Tohoku Journal of Experimental Medicine最新文献

Reprogramming of glucose metabolism is a hallmark of hepatocellular carcinoma (HCC); however, the intrinsic mechanisms underlying this phenomenon remain unclear. The present study aimed to investigate the role and potential mechanism of glycyl-tRNA synthetase (GARS) in HCC glycolysis. Our results revealed an increase in the expression of Kruppel-like factor 16 (KLF16) and forkhead box K1 (FOXK1) in HCC tissues and correlated with an unfavorable prognosis. Mechanistically, we demonstrated that KLF16 binds to the promoter region of GARS, thereby enhancing its transcription. Subsequently, the GARS protein then binds to FOXK1, resulting in reduced ubiquitination and increased stability of FOXK1. FOXK1 then promotes glycolysis by directly stimulating the transcription of lactate dehydrogenase A, pyruvate kinase M2 and glucose transporter 1 in HCC cells. Additionally, KLF16 knockdown inhibited glycolysis in HCCLM3 cells both in vitro and in vivo. Collectively, these findings indicate that the KLF16-GARS-FOXK1 axis plays a critical role in regulating HCC growth and glycolysis. Targeting this pathway may hold a promising therapeutic strategy for HCC treatment.

This study explores the regulatory effects of Heat Shock Protein A1B (HSPA1B) on gene expression related to blood pressure in Human Umbilical Vein Endothelial Cells (HUVECs) and delineates its underlying mechanisms. Given the global prevalence of hypertension as a major risk factor for cardiovascular and cerebrovascular diseases, understanding its molecular underpinnings is crucial. We utilized cloning, cell culture, RNA isolation, cDNA synthesis, PCR amplification, high-throughput sequencing, and alternative splicing analysis to evaluate the impact of HSPA1B overexpression on HUVECs. The findings revealed that HSPA1B overexpression leads to significant changes in gene expression and alternative splicing patterns, implicating various molecular pathways. Notably, genes associated with inflammation, immune response, apoptosis, and endothelial function were upregulated, while others were downregulated. These alterations suggest that HSPA1B may influence endothelial cell responses under stress conditions. This study provides insights into the molecular mechanisms that could contribute to hypertension development and identifies HSPA1B as a potential area for further research in therapeutic strategies to manage this condition.

Mobile radiography is useful for triaging patients during disasters. However, in the face of large-scale disasters, medical equipment, including X-ray systems, may be restricted because of power outages. Therefore, a novel mobile radiography system that can be used in any disaster was developed, and its basic performance was evaluated. This system is designed for use during power outages and can be recharged using both household and solar power sources. The reproducibility of the X-ray output of the system (irradiation dose, tube voltage, radiation quality and irradiation time) was excellent, confirming that radiography could be performed consistently. The entrance surface dose and scattered radiation during chest radiography were measured using a chest phantom. Both results were acceptable, verifying that the system is sufficiently safe from the viewpoint of radiation protection. This novel mobile radiology system is easy to carry and can generate solar power, making it useful during a power outage in the case of a large-scale disaster or when examinations need to be performed outside a hospital, such as at a first-aid station.

A 69-year-old female was admitted to our hospital due to muscle weakness and gait disturbance. She noted weight loss attributed to inadequate dietary intake and alcohol use approximately 4 months prior. The laboratory findings were as follows: K 2.9 mEq/L, Ca 3.7 mg/dL, Alb 2.4 mg/dL and creatine kinase (CK) 3,986 U/L. Muscle magnetic resonance imaging (MRI) demonstrated abnormal signals in the proximal lower limb muscles. Hypokalemia-induced rhabdomyolysis was suspected. However, her hypokalemia was initially refractory to potassium replacement. Further examination revealed hypomagnesemia (Mg 1.6 mg/dL), and thus oral magnesium supplementation was given alongside potassium. Afterward, the patient's clinical symptoms and electrolyte disorders normalized within10 days; her muscle weakness and myalgia with elevated levels of CK also resolved. Thus, the hypokalemia-induced rhabdomyolysis in this patient was attributed to the coexisting magnesium deficiency. Electrolyte abnormalities and trace element deficiencies can be complicated by states of malnutrition. Awareness of hypomagnesemia may be of crucial importance for the management of hypokalemia-induced rhabdomyolysis. This case report suggests that hypomagnesemia can worsen hypokalemia-induced rhabdomyolysis in patients with impaired nutritional status. Therefore, careful monitoring of electrolytes is required in patients with unusual rhabdomyolysis.

