Diterpenoids from Euphorbia peplus possessing cytotoxic and anti-inflammatory activities.

Phytochemical investigation into the medium polar fraction of the ethanol extract of Euphorbia peplus led to the identification of 32 diterpenoids with five structural types. Compounds 1-5 and 7-11 are reported for the first time, while the configuration of 6,7-epoxy group of 6 was revised to be ß-oriented. Compounds 1-5 feature a rare structural variation of the double bond at Δ1 migrating to Δ1(10) in the tigliane-type diterpenoid family. Biologically, compound 21 was found to be the only one to show moderate cytotoxic activity, associated with the presence of a benzoyloxy residue at C-16. Besides, compounds 4, 8, 12, 13, 16, and 19 show significant inhibitory activities against NO production induced by LPS in RAW264.7 macrophage cells, with IC50 values within 2-5 µM. Structure-activity relationship (SAR) analysis revealed that the ingenane-type diterpenoids have the best anti-inflammatory activity, and the esterification at 3-OH or 5-OH is crucial. Further biological researches demonstrated that 13, the predominant metabolite in this plant, exerts anti-inflammatory effects by blocking the activation of NF-κB and MAPK signaling pathways.

Rare flavanone-diarylheptanoid hybrids from Typha angustifolia shows anti breast cancer activity via activating TGF-ß1/Smad signaling pathway.

Four new flavanone-diarylheptanoid hetero dimers, typhatifolins A-D (1-4), were separated from the pollen of a widely distributed medicinal plant Typha angustifolia. Structures of these rare hybrids were elucidated by detailed interpretation of spectroscopic data, and their absolute configurations were determined on the basis of Mosher's method and ECD analyses. All the four compounds showed moderate to significant cytotoxicities against a panel of tumor cell lines with IC50 values ranging from 0.67 to 12.48 µM. Further in vitro antitumor evaluation for typhatifolin B (TTB, 2) on two breast cancer cells (4T1 and MDA-MB231) revealed that it could remarkably induce cell apoptosis and G0/G1 cycle arrest, as well as block cell migration and invasion. Mechanistically, TTB could exert its antitumor effect via activating the TGF-ß1 (transforming growth factor beta 1) signaling pathway as evidenced by RNA-seq analysis and immunoblotting experiments, which was further corroborated by treating cancer cells with a TGF-ß signaling inhibitor. Lastly, the in vivo anti breast cancer activity was demonstrated by applying the mixture of typhatifolins A-D to a preclinical animal model.

Diagnosis and treatment experience of atypical hepatic cystic echinococcosis type 1 at a tertiary center in China.

BACKGROUND: Some hydatid cysts of cystic echinococcosis type 1 (CE1) lack well-defined cyst walls or distinctive endocysts, making them difficult to differentiate from simple hepatic cysts. AIM: To investigate the diagnostic methods for atypical hepatic CE1 and the clinical efficacy of laparoscopic surgeries. METHODS: The clinical data of 93 patients who had a history of visiting endemic areas of CE and were diagnosed with cystic liver lesions for the first time at the People's Hospital of Xinjiang Uygur Autonomous Region (China) from January 2018 to September 2023 were retrospectively analyzed. Clinical diagnoses were made based on findings from serum immunoglobulin tests for echinococcosis, routine abdominal ultrasound, high-frequency ultrasound, abdominal computed tomography (CT) scan, and laparoscopy. Subsequent to the treatments, these patients underwent reexaminations at the outpatient clinic until October 2023. The evaluations included the diagnostic precision of diverse examinations, the efficacy of surgical approaches, and the incidence of CE recurrence. RESULTS: All 93 patients were diagnosed with simple hepatic cysts by conventional abdominal ultrasound and abdominal CT scan. Among them, 16 patients were preoperatively diagnosed with atypical CE1, and 77 were diagnosed with simple hepatic cysts by high-frequency ultrasound. All the 16 patients preoperatively diagnosed with atypical CE1 underwent laparoscopy, of whom 14 patients were intraoperatively confirmed to have CE1, which was consistent with the postoperative pathological diagnosis, one patient was diagnosed with a mesothelial cyst of the liver, and the other was diagnosed with a hepatic cyst combined with local infection. Among the 77 patients who were preoperatively diagnosed with simple hepatic cysts, 4 received aspiration sclerotherapy of hepatic cysts, and 19 received laparoscopic fenestration. These patients were intraoperatively diagnosed with simple hepatic cysts. During the follow-up period, none of the 14 patients with CE1 experienced recurrence or implantation of hydatid scolices. One of the 77 patients was finally confirmed to have CE complicated with implantation to the right intercostal space. CONCLUSION: Abdominal high-frequency ultrasound can detect CE1 hydatid cysts. The laparoscopic technique serves as a more effective diagnostic and therapeutic tool for CE.

