KIAA1429 regulates cell proliferation by targeting c-Jun messenger RNA directly in gastric cancer.

N6-methyladenosine (m6A) modification regulatory proteins are involved in the development of many types of cancer. KIAA1429 serves as a scaffold in bridging the catalytic core components of the m6A methyltransferase complex. The role of KIAA1429 in gastric cancer and its related mechanism has not been reported upon. The expression of KIAA1429 was detected in human gastric cancer tissues and cell lines by quantitative real-time polymerase chain reaction and western blot. The effects of KIAA1429 on gastric cancer proliferation were evaluated by cell counting kit assays, colony formation assays, flow cytometry assay, and in vivo experiments with nude mice. And messenger RNA (mRNA) high-throughput sequencing, RNA immunoprecipitation assay (RIP), luciferase assay, and a rescue experiment were used to identify the relationship between KIAA1429 and its specific targeted gene, c-Jun. We found that KIAA1429 was upregulated in gastric cancer tissues, and expressed lower in adjacent tissues. The upregulated KIAA1429 promoted proliferation and downregulated KIAA1429 was proved to inhibit proliferation of gastric cancer in vitro and in vivo. Then, we identified the potential KIAA1429 regulating gene as c-Jun by mRNAs high-throughput sequencing and RIP assay. By luciferase assay, we verified that KIAA1429 regulated the expression of c-Jun in an m6A-independent manner. Finally, the overexpression of c-Jun rescued the inhibition of proliferation caused by KIAA1429 knockdown in gastric cancer cells. KIAA1429 could act as an oncogene in gastric cancer by stabilizing c-Jun mRNA in an m6A-independent manner. This highlights the functional role for KIAA1429 as a potential prognostic biomarker and therapeutic target in gastric cancer.

[Study on the extraction of breviscapine from Erigeron breviscapus with ultrasonic wave technology optimized by central composite design-response surface method].

OBJECTIVE: To evaluate the effectiveness of ultrasound-assisted extraction and establish the optimized extraction conditions of breviscapine from Erigeron breviscapus. METHODS: On the basis of the single factor and according to the central composite design principles (CCD), the response surface method (RSM) with 3 factors and 3 levels was adopted and the independent variables were ultrasonic wave extracting time, ethanol concentration, and the ratio of solvent volume to Erigeron breviscapus mass, breviscapine extraction yield determinated by HPLC was used as response value. RESULTS: Ultrasonic wave extracting time of 24.5 min, ethanol concentration of 74.7% and the ratio of solvent volume to Erigeron breviscapus mass of 19.8 (mL/g) were selected as optimum conditions. Regression coefficients of binomial fitting complex model was 0. 9549 and the predicted breviscapine extraction yield was 0.641%, while the actual extraction yield was 0.632% (n = 5), with relative error of -1.14%. CONCLUSION: This study confirms the efficiency of ultrasound-assisted extraction as a simple, inexpensive and effective method to improve the extraction of breviscapine from Erigeron breviscapus. The observed and predicted values are close to each other, which proves that the optimization of supersonic extraction process of breviscapine from Erigeron breviscapus by CCD-RSM is reasonable and successful.

RNA methyltransferase NSUN2 promotes gastric cancer cell proliferation by repressing p57Kip2 by an m5C-dependent manner.

The RNA methyltransferase NSUN2 has been involved in the cell proliferation and senescence, and is upregulated in various types of cancers. However, the role and potential mechanism of NSUN2 in gastric cancer remains to be determined. Our study showed that NSUN2 was significantly upregulated in gastric cancers, compared to adjacent normal gastric tissues. Moreover, NSUN2 could promote gastric cancer cell proliferation both in vitro and in vivo. Further study demonstrated that CDKN1C (p57Kip2) was the potential downstream gene of regulated by NSUN2 in gastric cancer. NSUN2 could promote gastric cancer cell proliferation through repressing p57Kip2 in an m5C-dependent manner. Our findings suggested that NSUN2 acted as an oncogene through promoting gastric cancer development by repressing p57Kip2 in an m5C-dependent manner, which may provide a novel therapeutic target against gastric cancer.

