The Tohoku journal of experimental medicine
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Tohoku J. Exp. Med. · Sep 2021
ReviewCoagulation, Protease-Activated Receptors, and Diabetic Kidney Disease: Lessons from eNOS-Deficient Mice.
Endothelial nitric oxide synthase (eNOS) dysfunction is known to exacerbate the progression and prognosis of diabetic kidney disease (DKD). One of the mechanisms through which this is achieved is that low eNOS levels are associated with hypercoagulability, which promotes kidney injury. ⋯ Furthermore, pharmaceutical inhibition or genetic deletion of coagulation factors or PARs ameliorated inflammation in DKD in mice lacking eNOS. In this review, we summarize the relationship between eNOS, coagulation, and PARs and propose a novel therapeutic option for the management of patients with DKD.
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Tohoku J. Exp. Med. · Aug 2021
ReviewRegulation of Adaptive Cell Proliferation by Vagal Nerve Signals for Maintenance of Whole-Body Homeostasis: Potential Therapeutic Target for Insulin-Deficient Diabetes.
In insulin-resistant states such as obesity, pancreatic β-cells proliferate to prevent blood glucose elevations. Failure of this β-cells proliferative response leads to the development of diabetes. On the other hand, when organs are damaged, cells proliferate to repair the organs. ⋯ In contrast, there are as yet no applicable therapeutic strategies to increase functional β-cell mass in vivo. Therefore, we have conducted the basic investigations to tackle this issue based on the discovery of neuron-mediated liver-β-cell inter-organ crosstalk. This review introduces vagal signal-mediated regulatory systems of adaptive cell proliferation in vivo and efforts to develop cell-increasing therapies based on vagal nerve-mediated cell proliferation.
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Tohoku J. Exp. Med. · Jul 2021
Review Case ReportsIntestinal Perforation in a Patient with Colon Cancer during Treatment with Regorafenib: A Case Report and Review of the Literature.
The multikinase inhibitor, regorafenib, is known to exert its antitumor effects by targeting several kinases, inhibiting interstitial intracellular signaling and suppressing tumor cell proliferation. Regorafenib causes gastrointestinal perforation and gastrointestinal fistula as adverse events, and discontinuation is recommended if these adverse events occur during administration. However, there are no prescribed standards for re-administration after discontinuation and for administration in patients with a history of gastrointestinal perforation. ⋯ Based on a review of literature and our experience with the case presented here, we recommend that administration of regorafenib to patients with a history of gastrointestinal perforation should be avoided to the extent possible. Moreover, in case of prior administration of a drug reported to cause gastrointestinal perforation, such as an anti-VEGFR drug, the risk of gastrointestinal perforation should be considered during the administration of regorafenib. In the event of complaints, such as abdominal pain, gastrointestinal perforation should be considered as a differential diagnosis and appropriate tests and treatments should be initiated at an early stage.
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Tohoku J. Exp. Med. · Apr 2021
ReviewPrimary Cultures and Cell Lines for In Vitro Modeling of the Human Adrenal Cortex.
The human adrenal cortex is a complex endocrine organ that produces mineralocorticoids, glucocorticoids and androgens. These steroids are produced in distinct cell types located within the glomerulosa, fasciculata and reticularis of the adrenal cortex. Abnormal adrenal steroidogenesis leads to a variety of diseases that can cause hypertension, metabolic syndrome, infertility and premature adrenarche. ⋯ Immortalized human adrenocortical cell lines have proven to be of considerable value in studying the molecular and biochemical mechanisms controlling adrenal steroidogenesis and tumorigenesis. Current human adrenal cell lines include the original NCI-H295 and its substrains: H295A, H295R, HAC13, HAC15, HAC50 and H295RA as well as the recently established MUC-1, CU-ACC1 and CU-ACC2. The current review will discuss the use of primary cultures of fetal and adult adrenal cells as well as adrenocortical cell lines as in vitro models for the study of human adrenal physiology and pathophysiology.
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Tohoku J. Exp. Med. · Mar 2021
ReviewMental Health and Physical Activity among Children and Adolescents during the COVID-19 Pandemic.
Coronavirus disease 2019 (COVID-19) is causing disruptions in the global social system. Japanese children and adolescents have had their schools closed, government-mandated activity restrictions imposed, and interactions outside the home reduced. These restrictions can have a considerable psychological impact on children and adolescents. ⋯ Of the studies that reported a correlation, seven reported that physical activity improves psychological health. The impact of psychologically stressful situations such as COVID-19 on children and adolescents has been experienced worldwide. Physical activity has been correlated with psychological health, and it may improve psychological status; physical activity should be recommended to better support the psychological health of children and adolescents under the influence of COVID-19.