Feasibility and efficacy of pemafibrate for prevention of maternal high-fat intake-induced glucose metabolic dysfunction in offspring.

Given the significance of the intrauterine lipid environment in glucose metabolic homeostasis in offspring, the present study was undertaken to investigate the feasibility and efficacy of pemafibrate, a triglyceride-lowering peroxisome proliferator-activated agent, for maternal high-fat diet (HFD) intake-induced glucose metabolic dysfunction in offspring. A mouse model of HFD-induced gestational obesity was employed, and pemafibrate was orally administered from day 10 of gestation until delivery. The influences of maternal pemafibrate treatment on biological processes and toxicity were evaluated in both newborns and 12-week-old offspring. The findings of a dose-dependent decrease of ß cell islet mass and of impairment of glucose tolerance and insulin sensitivity in offspring suggest that maternal pemafibrate intervention can prevent maternal HFD-intake-induced diabetes in offspring. Of particular interest in the prevention of future glucose metabolic dysfunction in offspring, low-dose maternal pemafibrate treatment (0.02 mg/kg/day) had sufficient efficacy and appeared to be safe in offspring. Therefore, pemafibrate may be a potential agent for the prevention of maternal high-fat exposure-induced diabetes in offspring. Abbreviations: CD, control diet; DEG, differentially expressed genes; GTT, glucose tolerance test; HFD, high-fat diet; ITT, insulin tolerance test; MC, 0.5w/v% methyl cellulose 400 solution; PPAR, triglyceride-lowering peroxisome proliferator-activated receptor; RNA-seq, RNA sequencing; TC, total cholesterol; TG, triglycerides.

Perioperative Anaphylaxis in Japanese Secondary Care Institutions: Incidence, Causes, and the Imperative for Improved Diagnostic Practices.

Background This research investigates the incidence, suspected causes, and diagnostic procedures for perioperative anaphylaxis (POA), a potentially severe complication, in secondary care hospitals across Japan. Methodology We surveyed Saiseikai hospitals and gathered data on surgical procedures, POA occurrences, potential triggers, and diagnostic methods. Results Among 70,523 surgeries, seven were associated with POA, resulting in an approximate incidence rate of 0.01%. Rocuronium was the most commonly suspected trigger, followed by sugammadex, latex, and angiography contrast agents. Despite the importance of skin tests as the most basic and crucial diagnostic method, they were conducted in only three instances. No in vitro tests for drug identification were conducted, and in four cases, the cause was determined merely based on the timing of drug administration, indicating significant diagnostic limitations. Conclusions The study underscores the critical situation in Japan regarding insufficient diagnostic practices and difficulties in identifying triggering drugs rather than the consistent prevalence of POA in secondary care facilities. The findings emphasize the need for improved diagnostic proficiency and more rigorous drug identification practices to ensure prompt and accurate POA diagnosis. It is essential to conduct further research and interventions to increase patient safety during the perioperative period in secondary care settings.

Lack of ATP2B1 in CD4+ T Cells Causes Colitis.

BACKGROUND: The ATP2B1 gene encodes for a calcium pump, which plays a role in removing Ca2+ from cells and maintaining intracellular Ca2+ homeostasis. Reduction of the intracellular Ca2+ concentration in CD4+ T cells is thought to reduce the severity of colitis, while elevation of Ca2+ in CD4+ T cells induces T cell hyperactivity. Our aim was to clarify the role of ATP2B1 in CD4+ T cells and in inflammatory bowel disease development. METHODS: A murine CD4+ T cell-specific knockout (KO) of ATP2B1 was created using a Cre-loxP system. CD4+ T cells were isolated from thymus, spleen, and blood using fluorescence-activated cell sorting. To quantify messenger RNA levels, quantitative real-time polymerase chain reaction was performed. RESULTS: Although the percentages of CD4+ T cells in both KO mouse spleen and blood decreased compared with those of the control samples, both T-bet (a T helper 1 [Th1] activity marker) and GATA3 (a Th2 activity marker) expression levels were further increased in KO mouse blood CD4+ T cells (vs control blood). Diarrhea and colonic wall thickening (with mucosal changes, including crypt distortion) were seen in KO mice but not in control mice. Prior to diarrhea onset, the KO mouse colon length was already noted to be shorter, and the KO mouse stool water and lipid content were higher than that of the control mice. Tumor necrosis factor α and gp91 expressions were increased in KO mouse colon. CONCLUSIONS: Lack of ATP2B1 in CD4+ T cells leads to Th1 and Th2 activation, which contributes to colitis via elevation of tumor necrosis factor α and oxidative stress.

