular basement membranes (BMs) during vasculogenesis. In the present study we have investigated vessel formation in mice, teratomas and embryoid bodies (EBs) in the absence of perlecan. We found that perlecan was dispensable for blood vessel formation and maturation until embryonic day (E) 12.5. At later stages of development 40% of mutant embryos showed dilated microvessels in brain and skin, which ruptured and led to severe bleedings. Surprisingly, teratomas derived from perlecan-null ES cells showed efficient contribution of perlecan-deficient endothelial cells to an apparently normal tumor vasculature. However, in perlecan-deficient EBs the area occupied by an endothelial network and the number of vessel branches were significantly diminished. Addition of FGF-2 but not VEGF165 rescued the in vitro deficiency of the mutant ES cells. Furthermore, in the absence of perlecan in the EB matrix lower levels of FGFs are bound, stored and available for cell surface presentation. Altogether these findings suggest that perlecan supports the maintenance of brain and skin subendothelial BMs and promotes vasculo- and angiogenesis by modulating FGF-2 function

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Vascular defects in perlecan-null embryos.

<p>(A) Schematic view of the region of the forebrain shown in (B–E). (B–C) Nissl stained coronal sections of E12.5 forebrain: the cerebral microvasculature is tightly embedded into the neuronal tissue of E12.5 wild type embryos (B); the perlecan-deficient vessels are dilated and loosely incorporated in the tissue (C). (D–E) Laminin immunostained BMs of neuroepithelium and blood vessels in ventral forebrain sections. A region with a blood leakage in a mutant embryo is shown (arrow in E). (F–G) Whole-mount picture of wild type (F) and perlecan mutant (G) at E17.5. Hemorrhages (arrow in G) and edema in the skin is evident in the mutant embryo. (H–I) Hematoxilin and eosin staining of the skin sections of E16.5 embryos. The skin of the perlecan-null embryo shows increased interstitial spaces (arrowheads) and dilated vessels (arrow). Bars: (B and C) 125 µm; (D and E) 40 µm; (H and I) 50 µm.</p

Histological and immunohistochemical analysis of teratomas.

<p>Hematoxylin/eosin staining shows teratomas derived from wild type (A) and mutant (B) ES cells that are composed of a variety of differentiated cells. (C–D) Perlecan immunofluorescent labeling in wild type (C) and mutant (D) teratomas. In wild type perlecan is expressed in the stroma (s), and in BMs surrounding vessels (arrow in C) and other structures including glands. Perlecan-null teratomas also have perlecan expression in the tumor stroma (s) and vessels. (E–F) Double fluorescent labeling with PECAM-1 in red (E) and perlecan in green (F) reveal that the vasculature of the perlecan-null tumors is composed of a mixture of perlecan-positive (host-derived) and perlecan-negative (ES cell-derived; arrowheads) endothelial cells. (G) Quantification of perlecan-positive and perlecan-negative vessels per area in wild type (n = 10) and mutant teratomas (n = 10). Bars: (A–D) 250 µm; (E–F) 125 µm.</p

In vitro analysis of vessel formation in embryoid bodies.

<p>EBs were generated from control (+/+) and perlecan mutant (−/−) ES cells. (A–F) The data are shown from PECAM-1 immunostainings of 5+12 days EBs cultured in 5% FCS-containing DMEM. A prominent vascular network is formed in wild type EBs (A), while mutants form endothelial networks that are less dense and smaller (B). (C–D) Treatment with 20 ng/ml VEGF₁₆₅ stimulates the formation of large PECAM-positive vascularized areas both in control and mutant EBs. (E–F) Treatment with 20 ng/ml FGF-2 strongly induces the formation of extensive vascular networks in both control and perlecan-deficient EBs. (G) Binding of FGFR1-AP to control (+/+) and perlecan mutant (−/−) 5+9 days EBs. The EBs were grown until confluency in 96-well tissue culture plates and fixed. The fixed EBs were incubated with increasing concentration of FGF-2 and exposed to FGFR1-AP at a concentration of 300 µg/ml. After washing to remove unbound receptor bound FGFR1-AP was measured with AP chromogenic substrate. The data are means of 8 EBs per data-point. Statistical differences were tested by Students t-test (***, p<0.001). The experiment was repeated 3 times. Bars: (A–F) 1 mm.</p

Immunostaining and ultra-structural analysis of microvessels.

