[Knockdown of ACC1 promotes migration of esophageal cancer cell].

Objective: To investigate the effect of acetyl-CoA carboxylase 1 (ACC1) knockdown on the migration of esophageal squamous cell carcinoma (ESCC) KYSE-450 cell and underlying mechanism. Methods: Lentiviral transfection was conducted to establish sh-NC control cell and ACC1 knocking down cell (sh-ACC1). Human siRNA HSP27 and control were transfected by Lipo2000 to get si-HSP27 and si-NC. The selective acetyltransferase P300/CBP inhibitor C646 was used to inhibit histone acetylation and DMSO was used as vehicle control. Transwell assay was performed to detect cell migration. The expression of HSP27 mRNA was examined by reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) and the expressions of ACC1, H3K9ac, HSP27 and epithelial-mesenchymal transition-related proteins E-cadherin and Vimentin were detected by western blot. Results: The expression level of ACC1 in sh-NC group was higher than that in sh-ACC1 group (P<0.01). The number of cell migration in sh-NC group was (159.00±24.38), lower than (361.80±26.81) in sh-ACC1 group (P<0.01). The protein expression levels of E-cadherin and Vimentin in sh-NC group were statistically significant compared with sh-AAC1 group (P<0.05). The migrated cell number in sh-NC+ si-NC group was (189.20±16.02), lower than (371.60±38.40) in sh-ACC1+ si-NC group (P<0.01). The migrated cell number in sh-NC+ si-NC group was higher than that in sh-NC+ si-HSP27 group (152.40±24.30, P<0.01), and the migrated cell number in sh-ACC1+ si-NC group was higher than that in sh-ACC1+ si-HSP27 group (P<0.01). The protein expression levels of E-cadherin and Vimentin in sh-NC+ si-NC group were significantly different from those in sh-ACC1+ si-NC and sh-NC+ si-HSP27 groups (P<0.01). The protein expression levels of E-cadherin and Vimentin in sh-ACC1+ si-NC group were significantly different from those in sh-ACC1+ si-HSP27 group (P<0.01). After 24 h treatment with C646 at 20 µmmo/L, the migrated cell number in sh-NC+ DMSO group was (190.80±11.95), lower than (395.80±17.10) in sh-ACC1+ DMSO group (P<0.01). The migrated cell number in sh-NC+ DMSO group was lower than that in sh-NC+ C646 group (256.20±23.32, P<0.01). The migrated cell number in sh-ACC1+ DMSO group was higher than that in sh-ACC1+ C646 group (87.80±11.23, P<0.01). The protein expressions of H3K9ac, HSP27, E-cadherin and Vimentin in sh-NC+ DMSO group were significantly different from those in sh-ACC1+ DMSO group and sh-NC+ C646 group (P<0.01). The protein expression levels of H3K9ac, HSP27, E-cadherin and Vimentin in sh-ACC1+ DMSO group were significantly different from those in sh-ACC1+ C646 group (P<0.01). Conclusion: Knockdown of ACC1 promotes the migration of KYSE-450 cell by up-regulating HSP27 and increasing histone acetylation.

[Clinical and genetics characteristics of adult-onset cerebrotendinous xanthomatosis: analysis of a Chinese pedigree].

Objective: Clinical manifestations, imaging findings, pathologic features, and genetic mutations of Chinese adult patients with cerebrotendinous xanthomatosis (CTX) were analyzed in order to achieve a greater understanding of CTX that can improve early detection, diagnosis, and treatment. Methods: Clinical data including medical history, neurologic and auxiliary examinations, imaging findings, and genetic profile were collected for an adult patient with CTX admitted to the Sixth Medical Center of Chinese People's Liberation Army General Hospital in August 2020. Additionally, a systematic review of genetically diagnosed Chinese adult CTX cases reported in major databases in China and other countries was performed and age of onset, first symptoms, common signs and symptoms, pathologic findings, imaging changes, and gene mutations were analyzed. Results: The proband was a 39-year-old female with extensive, early-onset nervous system manifestations including cognitive dysfunction and ataxia. Systemic lesions included juvenile cataract and a tendon mass. Cranial magnetic resonance imaging revealed cerebral atrophy, symmetric white matter changes predominantly in the pyramidal tract, and lesions in the cerebellar dentate nucleus. A novel homozygous mutation in the sterol-27-hydroxylase (CYP27A1) gene (c.1477-2A>C) was identified. There were no family members with similar clinical presentation although some were carriers of the c.1477-2A>C mutation. The patient showed a good response to deoxycholic acid treatment. Totally there were 56 cases of adult CTX patients in China, mostly in East China (31/56, 55.4%), at a male-to-female ratio of 1.8 to 1. Multiple organs and tissues including nervous system, tendon, lens, lung, and skeletal muscle were affected in these cases. The most common neurologic manifestations were cognitive dysfunction (44/52, 84.6%) and ataxia (44/51, 86.3%). The cases were characterized by early onset, chronic progressive damage of multiple systems, long disease course, and delayed diagnosis, making the disease difficult to manage clinically and resulting in poor prognosis. The 2 most common genetic mutations in Chinese adult CTX patients were c.1263+1G>A and c.379C>T. Exon 2 of the CYP27A1 gene was identified as a mutation hot spot. Conclusions: Chinese adult patients with CTX have complex clinical characteristics, a long diagnostic cycle, and various CYP27A1 gene mutations. Early diagnosis and intervention can improve the prognosis of these patients.

