Experimental Study on Resin Anchoring with Reaming Bottom and Filling in Soft Rock.

This paper deals with the problem of the slippage failure of bolts in supporting soft rock, and the anchoring system being pulled out when conventional anchoring methods are used for bolts. This situation seriously threatens the safety of personnel and efficiency of work at the supporting soft rock. The main goal of this paper is to develop methods that will take full advantage of the potentially great supporting force that can be provided by bolts installed in soft rock. The study discusses the resin anchoring technique with reaming bottom and filling and proposes that replacing soft rock with high strength hard rock is an effective method to improve the anchoring force that prevents slip failure. The results of a comparative analysis of the different maximum diameters of reaming and the anchorage performance of the method using laboratory testing, numerical simulation, mechanics analysis, and field test are described. The results show that when the reaming diameter is less than five times that of the borehole, the anchorage force increases significantly. When the reaming diameter is more than five times that of the borehole, the increasing degree of anchoring force decreases obviously and the trend is gentle. The anchoring force of five times resin anchoring with reaming bottom and filling is 2.8 times that of conventional anchorage. The resin anchoring technique with reaming bottom and filling guarantees that bolts installed in soft rock will provide high supporting forces.

An inner-filter-effect based ratiometric fluorescent sensor for the detection of uranyl ions in real samples.

In this work, a ratiometric fluorescence system was designed for the detection of trace UO22+ in water based on the inner filter effect (IFE) between gold nanoparticles (AuNPs) and gold nanoclusters (AuNCs). IFE-induced fluorescence quenching was achieved due to the enhanced complementary overlap between the absorption spectra of AuNPs and the emission spectrum of AuNCs after the addition of UO22+. Blue carbon dots (B-CDs) were added to serve as reference fluorophores to expand the color tonality and make human eye recognition easier. The ratiometric fluorescent sensor demonstrated a unique fluorescence color change from red to blue when different doses of UO22+ were added, with a detection limit of 8.4 nM. Furthermore, the ratiometric fluorescent sensor was effectively used for UO22+ determination in real-world water samples, with acceptable recoveries.

Metformin inhibits gastric cancer cell proliferation by regulation of a novel Loc100506691-CHAC1 axis.

Long noncoding RNAs (lncRNAs) are a group of nonprotein coding transcripts that play a critical role in cancer progression. However, the role of lncRNA in metformin-induced inhibition of cell growth and its biological function in gastric cancer remain largely unknown. In this study, we identified an oncogenic lncRNA, Loc100506691, the expression of which was decreased in gastric cancer cells with metformin treatment. Moreover, Loc100506691 was significantly overexpressed in gastric cancer compared with adjacent normal tissues (p < 0.001), and high Loc100506691 expression was significantly correlated with poor survival of patients with gastric cancer. Additionally, Loc100506691 knockdown could significantly suppress gastric cancer cell growth in vitro, and ectopic Loc100506691 expression accelerated tumor growth in an in vivo mouse model. Analysis of the cell cycle revealed that Loc100506691 knockdown induced cell cycle arrest at the G2/M phase by impairing cell entry from the G2/M to G1 phase. Loc100506691 negatively regulated CHAC1 expression by modulating miR-26a-5p/miR-330-5p expression, and CHAC1 knockdown markedly attenuated Loc100506691 knockdown-induced gastric cancer cell growth and motility suppression. We concluded that anti-proliferative effects of metformin in gastric cancer may be partially caused by suppression of the Loc100506691-miR-26a-5p/miR-330-5p-CHAC1 axis.

A new langbeinite-type phosphate K2GdHf(PO4)3: synthesis, crystal structure, band structure and luminescence properties.

