Review of the Protective Mechanism of Curcumin on Cardiovascular Disease.

Cardiovascular diseases (CVDs) are the most common cause of death worldwide and has been the focus of research in the medical community. Curcumin is a polyphenolic compound extracted from the root of turmeric. Curcumin has been shown to have a variety of pharmacological properties over the past decades. Curcumin can significantly protect cardiomyocyte injury after ischemia and hypoxia, inhibit myocardial hypertrophy and fibrosis, improve ventricular remodeling, reduce drug-induced myocardial injury, improve diabetic cardiomyopathy(DCM), alleviate vascular endothelial dysfunction, inhibit foam cell formation, and reduce vascular smooth muscle cells(VSMCs) proliferation. Clinical studies have shown that curcumin has a protective effect on blood vessels. Toxicological studies have shown that curcumin is safe. But high doses of curcumin also have some side effects, such as liver damage and defects in embryonic heart development. This article reviews the mechanism of curcumin intervention on CVDs in recent years, in order to provide reference for the development of new drugs in the future.

Molecular mechanism of allosteric activation of the CRISPR ribonuclease Csm6 by cyclic tetra-adenylate.

Type III CRISPR systems are innate immune systems found in bacteria and archaea, which produce cyclic oligoadenylate (cOA) second messengers in response to viral infections. In these systems, Csm6 proteins serve as ancillary nucleases that degrade single-stranded RNA (ssRNA) upon activation by cOA. In addition, Csm6 proteins also possess cOA-degrading activity as an intrinsic off-switch to avoid degradation of host RNA and DNA that would eventually lead to cell dormancy or cell death. Here, we present the crystal structures of Thermus thermophilus (Tt) Csm6 alone, and in complex with cyclic tetra-adenylate (cA4) in both pre- and post-cleavage states. These structures establish the molecular basis of the long-range allosteric activation of TtCsm6 ribonuclease by cA4. cA4 binding induces significant conformational changes, including closure of the CARF domain, dimerization of the HTH domain, and reorganization of the R-X4-6-H motif within the HEPN domain. The cleavage of cA4 by the CARF domain restores each domain to a conformation similar to its apo state. Furthermore, we have identified hyperactive TtCsm6 variants that exhibit sustained cA4-activated RNase activity, showing great promise for their applications in genome editing and diagnostics.

Review of the Protective Mechanism of Paeonol on Cardiovascular Disease.

Cardiovascular disease (CVD) is one of the leading causes of death in the world. Paeonol(Pae) is a phenolic component extracted from peony bark, peony root and Xu Changqing. Studies have shown that Pae can protect cardiomyocytes by inhibiting oxidative stress, promoting mitochondrial fusion, regulating mitochondrial autophagy and inhibiting inflammation. In addition, Pae improves ventricular remodeling by inhibiting myocardial apoptosis, hypertrophy and fibrosis. Pae also has a good protective effect on blood vessels by inhibiting vascular inflammation, reducing the expression of adhesion molecules, inhibiting vascular proliferation, and inhibiting oxidative stress and endoplasmic reticulum stress(ERS). Pae also has the effect of anti-endothelial cell senescence, promoting thrombus recanalization and vasodilating. In conclusion, the molecular targets of Pae are very complex, and the relationship between different targets and signaling pathways cannot be clearly explained, which requires us to use systems biology methods to further study specific molecular targets of Pae. It has to be mentioned that the bioavailability of Pae is poor, and some nanotechnology-assisted drug delivery systems improve the therapeutic effect of Pae. We reviewed the protective mechanism of paeonol on the cardiovascular system, hoping to provide help for drug development in the treatment of CVD.

A new treatment strategy for airway obstruction induced by a giant benign goiter: A case report.

Severe respiratory distress induced by airway obstruction requires prompt attention for restoration of normal function in the airway passage. A large benign thyroid goiter that compresses the trachea is a rare occurrence. Emergency thyroidectomy with dyspnea can increase the chance of surgical complications in such cases. Here, a rare case of dyspnea induced by a large goiter is reported and a safe and effective therapeutic strategy for treatment was demonstrated. First, a self-expandable metal stent was placed to relieve airway obstruction. A week later, total thyroidectomy under general anesthesia was performed. After 3 months, the metal stent was surgically removed. The findings of the present case report demonstrated that life-threatening airway obstruction secondary to benign goiter could be effectively treated by placing an airway stent, followed by thyroidectomy.

Differentially expressed TUG1 and miR-145-5p indicate different severity of chronic heart failure and predict 2-year survival prognosis.

