Tohoku Journal of Experimental Medicine最新文献

The 2024 Noto Peninsula Earthquake, which reached a maximum intensity of 7, led to the deterioration of critical services including electricity, water, communication, and roads, resulting in 241 fatalities. The medical response of pharmacists during disasters has gained attention since the 2011 Great East Japan Earthquake. However, few studies have evaluated the challenges that hospital pharmacy departments face during disasters. T.T., the author, supported the hospital pharmacy department of the Anamizu General Hospital from February 2 to 4, 2024. He handled medication dispensing for inpatients, provided medication and instructions to outpatients, and reported to the local coordination headquarters. Furthermore, he stayed overnight in the department to handle on-call activities. Daily tasks included reporting and information sharing with the coordination headquarters. Regarding pharmacist support activities in medical facilities, challenges arose from the malfunctioning of automated tablet dispensing machines after the earthquake, worsening dispensing conditions and pharmaceutical supply issues. To avoid these problems, pharmacists should provide swift and continuous medical support until automated tablet dispensing machines' systems are restored after an earthquake. Additionally, it is considered beneficial for medical institutions to include in their business continuity plans a stockpile of medicines that can last for 7 days, as preparation for coping with earthquakes and similar emergencies. The findings of this report could be useful to all countries facing the possibility of disasters.

Cancer-associated fibroblasts (CAFs) are closely associated with tumor drug resistance. This study intended to delineate how CAFs induced DOX resistance in ovarian cancer. Differential gene expression analysis of ovarian cancer CAFs was completed using Gene Expression Omnibus database. CAFs and normal fibroblasts (NFs) were isolated from ovarian cancer tissues and adjacent normal tissues. The expressions of Holliday Junction Recognition Protein (HJURP), α-smooth muscle actin (α-SMA), and fibroblast activation protein alpha (FAP) were assessed by quantitative reverse transcription polymerase chain reaction and Western blot (WB), α-SMA and FAP were detected by immunofluorescence. A2780 cells were treated with CAF or NF conditioned medium (CM), and protein expression of HJURP was assessed by WB. A2780-DOX cells were constructed and cultured with CAF or NF CM, and cell viability and IC₅₀ value of DOX were assayed by Cell Counting Kit-8. Kits were used to test glutamine metabolism and mitochondrial tricarboxylic acid (TCA) cycle products, while WB was utilized to assess expressions of amino acid transporters. mRNA and protein levels of HJURP in CAFs derived from ovarian cancer were significantly higher than those in NFs. Culturing ovarian cancer cells with CAF CM could increase protein expressions of HJURP. HJURP derived from CAFs significantly enhanced viability of A2780-DOX cells and DOX resistance. CAF-derived HJURP fostered glutamine metabolism and mitochondrial TCA cycle in ovarian cancer resistant cells ultimately leading to ovarian cancer DOX resistance. CAF-derived HJURP drove ovarian cancer glutamine metabolism and DOX resistance.

Pelvic floor muscle exercise (PME), biofeedback, and electrical stimulation improve pelvic floor function, but the effect of their combination in patients with early-stage cervical cancer is unclear. This study intended to design a combined intervention encompassing these three interventions and explore its effect on pelvic floor function in postoperative patients with early-stage cervical cancer. Totally, 177 postoperative patients with early-stage cervical cancer were assigned to combination (N = 81) and PME (N = 96) groups according to actual interventions. Pelvic Floor Distress Inventory-Short Form 20 (PFDI-20), International Consultation on Incontinence Questionnaire Urinary Incontinence Short Form (ICIQ-UI-SF), and EORTC Core Quality of Life questionnaire (EORTC QLQ-C30) scores were assessed at the seventh day after surgery (W0), and at 4 (W4), 8 (W8), and 12 (W12) weeks after W0. PFDI-20 scores at W8 (P = 0.042) and W12 (P = 0.006), and ICIQ-UI-SF scores at W4 (P = 0.012), W8 (P = 0.024), and W12 (P = 0.003) were lower in the combination group versus PME group. PFDI-20 decline and ICIQ-UI-SF decline (W0-W12) were greater in the combination group versus PME group (both P = 0.007). Combined intervention (versus PME) was independently related to greater PFDI-20 decline (B = 5.548, P < 0.001) and ICIQ-UI-SF decline (W0-W12) (B = 1.544, P = 0.006). EORTC QLQ-C30 global health status scores at W12 were higher in the combination group versus PME group (P = 0.045), while EORTC QLQ-C30 function and symptom scores at any time points were not different between the two groups (all P > 0.05). Combined intervention achieves greater pelvic floor function improvement and better quality of life compared to PME in postoperative patients with early-stage cervical cancer.