This study sought to delineate the effects of calcitriol (CAL) and clarify its role in modulating TGF-β1/SMAD-mediated myocardial fibrosis in both animal and cellular models, instigated by isoproterenol (ISO). Cardiac dysfunction was precipitated through the subcutaneous administration of ISO in BALB/c mice, followed by an assessment of the remedial effects of CAL. CAL intervention ameliorated cardiac fibrosis induced by excessive ISO exposure, which was underscored by the reduction in myocardial hypertrophy and levels of interstitial fibrosis in the cardiac tissue. ISO exposure triggered the TGF-β1/SMAD pathway and suppressed vitamin D receptor (VDR) expression; effects that were nullified by CAL therapy. Cardiac fibroblasts (CFs) were extracted from myocardial ventricles of mice, and CCK-8 assays were conducted to evaluate the viability of CFs under treatments with ISO, sTβRII (a TGF-β1 inhibitor), and CAL. The CF survival rate was increased by ISO treatment, although this was counteracted via sTβRII or CAL treatment. In this cell model, ISO treatment activated TGF-β1/SMAD pathway and downregulated VDR expression, whereas CAL cotreatment exerted a converse effect on the TGF-β1/SMAD pathway and VDR expression. VDR knockdown demonstrated its role in CAL-mediated alleviation of cell fibrosis. Our observations indicated that VDR intervention enhanced the influence of ISO on the proliferation of CFs and markedly negated the protective effects of CAL on the viability of ISO-exposed CFs. These insights unveil a pioneering role for CAL in curbing ISO-provoked cardiac fibrosis and the proliferation of CFs via the restraint of the TGF-β1/SMAD pathway through engagement with the VDR.

Esophagectomy is a high-complexity procedure, and the relationship between hospital volume, measured by the annual number of esophageal surgeries per hospital, and treatment outcomes remains a subject of debate. This study used a nationwide administrative database to identify patients diagnosed with stage 2 and stage 3 esophageal cancer between April 1, 2016, and March 31, 2022. We focused on patients who underwent preoperative chemotherapy and thoracoscopic esophageal cancer surgery and examined the relationship between hospital volume, in-hospital mortality, and postoperative complications. The hospitals were categorized into two groups: the low-volume group (n = 2,629) with less than 12 thoracoscopic esophagectomies performed annually and the high-volume group (n = 5,325) with 12 or more. We conducted propensity score matching analysis to match pairs of patients between the low-volume and high-volume groups (n = 1,984, each). In the analysis after matching, the in-hospital mortality rates were higher in the low-volume group compared to the high-volume group (1.4% vs. 0.5%, p = 0.0022). Furthermore, the incidence of postoperative complications was significantly higher in the low-volume group compared to the high-volume group: wound infections (1.7% vs. 0.7%, p = 0.0337), anastomotic leakage (6.5% vs. 2.8%, < 0.0001), and recurrent laryngeal nerve paralysis (8.3% vs. 6.5%, p = 0.0291). However, the incidence of postoperative pneumonia was higher in the high-volume group (1.7% vs. 3.5%, p = 0.0003). The length of postoperative hospital stay was also significantly longer in the low-volume group compared to the high-volume group (24 days, IQR: 18-35 vs. 20 days, IQR: 16-28, p < 0.0001). Further analysis considering the patient's quality of life, access to hospitals, and careful discussion is necessary to determine the appropriateness of esophagectomy centralization.