Publications by authors named "H Kamimura"

321 Publications

Effects of a selective PPARα modulator, sodium-glucose cotransporter 2 inhibitor, and statin on the myocardial morphology of medaka nonalcoholic fatty liver disease model.

Biochem Biophys Res Commun 2022 Aug 3;625:116-121. Epub 2022 Aug 3.

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757, Asahimachi-Dori, Chuo-Ku, Niigata, Japan.

Objective: Nonalcoholic fatty liver disease (NAFLD) is associated with metabolic dysregulation and is linked with various cardiovascular complications, which often lead to poor prognostic outcomes. To develop a standard therapy for NAFLD and to urgently address its complications, the current study aimed to investigate the mechanisms of NAFLD-related heart disease and the therapeutic effects of drugs targeting various metabolic pathways.

Methods: To explore the mechanism of NAFLD-related heart disease, a medaka model of high-fat diet-induced NAFLD was utilized. The gross structural, histological, and inflammatory changes in the myocardium were evaluated in a time-dependent manner. In addition, the therapeutic effects of medicines used for NAFLD treatment including, selective peroxisome proliferator-activated receptor α modulator (SPPARMα, pemafibrate), sodium-glucose cotransporter 2 (SGLT2) inhibitor (tofogliflozin), and statin (pitavastatin), and their combinations on heart pathology were evaluated. To determine the mechanisms underlying the therapeutic effects, the expression of genes related to liver inflammation was assessed via whole transcriptome sequencing analysis.

Results: The fish with NAFLD-related heart injury presented with cardiomyocyte hypertrophy, which led to cardiac hypertrophy. This morphological change was caused by the infiltration of inflammatory cells, including macrophages and CD4 and CD8-positive lymphocytes, in the cardiac wall and the expression of transforming growth factor beta 1 in the cardiomyocytes. Further, the livers of the fish had upregulated expressions of senescence-associated secretory phenotype-related genes. Treatment with pemafibrate, tofogliflozin, and pitavastatin reduced these changes and, consequently, cardiomyopathy.

Conclusion: Our results demonstrated that NAFLD-related heart disease was attributed to the senescence-associated secretory phenotype-induced inflammatory activity in the cardiac wall, which resulted in myocardial hypertrophy. Moreover, the effects of SPPARMα, SGLT2 inhibitor, and statin on NAFLD-related heart disease were evident in the medaka NAFLD model.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbrc.2022.07.117DOI Listing
August 2022

Cumulative risk of developing a new symptom in patients with primary biliary cholangitis and its impact on prognosis.

JGH Open 2022 Aug 15;6(8):577-586. Epub 2022 Jul 15.

Division of Gastroenterology and Hepatology Niigata Prefecture Shibata Hospital Niigata Japan.

Background And Aim: Symptoms of primary biliary cholangitis (PBC) frequently impair one's quality of life (QOL). Nonetheless, with improved treatment, the prognosis of PBC also improves. QOL plays an important role in patients with PBC. In this study, we aimed to reevaluate the transition of new symptom development in PBC and its predictive factors.

Methods: This retrospective multicenter study enrolled 382 patients with PBC for symptom analysis. The impact of a newly developed symptom on PBC prognosis was investigated by Kaplan-Meier analysis with propensity score matching and logistic progression analysis.

Results: The cumulative risk of developing a new symptom after 10 and 20 years of follow-up was 7.6 and 28.2%, and specifically that of pruritus, which was the most common symptom, was 6.7 and 23.3%, respectively. In Cox hazard risk analysis, serum Alb level (hazard ratio [HR], 1.097; 95% confidence interval [CI], 1.033-1.165;  = 0.002), the serum D-Bil level (HR, 6.262; 95% CI, 2.522-15.553,  < 0.001), and Paris II criteria (HR, 0.435; 95% CI, 0.183-1.036;  = 0.037) were significant independent predictors of a new symptom. Kaplan-Meier analysis showed that the overall survival and liver-related death were not significant between patients with and without a new symptom.

Conclusion: The cumulative risk of new symptom development is roughly 30% 20 years after diagnosis and could be predicted by factors including serum albumin levels, serum D-Bil level, and Paris II criteria.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jgh3.12789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9344586PMC
August 2022

Involvement of DNA Damage Response via the Ccndbp1-Atm-Chk2 Pathway in Mice with Dextran-Sodium-Sulfate-Induced Colitis.