<p>(A–B) Perlecan is expressed in the sub-endothelial BMs of normal brain capillaries and is absent in the mutant tissue. (C–D) Laminin-1 is present in both wild type and perlecan-null BMs. (E–F) SMA is expressed in the microvessels sprouting into the brain parenchyma in wild type E17.5 (E), as well as mutant brains (F). (G–I) Ultrastructural analysis of endothelial cells from E14.5 brain capillaries. Note the tight association between the endothelial cell (ec) and the directly adjacent cells (ac) in the wild type brain capillary (G). The BM is visible on the upper surface of the adjacent cells (arrows in G). In the mutant brains, gaps are evident between the endothelial cells and the adjacent cells and pericytes (p) (arrows in H and I). (J–L) Electron micrographs of E16.5 skin microvessels. Electron dense material (arrows) is deposited at the abluminar side and appears as a BM-like structure in the wild type (J) as well as in the perlecan-null vessels (K,L).Vessel lumen (VL). Bars: (A–F) 250 µm; (G–L) 400<b> </b>nm.</p

Genetic abrogation of the fibronectin-α5β1 integrin interaction in articular cartilage aggravates osteoarthritis in mice

<div><p>The balance between synthesis and degradation of the cartilage extracellular matrix is severely altered in osteoarthritis, where degradation predominates. One reason for this imbalance is believed to be due to the ligation of the α5β1 integrin, the classic fibronectin (FN) receptor, with soluble FN fragments instead of insoluble FN fibrils, which induces matrix metalloproteinase (MMP) expression. Our objective was to determine whether the lack of α5β1-FN binding influences cartilage morphogenesis <i>in vivo</i> and whether non-ligated α5β1 protects or aggravates the course of osteoarthritis in mice. We engineered mice (<i>Col2a-Cre;Fn1</i>^{<i>RGE/fl</i>}), whose chondrocytes express an α5β1 binding-deficient FN, by substituting the aspartic acid of the RGD cell-binding motif with a glutamic acid (FN-RGE). At an age of 5 months the knee joints were stressed either by forced exercise (moderate mechanical load) or by partially resecting the meniscus followed by forced exercise (high mechanical load). Sections of femoral articular knees were analysed by Safranin-O staining and by immunofluorescence to determine tissue morphology, extracellular matrix proteins and matrix metalloproteinase expression. The articular cartilage from untrained control and <i>Col2a-Cre;Fn1</i>^{<i>RGE/fl</i>} mice was normal, while the exposure to high mechanical load induced osteoarthritis characterized by proteoglycan and collagen type II loss. In the <i>Col2a-Cre;Fn1</i>^{<i>RGE/fl</i>} articular cartilage osteoarthritis progressed significantly faster than in wild type mice. Mechanistically, we observed increased expression of MMP-13 and MMP-3 metalloproteinases in FN-RGE expressing articular cartilage, which severely affected matrix remodelling. Our results underscore the critical role of FN-α5β1 adhesion as ECM sensor in circumstances of articular cartilage regeneration.</p></div

OA progression in <i>Fn1</i>^<i>wt/wt</i> and <i>Fn1</i>^<i>RGE/-</i> cartilage exposed to high mechanical load.

<p>A) Safranin-O staining of representative medial femoral knee cartilage sections from control and <i>Fn1</i>^<i>RGE/-</i> mice after exposure to high load at 5, 10 and 15 days after OA induction (DAI). B) Controls of the contralateral femoral condyles stained with Safranin-O. Scale bars, 50 μm.</p