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Continuing development of Endoscopic Medical procedures Sailed through Man-made Cleverness.
The pathophysiology and time course of impairment in cutaneous microcirculatory function and structure remain poorly understood in people with diabetes, partly due to the lack of investigational tools capable of directly imaging and quantifying the microvasculature in vivo. We applied a new optical coherence tomography (OCT) technique, at rest and during reactive hyperemia (RH), to assess the skin microvasculature in people with diabetes with foot ulcers (DFU, n = 13), those with diabetes without ulcers (DNU, n = 9), and matched healthy controls (CON, n = 13). OCT images were obtained from the dorsal part of the foot at rest and following 5 min of local ischemia induced by inflating a cuff around the thigh at suprasystolic level (220 mmHg). One-way ANOVA was used to compare the OCT-derived parameters (diameter, speed, flow rate, and density) at rest and in response to RH, with repeated-measures two-way ANOVA performed to analyze main and interaction effects between groups. Data are means ± SD. At rest, microvs with diabetes with distinct disease severity.Mitochondria play a key role in homeostasis and are central to one of the leading hypotheses of aging, the free radical theory. Mitochondria function as a reticulated network, constantly adapting to the cellular environment through fusion (joining), biogenesis (formation of new mitochondria), and fission (separation). This adaptive response is particularly important in response to oxidative stress, cellular damage, and aging, when mitochondria are selectively removed through mitophagy, a mitochondrial equivalent of autophagy. Isoprenaline During this complex process, mitochondria influence surrounding cell biology and organelles through the release of signaling molecules. Given that the human placenta is a unique organ having a transient and somewhat defined life span of ∼280 days, any adaption or dysfunction associated with mitochondrial physiology as a result of aging will have a dramatic impact on the health and function of both the placenta and the fetus. Additionally, a defective placenta during gestation, resulting in reduced fetal growth, has been shown to influence the development of chronic disease in later life. In this review we focus on the mitochondrial adaptions and transformations that accompany gestational length and share similarities with age-related diseases. In addition, we discuss the role of such changes in regulating placental function throughout gestation, the etiology of gestational complications, and the development of chronic diseases later in life.Saturated fatty acid (SFA) induces proinflammatory response through a Toll-like receptor (TLR)-mediated mechanism, which is associated with cardiometabolic diseases such as obesity, insulin resistance, and endothelial dysfunction. Consistent with this notion, TLR2 or TLR4 knockout mice are protected from obesity-induced proinflammatory response and endothelial dysfunction. Although SFA causes endothelial dysfunction through TLR-mediated signaling pathways, the mechanisms underlying SFA-stimulated inflammatory response are not completely understood. To understand the proinflammatory response in vascular endothelial cells in high-lipid conditions, we compared the proinflammatory responses stimulated by palmitic acid (PA) and other canonical TLR agonists [lipopolysaccharide (LPS), Pam3-Cys-Ser-Lys4 (Pam3CSK4), or macrophage-activating lipopeptide-2)] in human aortic endothelial cells. The expression profiles of E-selectin and the signal transduction pathways stimulated by PA were distinct from those stimulated by canonical TLR agonists. Inhibition of long-chain acyl-CoA synthetases (ACSL) by a pharmacological inhibitor or knockdown of ACSL1 blunted the PA-stimulated, but not the LPS- or Pam3CSK4-stimulated proinflammatory responses. Furthermore, triacsin C restored the insulin-stimulated vasodilation, which was impaired by PA. From the results, we concluded that PA stimulates the proinflammatory response in the vascular endothelium through an ACSL1-mediated mechanism, which is distinct from LPS- or Pam3CSK4-stimulated responses. The results suggest that endothelial dysfunction caused by PA may require to undergo intracellular metabolism. This expands the understanding of the mechanisms by which TLRs mediate inflammatory responses in endothelial dysfunction and cardiovascular disease.Previous studies have suggested that increases in maternal cortisol or maternal stress in late pregnancy increase the risk of stillbirth at term. In an ovine model with increased maternal cortisol over the last 0.20 of gestation, we have previously found evidence of disruption of fetal serum and cardiac metabolomics and altered expression of genes related to mitochondrial function and metabolism in biceps femoris, diaphragm, and cardiac muscle. The present studies were designed to test for effects of chronically increased maternal cortisol on gene expression and metabolomics in placentomes near term. We hypothesized that changes in placenta might underlie or contribute to the alterations in fetal serum metabolomics and thereby contribute to changes in striated muscle metabolism. Placentomes were collected from pregnancies in early labor (143 ± 1 days gestation) of control ewes (n = 7) or ewes treated with cortisol (1 mg·kg-1·day-1 iv; n = 5) starting at day 115 of gestation. Transcriptomics and metabolomics were performed using an ovine gene expression microarray (Agilent 019921) and HR-MAS NMR, respectively. Multiomic analysis indicates that amino acid metabolism, particularly of branched-chain amino acids and glutamate, occur in placenta; changes in amino acid metabolism, degradation, or biosynthesis in placenta were consistent with changes in valine, isoleucine, leucine, and glycine in fetal serum. The analysis also indicates changes in glycerophospholipid metabolism and suggests changes in endoplasmic reticulum stress and antioxidant status in the placenta. These findings suggest that changes in placental function occurring with excess maternal cortisol in late gestation may contribute to metabolic dysfunction at birth.Caloric restriction (CR) followed by refeeding, a phenomenon known as catch-up growth (CUG), results in excessive lipid deposition and insulin resistance in skeletal muscle, but the underlying mechanisms remain elusive. Recent reports have suggested that vascular endothelial growth factor B (VEGF-B) controls muscle lipid accumulation by regulating endothelial fatty acid transport. Here, we found continuous activation of VEGF-B signaling and increased lipid uptake in skeletal muscle from CR to refeeding, as well as increased lipid deposition and impaired insulin sensitivity after refeeding in the skeletal muscle of CUG rodents. Inhibiting VEGF-B signaling reduced fatty acid uptake in and transport across endothelial cells. Knockdown of Vegfb in the tibialis anterior (TA) muscle of CUG mice significantly attenuated muscle lipid accumulation and ameliorated muscle insulin sensitivity by decreasing lipid uptake. Furthermore, we showed that aberrant histone methylation (H3K9me1) and acetylation (H3K14ac and H3K18ac) at the Vegfb promoter might be the main cause of persistent VEGF-B upregulation in skeletal muscle during CUG.
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