[Retracted] miR­206 inhibits cancer initiating cells by targeting EHF in gastric cancer.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the colony formation assay data shown in Figs. 2, 4 and 8 were strikingly similar to data that had already appeared in another article written by different authors at different research institutes [Chen W, Wang J, Liu S, Wang S, Cheng Y, Zhou W, Duan C and Zhang C: MicroRNA­361­3p suppresses tumor cell proliferation and metastasis by directly targeting SH2B1 in NSCLC. J Exp Clin Cancer Res 35: 76, 732516, 2016]. Owing to the fact that the contentious data in the above article had already been published prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 38: 1688­1694, 2017; DOI: 10.3892/or.2017.5794].

The Effect of GPX2 on the Prognosis of Lung Adenocarcinoma Diagnosis and Proliferation, Migration, and Epithelial Mesenchymal Transition.

Objective: To investigate the expression of glutathione peroxidase 2 (GPX2) in human lung adenocarcinoma tissues and its effect on the biological function of lung adenocarcinoma A549 cells. Methods: The expression of GPX2 in lung adenocarcinoma and its effect on survival were analyzed by the TCGA database and the GEPIA 2 database. A total of 45 cases of primary lung adenocarcinoma tissue specimens and 45 cases of their paracancerous tissue specimens were collected, and the expression of GPX2 in the two types of tissues was detected by immunohistochemistry. Lung adenocarcinoma A549 cells were divided into the GPX2 overexpression group (GPX2), the GPX2 knockdown group (si-GPX2), the empty vector group (Vector), the siRNA negative control group (si-NC), and the WT group; the mRNA level and protein expression of GPX2 in each group of A549 cells were detected by real-time fluorescence quantitative PCR and Western blotting; the proliferation activity of each group of cells was detected by the CCK-8 assay; the effect of GPX2 on cell migration and invasion ability was detected by the scratch assay and the Transwell invasion assay; the apoptosis of each group of cells was detected by flow cytometry; Western blotting was performed to detect the expression levels of Bax, Bcl-2, E-cadherin, vimentin, and MMP2 and MMP9 proteins in each group of cells. Results: Bioinformatics analysis showed that the expression of GPX2 was strongly correlated with the prognosis of lung adenocarcinoma patients (P < 0.01). The positive expression rates of GPX2 in lung adenocarcinoma and its paracancerous tissues were 66.0% and 15.7%, respectively (P < 0.05). The results of RT-qPCR and Western blotting showed that the expression level of GPX2 mRNA and protein in A549 cells in the GPX2 group increased, which was significantly higher than that in the WT group (P < 0.05); the expression levels of GPX2 mRNA and protein in A549 cells in the si-GPX2 group were the same, that is, significantly lower than the WT group (P < 0.05). GPX2 overexpression promoted the proliferation, migration, and invasion of A549 cells and inhibited their apoptosis; the results in the si-GPX2 group were opposite to those in the GPX2 group. Compared with the WT group, the expression of Bcl-2, vimentin, and MMP2 and MMP9 protein in the GPX2 group increased (P < 0.05), while the expression of Bax and E-cadherin protein decreased in the GPX2 group (P < 0.05); the results in the si-GPX2 group were opposite to those in the GPX2 group. Conclusion: The expression of GPX2 in lung adenocarcinoma is related to the prognosis of patients. It is proved that GPX2 can promote the migration and invasion of lung adenocarcinoma cells and is related to the EMT/ß-catenin pathway. Thus, GPX2 is expected to be an important target for the diagnosis and treatment of lung adenocarcinoma.