[The role and mechanism of tumor metastasis-associated gene 1 in radiosensitivity of HeLa cells].

Objective: To determine the effect of tumor metastasis-associated gene 1 (MTA1) on the sensitivity of HeLa cells to radiotherapy, and to clarify its molecular mechanism. Methods: The transcriptome differences between MTA1 knocked down Hela cells and control cells were analyzed, and the differentially expressed genes (DEGs) was used to perform Gene-Set Enrichment Analysis (GSEA) and Gene Ontology (GO) cluster analysis. Flow cytometry was used to detect apoptosis in MTA1-overexpressed HeLa cells and control cells before and after 10 Gy X-ray irradiation. Cloning formation assay and real-time cellular analysis (RTCA) were used to monitor the cell proliferation before and after 2 Gy X-ray irradiation. To dissect the underlying molecular mechanisms of MTA1 affecting the sensitivity of radiotherapy, the proteins encoded by the DEGs were selected to construct a protein-protein interaction network, the expression of γ-H2AX was detected by immunofluorescence assay, and the expression levels of γ-H2AX, ß-CHK2, PARP and cleaved caspase 3 were measured by western blot. Results: By transcriptome sequencing analysis, we obtained 649 DEGs, of which 402 genes were up-regulated in MTA1 knockdown HeLa cells and 247 genes were down-regulated. GSEA results showed that DEGs associated with MTA1 were significantly enriched in cellular responses to DNA damage repair processes. The results of flow cytometry showed that the apoptosis rate of MTA1 over-expression group (15.67±0.81)% after 10 Gy X-ray irradiation was significantly lower than that of the control group [(40.27±2.73)%, P<0.001]. After 2 Gy X-ray irradiation, the proliferation capacity of HeLa cells overexpressing MTA1 was higher than that of control cells (P=0.024). The numbers of colon in MTA1 over-expression group before and after 2 Gy X-ray irradiation were (176±7) and (137±7) respectively, higher than (134±4) and (75±4) in control HeLa cells (P<0.05). The results of immunofluorescence assay showed that there was no significant expression of γ-H2AX in MTA1 overexpressed and control HeLa cells without X-ray irradiation. Western blot results showed that the expression level of ß-CHK2 in MTA1-overexpressing HeLa cells (1.04±0.06) was higher than that in control HeLa cells (0.58±0.25, P=0.036) after 10 Gy X-ray irradiation. The expression levels of γ-H2AX, PARP, and cleaved caspase 3 were 0.52±0.13, 0.52±0.22, and 0.63±0.18, respectively, in HeLa cells overexpressing MTA1, which were lower than 0.87±0.06, 0.78±0.12 and 0.90±0.12 in control cells (P>0.05). Conclusions: This study showed that MTA1 is significantly associated with radiosensitivity in cervical cancer HeLa cells. MTA1 over-expression obviously reduces the sensitivity of cervical cancer cells to X-ray irradiation. Mechanism studies initially indicate that MTA1 reduces the radiosensitivity of cervical cancer cells by inhibiting cleaved caspase 3 to suppress apoptosis and increasing ß-CHK2 to promote DNA repair.

[Morvan syndrome with positive anti LGI1/CASPR2 antibodies in serum/cerebrospinal fluid:a case report and literature review].

