Search

Ischemia/reperfusion (I/R) injury of the lung can lead to extensive pulmonary damage. Sodium-glucose cotransporter-2 (SGLT2) inhibitors are insulin-independent, oral antihyperglycemic agents used for treating type 2 diabetes mellitus (T2DM). Although their cardioprotective properties have been reported, their potential roles in pulmonary protection in vivo are poorly characterized. Here, we tested a hypothesis that empagliflozin, an SGLT2 inhibitor, can protect lungs in a mouse model of lung I/R injury induced by pulmonary hilum ligation in vivo. We assigned C57/BL6 mice to sham-operated, nonempagliflozin-treated control, or empagliflozin-treated groups. Pulmonary I/R injury was induced by 1-hour left hilum ligation followed by 2-hour reperfusion. Using quantitative polymerase chain reaction (q-PCR) and Western blot analysis, we demonstrate that SGLT2 is highly expressed in mouse kidney but is weakly expressed in mouse lung (n = 5-6 per group, P < 0.01 or P < 0.001). Empagliflozin improved respiratory function, attenuated I/R-induced lung edema, lessened structural damage, inhibited apoptosis, and reduced inflammatory cytokine production and protein concentration in bronchoalveolar lavage (BAL) fluid [P < 0.05 or P < 0.001 versus control group (CON)]. In addition, empagliflozin enhanced phosphorylation of pulmonary extracellular signal-regulated kinases 1 and 2 (ERK1/2) post-I/R injury in vivo (P < 0.001, versus CON, n = 5 per group). We further showed that pharmacological inhibition of ERK1/2 activity reversed these beneficial effects of empagliflozin. In conclusion, we showed that empagliflozin exerts strong lung protective effects against pulmonary I/R injury in vivo, at least in part via the ERK1/2-mediated signaling pathway. SIGNIFICANCE STATEMENT: Pulmonary ischemia-reperfusion (I/R) can exacerbate lung injury. Empagliflozin is a new antidiabetic agent for type 2 diabetes mellitus. This study shows that empagliflozin attenuates lung damage after pulmonary I/R injury in vivo. This protective phenomenon was mediated at least in part via the extracellular signal-regulated kinases 1 and 2-mediated signaling pathway. This opens a new avenue of research for sodium-glucose cotransporter-2 inhibitors in the treatment of reperfusion-induced acute pulmonary injury.

Pulmonary ischemia and reperfusion (I/R) injury occurs in many clinical conditions and causes severe damage to the lungs. Diabetes mellitus (DM) predisposes to pulmonary I/R injury. We previously found that remote liver ischemia preconditioning protected lungs against pulmonary I/R injury. The aim of the present study was to investigate whether remote liver ischemic postconditioning (RLIPost) attenuates pulmonary damage induced by I/R injury in non-diabetic or diabetic rats. Male Sprague-Dawley rats were assigned into non-diabetic and diabetic groups. All rats except for the sham were exposed to 45 min of left hilum occlusion followed by 2 h of reperfusion. RLIPost was conducted at the onset of pulmonary reperfusion by four cycles of 5 min of liver ischemia and reperfusion. Lung injury was assessed by the wet/dry weight ratio, pulmonary oxygenation, histopathological changes, apoptosis and the expression of inflammatory cytokines. Reperfusion-associated protein phosphorylation states were determined. RLIPost offered strong pulmonary-protection in both non-diabetic and diabetic rats, as reflected in reduced water content and pulmonary structural damage, recovery of lung function, inhibition of apoptosis and inflammation after ischemia-reperfusion. RLIPost induced the activation of pulmonary STAT-3, a key component in the SAFE pathway, but not activation of the proteins in the RISK pathway, in non-diabetic rats. In contrast, RLIPost-induced pulmonary protection in diabetic lungs was independent of SAFE or RISK pathway activation. These results demonstrate that RLIPost exerts pulmonary protection against I/R-induced lung injury in non-diabetic and diabetic rats. The underlying mechanism for protection may be different in non-diabetic (STAT-3 dependent) versus diabetic (STAT-3 independent) rats.

