Extensive analysis of D7S486 in primary gastric cancer supports TESTIN as a candidate tumor suppressor gene

<p>Abstract</p> <p>Background</p> <p>High frequency of loss of heterozygosity (LOH) was found at D7S486 in primary gastric cancer (GC). And we found a high frequency of LOH region on 7q31 in primary GC from China, and identified D7S486 to be the most frequent LOH locus. This study was aimed to determine what genes were affected by the LOH and served as tumor suppressor genes (TSGs) in this region. Here, a high-throughput single nucleotide polymorphisms (SNPs) microarray fabricated in-house was used to analyze the LOH status around D7S486 on 7q31 in 75 patients with primary GC. Western blot, immunohistochemistry, and RT-PCR were used to assess the protein and mRNA expression of TESTIN (TES) in 50 and 140 primary GC samples, respectively. MTS assay was used to investigate the effect of TES overexpression on the proliferation of GC cell lines. Mutation and methylation analysis were performed to explore possible mechanisms of TES inactivation in GC.</p> <p>Results</p> <p>LOH analysis discovered five candidate genes (<it>ST7</it>, <it>FOXP2</it>, <it>MDFIC</it>, <it>TES </it>and <it>CAV1</it>) whose frequencies of LOH were higher than 30%. However, only <it>TES </it>showed the potential to be a TSG associated with GC. Among 140 pairs of GC samples, decreased <it>TES </it>mRNA level was found in 96 (68.6%) tumor tissues when compared with matched non-tumor tissues (<it>p </it>< 0.001). Also, reduced TES protein level was detected in 36 (72.0%) of all 50 tumor tissues by Western blot (<it>p </it>= 0.001). In addition, immunohistochemical staining result was in agreement with that of RT-PCR and Western blot. Down regulation of TES was shown to be correlated with tumor differentiation (<it>p </it>= 0.035) and prognosis (<it>p </it>= 0.035, log-rank test). Its overexpression inhibited the growth of three GC cell lines. Hypermethylation of <it>TES </it>promoter was a frequent event in primary GC and GC cell lines. However, no specific gene mutation was observed in the coding region of the <it>TES </it>gene.</p> <p>Conclusions</p> <p>Collectively, all results support the role of <it>TES </it>as a TSG in gastric carcinogenesis and that <it>TES </it>is inactivated primarily by LOH and CpG island methylation.</p

The landscape of tolerated genetic variation in humans and primates.

Personalized genome sequencing has revealed millions of genetic differences between individuals, but our understanding of their clinical relevance remains largely incomplete. To systematically decipher the effects of human genetic variants, we obtained whole-genome sequencing data for 809 individuals from 233 primate species and identified 4.3 million common protein-altering variants with orthologs in humans. We show that these variants can be inferred to have nondeleterious effects in humans based on their presence at high allele frequencies in other primate populations. We use this resource to classify 6% of all possible human protein-altering variants as likely benign and impute the pathogenicity of the remaining 94% of variants with deep learning, achieving state-of-the-art accuracy for diagnosing pathogenic variants in patients with genetic diseases

Diagnostic value of ROC curve evaluation of serum markers in acute cholecystitis with bacterial infection

Objective: To explore correlation of serum markers human neutrophil lipocalin and C-reactive protein with acute cholecystitis associated with bacterial infection, and to evaluate the diagnostic value of the markers. Method: The cross-sectional study was conducted from January 2018 to April 2020 at the Beijing Luhe Hospital, Capital Medical University, Beijing, China, and comprised acute cholecystitis patients who were divided into bacterial infection group A and non-bacterial infection group B. Serum human neutrophil lipocalin and C-reactive protein were measured for both the groups. Receiver operating characteristic curve was used to evaluate the diagnostic value of the two markers in acute cholecystitis associated with bacterial infection. Data was analysed using SPSS 25. Results: Of the 145 patients, 65(45%) were in group A; 36(55.38%) males and 29(44.62%) females with a mean age of 45.79±2.50 years. In group B there were 80(55%) subjects; 45(56.25%) males and 35(43.75%) females with a mean age of 46.16±2.52 years (p>0.05). In group A, there were 60(92.31%) cases of acute calculous cholecystitis, and 5(7.69%) had acute acalculous cholecystitis compared to 73(91.25%) and 7(8.75%), respectively, in group B (p>0.05). Serum human neutrophil lipocalin and C-reactive protein levels in group A were higher than group B (p<0.001). Serum human neutrophil lipocalin showed a high positive correlation with C-reactive protein in group A (r=0.800, p<0.001), and a moderate positive correlation in group B (r=0.683, p<0.001). Area under the curve of serum human neutrophil lipocalin associated with C-reactive protein was 0.901 ---Continu