Case report of a delayed iatrogenic Pipkin type III femoral head fracture-dislocation.

RATIONALE: Pipkin III femoral head fracture dislocation (FHFD) is rarely observed in clinical practice, and its outcome is alarming. A considerable proportion of Pipkin III fractures result from repeated or forceful closed reduction of an irreducible FHFD. Pipkin type III fractures pose a therapeutic challenge. Most patients underwent total hip arthroplasty. PATIENT CONCERNS: A 34-year-old man experienced high-energy trauma to the left hip from a terrible traffic accident. Radiography and computed tomography (CT) at the local hospital revealed a left posterior FHFD. Emergency close reduction of the hip was performed.48 hours later, the patient was transferred to our institution. New radiography and CT examinations demonstrated an iatrogenic femoral neck fracture (FNF) associated with FHFD. In addition, a right talar fracture was observed. DIAGNOSIS: Pipkin III fracture combined with contralateral talar fracture. INTERVENTIONS: Considering his Pipkin fracture classification (Pipkin Type-III) and the time to surgery after his injury (>48 hours), the patient underwent left total hip arthroplasty uneventfully, followed by below-ankle plaster cast immobilization for his right ankle. OUTCOMES: At the 6-month follow-up, the patient was able to walk pain-free, and plain radiographs were satisfactory, with no evidence of heterotopic ossification or osteonecrosis of the talus. LESSONS: Before emergency closed reduction, early recognition of the unique characteristics of an irreducible FHFD is essential to avoid iatrogenic femoral neck fracture.

Novel Quinic Acid Glycerates from Tussilago farfara Inhibit Polypeptide GalNAc-Transferase.

The discovery of a bioactive inhibitor tool for human polypeptide N-acetylgalactosaminyl transferases (GalNAc-Ts), the initiating enzyme for mucin-type O-glycosylation, remains challenging. In the present study, we identified an array of quinic acid derivatives, including four new glycerates (1-4) from Tussilago farfara, a traditional Chinese medicinal plant, as active inhibitors of GalNAc-T2 using a combined screening approach with a cell-based T2-specific sensor and purified enzyme assay. These inhibitors dose-dependently inhibited human GalNAc-T2 but did not affect O-linked N-acetylglucosamine transferase (OGT), the other type of glycosyltransferase. Importantly, they are not cytotoxic and retain inhibitory activity in cells lacking elongated O-glycans, which are eliminated by the CRISPR/Cas9 gene editing tool. A structure-activity relationship study unveiled a novel quinic acid-caffeic acid conjugate pharmacophore that directs inhibition. Overall, these new natural product inhibitors could serve as a basis for developing an inhibitor tool for GalNAc-T2.

21,24-Cyclolanostanes revisited: Structural revision and biological evaluation.

Chemical fractionation of the EtOH extract of a medicinal macro fungus, Inonotus obliquus, afforded an array of lanostane-type triterpenoids (1-11) including two new ones (1 and 8). The structures of these compounds were determined on the basis of spectroscopic analyses, single crystal X-ray crystallography of 3-6 and biosynthetic considerations. With the confirmatory structural information provided by X-ray diffraction analysis in hand, several previously reported 21,24-cyclolanostanes, such as inonotsutriols A-C and (20R,21S,24S)-21,24-cyclopenta-3ß,21,25-trihydroxylanosta-8-ene, were structurally corrected. In addition, the NMR data of other types of 21,24-cyclo triterpenoids were also re-examined and structural revisions were thus suggested. Compounds 2, 6 and 8 showed significant cytostatic effects against a panel of tumor cell lines with IC50 values ranging from 7.80 to 18.5 µM. Further assays established that compound 2 exerted promising in vitro anti-breast cancer potential by inhibiting the proliferation and migration of 4T1 cells.