Langbeinite-type compounds are a large family that include phosphates, sulfates and arsenates, and which are accompanied by interesting physical properties. This work reports a new disordered langbeinite-type compound, K2GdHf(PO4)3 [dipotassium gadolinium hafnium tris(phosphate)], and its structure as determined by single-crystal X-ray diffraction. Theoretical studies reveal that K2GdHf(PO4)3 is an insulator with a direct band gap of 4.600 eV and that the optical transition originates from the O-2p→Hf-5d transition. A Ce3+-doped phosphor, K2Gd0.99Ce0.01Hf(PO4)3, was prepared and its luminescence properties studied. With 324 nm light excitation, a blue emission band was observed due to the 5d1→4f1 transition of Ce3+. The average luminescence lifetime was calculated to be 5.437 µs and the CIE chromaticity coordinates were (0.162, 0.035). One may expect that K2Gd0.99Ce0.01Hf(PO4)3 can be used as a good blue phosphor for three-colour white-light-emitting diodes (WLEDs).

Impaired B cell anergy is not sufficient to breach tolerance to nuclear antigen in Vκ8/3H9 lupus-prone mice.

BACKGROUND: Systemic lupus erythematosus (SLE) is a severe autoimmune disease in which immune tolerance defects drive production of pathogenic anti-nuclear autoantibodies. Anergic B cells are considered a potential source of these autoantibodies due to their autoreactivity and overrepresentation in SLE patients. Studies of lupus-prone mice have shown that genetic defects mediating autoimmunity can breach B cell anergy, but how this breach occurs with regards to endogenous nuclear antigen remains unclear. We investigated whether B and T cell defects in congenic mice (c1) derived from the lupus-prone New Zealand Black strain can breach tolerance to nuclear self-antigen in the presence of knock-in genes (Vκ8/3H9; dKI) that generate a ssDNA-reactive, anergic B cell population. METHODS: Flow cytometry was used to assess splenic B and T cells from 8-month-old c1 dKI mice and serum autoantibodies were measured by ELISA. dKI B cells stimulated in vitro with anti-IgM were assessed for proliferation and activation by examining CFSE decay and CD86. Cytokine-producing T cells were identified by flow cytometry following culture of dKI splenocytes with PMA and ionomycin. dKI B cells from 6-8-week-old mice were adoptively transferred into 4-month-old wild type recipients and assessed after 7 days via flow cytometry and immunofluorescence microscopy. RESULTS: c1 dKI mice exhibited B cell proliferation indicative of impaired anergy, but had attenuated autoantibodies and germinal centres compared to wild type littermates. This attenuation appeared to stem from a decrease in PD-1hi T helper cells in the dKI strains, as c1 dKI B cells were recruited to germinal centres when adoptively transferred into c1 wild type mice. CONCLUSION: Anergic, DNA-specific autoreactive B cells only seem to drive profound autoimmunity in the presence of concomitant defects in the T cell subsets that support high-affinity plasma cell production.

Dinuclear cobalt and nickel complexes of a mercaptoacetic acid substituted 1,2,4-triazole ligand: syntheses, structures and urease inhibitory studies.

Because of its versatile coordination modes and strong coordination ability, the mercaptoacetic acid substituted 1,2,4-triazole 2-{[5-(pyridin-2-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}acetic acid (H2L) was synthesized and characterized. Treatment of H2L with cobalt and nickel acetate afforded the dinuclear complexes {µ-3-[(carboxylatomethyl)sulfanyl]-5-(pyridin-2-yl)-4H-1,2,4-triazol-4-ido-κ2N1,N5:N2,O}bis[aqua(methanol-κO)cobalt(II)] methanol disolvate, [Co2(C9H6N4O2S)2(CH3OH)2(H2O)2]·2CH3OH (1), and {µ-3-[(carboxylatomethyl)sulfanyl]-5-(pyridin-2-yl)-4H-1,2,4-triazol-4-ido-κ2N1,N5:N2,O}bis[diaquanickel(II)] methanol disolvate dihydrate, [Ni2(C9H6N4O2S)2(H2O)4]·2CH3OH·2H2O (2), respectively. Complex 1 crystallized in the monoclinic space group P21/c, while 2 crystallized in the tetragonal space group I41/a. Single-crystal X-ray diffraction studies revealed that H2L is doubly deprotonated and acts as a tetradentate bridging ligand in complexes 1 and 2. For both of the obtained complexes, extensive hydrogen-bond interactions contribute to the formation of their three-dimensional supermolecular structures. Hirshfeld surface analysis was used to illustrate the intermolecular interactions. Additionally, the urease inhibitory activities of 1, 2 and H2L were investigated against jack bean urease, where the two complexes revealed strong urease inhibition activities.

