Geldanamycin, an inhibitor of Hsp90, increases paclitaxel-mediated toxicity in ovarian cancer cells through sustained activation of the p38/H2AX axis.

Paclitaxel is a mitotic inhibitor used in ovarian cancer chemotherapy. Unfortunately, due to the rapid genetic and epigenetic changes in adaptation to stress induced by anticancer drugs, cancer cells are often able to become resistant to single or multiple anticancer agents. However, it remains largely unknown how paclitaxel resistance happens.

Low CDX1 expression predicts a poor prognosis for hepatocellular carcinoma patients after hepatectomy.

The caudal-type homeobox 1 (CDX1) transcription factor is a member of the caudal-related homeobox transcription factor gene family and has been reported to be down-regulated in a variety of cancers. However, the expression status and significance of CDX1 in hepatocellular carcinoma (HCC) is still controversial, and little is known about the role of CDX1 in HCC·In our previous study, we investigated the expression and clinical significance of CDX1 in HCC samples from 313 HCC patients. We found CDX1 was strikingly down-regulated in HCC samples.

Defining HIV and SIV Reservoirs in Lymphoid Tissues.

A primary obstacle to an HIV-1 cure is long-lived viral reservoirs, which must be eliminated or greatly reduced. Cure strategies have largely focused on monitoring changes in T cell reservoirs in peripheral blood (PB), even though the lymphoid tissues (LT) are primary sites for viral persistence. To track and discriminate viral reservoirs within tissue compartments we developed a specific and sensitive next-generation hybridization approach to detect vRNA, including vRNA+ cells and viral particles ("RNAscope"), vDNA+ cells ("DNAscope") and combined vRNA and vDNA with immunohistochemistry to detect and phenotype active and latently infected cells in the same tissue section.

Correlation of EGFR Del 19 with Fn14/JAK/STAT signaling molecules in non-small cell lung cancer.

Previous research has shown that p-EGFR (particularly mutated EGFR) may activate fibroblast growth factor-inducible 14 (Fn14) expression in non-small cell lung cancer (NSCLC), and the JAK/STAT signaling pathway may participate in this process. Thus, in order to verify this hypothesis, correlations among the expression levels of EGFR Del 19, Fn14 and JAK/STAT were detected and analyzed. The expression and location of these molecules were assessed using IHC, immunohistofluorescence, RT-qPCR and western blotting.

Inhibiting CREPT reduces the proliferation and migration of non-small cell lung cancer cells by down-regulating cell cycle related protein.

It has been reported that CREPT acts as a highly expressed oncogene in a variety of tumors, affecting cyclin D1 signal pathways. However, the distribution and clinical significance of CREPT in NSCLC remains poorly understood. Our study focused on the role of CREPT on the regulation ofnon-small cell lung cancer (NSCLC).

An optogenetic mouse model of rett syndrome targeting on catecholaminergic neurons.

Rett syndrome (RTT) is a neurodevelopmental disorder affecting multiple functions, including the norepinephrine (NE) system. In the CNS, NE is produced mostly by neurons in the locus coeruleus (LC), where defects in intrinsic neuronal properties, NE biosynthetic enzymes, neuronal CO2 sensitivity, and synaptic currents have been reported in mouse models of RTT. LC neurons in methyl-CpG-binding protein 2 gene (Mecp2) null mice show a high rate of spontaneous firing, although whether such hyperexcitability might increase or decrease the NE release from synapses is unknown.

Characterization of Rett Syndrome-like phenotypes in Mecp2-knockout rats.

Background: Rett Syndrome (RTT) is a neurodevelopmental disease caused by the disruption of the MECP2 gene. Several mouse models of RTT have been developed with Mecp2 disruptions. Although the mouse models are widely used in RTT research, results obtained need to be validated in other species.

Preoperative intra-aortic balloon pump improves the clinical outcomes of off-pump coronary artery bypass grafting in left ventricular dysfunction patients.

Severe left ventricular (LV) dysfunction patients undergoing off-pump coronary artery bypass grafting (OPCAB) are often associated with a higher mortality. The efficacy and safety of the preoperative prophylactic intra-aortic balloon pump (IABP) insertion is not well established. 416 consecutive patients with severe LV dysfunction (ejection fraction ≤35%) undergoing isolated OPCAB were enrolled in a retrospective observational study.

Detection of EML4-ALK fusion gene and features associated with EGFR mutations in Chinese patients with non-small-cell lung cancer.