Identifying the role of Wilms tumor 1 associated protein in cancer prediction using integrative genomic analyses.

The Wilms tumor suppressor, WT1 was first identified due to its essential role in the normal development of the human genitourinary system. Wilms tumor 1 associated protein (WTAP) was subsequently revealed to interact with WT1 using yeast two-hybrid screening. The present study identified 44 complete WTAP genes in the genomes of vertebrates, including fish, amphibians, birds and mammals. The vertebrate WTAP proteins clustered into the primate, rodent and teleost lineages using phylogenetic tree analysis. From 1,347 available SNPs in the human WTAP gene, 19 were identified to cause missense mutations. WTAP was expressed in bladder, blood, brain, breast, colorectal, esophagus, eye, head and neck, lung, ovarian, prostate, skin and soft tissue cancers. A total of 17 out of 328 microarrays demonstrated an association between WTAP gene expression and cancer prognosis. However, the association between WTAP gene expression and prognosis varied in distinct types of cancer, and even in identical types of cancer from separate microarray databases. By searching the Catalogue of Somatic Mutations in Cancer database, 65 somatic mutations were identified in the human WTAP gene from the cancer tissue samples. These results suggest that the function of WTAP in tumor formation may be multidimensional. Furthermore, signal transducer and activator of transcription 1, forkhead box protein O1, interferon regulatory factor 1, glucocorticoid receptor and peroxisome proliferator-activated receptor γ transcription factor binding sites were identified in the upstream (promoter) region of the human WTAP gene, suggesting that these transcription factors may be involved in WTAP functions in tumor formation.

Pulsed electrical stimulation protects neurons in the dorsal root and anterior horn of the spinal cord after peripheral nerve injury.

Most studies on peripheral nerve injury have focused on repair at the site of injury, but very few have examined the effects of repair strategies on the more proximal neuronal cell bodies. In this study, an approximately 10-mm-long nerve segment from the ischial tuberosity in the rat was transected and its proximal and distal ends were inverted and sutured. The spinal cord was subjected to pulsed electrical stimulation at T10 and L3, at a current of 6.5 mA and a stimulation frequency of 15 Hz, 15 minutes per session, twice a day for 56 days. After pulsed electrical stimulation, the number of neurons in the dorsal root ganglion and anterior horn was increased in rats with sciatic nerve injury. The number of myelinated nerve fibers was increased in the sciatic nerve. The ultrastructure of neurons in the dorsal root ganglion and spinal cord was noticeably improved. Conduction velocity of the sciatic nerve was also increased. These results show that pulsed electrical stimulation protects sensory neurons in the dorsal root ganglia as well as motor neurons in the anterior horn of the spinal cord after peripheral nerve injury, and that it promotes the regeneration of peripheral nerve fibers.

Two IL28B polymorphisms are associated with the treatment response of different genotypes of hepatitis C in different racial populations: A meta-analysis.

The purpose of this present meta-analysis is to provide an accurate estimation of the association between two IL28B polymorphisms (rs8099917 and rs12979860) and sustained virological response (SVR) to standard treatment of patients of different racial descent infected with different genotypes of hepatitis C virus (HCV), and also to investigate the possible factors in the IL28B gene that contribute to the different SVR rates of patients with different subtypes of HCV infection across different populations. The electronic database PubMed was searched. Asian patients with a common homozygote (TT vs. TG/GG, OR=3.17; CC vs. CT/TT, OR=3.75) attained a higher rate of SVR, and a similar result was observed in European patients (TT vs. TG/GG, OR=1.74; CC vs. CT/TT, OR=2.50). Furthermore, HCV1-infected patients with a common homozygote (TT vs. TG/GG, OR=2.95; CC vs. CT/TT, OR=4.34) appeared to have a higher SVR rate than those with HCV2/3 (TT vs. TG/GG, OR=1.56; CC vs. CT/TT, OR=1.37). The frequency of the common homozygote in Asian patients was high, followed by European patients and African patients. In all, Asian patients attained a higher SVR rate than European patients (P<0.05). Patients with HCV1 infection had a lower SVR rate than those with HCV2/3 infection (P<0.001). Our results suggest that both the common allele frequency and racial descent itself contribute to the difference in SVR rates across different population groups, and the common allele frequency may partly elucidate the different SVR rates in patients with different genotypes of HCV.

