Abstract
Bladder outlet obstruction (BOO) often results in lower urinary tract symptoms (LUTSs) and negatively affects quality of life. Here, we evaluated gene expression patterns in the urinary ...bladder during tissue remodeling due to BOO. We divided BOO model rats into two groups according to the degree of hypertrophy of smooth muscle in the bladder. The strong muscular hypertrophy group, which exhibited markedly increased bladder smooth muscle proportion and
HIF1α
mRNA levels compared with the control group, was considered a model for the termination of hypertrophy, whereas the mild muscular hypertrophy group was considered a model of the initiation of hypertrophy. Some genes related to urinary function showed different expression patterns between the two groups. Furthermore, we found that several genes, including D-box binding PAR bZIP transcription factor (
DBP
), were upregulated only in the mild muscular hypertrophy group.
DBP
expression levels were increased in bladder smooth muscle cells in response to hypoxic stress. DBP associated with enhancer and promoter regions of
NOS3
gene locus and upregulated
NOS3
gene expression under hypoxic conditions. These findings suggested that the regulatory systems of gene expression were altered during tissue remodeling following BOO. Furthermore, circadian clock components might be involved in control of urinary function via transcriptional gene regulation in response to hypoxic stimuli.
We developed a novel dividing device that can split needle biopsy tissues along longitude axis aiming to achieve definitive molecular-biological and genetical analysis with reference of pathological ...diagnosis of the side-by-side divided tissue as spatially matched information. The aim of this study was to evaluate the feasibility and potential usefulness of the novel dividing device to provide the appropriate materials for molecular diagnosis. The new device was examined using mouse xenograft tumors. Real-time quantitative PCR and genetic test were performed to evaluate the feasibility and usefulness of the device. All the samples from needle biopsy were successfully divided into two pieces. Quality and quantity from divided samples harbor high enough to perform gene expression analysis (real-time PCR) and genetic test. Using two divided samples obtained from xenograft tumor model by needle biopsy, the % length of xenograft tumor (human origin) was significantly correlated with the % human genomic DNA (p = 0.00000608, r = 0.987), indicating that these divided samples were spatially matched. The novel longitudinally dividing device of a needle biopsy tissue was useful to provide the appropriate materials for molecular-biological and genetical analysis with reference of pathological diagnosis as spatially matched information.
Follicular helper T (Tfh) cells represent a unique subset of helper CD4+ T cells in lymphoid follicles. Recently, Tfh cells were shown to play an important role in asthma through B cell ...differentiation. Conventional lung DCs are classified into two major subsets: conventional type 1 (cDC1) and type 2 (cDC2). Although the two subsets are different in driving particular T cell responses, the subset that induces Tfh cells in the asthmatic lung primarily has yet to be fully elucidated.
We evaluated Tfh cells, defined by the expression of CD4 and CXCR5, in HDM-challenged mice. Next, we characterized cDC1 and cDC2 purified from antigen-primed lung and examined their Tfh cell-inducing capacity. Additionally, the ability of lung DC-induced Tfh cells to cause germinal center B (GCB) cells to produce antigen-specific IgE was assessed.
In HDM-challenged mice, Bcl-6-expressing Tfh cells were significantly increased in the mediastinal lymph nodes. Lung cDC2, but not lung cDC1, increased after HDM priming, and cDC2 secreted larger amounts of IL-6 with higher ICOS-L expression than cDC1. In the co-cultures with OVA-specific naïve CD4+ T cells, cDC2 from OVA-primed lung induced Bcl-6-expressing Tfh cells more efficiently, together with larger amounts of IL-6 and IL-21, than cDC1. Blockage of IL-6 or ICOS-L significantly reduced Tfh cell induction. Finally, cDC2-induced Tfh cells enabled GCB cells to produce OVA-specific IgE.
In asthmatic lung, cDC2 is the primary DC subset responsible for Tfh cell differentiation and plays an important role in humoral immunity in asthma by inducing Tfh cells.
Strain development is critical for microbial production of bio-based chemicals. The stereo-complex form of polylactic acid, a complex of poly-
l
- and poly-
d
-lactic acid, is a promising polymer ...candidate due to its high thermotolerance. Here, we developed
Corynebacterium glutamicum
strains producing high amounts of
l
- and
d
-lactic acid through intensive metabolic engineering. Chromosomal overexpression of genes encoding the glycolytic enzymes, glucokinase, glyceraldehyde-3-phosphate dehydrogenase, phosphofructokinase, triosephosphate isomerase, and enolase, increased
l
- and
d
-lactic acid concentration by 146% and 56%, respectively. Chromosomal integration of two genes involved in the Entner–Doudoroff pathway (6-phosphogluconate dehydratase and 2-dehydro-3-deoxyphosphogluconate aldolase), together with a gene encoding glucose-6-phosphate dehydrogenase from
Zymomonas mobilis
, to bypass the carbon flow from glucose, further increased
l
- and
d
-lactic acid concentration by 11% and 44%, respectively. Finally, additional chromosomal overexpression of a gene encoding NADH dehydrogenase to modulate the redox balance resulted in the production of 212 g/L
l
-lactic acid with a 97.9% yield and 264 g/L
d
-lactic acid with a 95.0% yield. The optical purity of both
l
- and
d
-lactic acid was 99.9%. Because the constructed metabolically engineered strains were devoid of plasmids and antibiotic resistance genes and were cultivated in mineral salts medium, these strains could contribute to the cost-effective production of the stereo-complex form of polylactic acid in practical scale.
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