SALVIANOLIC ACID A ATTENUATES ANGIOTENSIN II-INDUCED CARDIAC FIBROSIS THROUGH REGULATING THE TXNIP SIGNALING PATHWAY.

ABSTRACT: Cardiac fibrosis, characterized by excessive collagen accumulation in heart tissues, poses a significant clinical challenge in various heart diseases and complications. Although salvianolic acid A (Sal A) from Danshen ( Salvia miltiorrhiza ) has shown promise in the treatment of ischemic heart disease, myocardial infarction, and atherosclerosis, its effects on cardiac fibrosis remain unexplored. Our study investigated the efficacy of Sal A in reducing cardiac fibrosis and elucidated its underlying molecular mechanisms. We observed that Sal A demonstrated significant cardioprotective effects against Angiotensin II (Ang II)-induced cardiac remodeling and fibrosis, showing a dose-dependent reduction in fibrosis in mice and suppression of cardiac fibroblast proliferation and fibrotic protein expression in vitro . RNA sequencing revealed that Sal A counteracted Ang II-induced upregulation of Txnip, and subsequent experiments indicated that it acts through the inflammasome and ROS pathways. These findings establish the antifibrotic effects of Sal A, notably attenuated by Txnip overexpression, and highlight its significant role in modulating inflammation and oxidative stress pathways. This underscores the importance of further research on Sal A and similar compounds, especially regarding their effects on inflammation and oxidative stress, which are key factors in various cardiovascular diseases.

Facile Deficiency Engineering in a Cobalt-Free Perovskite Air Electrode to Achieve Enhanced Performance for Protonic Ceramic Fuel Cells.

As a crucial component responsible for the oxygen reduction reaction (ORR), cobalt-rich perovskite-type cathode materials have been extensively investigated in protonic ceramic fuel cell (PCFC). However, their widespread application at a commercial scale is considerably hindered by the high cost and inadequate stability. In response to these weaknesses, the study presents a novel cobalt-free perovskite oxide, Ba0.95 La0.05 (Fe0.8 Zn0.2 )0.95 O3-δ (BLFZ0.95), with the triple-conducting (H+ |O2- |e- ) property as an active and robust air electrode for PCFC. The B-site deficiency state contributes significantly to the optimization of crystal and electronic structure, as well as the increase in oxygen vacancy concentration, thus in turn favoring the catalytic capacity. As a result, the as-obtained BLFZ0.95 electrode demonstrates exceptional electrochemical performance at 700 °C, representing extremely low area-specific resistance of 0.04 Ω cm2 in humid air (3 vol.% H2 O), extraordinarily high peak power density of 1114 mW cm-2 , and improved resistance against CO2 poisoning. Furthermore, the outstanding long-term durability is achieved without visible deterioration in both symmetrical and single cell modes. This study presents a simple but crucial case for rational design of cobalt-free perovskite cathode materials with appreciable performance via B-site deficiency regulation.

Early Progression of Abdominal Aortic Aneurysm is Decelerated by Improved Endothelial Barrier Function via ALDH2-LIN28B-ELK3 Signaling.

The involvement of endothelial barrier function in abdominal aortic aneurysm (AAA) and its upstream regulators remains unknown. Single-cell RNA sequencing shows that disrupted endothelial focal junction is an early (3 days) and persistent (28 days) event during Angiotensin II (Ang II)-induced AAA progression. Consistently, mRNA sequencing on human aortic dissection tissues confirmed downregulated expression of endothelial barrier-related genes. Aldehyde dehydrogenase 2 (ALDH2), a negative regulator of AAA, is found to be upregulated in the intimal media of AAA samples, leading to testing its role in early-stage AAA. ALDH2 knockdown/knockout specifically in endothelial cells (ECs) significantly increases expression of EC barrier markers related to focal adhesion and tight junction, restores endothelial barrier integrity, and suppresses early aortic dilation of AAA (7 and 14 days post-Ang II). Mechanically, ELK3 acts as an ALDH2 downstream regulator for endothelial barrier function preservation. At the molecular level, ALDH2 directly binds to LIN28B, a regulator of ELK3 mRNA stability, hindering LIN28B binding to ELK3 mRNA, thereby depressing ELK3 expression and impairing endothelial barrier function. Therefore, preserving vascular endothelial barrier integrity via ALDH2-specific knockdown in ECs holds therapeutic potential in the early management of AAAs.