The application of laparoscopy combined with indocyanine green fluorescence imaging technique for hepatic cystic echinococcosis.

BACKGROUND: With the mature application of laparoscopy in hepatobiliary surgery, laparoscopic treatment of hepatic cystic echinococcosis (CE) has made certain progress. But, due to the inherent limitations of laparoscopy and the growth characteristics of cystic echinococcosis, distinguishing the boundary between cystic lesion and normal hepatic parenchyma is pivotal importance for successful surgery. Indocyanine green (ICG) fluorescence imaging technology can view the boundary of lesion and normal tissue during the treatment of hepatic cystic echinococcosis. Applied laparoscopy combined with ICG fluorescence imaging technique for hepatic cystic echinococcosis may be an effective surgical strategy. METHODS: The clinical data contained nine patients with hepatic cystic echinococcosis who underwent laparoscopic surgery with indocyanine green fluorescence imaging technique in authors' institution from December 2018 to December 2019 were retrospectively analyzed. Indocyanine green was administered intravenously three days prior to surgery. The fluorescence acquisition system for real-time imaging was used during the surgery and the patients were followed up after surgery. RESULTS: Of reported nine patients, six are male and the remaining three are female. The average age is (36.4 ± 7.6) years. For all subjects, surgical procedures were performed under laparoscopy with indocyanine green fluorescence system. This technique showed the clear boundary of the hepatic cyst with normal liver parenchyma. Total cystectomy in six patients, subtotal cystectomy in two patients and partial hepatectomy in one patient were performed respectively. The average operation time was 3.8 ± 0.9 h, blood loss 206.0 ± 120.7 ml. Neither blood transfusion nor post-operative complication was experienced. The average abdominal drainage time was 3.4 ± 0.9 days with hospital stay 5.7 ± 2.1 days. During the 6-12 months follow-up period, neither recurrence nor intraperitoneal implantation was found. CONCLUSIONS: Applied laparoscopy combined with ICG fluorescence imaging technique for hepatic cystic echinococcosis is safe and feasible. Enhanced boundary image can assist surgeons to complete radical resection and reduce complications.

DPP-4 inhibition resembles exercise in preventing type 2 diabetes development by inhibiting hepatic protein kinase Cε expression in a mouse model of hyperinsulinemia.

OBJECTIVE: Interventions for hyperinsulinemia (HINS), an early indicator of type 2 diabetes mellitus (T2DM), can significantly reduce the T2DM risk. This study aims to determine how dipeptidyl peptidase-4 (DPP-4) inhibition prevents HINS progression to T2DM through ameliorating hepatic steatosis. METHODS: KKay mice were used as a HINS model and they underwent exercise or received a DPP-4 inhibitor, MK0626. Hepatic steatosis was examined and liver diacylglycerol levels were determined. Human hepatic cells (LO2) were treated with MK0626 or transfected with DPP-4 siRNA. Protein kinase C ε isoform (PKCε) and DPP-4 expression and insulin receptor substrate 1 (IRS-1) phosphorylation were assessed using immunohistochemistry and western blot. RESULTS: KKay mice developed HINS spontaneously at 7 weeks of age. Similar to exercise, MK0626 ameliorated hepatic steatosis and reduced the liver triglyceride and diacylglycerol content. Both exercise and MK0626 suppressed diacylglycerol-induced PKCε expression and restored insulin signaling, which was shown by tyrosine phosphorylation of IRS-1, in the livers of KKay mice. Additionally, silencing DPP-4 or MK0626 treatment decreased PKCε expression in LO2 cells. CONCLUSIONS: Our data demonstrate that DPP-4 inhibition resembles exercise and effectively delays T2DM onset by suppressing hepatic PKCε expression in the HINS mouse model.