Aberrant DNA Hypermethylation Silenced LncRNA Expression in Gastric Cancer.

BACKGROUND/AIM: Long noncoding RNAs (lncRNAs) are noncoding transcripts that are >200 nucleotides in length. However, the biological functions and regulation mechanisms of lncRNAs in gastric carcinogenesis remain unknown. MATERIALS AND METHODS: The expression levels of Linc00472 were analyzed by real-time PCR. The DNA methylation status was assessed using Combined Bisulfite Restriction Analysis (COBRA). The biological role of Linc00472 was assessed in AGS cells with Linc00472 overexpression. RESULTS: Using the next-generation sequencing approach, we identified DNA methylation-associated lncRNAs in gastric cancer cells. Among them, the expression level of Linc00472 significantly decreased in gastric cancer tissues compared to adjacent normal tissues. Furthermore, we observed a more frequent hypermethylation of CpG islands upstream of Linc00472 in gastric cancer tissues. Ectopic Linc00472 expression could significantly inhibit gastric cancer cell growth and migration. CONCLUSION: Epigenetically regulated Linc00472 expression plays a crucial role in modulating gastric cancer cell growth and motility.

Analysis of overlapping heterozygous novel submicroscopic CNVs and FANCA-VPS9D1 fusion transcripts in a Fanconi anemia patient.

Fanconi anemia (FA) is the most common inherited bone marrow failure syndrome with 22 FA-related genes identified to date. Fragment deletions are frequently occurring aberrances accounting for ~30% of pathogenic variants in them, especially in FANCA, most of which are the results of genomic rearrangement events mediated by the highly concentrated Alu elements interspersing in it. Owing to the capability to detect genome-wide copy number variations (CNVs) with the resolution of 400 kb or larger, cytogenomic microarray is the most widely used method in the clinic currently. However, thereis still a technical gap in the detection of CNVs ranging from hundreds of bp to hundreds of kb between microarray, Sanger sequencing, and direct targeted high-throughput sequencing (THS). Here, we report the analysis of overlapping heterozygous novel submicroscopic deletions of FANCA gene in a FA patient, and discuss the mechanism of the deletions and the formation of FANCA-VPS9D1 fusion transcripts. Our results support that both low-coverage whole-genome sequencing and bioinformatics analysis of THS data for submicroscopic CNVs surpass SNP array in efficacy and accuracy.

Increased risk of post-stroke epilepsy in Chinese patients with a TRPM6 polymorphism.

OBJECTIVES: We attempted to determine whether a functional polymorphism of TRPM6 (rs2274924) is associated with susceptibility to epilepsy following ischemic stroke, and to further explore the effect of this polymorphism on serum levels of Mg2+ in post-stroke patients. METHODS: We carried out a case-control study on 378 post-stroke epilepsy patients and 420 controls (stroke patients without secondary epilepsy). We used DNA sequencing to determine the genotypes of the TRPM6 rs2274924 polymorphism, and used the ion selective electrode method to measure serum levels of Mg2+. RESULTS: The distribution of the CC genotype and the frequency of the C allele were significantly higher in the post-stroke epilepsy patients than in the controls (P < 0.01). With regard to the post-stroke epilepsy patients, the serum levels of Mg2+ decreased significantly in the TRPM6 rs2274924 C allele carriers compared to the rs2274924 T allele carriers. CONCLUSION: The TRPM6 rs2274924 polymorphism may be associated with susceptibility to epilepsy following stroke, and the C allele may be associated with increased risk of post-stroke epilepsy. The TRPM6 rs2274924 polymorphism may also influence serum levels of Mg2+ in post-stroke epilepsy patients.

The presence of anti-nuclear antibodies alone is associated with changes in B cell activation and T follicular helper cells similar to those in systemic autoimmune rheumatic disease.