Coronary artery blockage causes myocardial infarction (MI), a frequent and serious cardiovascular disease. The early recurrence of post-MI ventricular fibrillation after defibrillation has been widely investigated and treated. This research investigated the relationship between electrophysiological indicators of early recurrence following defibrillation in post-MI ventricular fibrillation and sympathetic renal denervation's therapeutic benefits and probable causes. Animal models were used for experiments. Electrophysiological indications of early recurrence were reported after MI and defibrillation in ventricular fibrillation patients. After that, a selection of rats received sympathetic renal denervation, and the therapeutic results were compared to the control group. Electrocardiogram monitoring, myocardial histology, and neurotransmitter assays were done. Defibrillation therapy causes an early recurrence in ventricular fibrillation patients. Electrophysiological measures showed increased ST segment elevation and T wave alterations in the early recurrence group. In the sympathetic renal denervation intervention group, early recurrence was greatly decreased and the electrocardiogram (ECG) was more stable and regular. Myocardial histology showed decreased cellular damage and fibrosis in the sympathetic renal denervation group. Sympathetic renal denervation intervention significantly reduced sympathetic nerve activity, according to neurotransmitter measures. Electrophysiological indications of early recurrence following defibrillation in post-MI ventricular fibrillation are linked to sympathetic renal denervation's therapeutic benefits. Myocardial damage and fibrosis may be reduced, ECG features improved, and the early recurrence rate reduced by sympathetic renal denervation. One possible method of sympathetic renal denervation intervention is reduced sympathetic nerve activity.

Asthenozoospermia is a leading cause of male infertility, yet current pharmacotherapies yield suboptimal outcomes, underscoring the urgent need for novel treatment modalities. Herein, we induced asthenozoospermic mouse models using busulfan and investigated the therapeutic effects of Shenqi Qiangjing Granules (SQ) on testicular pathology, serum sex hormone and steroidogenic enzyme levels, and ferroptosis. Furthermore, utilizing GC-1 spg cell lines, we elucidated the role of the METTL3-mediated m⁶A modification in GPX4 mRNA stability. Treatment with SQ or Fer-1 (an inhibitor of ferroptosis) significantly ameliorated testicular pathological injury, restored abnormal serum sex hormone levels, and enhanced testicular steroidogenic enzyme expression, highlighting the therapeutic potential of targeting ferroptosis in asthenozoospermia. In elucidating the molecular mechanism of METTL3 in ferroptosis, we found that METTL3 regulates GPX4 mRNA stability, subsequently impacting ferroptosis and sperm quality. Knockdown of METTL3 mimicked the effects of SQ treatment, while overexpression of METTL3 partially reversed SQ-mediated effects on ferroptosis and asthenozoospermia, underscoring the pivotal role of METTL3 in SQ therapy. In conclusion, the METTL3-GPX4-ferroptosis axis emerges as a novel regulatory pathway in the pathogenesis of asthenozoospermia. Targeting this axis, particularly through interventions such as SQ treatment, holds promise for the management of male infertility.

Diabetes nephropathy (DN) is a main risk factor for acute coronary syndrome (ACS), but the molecular mechanism is unknown. This research used bioinformatics approaches to uncover potential molecular mechanisms and drugs for DN and ACS. GSE142153 and GSE19339 were downloaded from the Gene Expression Omnibus (GEO) database. The mutually different expression genes (DEGs) detected in the GSE142153 and GSE19339 datasets were then subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. After a protein-protein interaction network (PPI) analysis, hub genes and transcriptional regulators were tracked by Cytoscape Soft. Finally, potential therapeutic drugs were predicted by the DGIDB drug database. This study identified 274 mutual DEGs from the DN and ACS datasets. Functional analyses indicated that "RNA polymerase II" and the "IL-17 signaling pathway" might play an important role in DN and ACS. Through PPI network construction, the top ten genes were identified. Hub gene and transcription factor interactions were constructed. Seven drugs targeted at VEGFA, IL6, IL1B, and IL1A were evaluated. Four genes and seven drugs were evaluated that could provide a novel perspective for DN and ACS in the future.