Int J Med Sci
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Pancreatic cancer (PC) is a challenging and heterogeneous disease with a high mortality rate. Despite advancements in treatment, the prognosis for PC patients remains poor, with a high chance of disease recurrence. Biomarkers are crucial for diagnosing cancer, predicting patient prognosis and selecting treatments. ⋯ Furthermore, the infiltration of various immune cells, including B cells, neutrophils, CD8+ T cells, dendritic cells, and macrophages, was positively correlated with KDM1A, KDM5A, and KDM5B expression. Moreover, MetaCore pathway analysis revealed interesting connections between KDM1A and the cell cycle and proliferation, between KDM5A and DNA damage and double-strand break repair through homologous recombination, and between KDM5B and WNT/β-catenin signaling. These findings suggest that KDM1A, KDM5A and KDM5B may serve as promising biomarkers and therapeutic targets for PC, a disease of high importance due to its aggressive nature and urgent need for novel biomarkers to improve diagnosis and treatment.
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Endothelial dysfunction may contribute to pathogenesis of Takotsubo cardiomyopathy, but mechanism underlying endothelial dysfunction in the setting of catecholamine excess has not been clarified. The study reports that D1/D5 dopamine receptor signaling and small conductance calcium-activated potassium channels contribute to high concentration catecholamine induced endothelial cell dysfunction. For mimicking catecholamine excess, 100 μM epinephrine (Epi) was used to treat human cardiac microvascular endothelial cells. ⋯ The NO reduction was membrane potential independent, while ROS production was increased by the hyperpolarization. ROS (H2O2) suppressed NO production. The study demonstrates that high concentration catecholamine can activate D1/D5 and SK1-3 channels through NADPH-ROS and PKA signaling and reduce NO production, which may facilitate vasoconstriction in the setting of catecholamine excess.
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Background: Exploring potential biomarkers for predicting clinical outcomes and developing targeted therapies for acute myeloid leukemia (AML) is of utmost importance. This study aimed to investigate the expression pattern of the thioredoxin-interacting protein (TXNIP)/nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) pathway and its role in the prognosis of AML patients. Methods: In this study, we examined the prognostic value of TXNIP/NLRP3 pathway in AML patients using microarray data from Gene Expression Omnibus (GEO) and transcriptome data from the Cancer Genome Atlas (TCGA) to develop a prognostic model and validated the results by quantitative real-time PCR (qRT-PCR) in a validation cohort of 26 AML patients and 18 healthy individuals from Jinan University (JNU) database. ⋯ Moreover, both the training and validation results indicated that lower TXNIP, NLRP3, and IL1B expression were associated with favorable prognosis (GSE12417, P = 0.009; TCGA, P = 0.050; JNU, P = 0.026). According to the receiver operating characteristic curve analysis, this model demonstrated a sensitivity of 84% for predicting three-year survival. These data might provide novel predictors for AML outcome and direction for further investigation of the possibility of using TXNIP/NLRP3/IL1B genes in novel targeted therapies for AML.
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Objectives: Epidemiological evidence has shown that genetics and environment are associated with the risk of hypertension. However, the specific SNP effects of a cluster of crucial genes in the RAAS system on the risk of hypertension are unclear. Methods: A case-control study was performed on the baseline participants of Environment and Chronic Disease in Rural Areas of Heilongjiang China (ECDRAHC) study. ⋯ Results: After controlling the impact of confounding factors, multivariate logistic regression analysis revealed that the distribution of AGT/rs5046, LRP6/rs12823243 and ACE2/rs2285666 was associated with susceptibility to essential hypertension. In genetic score model, the score > -0.225 had a higher risk, the OR (95%CI) was 1.229 (1.110, 1.362). Conclusions: To the best of our knowledge, this is the first time a hypertension risk scoring model on RAAS associated gene cluster has been constructed, which will provide a novel approach for prevention and control of essential hypertension.
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Background Myasthenia gravis (MG) is an autoimmune neuromuscular disorder that most frequently affects the extraocular muscles (EOMs), which causes symptoms such as ptosis and restricted eye movement. The EOMs in MG patients are representative of autoimmune inflammatory changes in muscle tissue. Currently, there is no reliable, and sensitive imaging technique for monitoring EOM changes to assist in the evaluation of underlying pathological changes. ⋯ Combined MTR and T2-mapping values effectively distinguished between MG patients and healthy controls, and between different severities of EOM involvement, with a superior diagnostic accuracy compared with each parameter alone. Conclusion The combination of MTI and T2-mapping MRI techniques can provide key insight into the pathological changes in EOMs in MG patients. This approach enhances early diagnosis and treatment planning, and therefore may improve clinical outcomes.