Pharmacological Inhibition or Silencing of TREM1 Restrains HCC Cell Metastasis by Inactivating TLR/PI3K/AKT Signaling.

Hepatocellular carcinoma (HCC), a widely prevalent malignancy strongly linked to inflammation, remains a significant public health concern. Triggering receptor expressed on myeloid cells 1 (TREM1), a modulator of inflammatory responses identified in recent years, has emerged as a crucial facilitator in cancer progression. Despite its significance, the precise regulatory mechanism of TREM1 in HCC metastasis remains unanswered. In the present investigation, we observed aberrant upregulation of TREM1 in HCC tissues, which was significantly linked to poorer overall survival. Inhibition of TREM1 expression resulted in a significant reduction in HCC Huh-7 and MHCC-97H cell proliferation, invasion, and epithelial-mesenchymal transition (EMT) process. Furthermore, inhibiting TREM1 decreased protein expressions of toll-like receptor 2/4 (TLR2/4) and major myeloid differentiation response gene 88 (MyD88), leading to the inactivation of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) in HCC cells. Notably, these effects were reversed by treatment with TLR2-specific agonist (CU-T12-9), indicating a potential crosstalk between TREM1 and TLR2/4. Mechanistic studies revealed a direct interaction between TREM1 and both TLR2 and TLR4. In vivo studies demonstrated that inhibition of TREM1 suppressed the growth of HCC cells in the orthotopic implant model and its metastatic potential in the experimental lung metastasis model. Overall, our findings underscore the role of TREM1 inhibition in regulating EMT and metastasis of HCC cells by inactivating the TLR/PI3K/AKT signaling pathway, thereby providing deeper mechanistic insights into how TREM1 regulates metastasis during HCC progression.

Metformin improves high-fat diet-induced insulin resistance in mice by downregulating the expression of long noncoding RNA NONMMUT031874.2.

Metformin (MET) is the first-line therapeutic option for patients with type 2 diabetes that has garnered substantial attention over recent years. However, an insufficient number of studies have been performed to assess its effects on insulin resistance and the expression profile of long noncoding RNAs (lncRNAs). The present study divided mice into three groups: Control group, high-fat diet (HFD) group and HFD + MET group. A high-throughput sequencing analysis was conducted to detect lncRNA and mRNA expression levels, and differentially expressed lncRNAs were selected. Subsequently, the differentially expressed lncRNAs were validated both in vivo and in vitro (mouse liver AML12 cells treated with Palmitic acid) models of insulin resistance. After validating randomly selected lncRNAs via reverse transcription-quantitative PCR a novel lncRNA, NONMMUT031874.2, was identified, which was upregulated in the HFD group and reversed with MET treatment. To investigate the downstream mechanism of NONMMUT031874.2, lncRNA-microRNA (miR/miRNA)-mRNA co-expression network was constructed and NONCODE, miRBase and TargetScan databases were used, which indicated that NONMMUT031874.2 may regulate suppressor of cytokine signaling 3 by miR-7054-5p. For the in vitro part of the present study, AML12 cells were transfected with small interfering RNA to knock down NONMMUT031874.2 expression before being treated with palmitic acid (PA) and MET. The results showed that the expression of NONMMUT031874.2 was significantly increased whereas miR-7054-5p expression was significantly decreased by PA treatment. By contrast, after knocking down NONMMUT031874.2 expression or treatment with MET, the aforementioned in vitro observations were reversed. In addition, it was also found that NONMMUT031874.2 knockdown and treatment with MET exerted similar effects in alleviating insulin resistance and whilst decreasing glucose concentration in AML12 cells. These results suggest that MET treatment can ameliorate insulin resistance by downregulating NONMMUT031874.2 expression.

Optimal pathways involved in the treatment of sevoflurane or propofol for patients undergoing coronary artery bypass graft surgery.

The cardio-protection mechanisms of sevoflurane and propofol still remain unclear in patients undergoing coronary artery bypass grafting (CABG). We designed the present study to identify the optimal pathways through integrating differential co-expressed network (DCN)-based guilt by association (GBA) principle based on the expression data of E-GEOD-4386 downloaded from EMBL-EBI. Differentially expressed genes (DEGs) were firstly identified and then DCN and sub-DCN were established. The seed pathways were predicted through GBA principle using the area under the curve (AUC) for pathway categories, and the pathway terms with AUC >0.9 were defined as the seed pathways. KEGG pathway analysis was applied to the DEGs based on DAVIA to detect significant pathways. The final optimal pathways were identified based on the traditional pathway analysis and network-based pathway inference approach. There were 83 common, 99 sevoflurane-specific and 4 propofol-specific DEGs in the expression profile of artial samples. Finally, 8 and 4 pathway terms having the AUC >0.9 were identified and determined as the seed pathways in the propofol and sevoflurane group, respectively. TNF signaling pathway, NF-κB signaling pathway, as well as NOD-like receptor signaling pathway were the common optimal ones in these two groups. Only the pathway of cytokine-cytokine receptor interaction was unique to sevoflurane, and no pathway was specific to propofol. Our results suggested that sevoflurane and propofol might synergistically possess some cardio-protective properties in patients undergoing CABG.

