Jin Guo

BACKGROUND: Myocardial ischemia/reperfusion injury is the major cause of morbidity and mortality for cardiovascular diseases. Dopamine D2 receptors are expressed in cardiac tissues. However, the roles of dopamine D2 receptors in myocardial ischemia/reperfusion injury and cardiomyocyte apoptosis are unclear. Here we investigated the effects of both dopamine D2 receptors agonist (bromocriptine) and antagonist (haloperidol) on apoptosis of cultured neonatal rat ventricular myocytes induced by ischemia/reperfusion injury. METHODS: Myocardial ischemia/reperfusion injury was simulated by incubating primarily cultured neonatal rat cardiomyocytes in ischemic (hypoxic) buffer solution for 2 h. Thereafter, these cells were incubated for 24 h in normal culture medium. RESULTS: Treatment of the cardiomyocytes with 10 μM bromocriptine significantly decreased lactate dehydrogenase activity, increased superoxide dismutase activity, and decreased malondialdehyde content in the culture medium. Bromocriptine significantly inhibited the release of cytochrome c, accumulation of [Ca2+]i, and apoptosis induced by ischemia/reperfusion injury. Bromocriptine also down-regulated the expression of caspase-3 and -9, Fas and Fas ligand, and up-regulated Bcl-2 expression. In contrast, haloperidol (10 μM) had no significant effects on the apoptosis of cultured cardiomyocytes under the aforementioned conditions. CONCLUSIONS: These data suggest that activation of dopamine D2 receptors can inhibit apoptosis of cardiomyocytes encountered during ischemia/reperfusion damage through various pathways.

BACKGROUND: Osteosarcoma (OS) is a common primary bone malignancy. Long noncoding RNA HCG18 is known to play an important role in a variety of cancers. However, its role in OS and relevant molecular mechanisms are unclear. METHODS: Real-time quantitative PCR was performed to determine the expression of target genes. Function experiments showed the effects of HCG18 and miR-365a-3p on OS cell growth. RESULTS: HCG18 expression was increased in OS cell lines. Moreover, in vitro and in vivo experiments demonstrated that HCG18 knockdown inhibited OS cell proliferation. Mechanistically, HCG18 was defined as a competing endogenous RNA by sponging miR-365a-3p, thus elevating phosphoglycerate kinase 1 (PGK1) expression by directly targeting its 3'UTR to increase aerobic glycolysis. CONCLUSION: HCG18 promoted OS cell proliferation via enhancing aerobic glycolysis by regulating the miR-365a-3p/PGK1 axis. Therefore, HCG18 may be a potential target for OS treatment.

The Hippo pathway is an evolutionarily conserved regulator of tissue growth and cell fate during development and regeneration. Conversely, deregulation of the Hippo pathway has been reported in several malignancies. Here, we used integrative functional genomics approaches to identify TAZ, a transcription co-activator and key downstream effector of the Hippo pathway, as an essential driver for the propagation of TNBC malignant phenotype. We further showed in non-transformed human mammary basal epithelial cells that expression of constitutively active TAZ confers cancer stem cell (CSC) traits that are dependent on the TAZ and TEAD interacting domains. In addition, to gain a better understanding of how TAZ functions, we performed genetic-function analysis of TAZ. Significantly, we identified that both the WW and transcriptional activation domains of TAZ are critical for the induced CSC properties as well as tumorigenic potential as manifested in vitro and in human breast cancer xenograft in vivo. Collectively, our data suggest that pharmacological inhibition of TAZ activity may provide a novel means of targeting and eliminating breast CSCs.

AIM: To investigate the underlying mechanism by which CXCL12 and CXCL6 influences the metastatic potential of colon cancer and internal relation of colon cancer and stromal cells. METHODS: Western blotting was used to detect the expression of CXCL12 and CXCL6 in colon cancer cells and stromal cells. The co-operative effects of CXCL12 and CXCL6 on proliferation and invasion of colon cancer cells and human umbilical vein endothelial cells (HUVECs) were determined by enzyme-linked immunosorbent assay, and proliferation and invasion assays. The angiogenesis of HUVECs through interaction with cancer cells and stromal cells was examined by angiogenesis assay. We eventually investigated activation of PI3K/Akt/mTOR signaling by CXCL12 involved in the metastatic process of colon cancer. RESULTS: < 0.01). CXCL12 also enhanced the invasion of colon cancer cells. Stromal cell-derived CXCL12 promoted the secretion level of CXCL6 and co-operatively promoted metastasis of colon carcinoma through activation of the PI3K/Akt/mTOR pathway. CONCLUSION: the PI3K/Akt/mTOR signaling pathway. Blocking this pathway may be a potential anti-metastatic therapeutic target for patients with colon cancer.

We develop a fiber optical coherence tomography (OCT) system in the clinical utility of imaging port wine stains (PWS). We use our OCT system on 41 patients with PWS to document the difference between PWS skin and contralateral normal skin. The system, which operates at 4 frames with axial and transverse resolutions of 10 and 9 mum, respectively, in the skin tissue, can clearly distinguish the dilated dermal blood vessels from normal tissue. We present OCT images of patients with PWS and normal human skin. We obtain the structural parameters, including epidermal thickness and diameter and depth of dilated blood vessels. We demonstrate that OCT may be a useful tool for the noninvasive imaging of PWS. It may help determine the photosensitizer dose and laser parameters in photodynamic therapy for treating port wine stains.