To report a typical case of Morvan syndrome with positive anti-leucine rich glioma-inactivated 1(LGI1) and contactin-associated protein 2 (CASPR2) antibodies in serum and cerebrospinal fluid. A 39-years-old female initially presented weakness of extremeties. The main symptoms included paroxysmal limb pain, wheezing, itching, muscle twitching, epilepsy, hypomnesia, dysphoria, apathy, intractable insomnia, salivation and sweating. Tests of electrolytes found hypokalemia (2.7-3.1 mmol/L) and hyponatremia (130-136 mmol/L). Arterial blood gas analysis showed hypoxemia (oxygen saturation 50%-70%). Total thyroxine (TT4) was elevated to 207 nmol/L with positive thyroid peroxidase antibody (TPO-Ab) and thyroglobulin antibody (TG-Ab). LGI1and CASPR2 antibodies (CBA method) were positive in both serum and cerebrospinal fluid, and the remaining antibodies related to autoimmune encephalitis and paraneoplastic syndrome were negative. Head MRI was almost normal, while mild abnormalities were found in electroencephalogram. Electromyography showed slightly increased voltage of left quadriceps motor unit potential. After treated with corticosteroids, IVIG and mycophenolate mofetil, the patient completely improved. Cognitive function scores recovered from MoCA/MMSE (16/24) to MoCA/MMSE (26/29). Positivity of LGI1/CASPR2 antibodies both in serum/cerebrospinal fluid are rarely seen in patients with Morvan syndrome. Steroids and immunosuppressants are suggested for treatment as early as possible.

Investigation of microbiologically influenced corrosion inhibition of 304 stainless steel by D-cysteine in the presence of Pseudomonas aeruginosa.

The influence of D-cysteine (D-cys) on the microbiologically influenced corrosion (MIC) of 304 stainless steel caused by Pseudomonas aeruginosa was investigated in this work. Immersion tests in the sterile and P. aeruginosa-inoculated culture media with different D-cys concentrations were carried out. The results showed that the addition of D-cys inhibited the formation of P. aeruginosa biofilms on stainless steel surfaces. D-cys itself did not affect the corrosion of stainless steel but could decrease the corrosion rate of MIC of stainless steel caused by P. aeruginosa. X-ray photoelectron spectroscopy (XPS) analysis and scanning electrochemical microscopy (SECM) analysis indicated that the biofilm inhibition effect of D-cys greatly reduced the destructive effect of the adhered P. aeruginosa cells on the passive film of the stainless steel, thus inhibiting the MIC of the stainless steel.

[Advances of TRIM superfamily proteins in chronic liver disease and hepatocellular carcinoma].

The modification of proteins with ubiquitination is closely related to the occurrence and development of chronic liver disease and hepatocellular carcinoma. The tripartite motif (TRIM) family of proteins is one of the E3 ubiquitin ligase subfamily, which participates in various biological processes such as intracellular signal transduction, apoptosis, autophagy, and immunity by regulating the ubiquitination of target proteins. A growing body of research shows that the TRIM family of proteins plays an important role in chronic liver disease. This article systematically reviews the role and molecular mechanism of TRIM protein in the process of chronic liver disease, with the aim of exploring its potential application in the clinical diagnosis and treatment.

[Adherence to adjuvant with therapy imatinib in patients with gastrointestinal stromal tumor: a national multi-center cross-sectional study].

