Development of a novel strategy to reduce diagnostic errors in real-time polymerase chain reaction using probe-based techniques.

Real-time PCR assays are valuable tools for the rapid and accurate diagnosis of infectious diseases by identifying the nucleic acid sequences of pathogens. Here, we aimed to develop a recombinant plasmid-based standard for validating the sensitivity of different molecular diagnostic methods adopting the Jonstrup assay (J assay). Chimeric plasmid DNA (cpDNA) harboring various pathogen genes and the target site of the J assay was constructed.

Evolutionary dependency of cancer mutations in gene pairs inferred by nonsynonymous-synonymous mutation ratios.

Background: Determining the impact of somatic mutations requires understanding the functional relationship of genes acquiring mutations; however, it is largely unknown how mutations in functionally related genes influence each other.

Methods: We employed non-synonymous-to-synonymous or dNdS ratios to evaluate the evolutionary dependency (ED) of gene pairs, assuming a mutation in one gene of a gene pair can affect the evolutionary fitness of mutations in its partner genes as mutation context. We employed PanCancer- and tumor type-specific mutational profiles to infer the ED of gene pairs and evaluated their biological relevance with respect to gene dependency and drug sensitivity.

Curcumin inhibits the cancer‑associated fibroblast‑derived chemoresistance of gastric cancer through the suppression of the JAK/STAT3 signaling pathway.

The present study aimed to investigate whether the Janus‑activated kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) signaling pathway is a critical mechanism underlying the cancer‑associated fibroblast (CAF)‑induced chemoresistance of gastric cancer (GC). In addition, the present study tried to suggest a natural product to compromise the effects of CAF on the chemoresistance of GC. The results of cell proliferation assay revealed that the conditioned medium (CM) collected from CAFs further increased resistance to 5‑fluorouracil (5‑FU) in GC cell lines.

Correlation-based and feature-driven mutation signature analyses to identify genetic features associated with DNA mutagenic processes in cancer genomes.

Mutation signatures represent unique sequence footprints of somatic mutations resulting from specific DNA mutagenic and repair processes. However, their causal associations and the potential utility for genome research remain largely unknown. In this study, we performed PanCancer-scale correlative analyses to identify the genomic features associated with tumor mutation burdens (TMB) and individual mutation signatures.

Spatially Distinct Reprogramming of the Tumor Microenvironment Based On Tumor Invasion in Diffuse-Type Gastric Cancers.

Purpose: Histologic features of diffuse-type gastric cancer indicate that the tumor microenvironment (TME) may substantially impact tumor invasiveness. However, cellular components and molecular features associated with cancer invasiveness in the TME of diffuse-type gastric cancers are poorly understood.

Experimental Design: We performed single-cell RNA-sequencing (scRNA-seq) using tissue samples from superficial and deep invasive layers of cancerous and paired normal tissues freshly harvested from five patients with diffuse-type gastric cancer.

Alteration of gammaretroviral vector integration patterns by insertion of histone and leucine zipper into integrase.

Retroviral vectors show long-term gene expression in gene therapy through the integration of transgenes into the human cell genome. Murine leukemia virus (MLV), a well-studied gammaretrovirus, has been often used as a representative retroviral vector. However, frequent integrations of MLV-based vectors into transcriptional start sites (TSSs) could lead to the activation of oncogenes by enhancer effects of the genetic components within the vectors.

Effect of Di-(2-ethylhexyl)-phthalate on Sphingolipid Metabolic Enzymes in Rat Liver.

Di-(2-ethylhexyl)-phthalate (DEHP), the most widely utilized industrial plastizer and a ubiquitous environmental contaminant, can act on peroxisome proliferators-activated nuclear hormone receptor family (PPAR) isoforms. To understand the contribution of sphingolipid metabolism to DEHP-induced hepatotoxicity, effect of DEHP exposure on activities of sphingolipid metabolic enzymes in rat liver was investigated. DEHP (250, 500 or 750 mg/kg) was administered to the rats through oral gavage daily for 28 days.

Effects of chronic alcohol consumption on expression levels of APP and Aβ-producing enzymes.

Chronic alcohol consumption contributes to numerous diseases, including cancers, cardiovascular diseases, and liver cirrhosis. Epidemiological studies have shown that excessive alcohol consumption is a risk factor for dementia. Along this line, Alzheimer's disease (AD) is the most common form of dementia and is caused by the accumulation of amyloid-β (Aβ plaques in neurons.

