Murine small intestine intraepithelial lymphocytes (IELs) bear properties of both activated and nonactivated T cells, although the significance of that dichotomy remains unclear. In this study, we show that although IELs express CD69 in situ and ex vivo, and have cytotoxic activity ex vivo, most CD8+ IELs from normal mice are phenotypically similar to naive T cells in that they are CD45RBhigh, CD44low/int, and lack or have low levels of expression of CD25, Ly-6C, OX40, Fas ligand (FasL), and intracellular IFN-γ synthesis. Unlike CD8+ lymph node cells, IELs express high levels of the FasL gene, but do not express surface FasL until after CD3-mediated stimulation has occurred. Additionally, anti-CD3 stimulation of IELs in the presence of actinomycin-D did not inhibit FasL expression, suggesting that regulation FasL expression on IELs is controlled at least partially at the posttranscriptional level. Following CD3-mediated stimulation, IELs synthesize and secrete IFN-γ more rapidly and to greater levels than CD8+ lymph node cells, and they acquire the phenotype of fully activated effector cells as seen by an up-regulation of CD44, Ly-6C, OX40, FasL, and CD25 with the kinetics of memory T cells, with down-regulation of CD45RB expression. These findings indicate that contrary to previous interpretations, most small intestine IELs are not fully activated T cells, but rather that they are semiactivated T cells ready to shift to a fully activated state once a CD3-mediated signal has been received. These data also imply that under appropriate conditions it is possible for T cells to be sustained in a state of partial activation.

We have previously shown that stanniocalcin-1 (STC1) inhibits the transendothelial migration of macrophages and T cells, suppresses superoxide generation in macrophages, and attenuates macrophage responses to chemoattractants. To study the effects of STC1 on inflammation, in this study we induced a macrophage-and T-cell-mediated model of anti-glomerular basement membrane disease in STC1 transgenic mice, which display elevated serum STC1 levels and preferentially express STC1 in both endothelial cells and macrophages. We examined the following parameters both at baseline and after anti-glomerular basement membrane antibody treatment: blood pressure; C 3a levels; urine output; proteinuria; blood urea nitrogen; and kidney C 3 deposition, fibrosis, histological changes, cytokine expression, and number of T cells and macrophages. Compared with wild-type mice, after anti-glomerular basement membrane treatment STC1 transgenic mice exhibited: i) diminished infiltration of inflammatory macrophages in the glomeruli; ii) marked reduction in crescent formation and sclerotic glomeruli; iii) decreased interstitial fibrosis; iv) preservation of kidney function and lower blood pressure; v) diminished C 3 deposition in the glomeruli; and vi) reduced expression of macrophage inhibitory protein-2 and transforming growth factor-␤2 in the kidney. Compared with baseline , wild-type mice , but not STC1 transgenic mice , had higher proteinuria and a marked reduction in urine output. STC1 had minimal effects , however , on both T-cell number in the glomeruli and interstitium and on cytokine expression characteristic of either TH1 or TH2 activation. These data suggest that STC1 is a potent anti-inflammatory and renal protective protein. Stanniocalcin-1 (STC1) is a 25-kDa homodimeric glycoprotein hormone involved in calcium regulation in bony fish, 1 in which elevation of serum calcium triggers the release of STC1 from the corpuscles of Stannius, 2 organs associated with the kidneys.3 On circulation in the gill and intestine, STC1 inhibits calcium influx from the aquatic environment to the blood to maintain stable concentrations of calcium in the blood. 4 Mammalian STC1 mRNA is ubiquitously expressed, and the highest levels of STC1 expression are found in the ovary, kidney, prostate, and thyroid. [5][6][7] It was previously suggested that STC1 protein does not circulate in the blood of mammals 8 except during pregnancy and lactation 9 ; however, recent data suggest that mammalian STC1 is blood-borne , attached to a soluble protein. 10 The cellular distribution of STC1 mRNA and protein in mammalian organs is not always parallel. In the kidney for example, in situ hybridization revealed restricted expression of STC1 mRNA in the cortical and medullary collecting ducts, whereas the protein is detected along the entire nephron. 11,12 Similarly, the distribution of STC1 mRNA does not parallel the distribution of the protein in cellular elements of the ovary and pregnant uterus.