Objective: To analyze the current adherence to imatinib in patients with gastrointestinal stromal tumors (GIST) in China and its influencing factors. Methods: A cross-sectional survey was conducted. Study period: from October 1, 2020 to November 31, 2020. Study subjects: GIST patients taking imatinib who were diagnosed and treated in public tertiary level A general hospitals or oncology hospitals; those who had not been pathologically diagnosed, those who never received imatinib, or those who had taken imatinib in the past but stopped afterwards were excluded. The Questionnaire Star online surgery platform was used to design a questionnaire about the adherence to adjuvant imatinib therapy of Chinese GIST patients. The link of questionnaire was sent through WeChat. The questionnaire contained basic information of patients, medication status and Morisky Medication Adherence Scale. Results: A total of 2162 questionnaires from 31 provinces, autonomous regions, and municipalities were collected, of which 2005 were valid questionnaires, with an effective rate of 92.7%. The survey subjects included 1104 males and 901 females, with a median age of 56 (22-91) years old. Working status: 609 cases (30.4%) in the work unit, 729 cases (36.4%) of retirement, 667 cases of flexible employment or unemployment (33.3%). Education level: 477 cases (23.8%) with bachelor degree or above, 658 cases (32.8%) of high school, 782 cases (39.0%) of elementary or junior high school, 88 cases (4.4%) without education. Marital status: 1789 cases (89.2%) were married, 179 cases (8.9%) divorced or widowed, 37 cases (1.8%) unmarried. Two hundred and ninety-four patients (14.7%) had metastasis when they were first diagnosed, including 203 liver metastases, 52 peritoneal metastases, and 39 other metastases. One thousand eight hundred and sixty-nine patients underwent surgical treatment, of whom 1642 (81.9%) achieved complete resection. The median time of taking imatinib was 25 (1-200) months. Common adverse reactions of imatinib included 1701 cases (84.8%) of periorbital edema, 1031 cases (51.4%) of leukopenia, 948 cases (47.3%) of fatigue, 781 cases (39.0%) of nausea and vomiting, 709 cases (35.4%) of rash, and 670 cases (33.4%) of lower extremity edema. The score of the Morisky Medication Adherence Scale showed that 392 cases (19.6%) had poor adherence, 1023 cases (51.0%) had moderate adherence, and 590 cases (29.4%) had good adherence. Univariate analysis showed that gender, age, work status, economic income, residence, education level, marriage, the duration of taking medication and adverse reactions were associated with adherence to adjuvant imatinib therapy (all P<0.05). Multivariate analysis showed that female (OR=1.264, P=0.009), non-retirement (OR=1.454, P=0.001), monthly income ≤4000 yuan (OR=1.280, P=0.036), township residents (OR=1.332, P=0.005), unmarried or divorced or widowed (OR=1.362, P=0.026), the duration of imatinib medication >36 months (OR=1.478, P<0.001) and adverse reactions (OR=1.719, P=0.048) were independent risk factors for poor adherence to adjuvant imatinib. Among patients undergoing complete resection, 324 (19.7%) had poor adherence, 836 (50.9%) had moderate adherence, and 482 (29.4%) had good adherence. Meanwhile, 55 patients with good adherence (11.4%) developed recurrence after surgery, 121 patients with moderate adherence (14.5%) developed recurrence, 61 patients with poor adherence (18.8%) developed recurrence, and the difference was statistically significant (P=0.017). Conclusions: The adherence to adjuvant therapy with imatinib in Chinese GIST patients is relatively poor. Females, non-retirement, monthly income ≤4000 yuan, township residents, unmarried or divorced or widowed, the duration of imatinib medication >36 months, and adverse reactions are independently associated with poor adherence of GIST patients. Those with poor adherence have a higher risk of recurrence after surgery. Positive interventions based on the above risk factors are advocated to improve the prognosis of patients with GIST.

MiR-1266 suppresses the growth and metastasis of prostate cancer via targeting PRMT5.

The article "MiR-1266 suppresses the growth and metastasis of prostate cancer via targeting PRMT5, by C.-M. Sun, G.-M. Zhang, H.-N. Qian, S.-J. Cheng, M. Wang, M. Liu, D. Li, published in Eur Rev Med Pharmacol Sci 2019; 23 (15): 6436-6444-PMID: 31378882" has been withdrawn from the authors due to some inaccuracies (some data cannot be repeated by our further research). The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/18525.

Circular RNA hsa_circ_0017247 acts as an oncogene in bladder cancer by inducing Wnt/ß-catenin signaling pathway.

The article "Circular RNA hsa_circ_0017247 acts as an oncogene in bladder cancer by inducing Wnt/ß-catenin signaling pathway, by C.-T. Han, Q.-Y. Bao, S.-J. Cheng, M. Liu, H.-N. Qian, D. Li, published in Eur Rev Med Pharmacol Sci 2020; 24 (3): 1081-1087-DOI: 10.26355/eurrev_202002_20158-PMID: 32096177" has been withdrawn from the authors since they decided to perform further experiments. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/20158.

[Tough choice of surgical treatment for duodenal gastrointestinal stromal tumor: pancreaticoduodenectomy or local resection?]

The therapeutic choice of duodenal gastrointestinal stromal tumor (GIST) has always been the focus of surgeons because of its special anatomy location. So far, surgery is the preferable treatment for primary duodenal GIST, including pancreaticoduodenectomy (PD) and local resection (LR). Researches reveal that the prognosis of duodenal GIST is determined by the pathologic factors of the tumor itself, and is not significantly associated with the surgical procedure. The intervention with targeted drugs such as imatinib has given the duodenal GIST more opportunities for LR. Meanwhile, the technique development of the laparoscopy combined with endoscopic surgery and robotic surgery ensures the steps of minimally invasive treatment for duodenal GIST into a new era.

Circular RNA hsa_circ_0017247 acts as an oncogene in bladder cancer by inducing Wnt/ß-catenin signaling pathway.