Size-fractionated particulate elements in an inland city of China: Deposition flux in human respiratory, health risks, source apportionment, and dry deposition.

Size-resolved samples were collected using a 14-stage impactor during four seasons in Zhengzhou and analyzed for 26 elements to calculate the health risks from atmospheric particle-bound metals. High concentrations of heavy metals were observed in ultrafine (10.2 (Ni)-66.9 (Cd) ng m-3) or submicrometer (11.4 (Ni)-134 (Pb) ng m-3) mode in winter. Two size-dependent models were used to estimate the deposition of inhaled toxic metals in various regions of the human respiratory system. Results show that heavy metals deposited in the alveolar region ranged from 7.6 (As)-375 (Al) ng m-3 and were almost concentrated in ultrafine and fine modes. Cd (2.2-8.6) may cause accumulative non-carcinogenic health effects on children, and Cr (1.0 × 10-4-2.2 × 10-4) may lead to carcinogenic health risks for nearby residents around the sampling site. The major sources by principal component analysis that contributed to Cr and Cd in ultrafine and fine particles were coal combustion, vehicular and industrial emissions. The atmospheric dry deposition fluxes of Cr and Cd were between 0.7 and 1.9 µg m-2 day-1 calculated by a multi-step method. From the environmental and public health perspective, environmental agencies must control the emission of heavy metals in the atmosphere.

[Effect of hemoperfusion combined with continuous veno-venous hemofiltration on acute paraquat poisoning: a Meta-analysis].

OBJECTIVE: To comprehensively evaluate the clinical efficacy of hemoperfusion (HP) combined with continuous veno-venous hemofiltration (CVVH) on acute paraquat poisoning (APP). METHODS: Literatures of Chinese and English randomized controlled trials (RCTs), case control and cohort study on HP combined with CVVH in the treatment of APP from the PubMed, Embase, Wanfang, and CNKI up to November 2017 were enrolled (the subjects were > 16 years old). The obtained literatures were strictly screened and evaluated in quality, and data such as mortality, the life time of dead patients, inefficiency rate, incidence of multiple organ dysfunction syndrome (MODS) and acute respiratory distress syndrome (ARDS) were extracted. Meta-analysis was performed by RevMan 5.3. RESULTS: Twenty-one studies were included with 2 222 subjects, among whom 976 subjects were in HP combined with CVVH group (experimental group) and 1 246 subjects in HP group (control group). Compared with control group, the mortality in experimental group were significantly decreased [43.77% (362/827) vs. 55.26% (604/1 093), odds ratio (OR) = 0.68, 95% confidential interval (95%CI) = 0.56-0.82, P = 0.000 1], the life time of death patients was significantly prolonged [mean difference (MD) = 4.63, 95%CI = 2.60-6.66, P < 0.000 01], incidence of MODS [25.93% (70/270) vs. 55.36% (155/280), OR = 0.26, 95%CI = 0.14-0.49, P < 0.000 1], and incidence of ARDS [30.37% (82/270) vs. 51.07% (143/280), OR = 0.42, 95%CI = 0.30-0.61, P < 0.000 01], and inefficiency rate [8.72% (13/149) vs. 34.64% (53/153), OR = 0.17, 95%CI = 0.09-0.34, P < 0.000 01] were significantly reduced. Funnel chart showed that except the publication bias of mortality rate, there were less publication bias about other indicators among studies. CONCLUSIONS: HP combined with CVVH can significantly reduce the mortality of patients with APP compared with HP alone on the whole, prolong the life time and reduce the occurrence of MODS and ARDS, thus improving the treatment efficiency.