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ObjectiveThe study aims to evaluate the efficacy and safety of two Chinese herbal formulae for the treatment of stable COPD.MethodsA multicenter, double-blind, double-dummy, and randomized controlled trial (RCT) was conducted. All groups were treated with additional conventional medicines. There were a 6-month treatment and a 12-month follow-up for 5 times. Primary outcomes included lung function test, exacerbation frequency, score of SGRQ. Second outcomes consisted of 6MWD, BODE index, psychological field score, inflammatory factors and cortisol.ResultsA total of 331 patients were randomly divided into two active treatment groups (Bushen Yiqi (BY) granule group, n = 109; Bushen Fangchuan (BF) tablet group, n = 109) and a placebo group (n = 113). Finally 262 patients completed the study. BY granule & BF tablet increased the values of VC, FEV1 (%) and FEV1/FVC (%), compared with placebo. BY granule improved PEF. Both treatments reduced acute exacerbation frequency (P = 0.067), BODE index and psychological field score, while improved 6MWD. In terms of descent rang of SGRQ score, both treatments increased (P = 0.01). Both treatments decreased inflammatory cytokines, such as IL-8, and IL-17(P = 0.0219). BY granule obviously descended IL-17(P<0.05), IL-1β (P = 0.05), IL-6, compared with placebo. They improved the level of IL-10 and cortisol. BY granule raised cortisol (P = 0.07) and decreased TNF-α. Both treatments slightly descended TGF-β1. In terms of safety, subject compliance and drug combination, there were no differences (P>0.05) among three groups.ConclusionsBY granule and BF tablet were positively effective for the treatment of COPD, and the former performed better in general.Trial RegistrationChinese Clinical Trial Register center ChiCTR-TRC-09000530

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Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus (DM). However, the exact mechanism is not clearly understood. In this study, our results showed that 24 h urinary protein, kidney index, and glomerular area were decreased, while creatinine clearance ratio was increased in DN rats when the rats were treated with NAR 50 mg/d for 6 weeks. Mesangial cell (MMCs) proliferation was inhibited in the NAR group by 3,(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), and the cell cycle analysis showed that cells stayed in G2 phase in NAR group. And NAR treatment attenuated the deposition of ECM in DN rats and MMCs. Moreover, our data showed that let-7a was downexpressed in both DN rats and MMCs under high glucose condition. Surprisingly, NAR affected the expressions of Col4 and FN through upregulating let-7a in MMCs. In addition, we found that let-7a negatively regulated the expression of transforming growth factor-β1 receptor 1 (TGFBR1), and TGFBR1 was required for the let-7a-mediated downregulation of TGF-β1/smad signaling. Interestingly, NAR inhibited TGF-β1/smads signaling activation by upregulating let-7a. Therefore, our findings indicated that NAR ameliorated kidney injury by regulating let-7a/TGFBR1 signaling.

Protein 4.1N belongs to the protein 4.1 superfamily that links transmembrane proteins to the actin cytoskeleton. Recent evidence has shown that protein 4.1 is important in tumor suppression. However, the functions of 4.1N in the metastasis of breast cancer are largely unknown. In the present study, MCF-7, T-47D and MDA-MB-231 breast cancer cell lines with various metastatic abilities were employed. Protein 4.1N was found to be expressed in poorly metastatic MCF-7 and middle metastatic T-47D cell lines, and was predominantly associated with cell-cell junctions. However, no 4.1N expression was detected in the highly metastatic MDA-MB-231 cells. Moreover, re-expression of 4.1N in MDA-MB-231 cells inhibited cell adhesion, migration and invasion. The results suggest that protein 4.1N is a negative regulator of cell metastasis in breast cancer.

Fragile histidine triad (FHIT) is a suppressor gene related to cervical cancer through CpG island hypermethylation. Folate is a water-soluble B-vitamin and an important cofactor in one-carbon metabolism. It may play an essential role in cervical lesions through effects on DNA methylation. The purpose of this study was to observe effects of folate and FHIT methylation and HPV 16 on cervical cancer progression. In this study, DNA methylation of FHIT, serum folate level and HPV16 status were measured using methylation-specific polymerase chain reaction (MSP), radioimmunoassay (RIA) and polymerase chain reaction (PCR), respectively, in 310 women with a diagnosis of normal cervix (NC, n=109), cervical intraepithelial neoplasia (CIN, n=101) and squamous cell carcinoma of the cervix (SCC, n=101). There were significant differences in HPV16 status (χ 2 =36.64, P<0.001), CpG island methylation of FHIT (χ