Heat shock transcription factor 1 preserves cardiac angiogenesis and adaptation during pressure overload

To examine how heat shock transcription factor 1 (HSF1) protects against maladaptive hypertrophy during pressure overload, we subjected HSF1 transgenic (TG), knockout (KO) and wild type (WT) mice to a constriction of transverse aorta (TAC), and found that cardiac hypertrophy, functions and angiogenesis were well preserved in TG mice but were decreased in KO mice compared to WT ones at 4 weeks, which was related to HIF-1 and p53 expression. Inhibition of angiogenesis suppressed cardiac adaptation in TG mice while overexpression of angiogenesis factors improved maladaptive hypertrophy in KO mice. In vitro formation of vasculatures by microvascular endothelial cells was higher in TG mice but lower in KO mice than in WT ones. A siRNA of p53 but not a HIF-1 gene significantly reversed maladaptive hypertrophy in KO mice whereas a siRNA of HIF-1 but not a p53 gene induced maladaptive hypertrophy in TG mice. Heart microRNA analysis showed that miR-378 and miR-379 were differently changed among the three mice after TAC, and miR-378 or siRNA of miR-379 could maintain cardiac adaptation in WT mice. These results indicate that HSF1 preserves cardiac adaptation during pressure overload through p53-HIF-1-associated angiogenesis, which is controlled by miR-378 and miR-379

Changes of dendritic cells and fractalkine in type 2 diabetic patients with unstable angina pectoris: a preliminary report

<p>Abstract</p> <p>Background</p> <p>It has been shown that dendritic cells (DCs) and fractalkine play a role in accelerating progression of the inflamed atherosclerotic lesions and plaque rupture. We evaluated the numbers and functional changes of DCs and its subsets in human type 2 diabetes with or without unstable angina pectoris (UAP).</p> <p>Methods</p> <p>The study population consisted of 39 diabetic patients (DM:18 without CAD; DM + UAP: 21 with UAP), 18 non-diabetic UAP patients (UAP), and 15 healthy control (Normal). Peripheral blood DCs and its subsets were measured by three color flow cytometry. Serum levels of fractalkine, IL-12, and IFN-α were also measured. The functional status of the monocyte-derived DCs was analyzed by flow cytometry and allogeneic mixed T lymphocytes reaction.</p> <p>Results</p> <p>The percent and absolute numbers of DCs and mDC within the total leukocyte population was similar for Normal and DM, while significantly lower in DM + UAP. pDC numbers were not significantly altered. Serum fractalkine in DM + UAP was highest among the four groups (<it>p </it>= 0.04 vs. UAP, <it>p </it>= 0.0003 vs. DM, <it>p </it>< 0.0001 vs. Normal). Circulating mDC inversely correlated with serum fractalkine (r = -0.268, <it>p </it>= 0.01) level. Compared with DM and UAP, the costimulatory molecules CD86 and proliferation of T cells stimulated by DCs were significantly increased in DM + UAP group.</p> <p>Conclusions</p> <p>Our study suggested that increases in the fractalkine level and the number and functional changes of blood DCs might contribute to diabetic coronary atherosclerosis and plaque destabilization.</p

Proton pump inhibitor has no effect in the prevention of post-endoscopic sphincterotomy delayed bleeding: a prospective randomized controlled trial

Background and aimsBleeding is one of the common adverse events of endoscopic retrograde cholangiopancreatography (ERCP), which is mainly caused by endoscopic sphincterotomy (EST). At present, it remains unclear whether proton pump inhibitor (PPI) should be used to prevent post-EST bleeding. Therefore, we performed a randomized controlled trial to investigate whether PPI is effective in the prevention of post-EST delayed bleeding.MethodsConsecutive eligible patients were randomly assigned (1:1) to experimental group (PPI group) or control group (normal saline, NS group). The patients in PPI group received intravenous esomeprazole 40  mg and normal saline 100  mL every 12  h for 2  days after ERCP immediately, and followed by oral esomeprazole (Nexium) 20  mg once a day for 7  days. Correspondingly, patients in the control group received intravenous normal saline 100  mL and did not take PPIs or any acid-suppressing drugs during hospitalization and after discharge. All patients were followed up for 30  days after ERCP. The primary endpoint was the incidence and severity of post-EST delayed bleeding.ResultsBetween July 2020 and July 2022, 290 patients were randomly assigned to PPI group (n = 146) or NS group (n = 144). 5 patients from each group were excluded from the final analysis. There were 6 patients with post-EST delayed bleeding, with an incidence rate of 2.14%. The median time of delayed bleeding was 2.5  days after ERCP. 3 cases (2.12%, 3/141) occurred in the PPI group, with 1 case of mild and 2 cases of moderate bleeding. 3 cases (2.16%, 3/139) occurred in the NS group, with 2 cases of mild and 1 case of moderate bleeding. There was no significant difference in the incidence and the severity of post-EST delayed bleeding between the two groups (p = 1.000).ConclusionProphylactic use of PPI after EST does not reduce the incidence and severity of post-EST delayed bleeding in patients.Clinical Trial Registrationhttps://www.chictr.org.cn/searchproj.aspx, identifier ChiCTR2000034697

