Activation of the CaR-CSE/H2S pathway confers cardioprotection against ischemia-reperfusion injury.

Ischemia-reperfusion (I/R) injury is a multifactorial process triggered when an organ is subjected to transiently reduced blood supply. The result is a cascade of pathological complications and organ damage due to the production of reactive oxygen species following reperfusion. The present study aims to evaluate the role of activated calcium-sensing receptor (CaR)-cystathionine γ-lyase (CSE)/hydrogen sulfide (H2S) pathway in I/R injury. Firstly, an I/R rat model with CSE knockout was constructed. Transthoracic echocardiography, TTC and HE staining were performed to determine the cardiac function of rats following I/R Injury, followed by TUNEL staining observation on apoptosis. Besides, with the attempt to better elucidate how CaR-CSE/H2S affects I/R, in-vitro culture of human coronary artery endothelial cells (HCAECs) was conducted with gadolinium chloride (GdCl3, a CaR agonist), H2O2, siRNA against CSE (siCSE), or W7 (a CaM inhibitor). The interaction between CSE and CaM was subsequently detected. Plasma oxidative stress indexes, H2S and CSE, and apoptosis-related proteins were all analyzed following cell apoptosis. We found that H2S elevation led to the improvement whereas CSE knockdown decreased cardiac function in rats with I/R injury. Moreover, oxidative stress injury in I/R rats with CSE knockout was aggravated, while the increased expression of H2S and CSE in the aortic tissues resulted in alleviated the oxidative stress injury. Moreover, increased H2S and CSE levels were found to inhibit cell apoptotic ability in the aortic tissues after I/R injury, thus attenuating oxidative stress injury, accompanied by inhibited expression of apoptosis-related proteins. In HCAECs following oxidative stress treatment, siCSE and CaM inhibitor were observed to reverse the protection of CaR agonist. Coimmunoprecipitation assay revealed the interaction between CSE and CaM. Taken together, all above-mentioned data provides evidence that activation of the CaR-CSE/H2S pathway may confer a potent protective effect in cardiac I/R injury.

Current Status of Phage Therapy against Infectious Diseases and Potential Application beyond Infectious Diseases.

Intestinal microbiota plays a key role in regulating the pathogenesis of human disease and maintaining health. Many diseases, mainly induced by bacteria, are on the rise due to the emergence of antibiotic-resistant strains. Intestinal microorganisms include organisms such as bacteria, viruses, and fungi. They play an important role in maintaining human health. Among these microorganisms, phages are the main members of intestinal viromes. In particular, the viral fraction, composed essentially of phages, affects homeostasis by exerting selective pressure on bacterial communities living in the intestinal tract. In recent years, with the widespread use and even abuse of antibacterial drugs, more and more drug-resistant bacteria have been found, and they show a trend of high drug resistance and multidrug resistance. Therefore, it has also become increasingly difficult to treat serious bacterial infections. Phages, a natural antibacterial agent with strong specificity and rapid proliferation, have come back to the field of vision of clinicians and scholars. In this study, the current state of research on intestinal phages was discussed, with an exploration of the impact of phage therapy against infectious diseases, as well as potential application beyond infectious diseases.

[Effects of emulsified isoflurane preconditioning on LPS-induced acute lung injury in rats].

OBJECTIVE: To investigate the effects of emulsified isoflurane preconditioning on LPS-induced acute lung injury in rats. METHODS: Acute lung injury was induced by the administration of LPS 8 mg/kg intravenously in male Sprague-Dawley rats. The ratswere randomly assigned to 4 groups: LPS-induced acute lung injury group (LPS, n = 10); emulsified Isoflurane Preconditioning group (EISO, n = 10); Intralipid pre-treated group (INT, n = 10), and saline pre-reated control group (CON, n = 5). In the later 3 groups, 2 mL/kg NS, IL and EISO were infused intravenously for 30 min before the administration of LPS respectively. The animals were then observed for 5 hours. The mean arterial blood pressure(MAP) and heart rate(HR) were monitored hourly. Arterial blood gas (ABG) was measured for oxygenation index (OI) at the end of 5h. The blood samples were taken for the measurements of plasma tumor necrosis factor-alpha (TNF-alpha) and interleukin-6(IL-6). The lungs were removed for the measurements of wet/dry (W/D) weight ratio, as well as the levels of malondialdehyde (MDA), superoxide dismutase (SOD), myeloperoxidase (MPO). RESULTS: The OI of group CON was 435 +/- 30, group LPS 225 +/- 49, group EISO 367 +/- 41, and group INT 267 +/- 41. Compared with group CON, OI and pulmonary SOD activity significantly decreased while plasma TNF-alpha, IL-6 concentration and pulmonary MDA level, MPO activity increased in LPS, EISO and INT groups. The plasma TNF-alpha, IL-6 concentration, pulmonary MDA level and pulmonary MPO activity of group EISO were lower while OI and pulmonary SOD activity were higher than those of group LPS. CONCLUSION: The emulsified isoflurane pretreatment can ameliorate LPS-induced acute lung injury in rats.