New e:b-Friedo-Hopane Type Triterpenoids from Euphorbia peplus with Simiarendiol Possessing Significant Cytostatic Activity against HeLa Cells by Induction of Apoptosis and S/G2 Cell Cycle Arrest.

Seven rare e:b-friedo-hopane-type triterpenoids including four new (1-4) and three known (5-7) ones with 5 being first reported as a natural product, together with five other known triterpenoids (8-12), were isolated from the nonpolar fractions of the ethanolic extract of Euphorbia peplus. Structural assignments for these compounds were based on spectroscopic analyses and quantum chemical computation method. The structural variations for the C-21 isopropyl group, including dehydrogenation (1 and 3) and hydroxylation at C-22 (simiarendiol, 2), were the first cases among e:b-friedo-hopane-type triterpenoids. Simiarendiol (2) bearing a 22-OH showed significant cytostatic activity against HeLa and A549 human tumor cell lines with IC50 values of 3.93 ± 0.10 and 7.90 ± 0.31 µM, respectively. The DAPI staining and flow cytometric analysis revealed that simiarendiol (2) effectively induced cell apoptosis and arrested cell cycle at the S/G2 phases in a dose-dependent manner in HeLa cells.

Frequency and Risk Factors for Neovascular Glaucoma After Vitrectomy in Eyes with Diabetic Retinopathy: An Observational Study.

INTRODUCTION: Vitrectomy is one of the main treatments for proliferative diabetic retinopathy (PDR). Postoperative neovascular glaucoma, in which it is difficult to obtain satisfactory results using conventional filtering surgery, is one of the most serious complications of vitrectomy. It often requires destructive surgery, such as ciliary body photocoagulation or freezing, and the outcome with regard to visual acuity (VA) is extremely poor. The purpose of this study was to evaluate the prevalence of neovascular glaucoma (NVG) after modern vitrectomy techniques and investigate how variables assessed before and after vitrectomy are associated with patients who develop NVG after PDR surgery. METHODS: This was an observational study including the medical records of patients who underwent vitrectomy for PDR at Tianjin Eye Hospital from June 2014 to July 2016, were followed for at least 24 months postoperatively, and NVG developed within 2 years after surgery was recorded. Each patient underwent complete preoperative ophthalmic examinations in both preoperative and follow-up appointments. Factors associated with survival were determined using the Kaplan-Meier (KM) survival analysis to calculate the incidence of NVG after vitrectomy for PDR. Multivariable analysis was performed with the Cox regression proportional hazards model to verify the results of the analysis and eliminate interference factors between variables. All statistical analyses were performed using R statistical software ( http://www.r-project.org ) for Windows. RESULTS: In all, 238 patients (238 eyes) fulfilled the study criteria. NVG occurred in 11 of 238 eyes (4.6%). The percentages of NVG development after vitrectomy at 6, 12, and 24 months were 0.42%, 3.3%, and 4.6%, respectively. After step analysis, multivariable regression identified preoperative high intraocular pressure (IOP) combined with retinal vein occlusion (RVO), severe PDR, no postoperative intravitreal injection of ranibizumab (IVR), and higher HbA1c levels as significant predictors of NVG. CONCLUSION: Preoperative high IOP combined with RVO, severe PDR, no postoperative intravitreal injection of ranibizumab (IVR), and higher HbA1c levels are significant predictors of NVG after vitrectomy.

[Effect of siRNA-Interfering ß-Catenin Expression on MDR of Human Multiple Myeloma Cell Line].