Acetaldehyde dehydrogenase 2 (ALDH2) deficiency exacerbates pressure overload-induced cardiac dysfunction by inhibiting Beclin-1 dependent autophagy pathway

AbstractMitochondrial aldehyde dehydrogenase 2 (ALDH2) was demonstrated to play cardioprotective roles in cardiovascular diseases. Nonetheless, little is known about the roles and mechanisms of ALDH2 in pressure overload-induced cardiac damages. In this study, we revealed that ALDH2 deficiency overtly exacerbated transverse aortic constriction (TAC)-induced cardiac dysfunction. Cardiomyocyte enlargement was observed in both WT and ALDH2−/− mice in HE-stained myocardial tissue samples at 8weeks post TAC surgery. Mitochondrial morphology and structure were also significantly damaged post TAC surgery and the changes were aggravated in ALDH2−/− TAC hearts. ALDH2 deficiency also depressed myocardial autophagy in hearts at 8weeks post TAC surgery with a potential mechanism of repressing the expression of Beclin-1 and promoting the interaction between Bcl-2 and Beclin-1. These data indicate that ALDH2 deficiency exacerbates the pressure overload induced cardiac dysfunction partly by inhibiting Beclin-1 dependent autophagy pathway.This article is part of a Special Issue entitled: Autophagy and protein quality control in cardiometabolic diseases

The clinical effect of a strategy called transcystic gallbladder-preserving cholecystolithotomy based on endoscopic retrograde cholangiopancreatography for cholecystolithiasis: A retrospective study from a single center

BackgroundCholedocholithiasis complicated with cholecystolithiasis is a common disease. This study explores a novel strategy, called ERCP-based transcystic gallbladder-preserving cholecystolithotomy, for the simultaneous removal of common bile duct stones and gallbladder stones.MethodsFrom December 2018 to June 2021, all patients with cholecystolithiasis and common bile duct stones who met the criteria for gallbladder preservation in our hospital were included in the study and prospectively followed up.ResultsWe included 48 patients, including 20 patients with acute biliary pancreatitis. All patients successfully underwent ERCP to remove common bile duct stones. One patient had gallbladder perforation during gallbladder-preserving cholecystolithotomy. The guide wire successfully entered the gallbladder, and the transpapillary gallbladder metal-covered stent was successfully placed in 44 patients. The technical success rate was 91.67% (44/48). All stones were removed in 34 patients, for a clinical success rate of 77.27% (34/44). The total postoperative complication rate was 6.25% (3/48), with 2 cases of pancreatitis (4.17%) and 1 case of cholangitis (2.08%). Three patients were lost to follow-up. Among the 31 patients who were followed up for a mean of 27 months (6–40), 5 patients (16.13%) experienced gallstone recurrence. The recurrence rates at 12 months, 18 months, 24 months, 30 months and 36 months were 0%, 3.23%, 6.45%, 12.9%, and 16.13%, respectively.ConclusionFor patients with cholecystolithiasis and common bile duct stones, ERCP-based transcystic gallbladder-preserving cholecystolithotomy without gallbladder incision can preserve gallbladder structure, and this procedure is safe and feasible for the protection of gallbladder function.Clinical trial registration: The study was registered in the Chinese Clinical Trial Registry, and the registry number is ChiCTR1900028006

Aggravated myocardial infarction-induced cardiac remodeling and heart failure in histamine-deficient mice

