Osteocrin ameliorates adriamycin nephropathy via p38 mitogen-activated protein kinase inhibition

Natriuretic peptides exert multiple effects by binding to natriuretic peptide receptors (NPRs). Osteocrin (OSTN) binds with high affinity to NPR-C, a clearance receptor for natriuretic peptides, and inhibits degradation of natriuretic peptides and consequently enhances guanylyl cyclase-A (GC-A/NPR1) signaling. However, the roles of OSTN in the kidney have not been well clarified. Adriamycin (ADR) nephropathy in wild-type mice showed albuminuria, glomerular basement membrane changes, increased podocyte injuries, infiltration of macrophages, and p38 mitogen-activated protein kinase (MAPK) activation. All these phenotypes were improved in OSTN- transgenic (Tg) mice and NPR3 knockout (KO) mice, with no further improvement in OSTN-Tg/NPR3 KO double mutant mice, indicating that OSTN works through NPR3. On the contrary, OSTN KO mice increased urinary albumin levels, and pharmacological blockade of p38 MAPK in OSTN KO mice ameliorated ADR nephropathy. In vitro, combination treatment with ANP and OSTN, or FR167653, p38 MAPK inhibitor, reduced Ccl2 and Des mRNA expression in murine podocytes (MPC5). OSTN increased intracellular cyclic guanosine monophosphate (cGMP) in MPC5 through GC-A. We have elucidated that circulating OSTN improves ADR nephropathy by enhancing GC-A signaling and consequently suppressing p38 MAPK activation. These results suggest that OSTN could be a promising therapeutic agent for podocyte injury

オステオクリンはp38 MAPK阻害を介してアドリアマイシン腎症を軽減する

京都大学新制・課程博士博士(医学)甲第23805号医博第4851号新制||医||1058(附属図書館)京都大学大学院医学研究科医学専攻(主査)教授 長船 健二, 教授 寺田 智祐, 教授 稲垣 暢也学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

Novel Power Reduction Technique for ReRAM with Automatic Avoidance Circuit for Wasteful Overwrite

Low-power operations can be great advantageous for ReRAM devices. However, wasteful overwriting such as the SET operation to low-resistance state (LRS) device and the RESET operation to high-resistance state (HRS) device causes not only an increase in power but also the degradation of the write cycles due to repeatedly rewriting. Thus, in this paper, we proposed a novel automatic avoidance circuit for dealing with wasteful overwriting that uses a sense amplifier and estimated the energy consumption reduction rate by conducting a circuit simulation. As a result, this circuit helped to reliably avoid the wasteful overwriting operation to reduce about 99% and 97% of wasteful energy using VSRC and CSRC, respectively

Special feature of COVID-19 in FMODB: Fragment molecular orbital calculations and interaction energy analysis of SARS-CoV-2 related proteins

SARS-CoV-2 is the causative agent of coronavirus, globally known as COVID-19. There are ongoing researches to develop effective therapeutics and vaccines against COVID-19 using various methods. We currently conduct research based on the fragment molecular orbital (FMO) method for calculating the electronic structure of protein complexes and analyzing their quantitative molecular interactions. This enables us to extensively analyze the molecular interactions in residues or functional group units acting inside protein complexes. Such precise interaction data are available in the FMO database (FMODB). We have performed several FMO calculations on the structures of SARS-CoV-2 related proteins registered in the protein data bank and published the results of 681 structures, including three structural proteins and eleven nonstructural proteins, on the COVID-19 special page.These data not only aid the interpretation of experimentally determined structures but also the understanding of protein functions, which is useful for rational drug design for COVID-19

Clinical relevance of a newly developed endometrial receptivity test for patients with recurrent implantation failure in Japan

Abstract Purpose To assess the clinical efficacy of personalized embryo transfer (pET) guided by a new endometrial receptivity test, ERPeakSM, in patients with recurrent implantation failure (RIF). Methods Recurrent implantation failure patients of all ages at two private Japanese clinics from April 2019 to June 2020 were retrospectively analyzed. The intervention group (n = 244) received pET in accordance with endometrial receptivity testing results and was compared to control group (n = 306) receiving standardized timing, non‐personalized embryo transfer (npET). In propensity score matching analysis, the clinical pregnancy rate (CPR) and live birth rate (LBR) were compared between groups, and a subanalysis of advanced maternal age (AMA) (≥38 years old) versus non‐AMA (<38 years old) patients was also conducted. Results The CPR and LBR of the pET group were significantly higher than those of the npET group (37.7% vs. 20.0%, adjusted OR: 2.64; 95%CI, 1.70–4.11, p < 0.001 and 29.9% vs. 9.7%, adjusted OR: 4.13; 95%CI, 2.40–7.13, p < 0.001, respectively). Furthermore, in the subanalyses, the CPR and LBR of the pET group were significantly higher than those of the npET group in both the AMA non‐AMA patients. Conclusions The new ERPeakSM endometrial receptivity test is a useful alternative diagnostic tool for poor‐prognosis patients, regardless of age