OBJECTIVE: Bladder cancer (BLCA) is the most common genitourinary malignancy in the world. Recent studies have revealed that circular RNAs (circRNAs) are dysregulated in malignant tumors and participate in carcinogenesis. The purpose of our work is to uncover how hsa_circ_0017247 functions in BLCA. PATIENTS AND METHODS: In this research, Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) was conducted to monitor hsa_circ_0017247 expression in BLCA samples. Besides, proliferation assay, colony formation assay, and flow cytometry assay were performed in BLCA cells after hsa_circ_0017247 was knocked down. Meanwhile, the Western blot assay was conducted to explore the target signaling pathway of hsa_circ_0017247. Furthermore, tumor formation and metastasis assays were also conducted in vivo. RESULTS: Compared with the adjacent tissues, a significant upregulation in hsa_circ_0017247 expression was observed in BLCA samples. Functional assays showed that the inhibition of cell proliferation was induced via downregulating hsa_circ_0017247 in BLCA in vitro, while the promotion of cell proliferation was induced via downregulating hsa_circ_0017247 in BLCA in vitro. Moreover, the results of further experiments revealed that the targeted proteins in the Wnt/ß-catenin signaling pathway were downregulated via knockdown of hsa_circ_0017247 in BLCA. In addition, tumor formation and metastasis of BLCA were inhibited via knockdown of hsa_circ_0017247 in nude mice. CONCLUSIONS: We discovered a vital regulatory mechanism of hsa_circ_0017247 in BLCA which might serve as a new therapeutic intervention for BLCA patients.

[Role of lncRNA Fez family zinc finger protein 1 antisense RNA1 in hepatocellular carcinoma].

Objective: To investigate the effect of long-chain non-coding RNA Fez family zinc finger protein 1 antisense RNA1 (lncRNA FEZF1-AS1) on the biological function of hepatocellular carcinoma (HCC). Methods: SMMC771 and BEL-7402 cells were transfected with sh-FEZF1-AS1 and OE-FEZF1-AS1, respectively. The expression of lncRNA FEZF1-AS1 was detected by real-time quantitative PCR. Cell proliferation was detected by Cell Counting Kit-8 (CCK-8), and apoptosis was detected by flow cytometry. The effects of lncRNA FEZF1-AS1 on invasion and migration were detected by Transwell and wound healing assays. The expression levels of adhesion molecules were detected by Western blot. The effect of lncRNA FEZF1-AS1 on the in vivo growth was verified by nude mice xenograft experiments. Results: The silencing or ectopic expression of lncRNA FEZF1-AS1 inhibited or promoted the proliferation of hepatocellular carcinoma cells. CCK-8 assay showed that the proliferation abilities of SMMC7721 and BEL-7402 cells in sh-FEZF1-AS1 transfection group significantly decreased, achieving (35.43±4.06)% and (34.68±3.97)%, respectively, on the fifth day. There were significant differences between sh-FEZF1-AS1 group and sh-NC group [52.21±8.46)% and (53.76±7.64)%] (all P<0.05). In contrast, the proliferation ability of SMMC7721 and BEL-7402 cells transfected with OE-FEZF1-AS1 was significantly increased, achieving (83.49±6.92)% and (80.31±3.13)%, respectively, on the fifth day. There were significant differences between OE-FEZF1-AS1 and OE-NC group [53.03±8.84)% and (55.11±7.09)%] (all P<0.05). The subsequent flow cytometry results showed that cell apoptotic rates of SMMC7721 and BEL-7402 cells transfected with sh-FEZF1-AS1 were (13.02±1.38)% and (11.88±1.29)%, respectively, which were significantly higher than those in sh-NC groups [(5.57±1.46)% and (8.06±1.42)%, respectively, all P<0.05]. In contrast, the apoptotic rates of SMMC7721 and BEL-7402 cells transfected with OE-FEZF1-AS1 were (3.01±0.39)% and (3.22±0.43)%, which were significantly lower than those in OE-NC groups [(6.68±0.96)% and (6.63±0.45)%, all P<0.05]. In addition, knockdown or overexpression of lncRNA FEZF1-AS1 expression inhibited or enhanced the migration and invasion abilities as well as the levels of adhesion molecules in hepatocellular carcinoma cells. After 30 days of feeding under the same conditions, the tumor volumes of sh-FEZF1-AS1 and sh-NC SMMC7721 cells xenograft mice models were (0.26±0.03) cm(3) and (0.63±0.06) cm(3), respectively, showing significant difference (P<0.05). The tumor volumes of sh-FEZF1-AS1 and sh-NC BEL-7402 cells were (0.31±0.02) cm(3) and (0.72±0.08) cm(3), and the difference was statistically significant (P<0.05). Conclusion: lncRNA FEZF1-AS1 may strengthen the growth, migration and invasion of hepatocellular carcinoma cells.

