Oxygen is required to sustain aerobic organisms. Reactive oxygen species (ROS) are constantly released during mitochondrial oxygen consumption for energy production. Any imbalance between ROS production and its scavenger system induces oxidative stress. Oxidative stress, a critical contributor to tissue damage, is well-known to be associated with various diseases. The kidney is susceptible to hypoxia, and renal hypoxia is a common final pathway to end stage kidney disease, regardless of the underlying cause. Renal hypoxia aggravates oxidative stress, and elevated oxidative stress, in turn, exacerbates renal hypoxia. Oxidative stress is also enhanced in chronic kidney disease, especially diabetic kidney disease, through various mechanisms. Thus, the vicious cycle between oxidative stress and renal hypoxia critically contributes to the progression of renal injury. This review examines recent evidence connecting chronic hypoxia and oxidative stress in renal disease and subsequently describes several promising therapeutic approaches against oxidative stress.
Chondroitin sulfate (CS) chains are involved in the regulation of various biological processes. However, the mechanism underlying the catabolism of CS is not well understood. Hyaluronan (HA)-degrading enzymes, the hyaluronidases, are assumed to act at the initial stage of the degradation process, because HA is similar in structure to nonsulfated CS, chondroitin (Chn). Although human hyaluronidase-1 (HYAL1) and testicular hyaluronidase (SPAM1) can degrade not only HA but also CS, they are assumed to digest CS to only a limited extent. In this study, the hydrolytic activities of HYAL1 and SPAM1 toward CS-A, CS-C, Chn, and HA were compared. HYAL1 depolymerized CS-A and HA to a similar extent. SPAM1 degraded CS-A, Chn, and HA to a similar extent. CS is widely distributed from very primitive organisms to humans, whereas HA has been reported to be present only in vertebrates with the single exception of a mollusk. Therefore, a genuine substrate of hyaluronidases appears to be CS as well as HA.
Meningioma is derived from arachnoid cells covering the surface of the brain and spinal cord, and it has characteristics shared by mesothelioma arising from the pleura and peritoneum in that it takes an epithelioid appearance despite its mesenchymal origin. We examined the immunohistochemical expression of podoplanin and calretinin, both of which are well-known markers of mesothelioma, in 24 surgical cases of meningioma of various types. In most cases, a linear immunoreactivity for podoplanin was found along the cell surface of most neoplastic cells. An intracytoplasmic, finely granular, or diffuse immunoreactivity was also noted in some cells. These findings corresponded well to immunoreactivity for epithelial membrane antigen (EMA), but immunoreactivity for podoplanin was more crisp or sharply delineated and clear compared with that for EMA. These findings indicate that podoplanin can be used as an immunohistochemical marker that is equivalent to EMA in the differential diagnosis of meningioma. However, most meningiomas did not contain calretinin-immunoreactive cells, a finding that differs from the diffuse immunoreactivity seen in mesothelioma.
The coronavirus disease 2019 (COVID‐19) pandemic witnessed several clusters of children with fever and multisystem inflammation resembling Kawasaki disease (KD). Due to the evidence of a preceding severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection in most of these patients, post‐viral immunological reactions were thought to play an important role in the pathogenesis.
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The condition, called “pediatric inflammatory multisystem syndrome temporally associated with SARS‐CoV‐2 infection (PIMS‐TS)”, has thus far been reported mainly from Europe and the United States,
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and no cases have been diagnosed in Asia. We herein analyzed the clinical data on patients in whom KD was diagnosed during a local COVID‐19 epidemic to investigate the relationship between KD and SARS‐CoV‐2 infections in Japan, which has the highest KD incidence in the world.
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