Long non-coding RNAs (lncRNAs) and microRNAs (miRs) have critical roles in the progression of various diseases. The present study aimed to investigate the levels and clinical significance of lncRNA taurine upregulated gene 1 (TUG1) and miR-145-5p in patients with chronic heart failure (CHF) and explore their indicative value regarding disease severity. TUG1 and miR-145-5p levels were detected by reverse-transcription quantitative PCR. Correlations were examined using Pearson's correlation analysis. Receiver operating characteristic analysis was used to evaluate the diagnostic value of TUG1, miR-145-5p and brain natriuretic peptide (BNP). Survival analysis was performed by the Kaplan-Meier method. Cox regression analysis was used to evaluate the prognostic value of TUG1 and miR-145-5p. The levels of interleukin-6 and tumor necrosis factor-α in serum were detected by ELISA. The results indicated that TUG1 was upregulated and miR-145-5p was downregulated in patients with CHF and they were negatively correlated. TUG1 and miR-145-5p were associated with the left ventricle ejection fraction and were able to indicate the severity of CHF. Serum TUG1 and miR-145-5p had a certain diagnostic value and the combination of BNP, TUG1 and miR-145-5p had high diagnostic accuracy. TUG1 and miR-145-5p were closely associated with overall survival and may function as independent prognostic biomarkers for patients with CHF. In addition, TUG1 and miR-145-5p levels were markedly correlated with inflammation in CHF. Upregulated TUG1 and downregulated miR-145-5p may indicate the severity of CHF, may serve as diagnostic and prognostic biomarkers and may be involved in CHF progression by regulating inflammatory responses.

Hsa-miR-599 suppresses the migration and invasion by targeting BRD4 in breast cancer.

Breast cancer is the second leading cause of cancer-associated mortality in females in the USA. Hsa-miR-599 was demonstrated to function as a tumour suppressor during cancer progression. However, the function and mechanism of the hsa-miR-599 in human breast cancer remain elusive. Thus, the aim of the present study was to investigate the potential role of hsa-miR-599 in breast cancer biology. The expression levels of hsa-miR-599 in 40 pairs of surgical specimens and human breast cancer cell lines were detected using quantitative polymerase chain reaction analysis. The overexpression of hsa-miR-599 was established by transfecting mimics into the MCF-7 and MDA-MB-231 cell lines. Cell counting kit-8, colony formation and transwell assays were used to investigate the potential function of hsa-miR-599 in MCF-7 and MDA-MB-231 cell lines. Luciferase assays combined with western blot analysis was performed to validate the regulation of a putative target of hsa-miR-599. The results demonstrated that hsa-miR-599 was downregulated in the breast cancer tissues and breast cancer cell lines. Overexpression of hsa-miR-599 was revealed to inhibit the viability and proliferation of cell in vitro and tumour growth in vivo. The results of the luciferase assay indicate that bromodomain containing 4 (BRD4) is a direct target of hsa-miR-599. Furthermore, the xenograft mouse model demonstrated that overexpressed hsa-miR-599 reduced BRD4 expression. These results suggest that hsa-miR-599 serves as an oncosuppressive microRNA that impairs breast cancer tumorigenesis and progression by directly targeting BRD4. Furthermore, increased BRD4 expression partially reversed the suppressive effect of hsa-miR-599. In conclusion, the results of the present study demonstrated that hsa-miR-599 suppressed breast cancer progression by downregulating BRD4. The overexpression of hsa-miR-599 may be considered as a novel therapeutic target for the treatment of patients with breast cancer.

BRD4 induces cell migration and invasion in HCC cells through MMP-2 and MMP-9 activation mediated by the Sonic hedgehog signaling pathway.

Hepatocellular carcinoma (HCC) is a highly aggressive form of carcinoma with poor prognosis, and HCC-associated mortality primarily occurs due to migration and invasion of HCC cells. The manipulation of epigenetic proteins, such as BRD4, has recently emerged as an alternative therapeutic strategy. The present study aimed to investigate the novel mechanism of BRD4 involvement in the migration and invasion of HCC cells. Reverse transcription-quantitative polymerase chain reaction was used to assess BRD4 mRNA expression levels in HCC cell lines. This analysis demonstrated that BRD4 was significantly overexpressed in HCC cell lines compared with a human immortalized normal liver cell line. A short hairpin RNA (shRNA) was then used to suppress BRD4 expression in HCC cells, and resulted in impaired HCC cell proliferation, migration and invasion. When the HepG2 HCC cell line was treated with recombinant human sonic hedgehog (SHH) peptide, the migration and invasion capabilities of HepG2 cells that were inhibited by BRD4 silencing were restored. BRD4 induced cell migration and invasion in HepG2 cells through the activation of matrix metalloproteinase (MMP)-2 and MMP-9, mediated by the SHH signaling pathway. Taken together, the results of the present study demonstrated the importance of BRD4 in HCC cell proliferation and metastasis. Thus, BRD4 is a potential novel target for the development of therapeutic approaches against HCC.