[MicroRNA-328 regulates embryonic stem cells differentiation into insulin-producing cells by targeting TGF-ß2 in vitro].

Objective: To explore the role and its molecular mechanism of miR-328 during the differentiation of embryonic stem cells (ESCs) into insulin-producing cells (IPCs) in vitro. Method: Mouse embryonic stem cell line-mESCs-Nanog-GFP was induced in conditioned medium and divided into negative control group, miR-328 agomir transfected group, miR-328 antagomir transfected group and transforming growth factor ß2 (TGF-ß2) siRNA transfected group. The function of IPCs was identified by real-time quantitative PCR (qPCR) detecting system and immunofluorescence in above-mentioned groups. Methods of qPCR, immunofluorescence and enzyme-linked immunosorbent assay (ELISA) were used to detect effects of overexpression and inhibition of miR-328 on differentiation of multilineage precursor cells. We predicted the binding sites of miR-328 and TGF-ß2 by performing the bioinformatics analysis. Dual luciferase reporter gene and Western blotting were employed to identify the regulatory relationship between miR-328 and TGF-ß2. Results: mESCs could be transfected with miR-328 agomir, with an efficacy of 70%-80%. Up-regulated miR-328 in MPCs reduced the RNA expression of several key transcription factors which were crucial for early pancreatic development. Additionally, the insulin released by IPCs decreased in response to glucose stimulation (all P<0.05). However, overexpression of miR-328 led to the decrease of protein level of insulin and Nkx6.1 (all P<0.05). Transfection of miR-328 antagomir had the opposite effects (P<0.05). The dual luciferase reporter gene assay revealed that miR-328 functioned via binding to the 3' non-coding region (3'-UTR) of the TGF-ß2. Western blotting indicated that miR-328 regulated protein expression. After knockdown of miR-328, the relative expression of TGF-ß2 was 1.00±0.01. After co-transfection of miR-328 antagomir and TGF-ß2 siRNA, the relative expression of TGF-ß2 was 0.80±0.03. After downregulating TGF-ß2, the relative expression of TGF-ß2 was 0.20±0.01. Knockdown of TGF-ß2 down-regulated the expression of early pancreatic transcription factors (P<0.05) and inhibited Pdx1(+)cell differentiation. Conclusion: miR-328 can inhibit the differentiation of ESCs into IPCs via binding to 3' UTR of TGF-ß2, and provide a new regulatory pathway for the treatment of diabetes with stem cells.

MiR-1266 suppresses the growth and metastasis of prostate cancer via targeting PRMT5.

OBJECTIVE: To elucidate the correlation between microRNA-1266 (miR-1266) and prostate cancer (PCa) progression, and to investigate the possible underlying mechanism. PATIENTS AND METHODS: The expression level of miR-1266 and protein arginine methyltransferase 5 (PRMT5) in PCa tissues and cell lines was first detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). After up-regulating or down-regulating miR-1266 expression in cells, cell proliferation, migration and invasion abilities were detected. Possible target genes of miR-1266 were predicted and validated by bioinformatics analysis and dual-luciferase reporter gene assay, respectively. Finally, abnormal expression of PRMT5 was ascertained after transfection. RESULTS: MiR-1266 was lowly expressed in PCa tissues and cell lines, whereas PRMT5 exhibited the opposite results. Up-regulated expression of miR-1266 significantly inhibited the proliferation, migration and invasion abilities of PC-3 cells. However, the growth and migration of DU145 cells with low miR-1266 expression were significantly accelerated. Meanwhile, the number of invading cells was significantly increased. PRMT5 was verified as a potential target gene of miR-1266. Furthermore, results found that miR-1266 was negatively correlated with PRMT5. In addition, the expression of PRMT5 was remarkably decreased after miR-1266 overexpression, which could be restored after knockdown of miR-1266. CONCLUSIONS: MiR-1266 inhibits the growth and metastasis of PCa by targeting PRMT5. We may provide a potential and prospective therapeutic target for PCa.

Circ-CCDC66 accelerates proliferation and invasion of gastric cancer via binding to miRNA-1238-3p.

