Int J Med Sci
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Receptor-interacting protein 3 (Ripk3) plays a crucial part in acute lung injury (ALI) by regulating inflammation-induced endothelial damage in the lung tissue. The precise mechanisms through which Ripk3 contributes to the endothelial injury in ALI still remain uncertain. In the current research, we employed Ripk3-deficient (Ripk3-/-) mice to examine the role of Ripk3 in ALI progression, focusing on its effects on endothelial cells (ECs), mitochondrial damage and necroptosis. ⋯ Ripk3 upregulation suppressed the AMP-activated protein kinase (AMPK) pathway and activated Drp1-mediated mitochondrial fission, increasing mitochondrial permeability transition pore (mPTP) opening and PMVEC necroptosis. Conversely, Ripk3 deletion activated the AMPK/Drp1-mitochondrial fission pathway, preventing mPTP opening and PMVEC necroptosis in ALI. These findings demonstrated that Ripk3 promotes necroptosis through the AMPK/Drp1/mPTP opening pathway, identifying a potential therapeutic target for ALI treatment.
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Background: Blood pressure (BP) control can slow down the progression of chronic kidney disease (CKD) and protect against cardiovascular diseases, significantly improving patient survival. Herein, we analyzed the changes in BP control in adult CKD patients with hypertension in the United States from 1999-2000 to 2017-2018. Methods: National Health and Nutrition Examination Survey (NHANES) data from 1999-2000 to 2017-2018 were analyzed, including 5,510 adult CKD patients with BP above 140/90 mmHg or those under an antihypertensive regimen. ⋯ Although adult CKD patients with albumin-creatinine rate (ACR) 30-299 mg/g or ACR ≥300 mg/g were more likely to take antihypertensive medication than those with ACR <30 mg/g (PR: 2.76, 95% CI: 1.63-4.79 and PR: 4.59, 95% CI: 2.37-9.51), they were more likely to have uncontrolled BP than those with ACR <30 mg/g ((multivariable-adjusted prevalence ratio (PR): 2.25, 95% CI: 1.39-3.75 and PR: 3.14, 95% CI: 1.71-6.07). Adult CKD patients (eGFR ≥60 mL/min/1.73m2) being aware of their high BP diagnosis were less likely to take antihypertensive medication than those with eGFR 30-59 mL/min/1.73m2 (PR: 0.27, 95% CI: 0.09-0.65). Conclusions: These results show that BP control should be reinforced in adult CKD patients, particularly in those with ACR ≥300 mg/g, while patients with eGFR ≥60 mL/min/1.73m2 should enhance awareness of taking antihypertensive medication.
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Background: Doublecortin-like kinase 1 (DCLK1) has been revealed to be involved in modulating cancer stemness and tumor progression, but its role in prostate cancer (PCa) remains obscure. Castration-resistant and metastatic PCa exhibit aggressive behaviors, and current therapeutic approaches have shown limited beneficial effects on the overall survival rate of patients with advanced PCa. This study aimed to investigate the biological role and potential molecular mechanism of DCLK1 in the progression of PCa. ⋯ Consistent with the in vitro findings, the in vivo findings confirmed that DCLK1 promoted the tumorigenicity and stem cell-like traits of PCa cells via Hippo-YAP signaling. Conclusion: DCLK1 promotes stem cell-like characteristics by inducing LATS1-mediated YAP signaling activation, ultimately leading to PCa tumor growth and progression. Thus, our findings identify an attractive candidate for the development of cancer stem cell-targeted therapies to improve treatment outcomes in advanced PCa.
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Nucleus accumbens-associated protein 1 (NACC1) regulates various types of biological processes. It is a transcription factor associated with cancer. NACC1 is overexpressed in many human malignancies and can regulate the progression, metastasis, and drug resistance of cancer cells. ⋯ Concurrently, ADAM9 knockdown affected the activity of AML cells by decelerating the growth rate, promoting apoptosis, and blocking cell cycle progression. In addition, the AKT activator SC79 restored the inhibited cell proliferation after NACC1 knockdown and ADAM9 knockdown. In conclusion, our study suggested that the NACC1/ADAM9/PI3K/AKT axis is crucial for sustaining the survival of AML cells, indicating that NACC1 may be a viable target for treating AML.
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Pancreatic ductal adenocarcinoma (PDAC) is a major global health challenge owing to late diagnosis and inherently metastatic nature. Although surgical intervention offers a potential remedy, only few patients are eligible, and drug resistance further complicates treatment. The therapeutic limitations have catalyzed a search for alternative treatments, particularly natural products. ⋯ Molecular docking analysis revealed that HMTA potentially could interact with tubulin, and in vitro assay confirmed it suppresses tubulin polymerization. HMTA significantly inhibited BxPC-3 xenograft tumor growth in mice. Overall, these findings suggested that HMTA is a promising candidate for PDAC therapy.