Delaying routine health care has been prevalent during the COIVD-19 pandemic. Macro-level data from this period reveals that U.S.
View Article and Find Full Text PDFBackground: Approximately 750,000 people in the U.S. live with end-stage kidney disease (ESKD); the majority receive dialysis.
View Article and Find Full Text PDFIntroduction: Research career development awards (CDAs) facilitate development of clinician-scientists. This study compared the academic achievements of individuals in a structured institutional "pre-K" CDA program, the Mayo Clinic Kern Scholars program, with individuals who applied for but were not admitted to the Kern program ("Kern applicants"), and awardees of other unstructured internal CDAs.
Methods: This was a longitudinal cohort study of clinicians engaged in research at Mayo Clinic between 2010 and 2019.
The generation of reactive oxygen species has a pivotal role in both acute and chronic glomerular injuries in patients with lupus nephritis. As the transcription factor Nrf2 is a major regulator of the antioxidant response and is a primary cellular defense mechanism, we sought to determine a role of Nrf2 in the progression of lupus nephritis. Pathological analyses of renal biopsies from patients with different types of lupus nephritis showed oxidative damage in the glomeruli, accompanied by an active Nrf2 antioxidant response.
View Article and Find Full Text PDFThe role of Nrf2 in disease prevention and treatment is well documented; however the specific role of Nrf2 in skeletal muscle is not well described. The current study investigated whether Nrf2 plays a protective role in an STZ-induced model of skeletal muscle atrophy. Modulation of Nrf2 through siRNA resulted in a more robust differentiation of C2C12s, whereas increasing Nrf2 with sulforaphane treatment inhibited differentiation.
View Article and Find Full Text PDFThe Nrf2-Keap1 signaling pathway is a protective mechanism promoting cell survival. Activation of the Nrf2 pathway by natural compounds has been proven to be an effective strategy for chemoprevention. Interestingly, a cancer-promoting function of Nrf2 has recently been observed in many types of tumors due to deregulation of the Nrf2-Keap1 axis, which leads to constitutive activation of Nrf2.
View Article and Find Full Text PDFOxid Med Cell Longev
August 2013
Currently, the sole treatment option for patients with heart failure is transplantation. The battle of prolonging graft survival and modulating innate and adaptive immune responses is still being waged in the clinic and in research labs. The transcription factor Nrf2 controls major cell survival pathways and is central to moderating inflammation and immune responses.
View Article and Find Full Text PDFBackground: Heart failure (HF), a debilitating disease in a growing number of adults, exerts structural and neurohormonal changes in both cardiac and skeletal muscles. However, these alterations and their affected molecular pathways remain uncharacterized. Disease progression is known to transform skeletal muscle fiber composition by unknown mechanisms.
View Article and Find Full Text PDFJ Biochem Mol Toxicol
February 2013
Arsenic is present in the environment and has become a worldwide health concern due to its toxicity and carcinogenicity. However, the specific mechanism(s) by which arsenic elicits its toxic effects has yet to be fully elucidated. The transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) has been recognized as the master regulator of a cellular defense mechanism against toxic insults.
View Article and Find Full Text PDFAldose reductase (AR) is a key enzyme in the alternative glucose metabolism pathway, the polyol pathway. To date, AR is known to be involved in several secondary complications of diabetes and various kidney diseases. The goal of this study was to elucidate how the Nrf2-anti-oxidant response element (ARE) signal pathway plays a role in TGFβ1's regulation of AR expression in human renal mesangial cells (HRMCs).
View Article and Find Full Text PDFThe mammalian heart expresses two myosin heavy chain (MYH) genes (Myh6 and Myh7), which are major components of the thick filaments of the sarcomere. We have determined that a third MYH, MYH7B, is also expressed in the myocardium. Developmental analysis shows Myh7b expression in cardiac and skeletal muscle of Xenopus, chick and mouse embryos, and in smooth muscle tissues during later stages of mouse embryogenesis.
View Article and Find Full Text PDFMyoblasts aggregate, differentiate and fuse to form skeletal muscle during both embryogenesis and tissue regeneration. For proper muscle function, long-range self-organization of myoblasts is required to create organized muscle architecture globally aligned to neighboring tissue. However, how the cells process geometric information over distances considerably longer than individual cells to self-organize into well-ordered, aligned and multinucleated myofibers remains a central question in developmental biology and regenerative medicine.
View Article and Find Full Text PDFObjective: To determine whether dietary compounds targeting NFE2-related factor 2 (Nrf2) activation can be used to attenuate renal damage and preserve renal function during the course of streptozotocin (STZ)-induced diabetic nephropathy.
Research Design And Methods: Diabetes was induced in Nrf2(+/+) and Nrf2(-/-) mice by STZ injection. Sulforaphane (SF) or cinnamic aldehyde (CA) was administered 2 weeks after STZ injection and metabolic indices and renal structure and function were assessed (18 weeks).
Rationale: The proper function of cardiac muscle requires the precise assembly and interactions of numerous cytoskeletal and regulatory proteins into specialized structures that orchestrate contraction and force transmission. Evidence suggests that posttranscriptional regulation is critical for muscle function, but the mechanisms involved remain understudied.
Objective: To investigate the molecular mechanisms and targets of the muscle-specific fragile X mental retardation, autosomal homolog 1 (FXR1), an RNA binding protein whose loss leads to perinatal lethality in mice and cardiomyopathy in zebrafish.
The purpose of this investigation was to examine the expression of three commonly used housekeeping genes -- glyceraldehyde-3-phosphate dehydrogenase (GAPDH), beta(2)-microglobulin (beta(2)M), and RNA polymerase 2a (polR2a) -- in elderly (E) compared to young (Y) subjects. Nine young subjects (22.7 +/- 3.
View Article and Find Full Text PDFThe primary mechanism that contributes to decreasing skeletal muscle strength and size with healthy aging is not presently known. This study examined the contribution of the ubiquitin-proteasome pathway and apoptosis to skeletal muscle wasting in older adults (n = 21; mean age = 72.76 +/- 8.
View Article and Find Full Text PDFOBJECTIVE: To compare the effect of creatine supplementation on thermoregulation in males and females during exercise in a thermoneutral environment. DESIGN AND SETTING: Male and female subjects participated in 30 minutes of cycle ergometry in nonsupplemented (NS) and creatine-supplemented (Cr) conditions at 70% to 75% of predetermined peak oxygen consumption. SUBJECTS: Ten male and ten female subjects were evaluated with and without creatine supplementation.
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