OBJECTIVE: The aim of this study was to examine the expression of circ-CCDC66 in gastric cancer (GC) tissues and cell lines, as well as its correlation with the prognosis of GC. Moreover, the regulatory effects of circ-CCDC66 on biological behaviors of GC cells and its molecular mechanism were explored. PATIENTS AND METHODS: The relative expression level of circ-CCDC66 in GC tissues and cell lines was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The correlation between the circ-CCDC66 level and overall survival of GC patients was analyzed as well. The potential influences of circ-CCDC66 on proliferative and invasive abilities of GC cells were evaluated through 5-Ethynyl-2'-deoxyuridine (EdU), colony formation and transwell assay, respectively. Meanwhile, the cell cycle progression and apoptosis of GC cells affected by circ-CCDC66 were determined. In addition, the direct target miRNA of circ-CCDC66 was predicted and verified by bioinformatics method and Dual-Luciferase reporter gene assay, respectively. RESULTS: Circ-CCDC66 was significantly up-regulated in GC tissues and cell lines. Up-regulation of circ-CCDC66 indicated markedly worse prognosis of GC patients. Transfection of circ-CCDC66-siRNA remarkably attenuated proliferative and invasive abilities of BGC-823 and MGC-803 cells. Besides, GC cells were arrested in the G0/G1 phase, and the apoptotic rate was remarkably elevated after circ-CCDC66 knockdown. The Dual-Luciferase reporter gene assay verified that circ-CCDC66 bind to miRNA-1238-3p by competing with LHX2 (LIM-homeobox domain 2). MiRNA-1238-3p was significantly down-regulated in GC cells, whereas LHX2 was up-regulated. Furthermore, overexpression of miRNA-1238-3p in GC cells markedly suppressed the LHX2 level. CONCLUSIONS: Circ-CCDC66 is highly expressed in GC tissues and cell lines. Knockdown of circ-CCDC66 attenuates proliferative and invasive abilities of GC cells. Our results indicate that circ-CCDC66/miRNA-1238-3p/LHX2 axis may be a promising target for GC treatment.

Surgical management and outcomes of duodenal gastrointestinal stromal tumors.

BACKGROUND AND STUDY AIMS: This retrospective study purports to examine these characteristics and compare the surgical procedures available and appropriate for the treatment of patients affected by duodenal GISTs. PATIENTS AND METHODS: A retrospective examination of reports and studies carried out between May 2012 and March 2017, and covering patients with primary GISTs of the duodenum was performed using modules from the SPSS package. Comparisons of treatment effects resulting from the administration of two differential methods of surgical treatment namely pancreaticoduodenectomy (PD), and limited resection (LR), were effected on the reports of the GIST patients thus selected. RESULTS: Out of these 62 patients who had undergone resection of duodenal GISTs, 47 (76%) had limited resection (LR) and 15 (24%) underwent pancreaticoduodenectomy (PD). In Multivariate analyses, tumor size was an independent predictive factor for recurrence (p=0.008). ASA, tumor size, and PD were independent and significant prognostic factors on OS (p=0.021, p=0.024, and p=0.030, respectively). In the very low and low risk group, and high-risk group, there were no significant differences in the RFS (recurrence-free survival) and OS (overall survival) between the LR and PD groups. CONCLUSIONS: When technically feasible, LR should be given due consideration as a reliable and curative option for duodenal GISTs achieving satisfactory RFS and OS.

[Clinical effects of adjacent fasciocutaneous flaps in repairing small wounds with bone or steel plate exposure in anterior tibia].

Objective: To explore the clinical effects of adjacent fasciocutaneous flaps in repairing small wounds with bone or steel plate exposure in anterior tibia. Methods: Twelve patients with small wounds of bone or steel plate exposure in anterior tibia covering area of 2 cm×2 cm to 5 cm×3 cm were admitted to our unit from January 2014 to December 2016. A circular or elliptical adjacent fasciocutaneous flap was designed on the normal skin located at the inside or outside of the wound according to the size of wound after thorough debridement. The pedicle of the flap was located at the proximal end and transferred through the subcutaneous tunnel to cover the wound. The sizes of flaps were 3 cm×3 cm to 6 cm×4 cm. Flaps were fixed with interrupted sutures and drainage rubber sheets were placed under the flaps. The drainage rubber sheets were removed within 24 to 48 hours. The donor area was repaired by medium-thickness skin graft collected from homolateral outer thigh. Results: All the flaps of 9 patients survived. Two patients had necrosis at the distal end of the flaps and were cured by changing dressing. One patient had tension blisters on the flap and was cured by removing blisters and improving microcirculation. All patients were followed up for 3 months, and the flaps were good in blood supply, appearance, and color, with hypaesthesia. Conclusions: Repair of small wounds with bone or steel plate exposure in anterior tibia by adjacent fasciocutaneous flap is simple in surgical procedure and does not damage the well-known blood vessels, and the appearance, texture, and thickness of flaps are close to the skin of anterior tibia region. It is a good choice for repairing this kind of wounds and worth promoting in clinic.