OBJECTIVE: To investigate the effecr of siRNA-interfering ß-catenin expression on drug-resistance of multiple myeloma cells. METHODS: The multiple myeloma cell line RPMI-8226 was cultured in vitro. The maphalan-resistant cell model was established by concentration gradient ascending of durg, then the drug-resistant cell line was instantaneously transfected with ß-catenin siRNA, the sensitivity of RPMI 8226 cells to maphalan was detected by CCK-8 meltod before and after the transfection with siRNA; the mRNA and protein expression of ß-catenin was detected by qRT-PCR and Western blot respectively, the apoptosis of cells was detected by flow cytometry. RESULTS: IC50 of maphalan decreased from (5.29±0.19) µmol/L to (1.88±0.64) µmol/L, suggesting that the deplation of ß-eatenin restored the sensitivity of drug-resistant cell line RPMI-8226 to malphalan. The Western blot showed that after the instaintaneous transfection with ß-catenin siRNA, the ß-catenin protein expression level obviously decreased, compared with level before transfection. After transfection, the maplalan-inducing apoptosis rate of cells increased from (35±0.5)% to (54±0.4)%, suggesting that the ß-catinin gene may correlated with drug-resistance of cells. Interfering the expression of ß-catenin gene could enhance the sensitivity of drug-resistant RPMI-8226 cells to maphalan. CONCLUSION: The ß-catenin siRNA interfereuce can inhisit the ß-catenin gene expression in Wnt/ß-catenin signaling pathway, suppress the cell proliferation, enhence the toxicity of maphalan on drug-resistant RPMI-8226 cells, thus result in increase of cell apoptosis.

[Effect of Bushen Yanggu Decoction on Multidrug Resistance of Multiple Myeloma Cell Line KM3/BTZ].

OBJECTIVE: To explore the effect of Bushen Yanggu Decoction (BYD) on drug resistance and proliferation of human multiple myeloma-resistant KM3/BTZ cells. METHODS: Human multidrug-resistant KM3/BTZ cells were established by Bortezomib (BTZ) gradient induction. The effects of commonly used chemotherapeutic drugs and serum containing Bushen Yanggu Decoction (BYD) on the proliferation of KM3 cells and KM3/BTZ cells were detected by MTT assay. RT-qPCR and Western blot were used to detect the expression of Par-4, HSP27 and P-gp genes. Flow cytometry was used to detect cell apoptosis. RESULTS: The established KM3/BTZ cells could produce varying degree of resistance to commonly used chemotherapeutic drugs. Among them, the highest resistance index (RI) to BTZ was 20.269. MTT assay showed that the proliferation of KM3/BTZ cells treated with serum containing Bushen Yanggu Decoction was inhibited, and the inhibitory effect increased with the serum concentration incranse of Bushen Yanggu Decoction. The serum containing Bushen Yanggu Decoction could inhibit the proliferation of KM3/BTZ cells, and induce apoptosis, significantly reduce the drug-resistance of KM3/BTZ cells, up-regulate the expression of Par-4, down-regulate the expression of HSP27 and P-gp. CONCLUSION: Bushen Yanggu Decoction can effectively inhibit the proliferation of KM3/BTZ cells and induce apoptosis. Bushen Yanggu Decoction can effectively reverse the multidrug-resistance of KM3/BTZ cells. The mechanism may be related with the decrease of expression of HSP27 and P-gp and the increase of expression of Par-4.

Circulating SH2B1 is associated with an increased risk of gastric cancer.