Histamine has pleiotropic pathophysiological effects, but its role in myocardial infarction (MI)-induced cardiac remodeling remains unclear. Histidine decarboxylase (HDC) is the main enzyme involved in histamine production. Here, we clarified the roles of HDC-expressing cells and histamine in heart failure post-MI using HDC-EGFP transgenic mice and HDC-knockout (HDC−/−) mice. HDC+CD11b+ myeloid cell numbers markedly increased in the injured hearts, and histamine levels were up-regulated in the circulation post-MI. HDC−/− mice exhibited more adverse cardiac remodeling, poorer left ventricular function and higher mortality by increasing cardiac fibrogenesis post-MI. In vitro assays further confirmed that histamine inhibited heart fibroblast proliferation. Furthermore, histamine enhanced the signal transducer and activator of transcription (STAT)-6 phosphorylation level in murine heart fibroblasts, and the inhibitive effects of histamine on fibroblast proliferation could be blocked by JAK3/STAT6 signaling selective antagonist. STAT6-knockout (STAT6−/−) mice had a phenotype similar to that of HDC−/− mice post-MI; however, in contrast to HDC−/− mice, the beneficial effects of exogenous histamine injections were abrogated in STAT6−/− mice. These data suggest that histamine exerts protective effects by modulating cardiac fibrosis and remodeling post-MI, in part through the STAT6-dependent signaling pathway

RING finger 138 deregulation distorts NF-кB signaling and facilities colitis switch to aggressive malignancy

Prolonged activation of nuclear factor (NF)-кB signaling significantly contributes to the development of colorectal cancer (CRC). New therapeutic opportunities are emerging from targeting this distorted cell signaling transduction. Here, we discovered the critical role of RING finger 138 (RNF138) in CRC tumorigenesis through regulating the NF-кB signaling, which is independent of its Ubiquitin-E3 ligase activity involved in DNA damage response. RNF138(−/−) mice were hyper-susceptible to the switch from colitis to aggressive malignancy, which coincided with sustained aberrant NF-кB signaling in the colonic cells. Furthermore, RNF138 suppresses the activation of NF-кB signaling pathway through preventing the translocation of NIK and IKK-Beta Binding Protein (NIBP) to the cytoplasm, which requires the ubiquitin interaction motif (UIM) domain. More importantly, we uncovered a significant correlation between poor prognosis and the downregulation of RNF138 associated with reinforced NF-кB signaling in clinical settings, raising the possibility of RNF138 dysregulation as an indicator for the therapeutic intervention targeting NF-кB signaling. Using the xenograft models built upon either RNF138-dificient CRC cells or the cells derived from the RNF138-dysregulated CRC patients, we demonstrated that the inhibition of NF-кB signaling effectively hampered tumor growth. Overall, our work defined the pathogenic role of aberrant NF-кB signaling due to RNF138 downregulation in the cascade events from the colitis switch to colonic neoplastic transformation and progression, and also highlights the possibility of targeting the NF-кB signaling in treating specific subtypes of CRC indicated by RNF138-ablation

A spectral data release for 104 Type II Supernovae from the Tsinghua Supernova Group

We present 206 unpublished optical spectra of 104 type II supernovae obtained by the Xinglong 2.16m telescope and Lijiang 2.4m telescope during the period from 2011 to 2018, spanning the phases from about 1 to 200 days after the SN explosion. The spectral line identifications, evolution of line velocities and pseudo equivalent widths, as well as correlations between some important spectral parameters are presented. Our sample displays a large range in expansion velocities. For instance, the Fe~{\sc ii} $5169$ velocities measured from spectra at $t\sim 50$ days after the explosion vary from ${\rm 2000\ km\ s^{-1}}$to${\rm 5500\ km\ s^{-1}}$, with an average value of${\rm 3872 \pm 949\ km\ s^{-1}}$. Power-law functions can be used to fit the velocity evolution, with the power-law exponent quantifying the velocity decline rate. We found an anticorrelation existing between H$\beta$velocity at mid-plateau phase and its velocity decay exponent, SNe II with higher velocities tending to have smaller velocity decay rate. Moreover, we noticed that the velocity decay rate inferred from the Balmer lines (i.e., H$\alpha$and H$\beta$) have moderate correlations with the ratio of absorption to emission for H$\alpha$ (a/e). In our sample, two objects show possibly flash-ionized features at early phases. Besides, we noticed that multiple high-velocity components may exist on the blue side of hydrogen lines of SN 2013ab, possibly suggesting that these features arise from complex line forming region. All our spectra can be found in WISeREP and Zenodo