BACKGROUND: Diagnosis of systemic autoimmune rheumatic diseases (SARD) relies on the presence of hallmark anti-nuclear antibodies (ANA), many of which can be detected years before clinical manifestations. However, ANAs are also seen in healthy individuals, most of whom will not develop SARD. Here, we examined a unique cohort of asymptomatic ANA+ individuals to determine whether they share any of the cellular immunologic features seen in SARD. METHODS: Healthy ANA- controls and ANA+ (ANA ≥1:160 by immunofluorescence) participants with no SARD criteria, with at least one criterion (undifferentiated connective tissue disease (UCTD)), or meeting SARD classification criteria were recruited. Peripheral blood cellular immunological changes were assessed by flow cytometry and transcript levels of BAFF, interferon (IFN)-induced and plasma cell-expressed genes were quantified by NanoString. RESULTS: A number of the immunologic abnormalities seen in SARD, including changes in peripheral B (switched memory) and T (iNKT, T regulatory, activated memory T follicular helper) subsets and B cell activation, were also seen in asymptomatic ANA+ subjects and those with UCTD. The extent of these immunologic changes correlated with ANA titer or the number of different specific ANAs produced. Principal component analysis of the cellular data indicated that a significant proportion of asymptomatic ANA+ subjects and subjects with UCTD clustered  with patients with early SARD, rather than ANA- healthy controls. CONCLUSIONS: ANA production is associated with altered T and B cell activation even in asymptomatic individuals. Some of the currently accepted cellular features of SARD may be associated with ANA production rather than the immunologic events that cause symptoms in SARD.

MiR-193a-5p and -3p Play a Distinct Role in Gastric Cancer: miR-193a-3p Suppresses Gastric Cancer Cell Growth by Targeting ETS1 and CCND1.

BACKGROUND/AIM: MicroRNAs (miRNAs) are small non-protein-coding RNAs, that can be generated from the 5p or 3p arm of precursor miRNA (pre-miRNA). Differential miRNA arm selection has been reported between tumor and normal tissue in many cancer types; however, the biological function and mechanism of miRNA arm switching in gastric cancer remain unclear. MATERIALS AND METHODS: Profiles of miRNA expression in gastric cancer were obtained from The Cancer Genome Atlas (TCGA). The biological role of miR-193a-5p/-3p in tumor growth and invasive abilities was assessed through a gain-of-function approach. Target genes of miR-193a-3p were identified using bioinformatics and an experimental approach. RESULTS: The expression levels of miR-193a-5p, and not of miR-193a-3p, were significantly decreased in gastric cancer compared to adjacent normal tissues. Ectopic expressions of miR-193a-5p and miR-193a-3p revealed that they both inhibited gastric cancer cell growth, but only miR-193a-3p significantly suppressed cell invasion ability. Using a bioinformatics approach, we identified 18 putative target genes of miR-193a-3p. Both mRNA and protein levels of cyclin D1 (CCND1) and ETS proto-oncogene 1 (ETS1) were significantly decreased in AGS cells transfected with miR-193a-3p mimics. ETS1 or CCND1 knockdown significantly suppressed gastric cancer cell growth, similar to miR-193a-3p overexpression. CONCLUSION: Our results indicated that miR-193a-3p suppressed gastric growth and motility, at least partly, by directly targeting CCND1 and ETS1 expression.

Identification of a neutrophil-related gene expression signature that is enriched in adult systemic lupus erythematosus patients with active nephritis: Clinical/pathologic associations and etiologic mechanisms.

