Translational research : the journal of laboratory and clinical medicine
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The use of e-cigarettes has grown rapidly in recent years, raising concerns about their impact on human health, particularly on critical physiological barriers such as the blood-brain barrier (BBB), alveolar-capillary barrier, and vascular systems. This systematic review evaluates the current literature on the effects of e-cigarette exposure on these barrier systems. ⋯ Key findings include compromised pulmonary function, increased vascular stiffness, and neuroinflammation. The review highlights potential long-term health risks associated with e-cigarette use, such as cardiovascular disease, neurodevelopmental disorders, and multi-organ fibrosis, and emphasizes the need for public health interventions to regulate e-cigarette use, especially in vulnerable populations like pregnant women and adolescents.
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The organ-level molecular response to cardiac surgery with cardiopulmonary bypass (CPB) remains inadequately understood and may be heterogeneous. Here, we measured organ-specific gene expression in a piglet model of CPB with deep hypothermic circulatory arrest (DHCA). Infant piglets underwent peripheral CPB with 75 min of DHCA and 6 h of critical care after separation from CPB. ⋯ Key upregulated systems included ribosomal proliferation and mitochondrial assembly in the liver, oxidative stress response and proximal tubular repair in the kidney, myofilament structural genes and pro-hypertrophy pathways in the heart, and solute channels and arginine metabolism in the lung. Downregulation of adaptive immunity genes occurred in multiple organs. Transcriptomics could inform the investigation of targeted therapies and adverse event screening after cardiac surgery.
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Renal hedgehog interacting protein (Hhip) activates sodium-glucose cotransporter 2 (Sglt2) expression and promotes tubular senescence in murine diabetic kidney disease (DKD), yet its underlying mechanism(s) are poorly understood. Here we study the effect of the SGLT2 inhibitor, canagliflozin on tubulopathy (fibrosis and apoptosis) in Akita/HhipRPTC-transgenic (Tg) mice with overexpression of Hhip in their renal proximal tubular cells (RPTCs) and its relevant mechanisms. The DKD-tubulopathy with pronounced Sglt2 expression was aggravated in the kidney of Akita/HhipRPTC-Tg cf. ⋯ Further, Hhip stimulated β2-microglobulin, which further interacts with EVsHhip, together facilitating RPTC turn-over from cellular senescence to fibrosis and/or apoptosis, ultimately leading to advanced tubulopathy. In contrast, canagliflozin administration offset the action of Hhip in RPTCs, thereby preventing DKD progression. In conclusion, canagliflozin prevented excessive Hhip-mediated tubulopathy, possibly via the inhibition of excessive Hhip carried by extracellular vehicles in DKD.
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Renal ischemia-reperfusion injury (IRI) is a common clinical condition that currently lacks effective treatment options. Inhibitors targeting the sodium-glucose co-transporter-2 (SGLT-2), recognized for their role in managing hyperglycemia, have demonstrated efficacy in enhancing the health outcomes for diabetic patients grappling with chronic kidney disease. Nevertheless, the precise impact of SGLT-2 inhibitors on renal ischemia-reperfusion injury (IRI) and the corresponding transcriptomic alterations remain to be elucidated. ⋯ Empagliflozin exerted a renoprotective effect by downregulating lysosome-associated membrane proteins, primarily LAMP1, LAMP2, and LAMP4 (CD68), through the PI3K-Akt, MAPK, and mTOR signaling pathways, thereby inhibiting autophagic processes. In conclusion, this study highlights enhanced inflammation and disrupted metabolism as hallmark transcriptomic signatures of renal. Furthermore, it demonstrates the renoprotective effects of empagliflozin in alleviating renal IRI by modulating autophagic processes.
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Renal ischemia-reperfusion injury (IRI) is a prevalent clinical syndrome, yet its underlying pathogenesis remains largely unknown. Aldehyde dehydrogenase 2 (ALDH2), an enzyme responsible for detoxifying lipid aldehydes, has been suggested to play a protective role against IRI. In our study, we observed that Aldh2 knock-out C57BL/6 mice experienced more severe renal functional impairment following IRI. ⋯ ALDH2 specifically interacts with the N-terminal domain of NCOR1, which is responsible for its interaction with its E3 ligase SIAH2. This interaction inhibits the proteasome degradation of NCOR1, ultimately stabilizing the NCOR1 transcriptional repression complex. In summary, our research uncovers the role of ALDH2 in mitigating renal IRI by inhibiting 20-HETE synthesis through the transcriptional repression of Cyp4a.