Differentiation of ROMK potency from hERG potency in the phenacetyl piperazine series through heterocycle incorporation.

Following the discovery of small molecule acyl piperazine ROMK inhibitors and their initial preclinical validation as a novel diuretic agent, our group set out to discover new ROMK inhibitors with reduced risk for QT effects, suitable for further pharmacological experiments in additional species. Several strategies for decreasing hERG affinity while maintaining ROMK inhibition were investigated and are described herein. The most promising candidate, derived from the newly discovered 4-N-heteroaryl acetyl series, improved functional hERG/ROMK ratio by >10× over the previous lead.

Concentrated growth factor promotes Schwann cell migration partly through the integrin β1-mediated activation of the focal adhesion kinase pathway.

Nerve injury is a serious complication associated with dental implant surgery. Following nerve injury, the migration of Schwann cells (SCs) supports nerve regeneration. Concentrated growth factor (CGF) belongs to a new generation of biomaterials that contain fibrin matrix, as well as a number of growth factors that affect the migration of various types of cells, including endothelial cells and cancer cells.

Tenascin C affects mineralization of SaOS2 osteoblast-like cells through matrix vesicles.

Tenascin C (TNC) is an extracellular matrix glycoprotein involved in osteogenesis and bone mineralization. In a previous study, we identified TNC protein located in the matrix vesicles (MVs) of osteoblasts. MVs are determinant in the mineralization formation.

Association Between Dentin Matrix Protein 1 (rs10019009) Polymorphism and Ankylosing Spondylitis in a Chinese Han Population from Shandong Province.

Background: Ankylosing spondylitis (AS) is the most common rheumatic condition that is slowly progressive and predominantly affects adolescents. Pathological bone formation associated with AS is an important cause of disability. The aim of the study was to investigate the possible involvement of the genes related to endochondral ossification and ectopia ossification in genetic susceptibility to AS in a Chinese Han population.

Significance of Programmed Death Ligand 1 (PD-L1) Immunohistochemical Expression in Colorectal Cancer.

Introduction: The significance of programmed death ligand 1 (PD-L1) expression in the prognosis of patients with colorectal cancer remains to be determined.

Methods: We assessed the levels of PD-L1 expression in tumor-infiltrating immune cells as well as tumor cells, and evaluated the association between PD-L1 expression and clinical outcome in 262 colorectal cancer patients.

Results: In univariate analysis, TNM stage (p < 0.

Immunohistochemistry and microsatellite instability analysis in molecular subtyping of colorectal carcinoma based on mismatch repair competency.

Mismatch repair defective (MMRd) colorectal carcinoma (CRC) is a distinct molecular phenotype of colorectal cancer, including 12% of sporadic CRC and 3% of Lynch Syndrome. In order to investigate the clinicopathological characteristics of MMRd colorectal carcinoma, and to find the most effective method for preliminary screening, 296 CRC fulfilled revised Bethesda Guideline (RB) were selected from 1450 CRCs to perform both IHC staining for MLH1, MSH2, MSH6, PMS2 and MSI analysis. Sixty-eight tumors were classified as MSI-H by MSI test.

Diagnosis of adults Xp11.2 translocation renal cell carcinoma by immunohistochemistry and FISH assays: clinicopathological data from ethnic Chinese population.

This study aimed to assess the utility of transcription factor E3 (TFE3) break-apart fluorescence in situ hybridization (FISH) assay in diagnosis of Xp11.2 translocation renal cell carcinoma (Xp11.2 RCC) and to compare the clinicopathological features between adult Xp11.

Blood glucose fluctuation accelerates renal injury involved to inhibit the AKT signaling pathway in diabetic rats.

Blood glucose fluctuation is associated with diabetic nephropathy. However, the mechanism by which blood glucose fluctuation accelerates renal injury is not fully understood. The aim of the present study was to assess the effects of blood glucose fluctuation on diabetic nephropathy in rats and investigate its underlying mechanism.

PSCA polymorphisms and gastric cancer susceptibility in an eastern Chinese population.

The prostate stem cell antigen (PSCA) gene, which encodes a prostate-specific antigen (PSA), was identified as a gene involved in cell adhesion and proliferation. The associations between the PSCA rs2294008 and rs2976392 single nucleotide polymorphisms (SNPs) and gastric cancer (GCa) susceptibility were still controversial. To derive a more precise estimation of the associations, we conducted a case-control study of 1,124 cases and 1,192 controls in an eastern Chinese population.

PRELP (proline/arginine-rich end leucine-rich repeat protein) promotes osteoblastic differentiation of preosteoblastic MC3T3-E1 cells by regulating the β-catenin pathway.

Proline/arginine-rich end leucine-rich repeat protein (PRELP) is a collagen-binding proteoglycan highly expressed in the developing bones. Recent studies indicated that PRELP could inhibit osteoclastogenesis as a NF-κB inhibitor. However, its role during osteoblast differentiation is still unclear.

Specific immunohistochemical detection of the BRAF V600E mutation in primary and metastatic papillary thyroid carcinoma.

Purpose: To evaluate the clinical value of immunohistochemistry (IHC) using anti-BRAF V600E antibody (clone VE1) for specific detection of the BRAF V600E mutant protein in formalin-fixed paraffin-embedded papillary thyroid carcinoma (PTC) specimens.

Methods: A total of 118 PTC cases and 116 control cases processed between January 2008 and June 2010 were selected and created tissue microarrays (TMAs) for the study. BRAF V600E (VE1) IHC was performed on tissue sections from PTC cases to determine mutation status.

Ischemic preconditioning protects the brain against injury via inhibiting CaMKII-nNOS signaling pathway.

