Decreased Th1/Th2 ratio is one of the major characteristics of immunosuppression in sepsis. Both membrane adhesive protein Annexin-A1 (ANXA1) and transcription factor GATA-3 have been reported to play important roles in T cell differentiation. However, the relationship between ANXA1 and GATA-3 in Th1/Th2 shift is unknown. Our study investigated the interaction effects of ANXA1 and GATA-3 to influence T cell differentiation in CD4+T cells. We found that GATA-3 and ANXA1 were coexpressed on Th0/Th1/Th2 cytoplasm and nuclear. Overexpressed ANXA1 significantly increased the expression of IFNγand reduced IL-4 expression in T cells, while ANXA1-silenced T cells exhibited decreased production of IFNγand increased production of IL-4. Knockdown of ANXA1 promoted higher expression level of GATA-3 and low level of T-box transcription factor (T-bet/Tbx21). Further study demonstrated that ANXA1 regulated GATA-3 expression through the formyl peptide receptor like-1 (FPRL-1) downstream signaling pathways ERK and PKB/Akt. These results suggested that ANXA1 modulates GATA-3/T-bet expression induced Th0/Th1 differentiation. Moreover, we found that GATA-3 inhibited ANXA1 expression by binding to its promoter for the first time. It is proposed that the interactions between ANXA1 and GATA-3 may provide clues to understand the immunosuppression and have potential as new therapeutic targets in immunotherapy after sepsis.
A capacitive immunosensor on a glassy carbon electrode (GCE) was fabricated successfully by using an insulating poly (o‐phenylenediamine) (OPD) film. Two methods, covalently coupling and copolymerization, were developed to immobilize the antitransferrin onto the GCE for sensitively probing transferrin. The capacitance change of the electrode caused by the interaction between antigen–antibody was monitored by the potentiostatic step. The immunosensors demonstrated a highly specific response to transferrin in a sample solution. The stable insulating property of the OPD film made immunosensor renewable in acid elution. For the immunosensor fabricated by the covalently coupling method, the linear detection range was 0.1 to 45.0 ng/mL, with a detection limit of 0.061 ng/mL (S/N = 3). For immunosensor fabricated by the copolymerization method, the linear detection range was 5.0 to 17.5 ng/mL, with a detection limit of 2.0 ng/mL. This indicated that the immunosensor prepared by the covalently coupling method showed better sensitivity and a wider detection range than one fabricated by the copolymerization method. Compared with self‐assembled monolayers, the method of using the insulating OPD film simplified the process of immunosensor fabrication and provided a new approach to prepare capacitive immunosensor on carbon substrate.
Neuroblastoma is the most frequently diagnosed neural tumor of childhood. Abnormal function of the long intergenic non-coding RNA (lincRNA) LINC00673 has been implicated in various human malignancies. Genome-wide association studies revealed the LINC00673 rs11655237 C>T polymorphism to be associated with the risk of neuroblastoma, though the effect was not well defined, in part due to the small sample size in our earlier study. Herein, we verified the impact of LINC00673 rs11655237 C>T on the risk of neuroblastoma in 700 cases and 1516 controls from six centers in China. After pooling all enrolled patients, we observed a significant association between LINC00673 rs11655237 C>T and risk of neuroblastoma (TT vs. CC: adjusted odds ratio [OR]=1.58, 95% confidence interval [CI]=1.06-2.35, P=0.024; additive model: adjusted OR=1.20, 95% CI=1.03-1.39, P=0.020; recessive model: adjusted OR=1.50, 95% CI=1.02-2.22, P=0.040). Stratification analysis revealed a significant relationship between rs11655237 CT/TT and neuroblastoma risk in subgroups of males, patients whose tumor originated in the adrenal gland, and patients with clinical stage IV disease. These findings add new evidence of the importance of LINC00673 rs11655237 C>T to the risk of developing neuroblastoma.
Neuroblastoma is the most common seen solid neural tumor in children less than age one. As mutation in themiR-34b/cgene is observed in several types of human malignancies, there likely to be similar events that contribute to the pathogenesis of neuroblastoma. We hypothesize that polymorphism in themiR-34b/cgene might predispose to neuroblastoma. Here, we conducted this replication study by genotyping rs4938723 T>C frommiR-34b/cin Hunan children (162 subjects with neuroblastoma and 270 control subjects) and examined its effect on the risk of neuroblastoma. We determined such association using logistic regression, adjusted for age and gender. Relative to those with TT genotype, subjects with C allele had reduced neuroblastoma risk (TC vs. TT: adjusted,; additive model: adjusted,; TC/CC vs. TT: adjusted,). Stratified analysis revealed that rs4938723 TC/CC carriers were less likely to develop neuroblastoma for patients in the subgroups of,, females, males, tumors in retroperitoneal, tumors in other sites, and clinical stages II, III, IV, and III+IV. Our findings verifiedmiR-34b/crs4938723 C variant allele as a protective factor for the risk of neuroblastoma. Further investigation of howmiR-34b/crs4938723 T>C might modify neuroblastoma risk is warranted.
High-tension electricity can cause devastating injuries that may result in abdominal wall loss, visceral damage, and sometimes major threat to life. The visceral organ may be exposed after debridement and require flap cover, but the tensile strength of abdominal wall may be lack even if flap transplanted. From April 2007 through May 2015, 5 patients with severe abdominal electrical injury were treated at our hospital. Exploratory laparotomy was performed based on their clinical manifestations and debridement findings of abdominal wall at early stage, and decision regarding technique for reconstruction of abdominal wall was based on an assessment of the location and extent of the defect. Medical records were reviewed for these data. Clinical evaluation and debridement findings of the abdomen revealed 4 patients with suspicious visceral damage. Laparotomy was performed in 4 cases, and revealed obvious lesion in 3 cases, including segmental necrosis of small intestine, partial necrosis of diaphragm, left liver and gastric wall, and greater omentum. Five patients underwent abdominal wall reconstruction using island retrograde latissimus dorsi myocutaneous flap or free/island composite anterolateral thigh myocutaneous flap. All flaps survived, abdominal bulging occurred in 3 cases after follow-up of 12 to 36 months. The clinical manifestations and wound features of abdomen collectively suggest a possible requirement of laparotomy for severe abdominal electrical burns. Retrograde latissimus dorsi myocutaneous flap or composite anterolateral thigh myocutaneous flap is an effective option for reconstruction of abdominal wall loss, the long-term complication of abdominal bulging, however, remains a significant clinical challenge.