PEP-1-SOD1 fusion proteins block cardiac myofibroblast activation and angiotensin II-induced collagen production.

BACKGROUND: Oxidative stress is closely associated with cardiac fibrosis. However, the effect of copper, zinc-superoxide dismutase (SOD1) as a therapeutic agent is limited due to the insufficient transduction. This study was aimed to investigate the effect of PEP-1-SOD1 fusion protein on angiotensin II (ANG II)-induced collagen metabolism in rat cardiac myofibroblasts (MCFs). METHODS: MCFs were pretreated with SOD1 or PEP-1-SOD1 fusion protein for 2 h followed by incubation with ANG II for 24 h. Cell proliferation was measured by Cell Counting Kit-8. Superoxide anion productions were detected by both fluorescent microscopy and Flow Cytometry. MMP-1 and TIMP-1 were determined by ELISA. Intracellular MDA content and SOD activity were examined by commercial assay kits. Protein expression was analyzed by western blotting. RESULTS: PEP-1-SOD1 fusion protein efficiently transduced into MCF, scavenged intracellular O2 (-), decreased intracellular MDA content, increased SOD activity, suppressed ANG II-induced proliferation, reduced expression of TGF-ß1, α-SMA, collagen type I and III, restored MMP-1 secretion, and attenuated TIMP-1 secretion. CONCLUSION: PEP-1-SOD1 suppressed MCF proliferation and differentiation and reduced production of collagen type I and III. Therefore, PEP-1-SOD1 fusion protein may be a potential novel therapeutic agent for cardiac fibrosis.

Efficacy and safety of over-the-scope-clips in the therapy of acute nonvariceal upper gastrointestinal bleeding: Meta-analysis.

BACKGROUND: Acute nonvariceal upper gastrointestinal bleeding (ANVUGIB) is a frequent life-threatening acute condition in gastroenterology associated with high morbidity and mortality. Over-the-scope-clip (OTSC) is a new endoscopic hemostasis technique, which is being used in ANVUGIB and is more effective. AIM: To summarize and analyze the effects of the OTSC in prevention of recurrent bleeding, clinical success rate, procedure time, hospital stay, and adverse events in the treatment of ANVUGIB, to evaluate whether OTSC can replace standard endoscopic therapy as a new generation of treatment for ANVUGIB. METHODS: The literature related to OTSC and standard therapy for ANVUGIB published before January 2023 was searched in PubMed, Web of Science, EMBASE, Cochrane, Google, and CNKI databases. Changes in recurrent bleeding (7 or 30 days), clinical results (clinical success rate, conversion rate to surgery, mortality), therapy time (procedure time, hospital stay), and adverse events in the OTSC intervention group were summarized and analyzed, and the MD or OR of 95%CI is calculated by Review Manager 5.3. RESULTS: This meta-analysis involved 11 studies with 1266 patients. Total risk of bias was moderate-to-high. For patients in the OTSC group, 7- and 30-days recurrent bleeding rates, as well as procedure time, hospital stay, and intensive care unit stay, were greatly inhibited. OTSC could significantly improve the clinical success rate of ANVUGIB. OTSC therapy did not cause serious adverse and was effective in reducing patient mortality. CONCLUSION: OTSC may provide more rapid and sustained hemostasis, and thus, promote recovery and reduce mortality in patients with ANVUGIB. In addition, the safety of OTSC is assured.

[Retracted] MicroRNA­448 suppresses metastasis of pancreatic ductal adenocarcinoma through targeting JAK1/STAT3 pathway.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the western blot data shown in Figs. 4B and 7, the stratch­wound assay data shown in Figs. 2B and E and Fig. 6B, and the cellular images shown in Fig. 3 were strikingly similar to data appearing in different form in other articles written by different authors in different research institutions. Owing to the fact that the contentious data in the above article had already been published elsewhere prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 38: 1075­1082, 2017; DOI: 10.3892/or.2017.5781].

MicroRNA-448 suppresses metastasis of pancreatic ductal adenocarcinoma through targeting JAK1/STAT3 pathway.

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of malignant pancreatic tumor. MicroRNAs (miRNAs) are a group of small, non-protein coding, endogenous RNAs that play critical roles in tumorigenesis and progression of PDAC. In the present study, we demonstrated that miR-448 expression was downregulated in PDAC tissues and cell lines. Clinical association analysis indicated that low expression of miR-448 was associated with poor prognostic features and conferred a significant reduced survival of PDAC patients. Overexpression of miR-448 suppressed PDAC cell migration and invasion, while its loss showed the opposite effects on these cellular processes. In vivo experiments revealed that miR-488 restoration prohibited liver metastasis of PDAC in nude mice. Moreover, we found that Janus kinase 1 (JAK1) was a direct target gene of miR-448 in PDAC cells. We further demonstrated that the expression of JAK1 mRNA was upregulated in PDAC tissues. Notably, the expression of JAK1 mRNA was inversely correlated with the level of miR-448 in PDAC tissues. In addition, JAK1 knockdown showed similar effects of miR-448 on the metastasis of PDAC cells. JAK1/STAT3 pathway may be involved in the function of miR-448 in PDAC cells. Taken together, these findings suggest that miR-448 functions as a tumor suppressor in the development of PDAC through targeting the JAK1/STAT3 pathway.