ABSTRACT
Endoplasmic reticulum (ER) stress, as an emerging hallmark feature of cancer, has a considerable impact on cell proliferation, metastasis, invasion, and chemotherapy resistance. Ovarian cancer (OvCa) is one of the leading causes of cancer-related mortality across the world due to the late stage of disease at diagnosis. Studies have explored the influence of ER stress on OvCa in recent years, while the predictive role of ER stress-related genes in OvCa prognosis remains unexplored. Here, we enrolled 552 cases of ER stress-related genes involved in OvCa from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) cohorts for the screening of prognosis-related genes. The least absolute shrinkage and selection operator (LASSO) regression was applied to establish an ER stress-related risk signature based on the TCGA cohort. A seven-gene signature revealed a favorable predictive efficacy for the TCGA, International Cancer Genome Consortium (ICGC), and another GEO cohort (P<0.001, P<0.001, and P=0.04, respectively). Moreover, functional annotation indicated that this signature was enriched in cellular response and senescence, cytokines interaction, as well as multiple immune-associated terms. The immune infiltration profiles further delineated an immunologic unresponsive status in the high-risk group. In conclusion, ER stress-related genes are vital factors predicting the prognosis of OvCa, and possess great application potential in the clinic.
Subject(s)
Humans , Female , Ovarian Neoplasms/genetics , Cell Proliferation , Cytokines , Endoplasmic Reticulum Stress/geneticsABSTRACT
Studies have shown that spatial attention remarkably affects the trial-to-trial response variability shared between neurons. Difficulty in the attentional task adjusts how much concentration we maintain on what is currently important and what is filtered as irrelevant sensory information. However, how task difficulty mediates the interactions between neurons with separated receptive fields (RFs) that are attended to or attended away is still not clear. We examined spike count correlations between single-unit activities recorded simultaneously in the primary visual cortex (V1) while monkeys performed a spatial attention task with two levels of difficulty. Moreover, the RFs of the two neurons recorded were non-overlapping to allow us to study fluctuations in the correlated responses between competing visual inputs when the focus of attention was allocated to the RF of one neuron. While increasing difficulty in the spatial attention task, spike count correlations were either decreased to become negative between neuronal pairs, implying competition among them, with one neuron (or none) exhibiting attentional enhancement of firing rate, or increased to become positive, suggesting inter-neuronal cooperation, with one of the pair showing attentional suppression of spiking responses. Besides, the modulation of spike count correlations by task difficulty was independent of the attended locations. These findings provide evidence that task difficulty affects the functional interactions between different neuronal pools in V1 when selective attention resolves the spatial competition.
Subject(s)
Animals , Attention/physiology , Macaca mulatta , Neurons/physiology , Photic Stimulation , Primary Visual Cortex , Visual Cortex/physiologyABSTRACT
With the increase of obese people around the world,the complications associated with obesity are endangering human health,it has became an important factor affecting the quality of life and increasing social and economic burdens.Rouxen-Y gastric bypass (RYGB) is an effective surgical tool for the treatment of obesity and metabolic-related complications,meanwhile,it can also improve or cure the obesity-related metabolic diseases with reducing the body mass of patients.Free fat mass (FFM) is the main component of the human body and plays an important role in metabolic surgery for the prevention of bone loss,control of weight and alleviation of insulin resistance and so on.The loss of body mass is one of the manifestations of the changes in body composition and distribution after RYGB,and its performance is common after metabolic surgery.This article will summary the findings and investigate the reason of decreased FFM after RYGB and the preventive strategy for different reasons,and it will also provide to the principle of individualized management of patients and guide the clinical practice.
ABSTRACT
Objective To observe the changes of pre-and post-operative body fats of obese patients undergoing laparoscopic sleeve gastrectomy which were evaluated by dual-energy X-ray absorptiometry (DEXA) and investigate the correlation of the changes between body fat and insulin resistance.Methods The cohort study was conducted.The clinical data of 10 obese patients who were admitted to the Fourth Affiliated Hospital of China Medical University from October 2015 to February 2017 were collected.Ten obese patients received laparoscopic sleeve gastrectomy (LSG).The pre-and post-operative body fat masses in the different parts and regions of the whole body [whole body,upper limbs,lower limbs,trunk,region of android (region A) and region of gynoid (region G)] were measured by DEXA and pre-and post-operative indexes of insulin resistance (HOMA-IR) were calculated.Observation indicators:(1) fat parameters evaluated by DEXA and test results of other obesity related indicators;(2) test results of insulin sensitivity index.The patients were followed up by the professional team of metabolic surgery using telephone interview,outpatient and inpatient examinations up to February 2017,and DEXA using outpatient and inpatient examinations was performed at 6 months postoperatively.The measurement data with normal distribution were represented as-x ±s,and repeated measurement data were analyzed by the repeated measures