Purpose: Echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) and epidermal growth factor receptor (EGFR) define specific molecular subsets of lung cancer with distinct clinical features. We aimed at revealing the clinical features of EML4-ALK fusion gene and EGFR mutation in non-small-cell lung cancer (NSCLC).

Methods: We enrolled 694 Chinese patients with NSCLC for analysis.

The p38 MAPK inhibitor BIRB796 enhances the antitumor effects of VX680 in cervical cancer.

VX680 is a potent and selective inhibitor that targets the Aurora kinase family. The p38 mitogen-activated protein kinase (MAPK) regulates a large number of cellular pathways and plays an important role in the regulation of cell survival and apoptosis. This study aimed to evaluate the effect of VX680 on cervical cancer cells and investigate whether the effects on apoptosis are enhanced by the ablation of p38 MAPK activation.

A novel supramolecular polymer gel constructed by crosslinking pillar[5]arene-based supramolecular polymers through metal-ligand interactions.

A novel heteroditopic A-B monomer was synthesized and used to construct linear supramolecular polymers utilizing pillar[5]arene-based host-guest interactions. Specifically, upon addition of Cu(2+) ions, the supramolecular polymer chains are crosslinked through metal-ligand interactions, resulting in the formation of a supramolecular polymer gel. Interestingly, this self-organized supramolecular polymer can be used as a novel fluorescent sensor for detecting Cu(2+) ions.

Activation of ERK pathway is required for 15-HETE-induced angiogenesis in human umbilical vascular endothelial cells.

Angiogenesis plays a critical role in the progression of cardiovascular disease, retinal ischemia, or tumorigenesis. The imbalance of endothelial cell proliferation and apoptosis disturbs the establishment of the vasculogenesis, which is affected by several arachidonic acid metabolites. 15-Hydroxyeicosatetraenoic acid (15-HETE) is one of the metabolites.

A responsive supramolecular metallogel constructed by coordination-driven self-assembly of a crown ether-based [3]pseudorotaxane and a diplatinum(II) acceptor.

Herein, a stimuli-responsive supramolecular metallogel was prepared by orthogonal coordination-driven self-assembly of a crown ether-based [3]pseudorotaxane and a 180° organic di-Pt(II) acceptor.

MicroRNA-30c contributes to the development of hypoxia pulmonary hypertension by inhibiting platelet-derived growth factor receptor β expression.

Pulmonary arterial hypertension (PAH) is characterized by excessive proliferation and resistance to apoptosis of pulmonary artery smooth muscle cells (PASMCs). MicroRNAs have been implicated in the regulation of cell proliferation and might be implicated in the etiology of PAH. Data from in vivo and in vitro cell culture models showed that hypoxia inhibits microRNA-30c (miR-30c) expression in PASMCs.

Inhibition of CXCL12/CXCR4 suppresses pulmonary arterial smooth muscle cell proliferation and cell cycle progression via PI3K/Akt pathway under hypoxia.

Stromal cell-derived factor 1 (CXCL12) and its receptor CXC chemokine receptor 4 (CXCR4) are known to modulate hypoxia-induced pulmonary hypertension (PH) and vascular remodeling by mobilization and recruitment of progenitor cells to the pulmonary vasculature. However, little is known about CXCL12/CXCR4 regulating proliferation and cell cycle progression of pulmonary arterial smooth muscle cells (PASMCs). To determine whether CXCL12/CXCR4 regulates PASMC proliferation and the cell cycle, immunohistochemistry, Western blot, bromodeoxyuridine incorporation and cell cycle analysis were preformed in this study.

Supramolecular side-chain poly[2]pseudorotaxanes formed by orthogonal coordination-driven self-assembly and crown-ether-based host-guest interactions.

The themes of coordination-driven self-assembly, host-guest interactions, and supramolecular polymerization are unified in an orthogonal noninterfering fashion to deliver side-chain poly[2]pseudorotaxanes. Specifically, a bis(p-phenylene)-34-crown-10 derivative 1 bearing two pyridyl groups polymerizes into a side-chain poly[2]pseudorotaxane upon the addition of di-Pt(II) acceptor 4 in the presence of paraquat. Interestingly, by adding a competitive guest 3, the poly[2]pseudorotaxane can realize a conversion in one pot.

Effects of intra-aortic balloon pump on cerebral blood flow during peripheral venoarterial extracorporeal membrane oxygenation support.