Gastric cancer (GC) is one of the most common types of cancer in humans and the second leading cause of cancer-associated mortality worldwide. Identifying novel risk factors will facilitate the development of therapeutic strategies to prevent and treat GC. Increased expression of the Src homology 2 B adaptor protein 1 (SH2B1) may stimulate the malignant progression of lung cancer, esophageal cancer and neuroblastoma. However, its function in GC has not yet been investigated. To identify whether increased serum SH2B1 is a risk factor for GC, the present study performed a nested case-control study of patients within the Chinese cohort study. Levels of serum SH2B1 were measured in 563 patients diagnosed with GC during the follow-up period and in 1,126 matched healthy controls. The results demonstrated that high levels of serum SH2B1 were associated with an increased GC risk (odds ratio, 3.23; 95% confidence interval, 2.45-5.65). When analyses were stratified further by sex, age and smoking, an association between increased levels of SH2B1 and GC was identified in males but not in females. Furthermore, the association between SH2B1 levels and GC was more evident in younger than in older participants, and statistically significant in current smokers but not in nonsmokers. These results were not altered following the exclusion of outliers. Furthermore, it was demonstrated that overexpression of SH2B1 contributes to the malignant transformation of normal gastric epithelial cells. Thus, the present study demonstrated that elevated serum SH2B1 levels may increase the risk of GC.

DISC1 overexpression promotes non-small cell lung cancer cell proliferation.

Neuropsychiatric disorder-associated disrupted-in-schizophrenia-1 (DISC1) activates Wnt/ß-catenin signaling by inhibiting glycogen synthase kinase 3 beta (GSK3ß) phosphorylation, and may promote neural progenitor cell and pancreatic ß-cell proliferation. The present study found that DISC1 promotes non-small cell lung cancer (NSCLC) cell growth. Western blotting and immunohistochemistry analyses showed that DISC1 was highly expressed in NSCLC cell lines and patient tissues. DISC1 expression was negatively associated with phosphorylated (p-) GSK3ß, but positively correlated with a more invasive tumor phenotype and predicted poor NSCLC patient prognosis. siRNA-mediated DISC1 silencing increased p-GSK3ß expression and decreased expression of ß-catenin and Cyclin D1, while DISC1 upregulation produced the opposite results. DISC1 knockdown also reduced NSCLC cell proliferation rates in vitro. These results suggest that DISC1 promotes NSCLC growth, likely through GSK3ß/ß-catenin signaling, and that DISC1 may function as an oncogene and novel anti-NSCLC therapeutic target.

miR­206 inhibits cancer initiating cells by targeting EHF in gastric cancer.

Cancer initiating cells (CIC) are defined as the unique subpopulation in the tumors that possess the ability to initiate tumor growth and sustain self-renewal as well as metastatic potential. In this study, we found that EHF overexpression promoted formation of CIC traits and silencing it inhibited the traits in gastric cancer NCI­N87 cells. Overexpressing EHF downregulated the antitumor effect of 5-fluorouracil (5-FU) in NCI­N87 cells. We found that miR­206 downregulated EHF protein expression by targeting its 3'UTR in NCI­N87 cells and GES-1 cells. Overexpressing miR­206 inhibited formation of CIC in NCI­N87 cells. In gastric cancer tissues, EHF protein expression was upregulated and miR­206 was downregulated. We identified a negative correlation between EHF protein and miR­206 expression in gastric cancer tissues. Thus, we concluded that miR­206 inhibits formation of CICs by targeting EHF in gastric cancer.

miR-874 inhibits metastasis-relevant traits via targeting SH2B adaptor protein 1 (SH2B1) in gastric cancer.

Gastric cancer (GC) is one of the most common human cancers and the second leading cause of cancer-related mortality worldwide. The major cause of death is metastasis. Elucidating molecular mechanism of metastasis in gastric cancer will help us to further understand the pathogenesis and progression of the disease, and offer new targets for effective therapies. In this study, we found that SH2B1 overexpression promoted invasion, migration and anoilds resistance and silencing it inhibited invasion, migration and anoilds resistance in gastric cancer SGC-7901 cells. However, over-expressing or silencing it did not affect proliferation in the cells. miR-874 could degrade SH2B1 by targeting its 3'UTR and was negatively associated with metastasis traits in SGC-7901 cells. Its overexpression inhibited proliferation in the cells. Thus, we concluded that miR-874 inhibits metastasis-relevant traits via targeting SH2B1 in gastric cancer SGC-7901 cells.

