20(S)-ginsenoside Rg3 exerts anti-fibrotic effect after myocardial infarction by alleviation of fibroblasts proliferation and collagen deposition through TGFBR1 signaling pathways.

Background: Myocardial fibrosis post-myocardial infarction (MI) can induce maladaptive cardiac remodeling as well as heart failure. Although 20(S)-ginsenoside Rg3 (Rg3) has been applied to cardiovascular diseases, its efficacy and specific molecular mechanism in myocardial fibrosis are largely unknown. Herein, we aimed to explore whether TGFBR1 signaling was involved in Rg3's anti-fibrotic effect post-MI. Methods: Left anterior descending (LAD) coronary artery ligation-induced MI mice and TGF-ß1-stimulated primary cardiac fibroblasts (CFs) were adopted. Echocardiography, hematoxlin-eosin and Masson staining, Western-blot and immunohistochemistry, CCK8 and Edu were used to study the effects of Rg3 on myocardial fibrosis and TGFBR1 signaling. The combination mechanism of Rg3 and TGFBR1 was explored by surface plasmon resonance imaging (SPRi). Moreover, myocardial Tgfbr1-deficient mice and TGFBR1 adenovirus were adopted to confirm the pharmacological mechanism of Rg3. Results: In vivo experiments, Rg3 ameliorated myocardial fibrosis and hypertrophy and enhanced cardiac function. Rg3-TGFBR1 had the 1.78 × 10-7 M equilibrium dissociation constant based on SPRi analysis, and Rg3 inhibited the activation of TGFBR1/Smads signaling dose-dependently. Cardiac-specific Tgfbr1 knockdown abolished Rg3's protection against myocardial fibrosis post-MI. In addition, Rg3 down-regulated the TGF-ß1-mediated CFs growth together with collagen production in vitro through TGFBR1 signaling. Moreover, TGFBR1 adenovirus partially blocked the inhibitory effect of Rg3. Conclusion: Rg3 improves myocardial fibrosis and cardiac function through suppressing CFs proliferation along with collagen deposition by inactivation of TGFBR1 pathway.

Long non-coding RNA MALAT1 regulates cell proliferation and apoptosis via miR-135b-5p/GPNMB axis in Parkinson's disease cell model.

BACKGROUNDS: Parkinson's disease (PD) is a common age-related neurodegenerative disorder worldwide. This research aimed to investigate the effects and mechanism underlying long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in PD. METHODS: SK-N-SH and SK-N-BE cells were treated with MPP+ to establish the MPP+-stimulated cell model of PD, and MALAT1 expression was determined. Then, the effects of MALAT1 depletion on cell proliferation and apoptosis were determined in the MPP+-stimulated cell model of PD. Besides, the correlations between microRNA-135b-5p (miR-135b-5p) and MALAT1 or glycoprotein nonmetastatic melanoma protein B (GPNMB) in MPP+-stimulated cell model of PD were explored. RESULTS: MALAT1 was increasingly expressed and downregulation of MALAT1 promoted cell proliferation while inhibited apoptosis in MPP+-stimulated cells. Besides, miR-135b-5p was a target of MALAT1 and directly targeted to GPNMB. Further investigation indicated that suppression of MALAT1 regulated cell proliferation and apoptosis by miR-135b-5p/GPNMB axis. CONCLUSION: Our findings reveal that MALAT1/miR-135b-5p/GPNMB axis regulated cell proliferation and apoptosis in MPP+-stimulated cell model of PD, providing a potential biomarker and therapeutic target for PD.