Selenium attenuates A beta production and A beta-induced neuronal death.

The objective of the present study was to examine the role of selenium in the metabolism of A beta and in A beta-induced neuronal death. Selenium treatment significantly reduced A beta 40, A beta 42, and sAPP beta production by reducing A beta producing beta-secretase and gamma-secretase activities. The lipid peroxidation product 4-Hydroxynonenal (HNE)-induced transcription of beta-secretase (BACE1) was blocked by selenium.

Blocking of monocyte-associated B7-H1 (CD274) enhances HCV-specific T cell immunity in chronic hepatitis C infection.

The establishment of a chronic hepatitis C (CHC) infection is associated with defective HCV-specific T cell responses. Recent studies suggest that negative T cell regulators such as programmed death 1 (PD-1) contribute to the impairment of virus-specific T cell functions in chronic viral infections. However, the implication of peripheral monocytes from CHC patients in the inhibition of HCV-specific T cell responses is only partially defined.

Blockade of endogenous B7-H1 suppresses antibacterial protection after primary Listeria monocytogenes infection.

B7-H1 (also known as CD274 and PD-L1) is a cosignalling molecule regulating T-cell immunity positively or negatively in vivo. However, little is known about the role of endogenous B7-H1 in bacterial infection. We found that B7-H1 expression was up-regulated in various cell populations including CD4+ and CD8+ T cells, natural killer (NK) cells and macrophages following Listeria monocytogenes infection.

Interpretation of interleukin-2 receptor alpha positive cells during induction chemotherapy for adult acute myelogenous leukaemia patients.

To correlate clinical outcomes with the expression of interleukin-2 receptor alpha (CD25) positive cells during induction chemotherapy (IC) in adult patients with acute myeloid leukaemia (AML), we investigated the prognostic importance of subsets of peripheral blood (PB) CD45+CD25+ cells. Seventy-five patients with newly diagnosed AML received the same initial IC; and serial PB samples were taken. The gated CD45/CD25 cell populations were used to compare the intensity of immunophenotypic signals based on the treatment timeline.

B7-H1 (CD274) inhibits the development of herpetic stromal keratitis (HSK).

The co-signaling molecule B7-H1 (CD274) functions as both a co-inhibitor through programmed death-1 (PD-1) receptor and a co-stimulator via an as-yet-unidentified receptor on T cells. We investigated the physiological role of endogenous B7-H1 in the pathogenesis of herpetic stromal keratitis (HSK) caused by herpes simplex virus type 1 (HSV-1). Following HSV-1 infection of the cornea of mice, B7-H1 expression was up-regulated in the CD11b+ macrophage population in the draining lymph nodes (dLN) and in the inflamed cornea.

Co-inhibitory role of T-cell-associated B7-H1 and B7-DC in the T-cell immune response.

B7-H1 and B7-DC expressed on antigen-presenting cells inhibit the T-cell response via the PD-1 counter-receptor on T cells, and co-stimulate T-cell immunity under certain conditions via an unidentified co-stimulatory receptor. However, little is known about the functional consequence of T-cell-associated B7-H1 or B7-DC in the T-cell immune response. Therefore, we evaluated the physiological role of B7-H1 and B7-DC expressed on T cells in terms of cell proliferation and cytokine production by alloreactive T cells.

Tyrosine kinase-mediated activation of NADPH oxidase enhances proliferative capacity of diabetic vascular smooth muscle cells.

To investigate a potential molecular basis for a link between diabetes and atherosclerosis, experiments were performed to determine the role of NADPH oxidase in the enhanced proliferative capacity of vascular smooth muscle cells (VSMC) from OLETF rat, an animal model of type 2 diabetes. An enhanced proliferative response to 10% fetal bovine serum with an increased cell cycle progression from G1 to S phase as well as an augmented superoxide generation with an increased NADPH oxidase activity were observed in diabetic versus control VSMC. Both the enhanced proliferation and superoxide generation in diabetic VSMC were significantly attenuated not only by diphenyleneiodonium (10 microM) and apocynin (100 microM), NADPH oxidase inhibitors but also by protein tyrosine kinase inhibitors such as genistein (100 microM) and AG 112 (100 microM).