Tohoku Journal of Experimental Medicine最新文献

Macrophage polarization is implicated in the pathological mechanism of gastric cancer (GC). This study investigated how the miR-668-3p/ Nuclear factor kappa B inhibitor alpha (NFKBIA) axis drives macrophage polarization to contribute to GC progression. Inhibitors or shRNA were used to interfere with the expression of miR-668-3p or NFKBIA in the GC cell line. Subsequently, CCK-8, EdU, wound healing, and transwell assays were used to assess the biological behavior of the GC cells. Bioinformatics analysis predicted the target connection between miR-668-3p and NFKBIA, and a dual luciferase reporter gene experiment confirmed this relationship. After THP-1 macrophages were co-cultured with the supernatant of transfected GC cells, the M1 and M2 macrophage phenotypes were determined. Subsequently, these THP-1 macrophages were co-cultured with GC cells using the Transwell, and the biological behaviors of the GC cells were determiend. miR-668-3p inhibitor suppressed proliferation, invasion and migration of GC cells. The phenotype of M1 macrophage (IL-1β, TNF-α and IL-6) was boosted yet the phenotype of M2 macrophage (CD206, Fizz1 and IL-10) was declined by miR-668-3p inhibitor. NFKBIA was the target gene of miR-668-3p and it reversed the effects of miR-668-3p inhibitor on macrophage polarization and biological behaviors of the GC cells.miR-668-3p suppressed NFKBIA in GC cells to mediate M2 polarization of macrophages, thereby facilitating the tumorigenesis of GC.

Homeobox A1 (HOXA1) is implicated in the progression of various cancers, but its biological function in laryngeal cancer (LC) remains undefined, which is the foothold of our study. Bioinformatics analysis and survival analysis were performed to predict HOXA1 expression in LC tissues, and the prognostic relationship between high HOXA1 expression and LC. Whether high HOXA1 expression correlated with the clinical characteristics and prognosis of LC patients was analyzed. LC cell viability and sensitivity to cisplatin were determined by Methyl thiazolyl tetrazolium assay. The cell migration, invasion, and cell cycle after transfection were examined by Wound healing, Transwell, and flow cytometry assays, respectively. The corresponding mRNA and protein expressions were measured by quantitative real-time PCR or Western blot. A higher expression of HOXA1 was detected in LC tissues, which was found to be relevant to poor prognosis of LC patients. The association of high expression of HOXA1 with lymph node and clinical stage was also confirmed. Silencing of HOXA1 in LC cells enhanced the cell sensitivity to cisplatin, inhibited viability, migration, invasion and cell cycle, and reduced N-Cadherin, Vimentin, PCNA, p-AKT and p-mTOR expressions, while overexpression of HOXA1 had the opposite effects. Collectively, HOXA1 boosts migration, invasion and cell cycle, while suppressing cisplatin sensitivity of LC cells by mediating AKT/mTOR pathway, hinting that HOXA1 is a promising biomarker for diagnosis and prognosis of LC in clinical practice.

To investigate the protective effect and mechanism of astaxanthin on myocardial injury through activation of AMPK-mTOR pathway. In this study, 32 SPF adult male Wistar rats aged 8 to 10 weeks, weighing 250-300 g were divided into 4 groups (n = 8): sham surgery group (S group), autologous orthotopic liver transplantation group (T group), astaxanthin pretreatment surgery group (Group A) and compound C + astaxanthin pretreatment surgery group (Group C). Group A was given astaxanthin 500 mg/kg, group C received compound C 50 mg/kg + astaxanthin 500 mg/kg once a day for 2 weeks, group S and T received same volume of 0.9% saline. 8 h after portal vein opening, blood samples were collected to determine serum concentrations of TNF-α, IL-6 and HMGB 1 and myocardial injury markers. Myocardial tissue was collected to determine the MDA content, SOD activity and activation of AMPK-mTOR pathway. Compared with the S group, higher serum concentrations of TNF-α, IL-6, HMGB 1, CK-MB, cTnI, and H-FABP in groups T, A, and C, increased MDA content and decreased SOD activity, higher expression of activated Caspase-3 was observed; Compared with the T group, in group A, the serum concentrations of TNF-α, IL-6, and HMGB 1, CB-MB, cTnI, and H-FABP were significantly decreased, with decreased MDA content, increased SOD activity, the reduced expression of activated Caspase-3, elevated P-AMPK/AMPK, and decreased P-mTOR/mTOR. In Conclusion, Astaxanthin protects against liver ischemia-induced myocardial injury in rats mediating by the activation of the AMPK-mTOR pathway.