ANOVA.The correlation analysis was performed by the Pearson,and the degree of correlation was analyzed by the factor analysis and multiple linear regression.Results (1) Fat parameters evaluated by DEXA and test results of other obesity related indicators:all the 10 patients were followed up.The fat masses and percentages of the whole body,upper limbs,lower limbs,trunk,region A and region G,BMI,waist circumference and HOMA-IR were respectively (55.6± 13.7) kg,(6.2± 1.9) kg,(17.8± 3.6) kg,(31.7± 12.7) kg,(5.6±2.4)kg,(8.8±1.5)kg,50％±3％,54％±5％,50％±4％,52％±3％,57％±4％,52％±4％,(42± 8) kg/m2,(123±23) cm,8.7 ± 5.6 before operation and (37.4± 11.3) kg,(4.0± 1.2) kg,(11.2± 3.0) kg,(20.4±9.6) kg,(3.5± 1.7) kg,(5.1± 1.4) kg,43％±5％,46％±5％,42％±5％,46％±5％,48％±6％,46％ ± 5％,(30 ± 6) kg/m2,(101 ± 20) cm,3.5 ± 2.4 at 6 months postoperatively,with statistically significant differences between pre-and post-operations (F =11.282,6.308,15.789,6.083,7.836,9.027,5.485,7.743,8.620,3.743,4.704,5.421,13.281,14.258,4.465,P＜0.05).The waist-hip ratio and percentage of region A/ percentage of region G (A/G) were 0.94±0.09,1.10±0.09 before operation and 0.93±0.12,1.05±0.13 at 6 months postoperatively,with no statistically significant difference between pre-and post-operations (F=0.324,1.361,P＞0.05).(2) Test results of insulin sensitivity index:there was a positive correlation in the fat masses of the whole body,trunk,region A and region G,BMI,waist circumference and HOMA-IR (r =0.873,0.874,0.894,0.696,0.843,0.816,P＜0.05),and no correlation between the fat masses of the upper and lower limbs and HOMA-IR (r =0.442,0.242,P＞0.05).The principal component of F1 and F2 were constructed by the factor analysis,F1 (trunk for the most) reflected the fat mass of the different parts of the whole body and F2 reflected the fat mass of peripheral limbs,the model of F1 was reasonable (t =5.033,P＜0.05).The contribution rate of the whole body,upper and lower limbs,trunk,region A,region G,BMI and waist circumference were respectively 0.994,0.633,0.487,0.887,0.900,0.897,0.959,0.897 in the F1 and -0.030,0.716,0.829,-0.446,-0.405,0.423,-0.201,-0.283 in the F2,and the whole body fat mass (BFM) made a largest contribution rate for the preoperative HOMA-IR (0.994).There was a positive correlation between decrease of fat mass in region G and improvement of HOMA-IR at 6 months postoperatively (r =0.717,P＜0.05).Conclusion BFM is an important index to evaluate the insulin resistance in female patients,and the decrease of fat mass in the region G is an important factor for the early remission of insulin resistance in female patients after laparoscopic sleeve gastrectomy.
ABSTRACT
To obtain the functional fusion protein of rhoptry protein 2, compound rhoptry protein2 and surface antigen 1 of Toxoplasma gondii. the ROP2 and P30 genes from genomic DNA of T.gondii RH strain were amplified by PCR, and were inserted into pMD18-T cloning vector. Then the ROP2 fragment was subcloned to pET-30a(+) plasmid digested by EcoRⅠand Hind Ⅲ to construct plasmid pET-ROP2. Furthermore,the P30 fragment was subcloned into pET-ROP2 digested by BglⅡand EcoRⅠto create plasmid pET-ROP2-P30, the resulting recombinant plasmids , transformed into E.coli BL21 (DE3), were induced with IPTG. and the proteins identified by SDS-PAGE were further purified and refolded. The biological activity was analyzed by Western blot with specific antibody. It was found that the sizes of ROP2 and ROP2-P30 were 1212 and 1896bp with corresponding molecular weight 50- kDa and 75-kDa, respectively. The recombinant protein ROP2 (50-kDa) could specifically react with rabbit-polyclonal antiserum, and complex fusion protein ROP2-P30 (75- kDa) could react with P30 monoclonal antibody.
ABSTRACT
To provide the basis for preparation of diagnostic kits and vaccines in Toxoplasma gondii infection, the gene coding for the qualified recombinant p30 protein (SAG1) of this parasite was amplified by PCR, and the amplified gene was cloned into prokaryotic expression vector pET-30a(+) to construct the recombinant plasmid, and then transformed to E.coli DH5α. The positive recombinant plasmid was screened by PCR and double enzymes digestion, and the nucleotide sequence of p30 gene was determined by automated DNA sequencing. Meanwhile, the identified recombinant plasmid was transformed to E.coli BL21(DE3) with the expression of p30 on bacteria induced by IPTG and the expressed protein was identified by SDS-PAGE. The protein obtained was then further purified and refolded, and its biological activity was checked by Western blotting. It was shown that the size of the amplified gene was 750 bp with molecular weight of 30 ku, and this protein could specifically react with monoclonal antibody against p30 protein.
ABSTRACT
Objective To study the protective effect of ROP2 nuclei acid vaccine in mice.Methods Forty-two BALB/c mice were divided into three groups.Each mouse in experiment group was injected with 50 ?g recombinant plasmid pc-DNA3-ROP2 through musculus quadriceps fexoris.In control groups,each mouse was injected with 50 ?g blank plasmid pc-DNA3 and with 50 ?l PBS respectively.All mice were immunized for three times with an interval of three weeks.The volume was doubled for the final injection in the two plasmid groups.Blood,spleens and lymph nodes of 4 mice in each group were taken for the detection of CD4+,CD8+ T cells and cytokines 2 weeks after the final immunization.The rest mice in 3 groups were challenged with 500 tachyzoites of Toxoplasm gondii RH strain for further observation.Results The vaccine induced strong cellular and humoral immune response.The titer of antibody in serum was high after inoculation and recognized ROP2 protein antigen expressed in vitro.The lymphocyte phenotype was analyzed.CD4+ T cells proliferated sharply(69.5?3.4)%,and the ratio of CD4+/CD8+ increased considerably by(4.69?1.32)%(P