MicroRNA-1290 promotes esophageal squamous cell carcinoma cell proliferation and metastasis.

AIM: To investigate the biological role of miR-1290 in esophageal squamous cell carcinoma (ESCC) progression and invasion and the underlying mechanism. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to evaluate miR-1290 expression in ESCC tissue samples. The roles of miR-1290 in cell proliferation, migration and invasion were identified using miR-1290 mimic-transfected cells. In addition, the regulatory effect of miR-1290 on suppressor of cancer cell invasion (SCAI) was evaluated using qRT-PCR, Western blot analysis and a dual luciferase reporter assay. RESULTS: miR-1290 was significantly upregulated in ESCC tissue samples compared with normal adjacent tissues (9.213 ± 1.150 vs 1.000 ± 0.0), (P < 0.01). Upregulation of miR-1290 was associated with tumor differentiation (P = 0.021), N classification (P = 0.006) and tumor-node-metastasis stage (P = 0.021) in ESCC patients. Moreover, ectopic miR-1290 expression potently promoted ESCC cell growth (P < 0.01), migration (P < 0.01) and invasion (P < 0.01) in vitro. miR-1290 overexpression in ESCC cell lines decreased SCAI expression at the translational level and reduced SCAI-driven luciferase-reporter activity (P < 0.01). CONCLUSION: Our findings suggested that miR-1290 may play an oncogenic role in cellular processes of ESCC.

Missed diagnosis of early gastric cancer or high-grade intraepithelial neoplasia.

AIM: To investigate the causes of missed diagnosis of early gastric cancer (EGC) or high-grade intraepithelial neoplasia (HGIN) in Chongqing, China. METHODS: The present study summarizes 103 cases of EGC/HGIN detected by esophagogastroduodenoscopy (EGD) and pathological analysis from January 2010 to December 2011. Dimethyl silicone oil was administrated orally 15 min before the EGD procedures. The stomach was cleaned by repeated washing with saline when the gastroscope entered the stomach cavity. Suspected EGC lesions were subject to conventional biopsy sampling and pathological examinations. The correlation between lesion locations, endoscopic morphology of cancerous sites, training level of the examiners, pathological biopsies, and missed diagnosis was analyzed. RESULTS: Twenty-three cases were missed among the 103 cases (22.23%) of EGC/HGIN. The rate of missed EGC in the gastroesophageal junction (8/19, 42.1%) was significantly higher than at other sites (15/84, 17.86%) (χ² = 5.253, P = 0.022). In contrast, the rate of missed EGC in the lower stomach body (2/14, 14.29%) was lower than at other sites (21/89, 23.6%), but there were no significant differences (χ² = 0.289, P = 0.591). The rate of missed EGC in the gastric antrum (5/33, 15.15%) was lower than at other sites (18/70, 25.71%), but there were no significant differences (χ² = 1.443, P = 0.230). Endoscopists from less prestigious hospitals were more prone to not diagnosing EGC than those from more prestigious hospitals (χ² = 4.261, P = 0.039). When the number of biopsies was < 4, the rate of missed diagnosis was higher (20/23, 89.96%) than for when there were > 4 biopsies (3/23, 13.04%) (P < 0.001). In addition, there was no significant difference in the rate of missed diagnosis in patients with 1-3 biopsy specimens (χ² = 0.141, P = 0.932). CONCLUSION: Endoscopists should have a clear understanding of the anatomical characteristics of the esophagus/stomach, and endoscopic identification of early lesions increases with the number of biopsies.

[Studies on cultivation measures of Angelica dahurica].

OBJECTIVE: To evaluate the effect of seedingtime, density of crop and fertilization on the yield of Angelica dahurica. METHOD: Use weighing method to measure the output of A. dahurica. RESULT: The highest yield of seeding-time is 8373 kg/hm' on April 20, which is considerably different compared with April 5 and May 5; the highest yield of the density is 9300 kg/hm2 on 330,000 plants/hm2; the yield of fertilization tests all are considerable higher than that of the contrast. CONCLUSION: The appropriate seeingtime of A. dahurica is the first or second ten days of April, the appropriate density is 330,000 plants/hm2, and the appropriate amount of fertilization is N24P20, i.e pure N 360 kg and P20, 300 kg per hectare.

[Research of Typing for HLA-A, -B on Cord Blood Lymphocytes]

Serological typing for HLA-A, -B has been used for a long time. Recently with the developing of molecular biology technologies, HLA-A, -B typing is now turning to genotyping methods. In our study, the capacity of PCR-SSP in solving problems in HLA-A, -B typing with serological methes was evaluated. With this aim the serological method was compared with PCR-SSP in 102 cord blood samples, and the results showed that 18.6% of 102 cord blood samples can't give a satisfactory detection, for 14 samples, give discrepant results with the 2 methods. It is mainly due to weak expression of HLA class I cord blood lymphocytes and the cross reaction of some antigens. About B 15 group, the further study was made, it was found that most of the B 15 splits is wrongly disassigned, especially among the B62-B75, B75/*1511(+)-B75/*1511(-), B46-*1511 antigens. It was concluded that DNA typing is more preferable than serological typing, about B 15 group, the subtyping or high resolution typing can be fulfilled at first in China.