This study was to retrospectively analyze the incidence of deep vein thrombosis (DVT) in patients undergoing total joint arthroplasty (TJA) and analyze the risk factors for DVT. 113 patients with TJA were divided into the DVT group (n = 11) and the non-DVT group (n = 102) according to the postoperative ultrasound diagnosis, and the incidence of DVT after TJA was calculated. Logistic regression was used to analyze the correlation between DVT and patients' age, medical history, surgical factors, blood indexes to identify the risk factors of DVT after TJA. Receiver operator characteristic (ROC) curve was constructed to evaluate the diagnostic accuracy of risk factors for DVT. According to the results of ultrasound examination, DVT occurred in 11 of 113 patients after TJA, and the incidence rate of DVT was 9.73%. Univariate analysis showed that the levels of age, diabetes mellitus, operation time, intraoperative blood loss, intraoperative blood transfusion, antithrombin-Ⅲ (AT-Ⅲ), plasma protein C (PC), soluble platelet endothelial cell adhesion molecules-1 (SPECAM-1) and tissue-type plasminogen activator (t-PA) in the DVT group were significantly different from those in the non-DVT group (P < 0.05). Multivariate analysis showed that combined diabetes, decreased PC and t-PA were risk factors for DVT (P < 0.05). ROC analysis showed that PC combined with t-PA had the highest diagnostic accuracy for DVT. Patients with diabetes mellitus are at high risk for DVT after TJA, the increase of D-dimer, the decrease of PC and t-PA after 24 h of TJA is the the risk factors for DVT occurrence.

Acute aortic dissection is often a life-threatening disorder; in particular, type A aortic dissection necessitates urgent surgical intervention. Therefore, in regions where there are no cardiovascular surgeons, its treatment is quite challenging. Our facility, the Nasu Red Cross Hospital, located in the northern part of Tochigi Prefecture, is a core hospital for advanced emergency medical care, with eight cardiologists who can provide emergency coronary angioplasty for patients with acute coronary syndrome. However, we have no cardiovascular surgery section, so it is challenging to treat patients who require urgent surgical intervention. Therefore, we promptly transfer patients with type A aortic dissection to 8 facilities inside and outside the prefecture that have cardiovascular surgery sections. In regional hospitals like ours, without cardiovascular surgeons, it is necessary to provide a qualified diagnosis, initiate treatment for patients with acute aortic dissection including immediate blood pressure lowering and pain control using narcotics, and transfer patients eligible for urgent surgical intervention promptly to facilities with cardiovascular surgery sections. For smooth patient transfer, it is essential to build a close medical cooperation system that has daily interactions.

Adequate cervical ripening is essential before labor induction. However, effective methods for cervical ripening are limited in Japan. Although the controlled-release dinoprostone vaginal delivery system (PROPESS) was approved in Japan in 2020, it has not gained widespread acceptance over traditional methods. This observational study aimed to analyze the characteristics and precautions of the PROPESS based on cases of administration for cervical ripening conducted at five hospitals in the Mie Prefecture, Japan, between April 2020 and September 2021. We retrospectively evaluated cases wherein PROPESS was used for cervical ripening to determine its clinical characteristics. A total of 123 pregnant women were included in this study. The most common reason for PROPESS device removal was painful regular uterine contractions within 3 min after administration. Among these women, 48.5% had PROPESS removed within 4 h after administration. PROPESS removal due to non-reassuring fetal status occurred in 12 of the 123 (9.8%) women, with removal occurring within 4 h after administration in 8 of these cases. Among these eight cases, four (50.0%) had accompanying uterine hyperstimulation. The peak time from PROPESS administration to vaginal delivery was 28-32 h for primiparas and 4-8 h for multiparas. This study provides a comprehensive overview of PROPESS usage, highlighting the need for strict monitoring within 4 h after PROPESS administration to ensure its safety. This study provides valuable insights for facilities in Japan planning to implement the PROPESS in the future.

The purpose of this project was to characterize the longitudinal dynamic serum sodium trajectory of sepsis patients with lactic acidosis (LA) admitted to the intensive care unit (ICU), and to explore the association between these trajectories and the 30-day mortality rate of patients. Data on patients admitted to the ICU with a diagnosis of LA combined with sepsis from 2008-2019 were collected from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database. Patients admitted to the ICU for > 24 hours and for the first time were sorted into 3 groups based on their serum sodium levels at admission. The Group-based Trajectory Modeling (GBTM) method was applied to analyze the trajectory changes of serum sodium in each group of patients over 72 hours. Patients' survival differences between different trajectory groups were compared using Kaplan-Meier (K-M) survival curves. Subgroup analysis was carried out to determine the influencing factors of the relationship between dynamic changes in serum sodium and patient survival. This study included 514 patients with LA complicated by sepsis, who were clustered into three groups based on their admission serum sodium levels, with 378 patients in the normal blood sodium (135-145 mEq/L) group, 116 patients in the hyponatremia (< 135 mEq/L) group, and 20 patients in the hypernatremia (> 145 mEq/L) group. GBTM analysis generated three different serum sodium trajectories. The K-M curve results demonstrated that patients with relatively stable serum sodium levels within the normal range (Class 2) had lower 30-day mortality compared to groups with larger fluctuations in sodium levels (Class 1, Class 3). Subgroup analysis uncovered notable interactions (P < 0.05) between different trajectories of serum sodium and covariates such as race, marital status, Glasgow Coma Scale (GCS), Sequential Organ Failure Assessment (SOFA), renal replacement therapy (RRT), congestive heart failure, kidney disease, liver disease, and diabetes. Among patients with LA complicated by sepsis, those with stable and normal fluctuations in serum sodium levels had better 30-day survival rates. GBTM is a refined method to describe the evolution of serum sodium and its association with clinical outcomes, which may enhance the current understanding of blood sodium level regulation.