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Role of Macroautophagy in Mammalian Male Reproductive Physiology
Get PDFjournal articlePhysiologically, autophagy is an evolutionarily conserved and self-degradative process in cells. Autophagy carries out normal physiological roles throughout mammalian life. Accumulating evidence shows autophagy as a mechanism for cellular growth, development, differentiation, survival, and homeostasis. In male reproductive systems, normal spermatogenesis and steroidogenesis need a balance between degradation and energy supply to preserve cellular metabolic homeostasis. The main process of autophagy includes the formation and maturation of the phagophore, autophagosome, and autolysosome. Autophagy is controlled by a group of autophagy-related genes that form the core machinery of autophagy. Three types of autophagy mechanisms have been discovered in mammalian cells: macroautophagy, microautophagy, and chaperone-mediated autophagy. Autophagy is classified as non-selective or selective. Non-selective macroautophagy randomly engulfs the cytoplasmic components in autophagosomes that are degraded by lysosomal enzymes. While selective macroautophagy precisely identifies and degrades a specific element, current findings have shown the novel functional roles of autophagy in male reproduction. It has been recognized that dysfunction in the autophagy process can be associated with male infertility. Overall, this review provides an overview of the cellular and molecular basics of autophagy and summarizes the latest findings on the key role of autophagy in mammalian male reproductive physiology.journal articl
Therapeutic Drug Monitoring of Oral Voriconazole in an Infant Less than Six Months of Age and Pharmacokinetics Changes Induced by Development of CYP2C19 in the Growth Process : A Novel Case Report
Get PDFjournal articleTherapeutic drug monitoring (TDM) is recommended for voriconazole (VRCZ) to avoid adverse events and maximize antifungal efficacy. Currently, the appropriate dose for patients under the age of 2 years is unknown. Here, we report the case of a 1.5-month-old infant with inborn errors of immunity who was orally administered VRCZ. This patient’s plasma concentration decreased significantly from 3.8 µg/mL (day 6) to 0.09 µg/mL (day 21), leading to repeated dose escalations to achieve the target concentration (1.38 µg/mL, day 58). The signal intensity ratio of VRCZ to its main metabolite, N-oxide VRCZ, in LC/MS/MS also decreased from 5.30 (day 6) to 0.57 (day 64). Consequently, we suspected that VRCZ metabolism may be enhanced during infant growth. To our knowledge, this is the first report of remarkable changes in VRCZ pharmacokinetics with metabolic activity enhanced by the growth process. In conclusion, we propose that frequent TDM helped to maintain adequate VRCZ plasma concentration in a infants less than 6 months of age.journal articl
Evaluation of oxidative stress in foals with Rhodococcus equi infection-induced pneumonia for the judgment of therapeutic effect
Get PDFjournal articleForty-five foals with Rhodococcus equi infection and pneumonia symptoms were classified into a surviving group and a dead group. Using serum samples, the oxidative stress index (OSI) was determined at the first visit and the follow-up visit. The OSI of the surviving group was significantly lower at the follow-up than that at the first visit. No significant difference was observed between the OSI of the dead group at the first and follow-up visits. In the surviving group, treatment at the first visit mitigated inflammation and reduced OSI. However, in the dead group, poor response to the treatment provided at the first visit led to continued inflammation, and no change was observed the OSI.journal articl
Influence of the Hypoxia-Activated Prodrug Evofosfamide (TH-302) on Glycolytic Metabolism of Canine Glioma : A Potential Improvement in Cancer Metabolism
Get PDFjournal articleThe transcription factor hypoxia-inducible factor 1α (HIF-1α) drives metabolic reprogramming in gliomas (GLs) under hypoxic conditions, promoting glycolysis for tumor development. Evofosfamide (EVO) releases a DNA-alkylating agent within hypoxic regions, indicating that it may serve as a hypoxia-targeted therapy. The aim of this study was to investigate the glycolytic metabolism and antitumor effects of EVO in a canine GL model. Our clinical data showed that overall survival was significantly decreased in GL dog patients with higher HIF-1α expression compared to that of those with lower HIF-1α expression, and there was a positive correlation between HIF-1α and pyruvate dehydrogenase kinase 1 (PDK1) expression, suggesting that glycolytic activity under hypoxia conditions may contribute to poor outcomes in canine GL. Our glycolysis assay tests showed that the glycolytic ATP level was higher than the mitochondrial ATP level in three types of canine GL cell lines by activating the HIF-1 signal pathway under hypoxia conditions, resulting in an overall increase in total cellular ATP production. However, treatment with EVO inhibited the glycolytic ATP level in the GL cell lines under hypoxia conditions by targeting HIF-1α-positive cells, leading to decrease in total cellular ATP production. Our in vivo tests showed that EVO significantly reduced tumor development compared to controls and temozolomide in murine GL models. A metabolic analysis demonstrated that EVO effectively suppressed glycolytic metabolism by eliminating HIF-1α-positive cells, suggesting that it may restore metabolism in canine GLs. The evidence presented here supports the favorable preclinical evaluation of EVO as a potential improvement in cancer metabolism.journal articl
A Study on the Intermediate Support Organizations for Agri - Social Welfare Linkage in Hokkaido areas
Get PDFjournal article道内で農作業請負を仲介する中間支援組織5つを比較分析した。自治体は農業者や福祉事業者からの相談を契機とした仲介が中心だが,民間事業者は手数料を得ながら自ら契約を広げている。また,自治体による事例集公表は発掘主体数を増加させる一因と考えられた。さらに,自立支援協議会に比べ任意協議会による仲介は,障害特性を理解し農作業配分できる専門人材の配置・活動や報酬単価の設定・例示に関与しやすいと考えられた。journal articl
Adverse effects of thyroid-hormone-disrupting chemicals 6-propyl-2-thiouracil and tetrabromobisphenol A on Japanese medaka (Oryzias latipes)
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