Long non-coding RNA MALAT1 regulates cell proliferation and apoptosis via miR-135b-5p/GPNMB axis in Parkinson's disease cell model

BACKGROUNDS: Parkinson's disease (PD) is a common age-related neurodegenerative disorder worldwide. This research aimed to investigate the effects and mechanism underlying long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in PD. METHODS: SK-N-SH and SK-N-BE cells were treated with MPP+ to establish the MPP+-stimulated cell model of PD, and MALAT1 expression was determined. Then, the effects of MALAT1 depletion on cell proliferation and apoptosis were determined in the MPP+-stimulated cell model of PD. Besides, the correlations between microRNA-135b-5p (miR-135b-5p) and MALAT1 or glycoprotein nonmetastatic melanoma protein B (GPNMB) in MPP+-stimulated cell model of PD were explored. RESULTS: MALAT1 was increasingly expressed and downregulation of MALAT1 promoted cell proliferation while inhibited apoptosis in MPP+-stimulated cells. Besides, miR-135b-5p was a target of MALAT1 and directly targeted to GPNMB. Further investigation indicated that suppression of MALAT1 regulated cell proliferation and apoptosis by miR-135b-5p/GPNMB axis. CONCLUSION: Our findings reveal that MALAT1/miR-135b-5p/GPNMB axis regulated cell proliferation and apoptosis in MPP+-stimulated cell model of PD, providing a potential biomarker and therapeutic target for PD.

Epidemic of Klebsiella pneumoniae ST11 clone coproducing KPC-2 and 16S rRNA methylase RmtB in a Chinese University Hospital.

BACKGROUND: Emergence of rmtB-positive Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-KP) poses a great threat to antimicrobial treatment options. METHODS: From January 2010 to December 2010, non-duplicate KPC-KP isolates from our hospital were screened for rmtB and multiple other resistance determinants with PCR. Subsequent studies included MIC determination, PFGE, and multilocus sequence typing. Records from patients with KPC-KP isolated were retrospectively reviewed. Comparisons of molecular and clinical characteristics between rmtB-positive and rmtB-negative isolates were systematically performed, as well as the environmental colonization study in ICU wards. RESULTS: A total of 84 KPC-KP strains were collected, including 48 rmtB-positive KPC-KP (RPKP) and 36 rmtB-negative KPC-KP (RNKP) isolates. All KPC-KP isolates were multidrug resistant, with colistin and tigecycline being the most active agents. Compared with RNKP, RPKP displayed a much severer resistance phenotype. Susceptibility rates for amikacin (0% for RPKP versus 88.9% for RNKP, p < 0.01), fosfomycin (8.5% for RPKP versus 88.9% for RNKP, p < 0.01), and minocycline (6.7% for RPKP versus 52.8% for RNKP, p < 0.01), were all significantly lower in RPKP strains. Isolates belonging to PFGE pulsetype A and sequence type 11 were predominant in both groups, including 39 (81.3%) RPKP and 22 (61.1%) RNKP isolates. Nevertheless, RNKP showed more complex genetic backgrounds compared with RPKP. Diverse clinical characteristics were found in both cohorts, however, no significant differences were observed between RPKP and RNKP patients. CONCLUSIONS: RPKP strains have spread widely and gradually replaced RNKP in our hospital. They seemed to show much severer resistance phenotypes compared with RNKP and had a bigger dissemination potential. Prudent use of available active agents combined with good control practices is therefore mandatory.

[Electrophysiological effect of atorvastatin on isolated rat hearts injured by ischemia/reperfusion].

OBJECTIVE: To investigate the myocardial electrophysiological effect and its underlying mechanisms of atorvastatin (Ator) on isolated rat hearts injured by ischemia/reperfusion (I/R). METHODS: Isolated SD rat hearts were mounted on Langendorff system, and a local I/R was induced by ligation (30 min) and release (15 min) of the left anterior descending artery. During the reperfusion period, the effect of Ator on diastolic excitation threshold (DET), effective refractory period (ERP) and ventricular fibrillation threshold (VFT) on rat heart were measured. RESULT: Compared with the control group, medium concentration of Ator prolonged the ERP in normal rat hearts; low, medium and high concentration of Ator significantly inhibited the decrease of DET, ERP and VFT induced by I/R. However, pretreatment with L-NAME cancelled these cardiac electrophysiological effects of Ator. CONCLUSION: Ator reduced electrophysiological alteration induced by I/R in isolated rat hearts, which may be mediated by activating nitric oxide pathway to enhance the myocardial electrophysiological stability.