[Construction of suppression subtractive hybridization (SSH) library of copepod Pseudodiaptomous annandalei and its ferritin cDNA cloning and differential expression under nickel stress].

To study the molecular response mechanisms of copepod to nickel stress, a suppression subtractive hybridization (SSH) cDNA library of Pseudodiaptomous annandalei under nickel stress was constructed by using SSH technique, and a total of 140 clones were randomly picked from the growing colonies and identified by PCR. The recombinant rate of the library was 98.6%, and the volume of the library was 1.12 x 10(6) cfu. After the recombinant plasmids were sequenced, a partial cDNA fragment of ferritin was recognized based on BLAST searches in NCBI, with a size of 859 bp and continuously encoding 170 amino acid residues. The semi-quantitative PCR results showed that the ferritin cDNA under 24 h nickel stress was distinctly up-regulated. The successful construction of the SSH library and the obtaining of ferritin cDNA fragment would supply basis for the further study of the molecular response mechanisms of copepod to nickel stress.

Cytotoxic polyphenols against breast tumor cell in Smilax china L.

ETHNOPHARMACOLOGICAL RELEVANCE: Smilax china L., referred to 'Ba Qia' (or 'Jin Gang Teng') in China, is a small vine that grows in the southern parts of China. The roots and tubers of S. china L. have been applied not only as traditional Chinese medicine (TCM) for treatment of diuretic, rheumatic arthritic, detoxication, lumbago, gout, tumor, and inflammatory diseases, but also as food in some area of China. AIM OF STUDY: To investigate the breast tumor cell toxic components in S. china L. continuously and systematically. MATERIALS AND METHODS: Three fractions and six polyphenols were isolated from roots and tubers of S. china L. under bioassay-guided screenings. The structures of six compounds were elucidated by spectroscopic methods and comparison with published data. Their breast tumor cytotoxicity and apoptosis of purified components were performed. RESULTS: Six polyphenols were obtained on the basis of a bioassay-guided separation of the ethyl acetate extract, and their breast tumor cytotoxic activities were tested. They showed anti-tumor activities against MCF-7 and MDA-MB-231 with IC50 value of 2.1-38.9 microg/mL, and can induce apoptosis for MCF-7 and MDA-MB-231. CONCLUSIONS: Among these six polyphenols, five (1, 3-6) were reported for the 1st time with in vitro activities on anti-breast tumor cell. It is likely that these polyphenols are the active components of S. china L. responsible for the anti-breast tumor cell activities.

[Treatment of tibial fracture with interlocking intramedullary nail and tripus].

OBJECTIVE: To explore the method and effect of inter-locking intramedullary nail and tripus in closed reduction for treating tibial fracture. METHODS: One hundred and twenty-six patients of tibial fractures were treated by inter-locking intramedullary nail and tripus in closed reduction. There were 76 males and 50 females aged from 25 to 68, the mean age was 38; There were 86 close fractures and 40 open fractures (Gustilo I and II type). AO classification system was used for all cases, fracture type A in 49 cases, type B in 41 cases, type C in 36 cases. RESULTS: All patients were followed up for 10 to 16 months. Fratures were cured, according to the criteria of Johner-Wruhs, the results were excellent in 103 cases, good in 18 cases, fair in 5 cases. CONCLUSION: Inter-locking intramedullary nail is the optimal operation method in treating tibial fracture. Static locking should be a routine way, and closed reduction, no stripping periosteum, infectious rate and complications are reduced. Through tripus work intensity are reduced and reduction easily during operation.