Capturing intracellular oncogenic microRNAs with self-assembled DNA nanostructures for microRNA-based cancer therapy.

Aberrantly overexpressed oncogenic microRNAs (miRNAs, miRs) are excellent targets for therapeutic interventions. Nevertheless, thus far, little progress has been made in developing miRNA-based drugs and techniques for clinical applications, especially for overexpressed miRNAs. In this study, we demonstrate that self-assembled DNA nanostructures bearing multiple DNA sequences that are complementary to a target miRNA can effectively capture the overexpressed oncogenic miRNA and subsequently inhibit cancer cell proliferation. Specifically, a DNA nanotube structure that carries functional DNA segments (single-stranded, duplex and hairpin forms) was designed and synthesized to capture two well-known overexpressed miRNAs, miR-21 and miR-155. It was found that all three DNA nanotubes significantly reduced both miRNA levels and inhibited cancer cell growth. Moreover, the capture efficiency was highly concentration dependent and was associated with the structural design of the DNA nanotube. These results demonstrate that through careful design, programmable DNA nanostructures can hijack the natural cellular machinery and can serve as nucleic acid drugs themselves. The concept of using self-assembled DNA nanostructures to disrupt the intracellular machinery for therapeutic purposes opens a new paradigm for exploiting self-assembled DNA nanostructures for miRNA-based anticancer therapy.

[Effects of MTA1 on biological behaviors of gastric cancer cells].

Objective: To study the effects of metastasis associated 1 (MTA1) on biological characteristics such as migration, invasion and proliferation of gastric cancer (GC) cells. Methods: pSilencer3.1-MTA1-siRNA vector was used to establish human gastric cancer BGC-823 cell lines with constitutive MTA1-knockdown. Boyden, wound healing, clony forming assay and 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) assay were performed to identify the effects of MTA1-deficiency on the biological behaviors of BGC-823 cells in vitro. Simultaneously, MTA1 overexpressed BGC-823 cell line was established by pcDNA3-MTA1 plasmid transfection for reverse verification. In addition, the role of MTA1 in the tumorigenicity of gastric cancer BGC823 cells in vivo was examined by subcutaneous injection of BGC-823 cells expressing different MTA1 levels into nude mice. Reverse transcription-polymerase chain reaction (RT-PCR) and western blot were used to detect the expression levels of integrin ß1, cyclin D1 and uPAR in pSilencer3.1-MTA1-siRNA, pcDNA3-MTA1 transfected cells and control cells. Results: MTA1 knocked down or upregulated BGC-823 cell lines were successfully generated by transfecting pSilencer3.1-MTA1-siRNA or pcDNA3-MTA1 vector with lipofectamine 2000, respectively. The Boyden and wound healing experiments showed metastasis and invasion ability in MTA1 knocked down cells (25±2, 12±1) were significantly decreased when compared with those of control (78±2, 50±2) and MTA1-overexpressed groups (218±2, 269±3; P<0.05). The results of MTT assay and colony forming assay were significantly decreased when compared with those of showed that MTA1 overexpressed cells grew more rapidly and formed more colonies in vitro and induced worse malignant tumors in vivo, while MTA1 knocked down cells presented the reversed phenotype[control group (1 482.41±511.90) mm(3,) (1.39±0.29)g; MTA1 overexpressed group [(3 158.73±1 823.22) mm(3,) (2.23±0.51)g; MTA1-downregulated group (711.32±284.30)mm(3,) (0.87±0.21) g ; P<0.05)]. In addition, RT-PCR result showed that the expression level of MTA1 was positively correlated with the known metastasis-related genes (integrinß1, cyclinD1, uPAR). Conclusions: MTA1 promotes the invasion, migration and proliferation of human gastric cancer BGC-823 cells. On the contrary, down-regulation of MTA1 significantly inhibits tumorigenicity of BGC-823 cells and induces favorable phenotypes. MTA1 may promote the malignant phenotype of BGC-23 cells via regulating the expressions of integrinß1, cyclinD1 and uPAR.