[Changes of Toll-like Receptor mRNA and Related Cytokines in Patients with Hepatic Alveolar Echinococcosis].

Objective: To investigate the expression of Toll-like receptor 2（TLR2） and TLR4 mRNA in peripheral blood mononuclear cells （PBMC） and in the liver of patients with hepatic alveolar echinococcosis (HAE), and their correlations with related cytokines in plasma. Methods: Twenty-eight HAE patients hospitalized in the First Affiliated Hospital of Xinjiang Medical University during January 2012 and June 2015 and 28 healthy volunteers as a control were enrolled in this study. Plasma levels of interferon-γ （IFN-γ）, interleukin-5 （IL-5）, IL-23, and IL-10 were measured by ELISA. qRT-PCR was performed to detect TLR2 and TLR4 mRNA levels in PBMCs and hepatic tissues. The percentage of peripheral blood eosinophil （Eo%） was determined by a hematology analyzer. The correlations of TLR2 and TLR4 mRNA levels in PBMCs with levels of related cytokines and Eo% were analyzed with the Spearman Correlation method. Results: ELISA results showed that the plasma levels of IFN-γ, IL-5, IL-23, and IL-10 in the HAE group were （301.100±47.290）, （43.420±11.380）, （86.580±31.990） and （8.766±7.568） pg/ml respectively, which were higher than those in the control［（301.100±67.790）, （40.970±6.310）, （46.770±15.490） and （6.272±10.360） pg/mlï¼½ with a statistical significance for IL-23 （P<0.01）. Results of qRT-PCR showed that the expression level of TLR2 in the HAE group （0.100±0.084） was significantly higher than that in the control （0.055±0.040） （P<0.05）, while the expression level of TLR4 in the HAE group （0.004±0.003） was comparable to that in the control（0.003±0.002）（P>0.05）. The expression of TLR2 and TLR4 mRNA in HAE lesions in the HAE group（29.680±25.650 and 21.340±16.640, respectively） were both significantly higher than that in para-lesion regions（2.308±4.140 and 5.541±9.233） and that in tissues of the control （1.112±1.431 and 1.100±1.734）（P<0.01）. There was also a significant difference in Eo% between the HAE（0.448±0.240） and the control（0.110±0.100） groups. Spearman correlation coefficients revealed a positive correlation of TLR2 mRNA in PBMCs with plasma IL-23 level and peripheral blood Eo% in HAE subjects（r=0.368, r=0.382, respectively）. Conclusion: There are increases in TLR2 and TLR4 mNRA expression in PBMCs and in HAE lesions in HAE patients. The TLR2 mNRA expression in PBMCs positively correlates with plasma IL-23 level and peripheral Eo%.

Expression of Toll-Like Receptors 2 and 4 and Related Cytokines in Patients with Hepatic Cystic and Alveolar Echinococcosis.

Several studies have demonstrated the important role of Toll-like receptors in various parasitic infections. This study aims to explore expression of Toll-like receptors (TLRs) and related cytokines in patients with human cystic echinococcosis (CE) and alveolar echinococcosis (AE). 78 subjects including AE group (N = 28), CE group (N = 22), and healthy controls (HC, N = 28) were enrolled in this study. The mRNA expression levels of TLR2 and TLR4 in blood and hepatic tissue and plasma levels related cytokines were detected by using ELISA. Median levels of TLR2 mRNA in AE and CE groups were significantly elevated as compared with that in healthy control group. Median levels of TLR4 expression were increased in AE and CE. Plasma concentration levels of IL-5, IL-6, and IL-10 were slightly increased in AE and CE groups compared with those in HC group with no statistical differences (p > 0.05). The IL-23 concentration levels were significantly higher in AE and CE groups than that in HC subjects with statistical significance. The increased expression of TLR2 and IL-23 might play a potential role in modulating tissue infiltrative growth of the parasite and its persistence in the human host.