J Clin Med 2022 Jun 25;11(13). Epub 2022 Jun 25.

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan.

The dextran sodium sulfate (DSS)-induced colitis mouse model has been widely utilized for human colitis research. While its mechanism involves a response to double-strand deoxyribonucleic acid (DNA) damage, ataxia telangiectasia mutated (Atm)-checkpoint kinase 2 (Chk2) pathway activation related to such response remains unreported. Recently, we reported that cyclin D1-binding protein 1 () activates the pathway reflecting DNA damage in its knockout mice. Thus, this study aimed to examine the contribution of and the Atm-Chk2 pathway in DSS-induced colitis. We assessed the effect of DSS-induced colitis on colon length, disease activity index, and histological score and on the Atm-Chk2 pathway and the subsequent apoptosis in -knockout mice. DSS-induced colitis showed distal colon-dominant Atm and Chk2 phosphorylation, increase in TdT-mediated dUTP-biotin nick end labeling and cleaved caspase 3-positive cells, and histological score increase, causing disease activity index elevation and colon length shortening. These changes were significantly ameliorated in -knockout mice. In conclusion, contributed to Atm-Chk2 pathway activation in the DSS-induced colitis mouse model, causing inflammation and apoptosis of mucosal cells in the colon.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm11133674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9267230PMC
June 2022

Involvement of the liver-gut peripheral neural axis in nonalcoholic fatty liver disease pathologies via hepatic HTR2A.

Dis Model Mech 2022 Jul 26;15(7). Epub 2022 Jul 26.

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan.

Serotonin (5-HT) is one of the key bioamines of nonalcoholic fatty liver disease (NAFLD). Its mechanism of action in autonomic neural signal pathways remains unexplained; hence, we evaluated the involvement of 5-HT and related signaling pathways via autonomic nerves in NAFLD. Diet-induced NAFLD animal models were developed using wild-type and melanocortin 4 receptor (MC4R) knockout (MC4RKO) mice, and the effects of the autonomic neural axis on NAFLD physiology, 5-HT and its receptors (HTRs), and lipid metabolism-related genes were assessed by applying hepatic nerve blockade. Hepatic neural blockade retarded the progression of NAFLD by reducing 5-HT in the small intestine, hepatic HTR2A and hepatic lipogenic gene expression, and treatment with an HTR2A antagonist reproduced these effects. The effects were milder in MC4RKO mice, and brain 5-HT and HTR2C expression did not correlate with peripheral neural blockade. Our study demonstrates that the autonomic liver-gut neural axis is involved in the etiology of diet-induced NAFLD and that 5-HT and HTR2A are key factors, implying that the modulation of the axis and use of HTR2A antagonists are potentially novel therapeutic strategies for NAFLD treatment. This article has an associated First Person interview with the first author of the paper.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1242/dmm.049612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9346519PMC
July 2022

A Case of Necrotizing Periodontitis in a Care-Requiring Elderly Person Treated and Managed by Interprofessional Collaboration.

Dent J (Basel) 2022 May 7;10(5). Epub 2022 May 7.

Division of Molecular Signaling and Biochemistry, Kyushu Dental University, Kitakyushu 803-8580, Japan.

Background: Necrotizing periodontitis (NP) is a reactive and destructive inflammatory process that occurs in response to bacterial infection. Predisposing factors such as compromised host immune responses contribute significantly to NP pathogenesis. NP occasionally progresses to a more advanced and life-threatening state.

Case Presentation: A 73-year-old man in need of nursing care visited our dental clinic with severe gingival pain and intraoral bleeding. He had a disability and was immunocompromised because his medical history included cerebral infarction and type 2 diabetes mellitus. He was diagnosed with NP based on his typical symptoms, such as prominent bleeding and suppurative discharge from the gingiva, in addition to crater-shaped ulcerations of the interdental papillae. To improve daily oral hygiene, periodontists, dentists, and dental hygienists educated care workers and other staff at the nursing home on appropriate oral cleansing, including brushing three times a day using the Bass technique. Basic periodontal therapy, including whole-mouth scaling and debridement of the root surfaces using hand and ultrasonic instruments, was also performed. After this basic treatment of NP, we extracted the hopeless teeth. Currently, dentists visit the patient fortnightly to manage his oral hygiene. To date, good oral health has been maintained.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/dj10050079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9140147PMC
May 2022
-->