The Engrailed-1 Gene Stimulates Brown Adipogenesis

As a thermogenic organ, brown adipose tissue (BAT) has received a great attention in treating obesity and related diseases. It has been reported that brown adipocyte was derived from engrailed-1 (EN1) positive central dermomyotome. However, functions of EN1 in brown adipogenesis are largely unknown. Here we demonstrated that EN1 overexpression increased while EN1 knockdown decreased lipid accumulation and the expressions of key adipogenic genes including PPARγ2 and C/EBPα and mitochondrial OXPHOS as well as BAT specific marker UCP1. Taken together, our findings clearly indicate that EN1 is a positive regulator of brown adipogenesis

Value of indomethacin suppository for preoperative analgesia and anti-inflammation in laparoscopic appendectomy: a protocol of prospective, double-blinded, single-centre, randomised controlled trial in China

Introduction Postoperative pain has always been a problem for patients and surgeons. Local inflammation, surgical trauma and pain in the body can cause a systemic stress response and immune imbalance, which can affect the patient’s rapid recovery. Currently, most of the perioperative pain management is focused on the postoperative phase. The non-steroidal anti-inflammatory drug indomethacin suppository has antipyretic and analgesic effects. This study will evaluate the value of indomethacin suppository for analgesia and anti-inflammation before laparoscopic appendectomy (LA).Methods and analysis A single-centre, double-blinded (clinician, assessor, data entry), randomised controlled trial will be conducted in 128 adult patients undergoing LA under emergency general anaesthesia with a Visual Analogue Scale (VAS) &gt;2. The trial was divided into two groups (n=64) using a randomised number table: group A will be given 100 mg of indomethacin suppository rectally and group B will be given 8 mg of intravenous lornoxicam. The postoperative analgesic effect, inflammatory response and incidence of postoperative adverse effects will be compared.Ethics and dissemination The study is in accordance with the Declaration of Helsinki and will be conducted in accordance with the principles of Good Clinical Practice. This trial was approved by the Ethics Committee of Beijing Luhe Hospital, Capital Medical University (2021-LHKY-123-02). We will disseminate our study findings at national and international paediatric research conferences.Trial registration number Chinese Clinical Trial Registry (ChiCTR2200062004)

Hypoxia-inducible factor-1α polymorphisms and risk of cancer metastasis: a meta-analysis.

BACKGROUND: HIF-1α is a major regulator in tumor progression and metastasis which responds to hypoxia. Many studies have demonstrated that hypoxia-inducible factor1-α (HIF-1α) polymorphisms are significantly associated with cancer metastasis, but the results are inconsistent. We conducted a comprehensive meta-analysis to estimate the associations between HIF-1α C1772 T polymorphism and cancer metastasis. METHODS: Comprehensive searches were conducted on PubMed and EMBASE database. Fifteen studies were included in the meta-analysis. We used the OR and 95%CI to assess the associations between HIF-1α C1772T polymorphism and cancer metastasis. Heterogeneity and publication bias were also assessed by Q test, I (2), and funnel plot. RESULTS: Totally, fifteen studies including 1239 cases with metastasis-positive (M+) and 2711 cases with metastasis-negative (M-) were performed in this meta-analysis. The results showed that HIF-1a C1772T polymorphism was associated with the increased risk of cancer metastasis (T allele vs. C allele, OR  = 1.36, 95% CI  = 1.12-1.64; TT+ TC vs. CC, OR  = 1.39, 95% CI  = 1.13-1.71; TT vs. TC+ CC, OR  = 1.93, 95% CI  = 0.86-4.36). In the subgroup analyses, the significant associations remained significant among Asians, Caucasians and other cancers in the dominant model. Publication bias was not observed in the analysis. CONCLUSIONS: Our results indicate that the HIF-1αC1772T polymorphism T allele may increase the risk of cancer metastasis, which might be a potential risk factor of cancer progress