Although studies have shown that cerebral ischemic preconditioning (IPC) can ameliorate ischemia/reperfusion (I/R) induced brain damage, but its precise mechanisms remain unknown. Therefore, the aim of this study was to investigate the neuroprotective mechanisms of IPC against ischemic brain damage induced by cerebral I/R and to explore whether the Calcium/calmodulin-dependent protein kinase II (CaMKII)-mediated up-regulation of nNOS ser847-phosphorylation signaling pathway contributed to the protection provided by IPC. Transient global brain ischemia was induced by 4-vessel occlusion in adult male Sprague-Dawley rats.

Folate-targeting redox hyperbranched poly(amido amine)s delivering MMP-9 siRNA for cancer therapy.

For effective gene delivery to breast cancer MCF-7 cells, a folate-targeting redox gene carrier was synthesized by Michael addition polymerization between 1-(2-aminoethyl)piperazine and N,N'-cystaminebisacrylamide. Folate was then conjugated through an amidation reaction. The obtained folate-modified hyperbranched poly(amido amine)s (FA-PAAs) degraded in the presence of glutathione and displayed excellent transfection efficiency in vitro.

[Effects of cultivation patterns on the radiation use and grain yield of winter wheat].

Taking winter wheat cultivar 'Tainong 18' as test material, this paper set three treatments, local farmer's traditional cultivation pattern (FP), super high yield pattern (SH) and high yield high efficiency pattern ( HH) to investigate the effects of cultivation patterns on the intercepted photosynthetically active radiation (IPAR), PAR use efficiency (RUE), dry matter (DM) accumulation, harvest index (HI), grain yield and fertilizers' partial factor productivity (PFP) in 2012-2013. The results showed that IPAR, RUE and DM accumulation of the total growth stage and grain yield under SH pattern were significantly higher than those under FP pattern. IPAR of the total growth stage under HH pattern was lower than that under FP pattern, but RUE, DM accumulation and HI were significantly higher than that under FP pattern, so grain yield was higher than that under FP pattern.

Detection of lung adenocarcinoma with ROS1 rearrangement by IHC, FISH, and RT-PCR and analysis of its clinicopathologic features.

Objective: To detect ROS1 rearrangement using three different assays, including immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and reverse transcription polymerase chain reaction (RT-PCR), and to analyze the clinicopathologic features of ROS1 rearrangement in patients with lung adenocarcinoma.

Methods: One hundred eighty-three consecutive patients with lung adenocarcinoma with operation and follow-up data were analyzed for ROS1 rearrangement by IHC, FISH, and RT-PCR. PCR products of the RT-PCR-positive samples were sequenced for confirmation of the specific fusion partners.

Exosomes derived from mineralizing osteoblasts promote ST2 cell osteogenic differentiation by alteration of microRNA expression.

Mineralizing osteoblasts (MOBs) can release exosomes, although the functional significance remains unclear. In the present study, we demonstrate that exosomes derived from mineralizing pre-osteoblast MC3T3-E1 cells can promote bone marrow stromal cell (ST2) differentiation to osteoblasts. We reveal that MOB-derived exosomes significantly influence miRNA profiles in recipient ST2 cells, and these changes tend to activate the Wnt signaling pathway by inhibiting Axin1 expression and increasing β-catenin expression.

[Anaplastic lymphoma kinase-positive adenocarcinoma of lung: a cytopathologic analysis].

Objective: To study the cytomorphologic features of anaplastic lymphoma kinase (ALK)-rearranged pulmonary adenocarcinoma.

Methods: The morphologic features in 153 pulmonary adenocarcinoma cytology specimens encountered during the period from September, 2011 to April, 2015 in Shanghai Cancer Hospital were retrospectively reviewed. Fluorescence in-situ hybridization (FISH) and/or immunohistochemistry (Ventana D5F3) for ALK gene rearrangement were carried out.

Current inversions induced by resonant coupling to surface waves in a nanosized water pump.

We conducted a molecular dynamics simulation to investigate current inversions in a nanosized water pump based on a single-walled carbon nanotube powered by mechanical vibration. It was found that the water current depended sensitively on the frequency of mechanical vibration. Especially in the resonance region, the nanoscale pump underwent reversals of the water current.

Therapeutic effects of bone marrow mesenchymal stem cells expressing interleukin-12 in mice bearing malignant ascites tumor.

This study is to investigate the therapeutic effects of bone marrow mesenchymal stem cells (BMSCs) expressing interleukin (IL)-12 on malignant ascites tumor-bearing mice and the related mechanisms. Malignant ascites tumor mouse model was established by the intraperitoneal inoculation with MethA or H22 tumor cells. Mouse BMSCs were transfected with lentiviral vector containing IL-12, and then transplanted into these mouse models via intraperitoneal injection.

Family History of Cancer and Head and Neck Cancer Risk in a Chinese Population.

Background: The aim of this study was to investigate whether family history of cancer is associated with head and neck cancer risk in a Chinese population.

Materials And Methods: This case-control study included 921 cases and 806 controls. Recruitment was from December 2010 to January 2015 in eight centers in East Asia.

Effects of paroxetine on spatial memory function and protein kinase C expression in a rat model of depression.

The aim of the present study was to investigate the effects of paroxetine on the spatial memory and expression level of protein kinase C (PKC) in a rat model of depression. Rat models of depression were established by chronic unpredictable mild stress. The spatial learning and memory function of the rats were assessed by the Morris water maze test.

Oral lesions, chronic diseases and the risk of head and neck cancer.

Objectives: The aim of our study is to explore the role of the history of oral lesions and chronic diseases on the risk of head and neck cancer in a Chinese population.

Materials And Methods: Our case-control study included 921 head and neck cancer cases and 806 controls. We obtained medical history information by administering questionnaires to both cases and controls.