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.

Combined SUVmax and localized colonic wall thickening parameters to identify high-risk lesions from incidental focal colorectal 18F-FDG uptake foci.

Objective: To evaluate the detection ability of 18F-FDG PET/CT for identifying high-risk lesions (high-risk adenomas and adenocarcinoma) from incidental focal colorectal 18F-FDG uptake foci combining maximum standard uptake value (SUVmax) and localized colonic wall thickening (CWT). The secondary objective was to investigate the factors of missed detection of high-risk adenomas by 18F-FDG PET/CT. Patients and methods: A total of 6394 patients who underwent 18F-FDG PET/CT in our hospital from August 2019 to December 2021 were retrospectively analysed, and 145 patients with incidental focal colorectal 18F-FDG uptake foci were identified. The optimal cut-off value of SUVmax for 18F-FDG PET/CT diagnosis of high-risk lesions was determined by receiver operating characteristic (ROC) curves. SUVmax and localized CWT were combined to identify high-risk lesions from incidental focal colorectal 18F-FDG uptake foci. The characteristics of incidental adenomas detected and high-risk adenomas missed by 18F-FDG PET/CT were compared. Results: Of the 6394 patients, 145 patients were found to have incidental focal colorectal FDG uptake foci (2.3%), and 44 patients underwent colonoscopy and pathological examination at the same time. In fact, 45 lesions, including 12 low-risk lesions and 33 high-risk lesions (22 high-risk adenomas, 11 adenocarcinoma), were found by colonoscopy. The area under the ROC curve of SUVmax for low-risk lesions and high-risk lesions was 0.737, and the optimal cut-off value was 6.45 (with a sensitivity of 87.9% and specificity of 58.3%). When SUVmax ≥6.45, the combination of localized CWT parameters has little influence on the sensitivity and specificity of detection; when SUVmax <6.45, the combination of localized CWT parameters can improve the specificity of detection of high-risk lesions, but the sensitivity has little change. In addition, the size of high-risk adenomas discovered incidentally by 18F-FDG PET/CT was larger than that of high-risk adenomas missed, but there was no significant difference in lesion location, pathological type or intraepithelial neoplasia between the two groups. Conclusions: The combination of SUVmax and localized CWT parameters of 18F-FDG PET/CT helped identify high-risk lesions from incidental focal colorectal 18F-FDG uptake foci, especially for lesions with SUVmax <6.45. Lesion size may be the only factor in 18F-FDG PET/CT missing high-risk adenomas.

Coronary artery disease as an independent predictor of short-term and long-term outcomes in patients with type-B aortic dissection undergoing thoracic endovascular repair.

Background and aims: Previous studies reported a high prevalence of concomitant coronary artery disease (CAD) in patients with Type B aortic dissection (TBAD). However, there is too limited data on the impact of CAD on prognosis in patients with TBAD. The present study aimed to assess the short-term and long-term impact of CAD on patients with acute or subacute TBAD undergoing thoracic endovascular aortic repair (TEVAR). Methods: We retrospectively evaluated 463 patients with acute or subacute TBAD undergoing TEVAR from a prospectively maintained database from 2010 to 2017. CAD was defined before TEVAR by coronary angiography. Multivariable logistic and cox regression analyses were performed to evaluate the relationship between CAD and the short-term as well as long-term outcomes. Results: According to the results of coronary angiography, the 463 patients were divided into the following two groups: CAD group (N = 148), non-CAD group (N = 315). In total, 12 (2.6%) in-hospital deaths and 54 (12%) all-cause deaths following a median follow-up of 48.1 months were recorded. Multivariable analysis revealed that CAD was an independent predictor of in-hospital major adverse clinical events (MACE) (odd ratio [OR], 2.33; 95% confidence interval [CI], 1.07-5.08; p = 0.033), long-term mortality [hazard ratio (HR), 2.11, 95% CI, 1.19-3.74, P = 0.011] and long-term MACE (HR, 1.95, 95% CI, 1.26-3.02, P = 0.003). To further clarify the relationship between the severity of CAD and long-term outcomes, we categorized patients into three groups: zero-vessel disease, single-vessel disease and multi-vessel disease. The long-term mortality (9.7 vs. 14.4 vs. 21.2%, P = 0.045), and long-term MACE (16.8 vs. 22.2 vs. 40.4%, P = 0.001) increased with the number of identified stenosed coronary vessels. Multivariable analysis indicated that, multi-vessel disease was independently associated with long-term mortality (HR, 2.38, 95% CI, 1.16-4.89, P = 0.018) and long-term MACE (HR, 2.79, 95% CI, 1.65-4.73, P = 0.001), compared with zero-vessel disease. Conclusions: CAD was associated with short-term and long-term worse outcomes in patients with acute or subacute TBAD undergoing TEVAR. Furthermore, the severity of CAD was also associated with worse long-term prognosis. Therefore, CAD could be considered as a useful independent predictor for pre-TEVAR risk stratification in patients with TBAD.

Soluble epoxide hydrolase inhibitor, TUPS, attenuates isoproterenol/angiotensin II-induced cardiac hypertrophy through mammalian target of rapamycin-mediated autophagy inhibition.

OBJECTIVES: To investigate the potential role and mechanism of TUPS, a soluble epoxide hydrolase inhibitor, in cardiac hypertrophy. METHODS: Rat and H9C2 cell models of cardiac hypertrophy were induced by isoproterenol and angiotensin II, respectively, followed by TUPS treatment. The expression of hypertrophic markers, ANP and BNP, was determined by quantitative real-time PCR. The abundance of Beclin-1, LC3, p-AMPK and phosphorylated-mammalian target of rapamycin (p-mTOR) proteins was analysed by Western blot and immunohistocytology. Cell morphology and viability were evaluated by F-actin staining and MTS. H9C2 cells were transfected with GFP-LC3 to evaluate autophagy flux. KEY FINDINGS: TUPS significantly inhibited rat heart size, heart weight-to-body weight ratio, heart wall thickness, hypertrophic H9C2 cell swelling and viability suppression as well as the expression of ANP and BNP genes in hypertrophic models. In addition, autophagic markers Beclin-1 and LC3 were elevated in both cellular and animal models, which were suppressed by TUPS, with corresponding changes of autophagy flux. The abundance of p-AMPK was increased, while p-mTOR was decreased in hypertrophic cells, which were abolished by TUPS. Rapamycin decreased p-mTOR level, increased Beclin-1 and LC3 expression and induced cell size enlargement and cell viability inhibition in hypertrophic H9C2 cells treated with TUPS. CONCLUSIONS: TUPS inhibits cardiac hypertrophy by regulating mTOR/autophagy axis.

Molecular cloning and characterization of a mouse spermatogenesis-related ring finger gene znf230.

Complete cDNA of mouse gene znf230 was cloned by rapid amplification of cDNA ends (RACE). This cDNA is 982 base pairs (bp) in length and encodes a 230 amino acids (aa) protein with a ring finger domain at its C-terminus. Ninety-one and 98% nucleotide (nt) and aa sequence identity are observed with its human homolog. Revealed by Northern blot and reverse transcriptase-polymerase chain reaction (RT-PCR), this cDNA is only detected in testicular tissue, whereas the longer transcripts of 2.4 and 4.4kb are ubiquitously expressed. The expression of znf230 in testis is developmentally regulated and first detected at day 6 postnatal (pn). It reaches adult level between day 14 and 21 pn during which round spermatids appear in seminiferous tubule. The protein of znf230 exhibits DNA binding activity and its ring finger domain may function as an activator module in transcription. Therefore, it is postulated that znf230 may function as a testis specific transcription factor during mouse spermatogenesis.