Type 2 diabetes mellitus (DM2) is increasing in incidence, creating worldwide public health concerns and impacting morbidity and mortality rates. An increasing number of studies have demonstrated shared associations between DM2 and malignancy, including key clinical, biochemical, and metabolic commonalities. This paper will attempt to explore the relationship between the various types of cancer and diabetes, the common metabolic pathways underlying cancer development, and the potential impact of various antidiabetes therapies on cancer risk.
Electrophilic aldehyde (4-hydroxynonenal; 4-HNE), formed after lipid peroxidation, is a mediator of mitochondrial dysfunction and implicated in both the pathogenesis and the progression of cardiovascular disease. Manganese superoxide dismutase (MnSOD), a nuclear-encoded antioxidant enzyme, catalyzes the dismutation of superoxide radicals (O 2 •- ) in mitochondria. To study the role of MnSOD in the myocardium, we generated a cardiomyocyte-specific SOD2 ( SOD2Δ ) deficient mouse strain. Unlike global SOD2 knockout mice, SOD2Δ mice reached adolescence; however, they die at ~4 months of age due to heart failure. Ultrastructural analysis of SOD2Δ hearts revealed altered mitochondrial architecture, with prominent disruption of the cristae and vacuole formation. Noninvasive echocardiographic measurements in SOD2 Δ mice showed dilated cardiomyopathic features such as decreased ejection fraction and fractional shortening along with increased left ventricular internal diameter. An increased incidence of ventricular tachycardia was observed during electrophysiological studies of the heart in SOD2Δ mice. Oxidative phosphorylation (OXPHOS) measurement using a Seahorse XF analyzer in SOD2Δ neonatal cardiomyocytes and adult cardiac mitochondria displayed reduced O 2 consumption, particularly during basal conditions and after the addition of FCCP (H + ionophore/uncoupler), compared to that in SOD2f l hearts. Measurement of extracellular acidification (ECAR) to examine glycolysis in these cells showed a pattern precisely opposite that of the oxygen consumption rate (OCR) among SOD2Δ mice compared to their SOD2 fl littermates. Analysis of the activity of the electron transport chain complex identified a reduction in Complex I and Complex V activity in SOD2Δ compared to SOD2f l mice. We demonstrated that a deficiency of SOD2 increases reactive oxygen species (ROS), leading to subsequent overproduction of 4-HNE inside mitochondria. Mechanistically, proteins in the mitochondrial respiratory chain complex and TCA cycle (NDUFS2, SDHA, ATP5B, and DLD) were the target of 4-HNE adduction in SOD2Δ hearts. Our findings suggest that the SOD2 mediated 4-HNE signaling nexus may play an important role in cardiomyopathy.
Background The prevalence of disordered eating is increasing among adolescents in Asia. The prevalence and predictors of disordered eating in boys have often gone unrecognized. This study examined gender-specific responses to multifaceted factors associated with disordered eating, including personal, behavioral, family, and school-related characteristics. Methods After excluding responses with incomplete information, a sample of 729 adolescents (48.97% boys) between the ages of 13 and 16 were surveyed through convenience sampling from 37 classrooms in three junior high schools in New Taipei City of Taiwan were analyzed. The Eating Attitudes Test-26 questionnaire was used to identify disordered eating. Results No difference in the prevalence of disordered eating between the genders was found. Adolescent girls exhibit a preoccupation with fatness and a desire to be thinner, whereas boys are more likely to engage in extreme dieting behaviors such as vomiting, keeping the stomach empty, and avoiding sweets. Girls engaging in disordered eating reported relatively high levels of interpersonal stress involving family member weight-teasing, low peer acceptance, and high peer pressure to control weight. High intensity of regular exercise was found in girls with disordered eating. The perception of body weight is a more critical factor of engaging in disordered eating for boys than girls. Adolescents with immigrant parents were associated with disordered eating among both genders. Conclusions Changing gender-specific weight-related norms in schools and families is essential to reduce the prevalence of disordered eating, particularly among girls. Future studies using representative samples to confirm this study’s findings are warranted.
Background The loss of endothelial integrity increases the risk of intracerebral hemorrhage during ischemic stroke. Adjunct therapeutic targets for reperfusion in ischemic stroke are in need to prevent blood‐brain barrier disruption. Recently, we have shown that endothelial permeability is mediated by lysophosphatidic acid (LPA), but the role of autotaxin, which produces LPA, remains unclear in stroke. We investigate whether autotaxin/LPA axis regulates blood‐brain barrier integrity after cerebral ischemia. Methods and Results Ischemic stroke was induced in mice by middle cerebral artery occlusion for 90 minutes, followed by 24‐hour reperfusion. The therapeutic efficacy of autotaxin/LPA receptor blockade was evaluated using triphenyl tetrazolium chloride staining, Evans blue permeability, infrared imaging, mass spectrometry, and XF24 analyzer to evaluate blood‐brain barrier integrity, autotaxin activity, and mitochondrial bioenergetics. In our mouse model of ischemic stroke, the mRNA levels of autotaxin were elevated 1.7‐fold following the cerebral ischemia and reperfusion (I/R) group compared with the sham. The enzymatic activity of autotaxin was augmented by 4‐fold in the I/R group compared with the sham. Plasma and brain tissues in I/R group showed elevated LPA levels. The I/R group also demonstrated mitochondrial dysfunction, as evidenced by decreased ( P <0.01) basal oxygen consumption rate, mitochondrial ATP production, and spare respiratory capacity. Treatment with autotaxin inhibitors (HA130 or PF8380) or autotaxin/LPA receptor inhibitor (BrP‐LPA) rescued endothelial permeability and mitochondrial dysfunction in I/R group. Conclusions Autotaxin‐LPA signaling blockade attenuates blood‐brain barrier disruption and mitochondrial function following I/R, suggesting targeting this axis could be a new therapeutic approach toward treating ischemic stroke.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.