ATP2B1 deficiency in CD4+ T cells leads to T helper 1/T helper 2 activation, which in turn increases tumor necrosis factor α and oxidative stress. These changes contribute to colitis, which is characterized by diarrhea and colonic wall thickening.

Amelioration of oxygen-induced retinopathy in neonatal mice with fetal growth restriction.

Introduction: With the aim of optimizing the balance of maintaining a safe oxygen saturation and reducing the risk of retinopathy of prematurity in human neonates with fetal growth restriction (FGR), the present study investigated the distinct effects of oxygen supplementation on the retinal neovasculature using a murine premature neonatal oxygen-induced retinopathy (OIR) model with or without fetal growth restriction. Methods: For comparison with normal birth-weight neonates, maternal low-protein diet-induced FGR neonates were subjected to fluctuating oxygen levels to generate oxygen-induced retinopathy. The retinal neovasculature was histologically evaluated, and comprehensive transcriptome analysis was conducted. Results: Compared to OIR neonates with normal birth weight, significant amelioration of the neovasculature, as indicated by decreases in the number of branch junctions, vascular distribution, maximal vascular radius and microaneurysm-like tufts, was observed in OIR mice with FGR. The results of retinal RNA-sequencing revealed downregulation of angiogenic factors that trigger pathological retinal neovascularization, such as the mitogen-activated protein kinase pathway and corresponding upstream signaling pathways in OIR mice with FGR. Conclusion: Our findings demonstrated that FGR neonates have a higher capacity for retinal oxygen stress, and the risk of OIR development is attenuated compared to that in mature neonates with normal birth weight.

The WHO Global report 2023 on hypertension warning the emerging hypertension burden in globe and its treatment strategy.

Thirty-year % increase of adults with hypertension in the European/ Americas and South-East Asia/ Western Pacific (WHO region). Create using the data from: World Health Organization. Global report on hypertension: the race against a silent killer. Geneva, Switzerland: 2023.

Hypertension facilitates age-related diseases. ~ Is hypertension associated with a wide variety of diseases?~.

Hypertension, a disease whose prevalence increases with age, induces pathological conditions of ischemic vascular disorders such as cerebral infarction and myocardial infarction due to accelerated arteriosclerosis and circulatory insufficiency of small arteries and sometimes causes hemorrhagic conditions such as cerebral hemorrhage and ruptured aortic aneurysm. On the other hand, as it is said that aging starts with the blood vessels, impaired blood flow associated with vascular aging is the basis for the development of many pathological conditions, and ischemic changes in target organs associated with vascular disorders result in tissue dysfunction and degeneration, inducing organ hypofunction and dysfunction. Therefore, we hypothesized that hypertension is associated with all age-related vascular diseases, and attempted to review the relationship between hypertension and diseases for which a relationship has not been previously well reported. Following our review, we hope that a collaborative effort to unravel age-related diseases from the perspective of hypertension will be undertaken together with experts in various specialties regarding the relationship of hypertension to all pathological conditions.

Institutional Review Board Considerations for Clinical Trials.

To protect subjects who participate in human research, Institutional Review Boards (IRBs) play an important role in reviewing research and determining the validity of a study by comprehensively examining it for ethical issues, including invasiveness and management of personal information. They conduct regular and independent reviews to protect the health, rights, and welfare of research subjects. When we as researchers conduct clinical research, we must obtain IRB approval and submit our research for investigation of ethical issues before we begin.

Animal Models of Vasculitis.

The diagnosis of vasculitis in rheumatoid arthritis (RV) is associated with considerable mortality; therefore, understanding the basic mechanisms underlying the pathogenesis of vasculitis is very important. Animal models of vasculitis have contributed to elucidating such mechanisms. We here introduce a Candida albicans water-soluble glycoprotein (CAWS)-induced vasculitis model and the methodological approach to evaluate inflammatory vascular change.

2023 update and perspectives.

Total 276 manuscripts were published in Hypertension Research in 2022. Here our editorial members picked up the excellent papers, summarized the current topics from the published papers and discussed future perspectives in the sixteen fields. We hope you enjoy our special feature, 2023 update and perspectives in Hypertension Research.