Both a lack of biomarkers and relatively ineffective treatments constitute impediments to management of lupus nephritis (LN). Here we used gene expression microarrays to contrast the transcriptomic profiles of active SLE patients with and without LN to identify potential biomarkers for this condition. RNA isolated from whole peripheral blood of active SLE patients was used for transcriptomic profiling and the data analyzed by linear modeling, with corrections for multiple testing. Results were validated in a second cohort of SLE patients, using NanoString technology. The majority of genes demonstrating altered transcript abundance between patients with and without LN were neutrophil-related. Findings in the validation cohort confirmed this observation and showed that levels of RNA abundance in renal remission were similar to active patients without LN. In secondary analyses, RNA abundance correlated with disease activity, hematuria and proteinuria, but not renal biopsy changes. As abundance levels of the individual transcripts correlated strongly with each other, a composite neutrophil score was generated by summing all levels before examining additional correlations. There was a modest correlation between the neutrophil score and the blood neutrophil count, which was largely driven by the dose of glucocorticosteroids and not the proportion of low density and/or activated neutrophils. Analysis of longitudinal data revealed no correlation between baseline neutrophil score or changes over the first year of follow-up with subsequent renal flare or treatment outcomes, respectively. The findings argue that although the neutrophil score is associated with LN, its clinical utility as a biomarker may be limited.

Ten-eleven translocation 1 dysfunction reduces 5-hydroxymethylcytosine expression levels in gastric cancer cells.

A sixth base, 5-hydroxymethylcytosine (5hmC), is formed by the oxidation of 5-methylcytosine (5mC) via the catalysis of the ten-eleven translocation (TET) protein family in cells. Expression levels of 5hmC are frequently depleted during carcinogenesis. However, the detailed mechanisms underlying the depletion of 5hmC expression in gastric cancer cells remains unclear, and further research is required. The present study examined the expression levels of 5mC and 5hmC and the expression levels of TET1 and TET2 in gastric cancer tissues using immunohistochemistry. The results revealed that 5hmC expression levels were markedly lower in gastric cancer tissues compared with corresponding adjacent normal tissues. Furthermore, a decrease in 5hmC expression levels was associated with a decrease in TET1 protein expression levels in gastric cancer tissues. The ectopic expression level of TET1 may increase the 5hmC expression level in gastric cancer cells. In addition, the results revealed that TET1 protein expression was markedly different in regards to subcellular localization, and mislocalization was significantly associated with the depletion of 5hmC expression levels in gastric cancer. Together, the results of the present study indicated that TET1 dysfunction reduces 5hmC expression levels, and this phenomenon may serve a crucial role in gastric cancer progression.

Characteristics of recurrent papillary thyroid cancer in metabolic syndrome patients / 西安交通大学学报(医学版)

Objective To explore the characteristics and components of recurrent papillary thyroid cancer in patients with metabolic syndrome .Methods We retrospectively reviewed the information of the patients with recurrent papillary thyroid cancer after initial surgery during January 1st ,2010 and December 31st ,2015 in the First Affiliated Hospital of Zhengzhou University .We compared tumor size ,lymph node metastasis ,recurrence time and postoperative invasion rate in metabolic syndrome and non-metabolic syndrome groups . Results Totally 82 patients were included with 34 men and 48 women .There was no significant difference between patients with and those without metabolic syndrome grouped by the classic diagnosis approach .However ,the lymph node metastasis grade of recurrent papillary thyroid cancer patients who also suffered from at least two metabolic disorders ,was lower ,especially in women (P=0 .002) .Moreover ,patients with metabolic disorders had shorter recurrence time (Pdiabetes=0 .034 , Pdyslipidemia =0 .037 , PBMI =0 .004 , PMetS2 =0 .036) .Conclusion Papillary thyroid cancer patients with metabolic disorder ,especially with two or more components of metabolic syndrome and overweight and/or obesity ,may have an increasing risk of recurrence .

Adjuvant hepatic arterial infusion chemotherapy is beneficial for selective patients with Hepatocellular carcinoma undergoing surgical treatment.