Background: The addition of an intra-aortic balloon pump (IABP) during peripheral venoarterial extracorporeal membrane oxygenation (VA ECMO) support has been shown to improve coronary bypass graft flows and cardiac function in refractory cardiogenic shock after cardiac surgery. The purpose of this study was to evaluate the impact of additional IABP support on the cerebral blood flow (CBF) in patients with peripheral VA ECMO following cardiac procedures.

Methods: Twelve patients (mean age 60.

microRNA-199a is able to reverse cisplatin resistance in human ovarian cancer cells through the inhibition of mammalian target of rapamycin.

microRNAs (miRNAs/miRs) may have a crucial function in tumor metastasis through the regulation of a plethora of signaling pathways. Increasing evidence has shown that miR-199a is important in regulating the tumor metastasis of ovarian cancer, although the precise biological function of miR-199a is unclear at present. In the current study, it was observed that the expression levels of miR-199a were higher in OV2008 cells compared with C13* cells.

[Expression of IL-27 in multiple myeloma and its cell lines].

Objective: To study the expression and significance of IL-27 in patients with multiple myeloma (MM) and in the supernatant of MM cell lines U266 and RPMI8226 cells culture medium.

Methods: A total of 20 MM patients and 20 controls were enrolled in this study. The expressions of IL-27 and IL-6 in MM patient's blood plasma, and the expression of IL-27 in U266 and RPMI8226 culture supernatant were measured by enzyme-linked immunosorbent assay (ELISA).

Urinary trypsin inhibitor attenuated inflammatory response of patients undergoing cardiopulmonary bypass by inducing activated Treg cells.

The urinary trypsin inhibitor (ulinastatin) is used in the clinic to prevent inflammatory responses in patients undergoing cardiopulmonary bypass (CPB); however, the anti-inflammatory mechanism is unclear. In the current study, we recruited 40 patients undergoing selective cardiac valve replacement surgery; and these patients were randomly divided into two groups (ulinastatin group [UG] and control group [CG]). We collected peripheral blood preoperatively, at the end of CPB, and postoperative days 1 and 3 and analyzed the kinetic changes in regulatory T (Treg) cell subsets.

Biliverdin reductase/bilirubin mediates the anti-apoptotic effect of hypoxia in pulmonary arterial smooth muscle cells through ERK1/2 pathway.

Inhibition of pulmonary arterial smooth muscle cell (PASMC) apoptosis induced by hypoxia plays an important role in pulmonary arterial remodeling leading to aggravate hypoxic pulmonary arterial hypertension. However, the mechanisms of hypoxia acting on PASMC apoptosis remain exclusive. Biliverdin reductase (BVR) has many essential biologic roles in physiological and pathological processes.

Reduced inflammation and lymphoid tissue immunopathology in rhesus macaques receiving anti-tumor necrosis factor treatment during primary simian immunodeficiency virus infection.

Background: Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infections induce robust, generalized inflammatory responses that begin during acute infection and lead to pathological systemic immune activation, fibrotic damage of lymphoid tissues, and CD4⁺ T-cell loss, pathogenic processes that contribute to disease progression.

Methods: To better understand the contribution of tumor necrosis factor (TNF), a key regulator of acute inflammation, to lentiviral pathogenesis, rhesus macaques newly infected with SIVmac239 were treated for 12 weeks in a pilot study with adalimumab (Humira), a human anti-TNF monoclonal antibody.

Results: Adalimumab did not affect plasma SIV RNA levels or measures of T-cell immune activation (CD38 or Ki67) in peripheral blood or lymph node T cells.

Differential infection patterns of CD4+ T cells and lymphoid tissue viral burden distinguish progressive and nonprogressive lentiviral infections.

Nonhuman primate natural hosts for simian immunodeficiency viruses (SIV) develop a nonresolving chronic infection but do not develop AIDS. Mechanisms to explain the nonprogressive nature of SIV infection in natural hosts that underlie maintained high levels of plasma viremia without apparent loss of target cells remain unclear. Here we used comprehensive approaches (ie, FACS sorting, quantitative RT-PCR, immunohistochemistry, and in situ hybridization) to study viral infection within subsets of peripheral blood and lymphoid tissue (LT) CD4(+) T cells in cohorts of chronically SIV-infected rhesus macaques (RMs), HIV-infected humans, and SIVsmm-infected sooty mangabeys (SMs).