The guided bone regeneration (GBR) technique is an effective treatment for small and medium-sized bone defects in the oral and maxillofacial region. However, currently available collagen membranes have limited functionality and are inadequate for clinical requirements. To address this challenge, this study pioneeringly developed a multifunctional bilayer membrane. Specifically, a bimetallic/polydopamine network (BPN), consisting of silver, magnesium, and dopamine, was successfully synthesized for the first time and integrated with collagen and hydroxyapatite. The resulting material was characterized, and its physicochemical properties, along with its barrier, osteogenic, angiogenic, antibacterial, hemostatic, and biosafety effects, were evaluated through both in vitro and in vivo studies. The results indicated that the BPN, composed of magnesium ions, silver nanoparticles (Ag NPs), and polydopamine (PDA), exhibited excellent thermal stability and slow release of silver and magnesium elements. The BPN/Col-HA membrane featured a bilayer structure with uniform distribution of silver and magnesium. It also demonstrated good hydrophilicity, suitable degradation and mechanical properties, as well as sustained release of silver and magnesium. In vitro experiments showed that the BPN/Col-HA membrane possessed desirable barrier, osteogenic, angiogenic, antibacterial, hemostatic, and biocompatible properties. In vivo results further confirmed its biosafety, hemostatic efficacy, and ability to effectively promote bone defect repair and angiogenesis. Thus, the BPN/Col-HA membrane emerges as a multifunctional GBR membrane with potential for clinical translation. [ABSTRACT FROM AUTHOR]

Aims The atherosclerotic profile and advanced plaque subtype burden in symptomatic patients ≤45 years old have not been established. This study aimed to assess the prevalence and predictors of coronary artery calcium (CAC), plaque subtypes, and plaque burden by coronary computed tomography angiography (CCTA) in symptomatic young patients. Methods and results We included 907 symptomatic young patients (18–45 years) from Montefiore undergoing CCTA for chest pain evaluation. Prevalence and predictors of CAC, plaque subtypes, and burden were evaluated using semi-automated software. In the overall population (55% female and 44% Hispanic), 89% had CAC = 0. The likelihood of CAC or any plaque by CCTA increased with >3 risk factors {RFs, odds ratio [OR] 7.13 (2.14–23.7) and OR 10.26 (3.36–31.2), respectively}. Any plaque by CCTA was present in 137 (15%); the strongest independent predictors were age ≥35 years [OR 3.62 (2.05–6.41)] and family history of premature coronary artery disease (FHx) [OR 2.76 (1.67–4.58)]. Stenosis ≥50% was rare (1.8%), with 31% of those having CAC = 0. Significant non-calcified plaque (NCP, 37.2%) and low-attenuation plaque (LAP, 4.24%) burdens were seen, even in those with non-obstructive stenosis. Among patients with CAC = 0, 5% had plaque, and the only predictor of exclusively NCP was FHx [OR 2.29 (1.08–4.86)]. Conclusion In symptomatic young patients undergoing CCTA, the prevalence of CAC or any coronary atherosclerosis was not negligible, and the likelihood increased with RF burden. The presence of coronary stenosis ≥50% was rare and most often accompanied by CAC >0, but there was a significant burden of NCP and LAP even within the non-obstructive group. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by SFTS virus (SFTSV), identified in China in 2009 (1) and subsequently in South Korea (2) and Japan [...]

Background: Adverse cardiac events are common following transcatheter aortic valve replacement (TAVR). Our aim was to investigate the low left ventricular stroke volume index (LVSVI) 30 days after TAVR as an early echocardiographic marker of survival. Hypothesis: Steady‐state (30‐day) LVSVI after TAVR is associated with 1‐year mortality. Methods: A single‐center retrospective analysis of all patients undergoing TAVR from 2017 to 2019. Baseline and 30‐day post‐TAVR echocardiographic LVSVI were calculated. Patients were stratified by pre‐TAVR transaortic gradient, surgical risk, and change in transvalvular flow following TAVR. Results: This analysis focuses on 238 patients treated with TAVR. The 1‐year mortality rate was 9% and 124 (52%) patients had normal flow post‐TAVR. Of those with pre‐TAVR low flow, 67% of patients did not normalize LVSVI at 30 days. The 30‐day normal flow was associated with lower 1‐year mortality when compared to low flow (4% vs. 14%, p =.007). This association remained significant after adjusting for known predictors of risk (adjusted odds ratio [OR] of 3.45, 95% confidence interval: 1.02–11.63 [per 1 ml/m2 decrease], p =.046). Normalized transvalvular flow following TAVR was associated with reduced mortality (8%) when compared to those with persistent (15%) or new‐onset low flow (12%) (p =.01). Conclusions: LVSVI at 30 days following TAVR is an early echocardiographic predictor of 1‐year mortality and identifies patients with worse intermediate outcomes. More work is needed to understand if this short‐term imaging marker might represent a novel therapeutic target. [ABSTRACT FROM AUTHOR]