BACKGROUND: Recurrence rate after curative surgical resection of Hepatocellular carcinoma (HCC) remains high. Postoperative hepatic arterial infusion chemotherapy (HAIC) has been suggested to improve survival. This study is to investigate the efficacy of HAIC in the patients with poor tumor factors such as vascular invasion or multiplicity. METHODS: From 2006 to 2014, 221 patients with HCC undergoing hepatectomy and pathologically staged as ≧ T2 (American Joint Committee on Cancer TNM staging system, 7th edition) were included. 61 patients received adjuvant HAIC with 5-fluorouracil, cisplatin, and epirubicin. 160 patients received surgery alone. The overall survival time (OST) and disease free survival time (DFST) were compared between the two groups. RESULTS: In all patients, the multivariate analysis of survival data showed that resection margin less than 10 mm was the independent poor prognostic factors. The median OST and DFST between the HAIC and surgery alone groups were 56.4 vs. 56.9 months (p = 0.76), and 50.6 vs. 54.5 months (p = 0.905), respectively. There was no significant difference. For patients with multiple tumors and concomitantly microvascular invasion, the OST was better in the HAIC group (69.7 vs. 54.6 months, p < 0.05). Based on the image and operative finding, we classified multiple HCC's into two types. Type A: multiple small nodules were close to each other or a huge tumor with several satellite nodules. Type B: two or more tumors scattering in separate segments. Our study showed that type A group benefits from adjuvant HAIC much more than type B. (the median OST in type A versus type B were 85.06 vs. 41.53 months, p = 0.0036). CONCLUSION: The surgical outcome for the patients with multiple HCC's and vascular invasion was poor. Our study showed adjuvant HAIC was beneficial in these patients and formed the basis for further randomized controlled trials.

Multiple tolerance defects contribute to the breach of B cell tolerance in New Zealand Black chromosome 1 congenic mice.

Lupus is characterized by a loss of B cell tolerance leading to autoantibody production. In this study, we explored the mechanisms underlying this loss of tolerance using B6 congenic mice with an interval from New Zealand Black chromosome 1 (denoted c1(96-100)) sufficient for anti-nuclear antibody production. Transgenes for soluble hen egg white lysozyme (sHEL) and anti-HEL immunoglobulin were crossed onto this background and various tolerance mechanisms examined. We found that c1(96-100) mice produced increased levels of IgM and IgG anti-HEL antibodies compared to B6 mice and had higher proportions of germinal center B cells and long-lived plasma cells, suggesting a germinal center-dependent breach of B cell anergy. Consistent with impaired anergy induction, c1(96-100) double transgenic B cells showed enhanced survival and CD86 upregulation. Hematopoietic chimeric sHEL mice with a mixture of B6 and c1(96-100) HEL transgenic B cells recapitulated these results, suggesting the presence of a B cell autonomous defect. Surprisingly, however, there was equivalent recruitment of B6 and c1(96-100) B cells into germinal centers and differentiation to splenic plasmablasts in these mice. In contrast, there were increased proportions of c1(96-100) T follicular helper cells and long-lived plasma cells as compared to their B6 counterparts, suggesting that both B and T cell defects are required to breach germinal center tolerance in this model. This possibility was further supported by experiments showing an enhanced breach of anergy in double transgenic mice with a longer chromosome 1 interval with additional T cell defects.

Invariant NKT Cell Activation Is Potentiated by Homotypic trans-Ly108 Interactions.

Invariant NKT (iNKT) cells are innate lymphocytes that respond to glycolipids presented by the MHC class Ib molecule CD1d and are rapidly activated to produce large quantities of cytokines and chemokines. iNKT cell development uniquely depends on interactions between double-positive thymocytes that provide key homotypic interactions between signaling lymphocyte activation molecule (SLAM) family members. However, the role of SLAM receptors in the differentiation of iNKT cell effector subsets and activation has not been explored. In this article, we show that C57BL/6 mice containing the New Zealand Black Slam locus have profound alterations in Ly108, CD150, and Ly9 expression that is associated with iNKT cell hyporesponsiveness. This loss of function was only apparent when dendritic cells and iNKT cells had a loss of SLAM receptor expression. Using small interfering RNA knockdowns and peptide-blocking strategies, we demonstrated that trans-Ly108 interactions between dendritic cells and iNKT cells are critical for robust activation. LY108 costimulation similarly increased human iNKT cell activation. Thus, in addition to its established role in iNKT cell ontogeny, Ly108 regulates iNKT cell function in mice and humans.

Isocitrate Dehydrogenase 2 Dysfunction Contributes to 5-hydroxymethylcytosine Depletion in Gastric Cancer Cells.

The isocitrate dehydrogenase (IDH) family of enzymes comprises of the key functional metabolic enzymes in the Krebs cycle that catalyze the conversion of isocitrate to α-ketoglutarate (α-KG). α-KG acts as a cofactor in the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). However, the relationship between 5hmC and IDH in gastric cancer remains unclear. Our study revealed that the 5hmC level was substantially lower and 5mC level was slightly higher in gastric cancer tissues; however, 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) levels did not change significantly in these tissues. We further examined the expression levels of IDH1 and IDH2 in gastric cancer tissues and observed that IDH2 levels were significantly lower in gastric cancer tissues than in the adjacent normal tissues. The ectopic expression of IDH2 can increase 5hmC levels in gastric cancer cells. In conclusion, our results suggested that IDH2 dysfunction is involved in 5hmC depletion during gastric cancer progression.

IL-10 Production Is Critical for Sustaining the Expansion of CD5+ B and NKT Cells and Restraining Autoantibody Production in Congenic Lupus-Prone Mice.

The development and progression of systemic lupus erythematosus is mediated by the complex interaction of genetic and environmental factors. To decipher the genetics that contribute to pathogenesis and the production of pathogenic autoantibodies, our lab has focused on the generation of congenic lupus-prone mice derived from the New Zealand Black (NZB) strain. Previous work has shown that an NZB-derived chromosome 4 interval spanning 32 to 151 Mb led to expansion of CD5+ B and Natural Killer T (NKT) cells, and could suppress autoimmunity when crossed with a lupus-prone mouse strain. Subsequently, it was shown that CD5+ B cells but not NKT cells derived from these mice could suppress the development of pro-inflammatory T cells. In this paper, we aimed to further resolve the genetics that leads to expansion of these two innate-like populations through the creation of additional sub-congenic mice and to characterize the role of IL-10 in the suppression of autoimmunity through the generation of IL-10 knockout mice. We show that expansion of CD5+ B cells and NKT cells localizes to a chromosome 4 interval spanning 91 to 123 Mb, which is distinct from the region that mediates the majority of the suppressive phenotype. We also demonstrate that IL-10 is critical to restraining autoantibody production and surprisingly plays a vital role in supporting the expansion of innate-like populations.

Stromal cell-derived factor 1 promoted migration of adipose-derived stem cells to the wounded area in traumatic rats.

BACKGROUND: Adipose-derived stem cells (ADSCs) were effective in treating wound. Stromal cell-derived factor-1 (SDF-1), a chemokine usually called CXCL12, is well known for its chemotaxis in induction of cell migration. However, little is known about the SDF-1responsible for the complex migration of ADSCs from residence to injured sites. OBJECTIVE: Herein, we firstly showed SDF-1 is a major regulator involved in migration of ADSCs during wound repair in vivo. METHODS: Trauma in rats was induced by surgical operation. The levels of SDF-1 in wounded tissue were assayed by ELISA. ADSCs were labeled with Green Fluorescent Protein (GFP), and then were transferred to injured rats by intracarotid injection. The plasma levels of ADSCs during wound healing were detected by flow cytometry, and ADSCs in injured tissue were evaluated by bioluminescence imaging in vivo and laser confocal microscopy (LCM), respectively. RESULTS: ADSCs were successfully labeled with GFP. SDF-1 level reached to the peak value on 24 h after injury and then decreased continuously. Additionally, levels of plasma ADSCs in SDF-1 treated rats reached to the peak value (12%) at d21 after medicine delivery, while those of normal and injured rats showed the peak values of 6.28% and 9.84% at d7 and d21, respectively. Finally, the results of LCM indicated treatment of ectogenic SDF-1 obviously enhanced GFP-ADSCs distribution in wounded tissues. CONCLUSION: Our results indicated that SDF-1 treatment obviously promoted the migration and directed distribution of ADSCs in traumatic tissue.