MFAP2 enhances cisplatin resistance in gastric cancer cells by regulating autophagy.

Background: Cisplatin (CDDP) is of importance in cancer treatment and widely used in advanced gastric cancer (GC). However, its clinical usage is limited due to its resistance, and the regulatory mechanism of CDDP resistance in GC has not yet been fully elucidated. In this study, we first conducted a comprehensive study to investigate the role of MFAP2 through bioinformatics analysis. Methods: The Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were applied to downloadgene expression data and clinicopathologic data, and the differentially expressed genes (DEGs) were further analyzed. Then, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and survival analysis were conducted. Furthermore, according to the clinicopathological characteristics of TCGA, clinical correlation analysis was conducted, and a receiver operating characteristic curve (ROC) was plotted. Results: We revealed that FAP, INHBA and MFAP2 were good diagnostic factors of GC. However, the mechanism of MFAP2 in GC remains elusive, especially in the aspect of chemotherapy resistance. We developed the CDDP-resistant cell line, and found that MFAP2 was upregulated in CDDP-resistant cells, and MFAP2-knockdown improved CDDP sensitivity. Finally, we found that MFAP2 enhanced CDDP resistance by inducing autophagy in drug-resistant cell lines. Conclusions: The above results suggested that MFAP2 could affect the chemotherapy resistance by altering the level of autophagy in GC patients as a potential therapeutic target.

Association of mitochondrial displacement loop polymorphisms with diarrhea-predominant irritable bowel syndrome: A preliminary study.

OBJECTIVES: To investigate whether single nucleotide polymorphisms (SNPs) in the mitochondrial displacement loop (D-loop) were associated with irritable bowel syndrome (IBS). METHODS: Altogether 40 participants were recruited and classified into three groups, including 20 that fulfilled the Rome III criteria for diarrhea-predominant IBS (IBS-D), 10 with constipation-predominant IBS (IBS-C), and 10 healthy volunteers (controls). DNA was extracted from biopsy specimens of the colon obtained during routine colonoscopies. The mitochondrial D-loop was sequenced and variants were identified in comparison with the reference sequence from GenBank. We searched GenBank and MITOMAP to determine whether a variant could be considered an SNP. RESULTS: No significant differences in sex, age and body mass index were found among the three groups. The average numbers of SNPs in the IBS-D, IBS-C and control groups were 12.2 ± 2.7, 9.8 ± 1.8 and 9.9 ± 2.1, respectively. The frequency of SNPs was significantly higher in the IBS-D group than in the IBS-C group and controls (P < 0.05). No significant difference was found between the latter two groups. Each SNP was compared among the three groups and the frequency of 199C was found to be significantly higher in the control group than in the IBS-D group (P = 0.03), but no significant difference in its frequency was found between the IBS-C group and controls. CONCLUSIONS: Patients with IBS-D have a higher incidence of SNPs in the mitochondrial D-loop than controls. The genotype 199C may be associated with a lower risk of IBS-D.

Relationship between varicocele and sperm DNA damage and the effect of varicocele repair: a meta-analysis.

Varicocele, a cause of male infertility, occurs in nearly 40% of infertile males. It has been postulated that varicoceles may cause sperm DNA damage. Sperm DNA integrity has been recognized as one of the important determinants of normal fertilization and embryo growth in natural and assisted conception. Eighty-three human studies were identified after an extensive literature search involving the role of varicoceles in sperm DNA damage. Of the 83 studies, 12 were selected that measured similar types of reactive sperm DNA damage. Seven studies determined the damage of sperm DNA in varicocele-associated patients and six studies evaluated the efficacy of varicocelectomy. One study was a duplicate because both outcomes were included. Data were analysed using RevMan software. The overall estimate showed that patients with varicoceles have significantly higher sperm DNA damage than controls, with a mean difference of 9.84% (95% CI 9.19 to 10.49; P<0.00001). A varicocelectomy can improve sperm DNA integrity, with a mean difference of -3.37% (95% CI -4.09 to -2.65; P<0.00001). In conclusion, there is increased sperm DNA damage in patients with varicoceles and varicocelectomy may be a possible treatment; however, more studies with appropriate controls are needed to confirm this finding. A varicocele is an important cause of male infertility and occurs in nearly 40% of infertile males. The recent understanding of the effect of varicoceles in male reproduction has led some researchers to postulate varicoceles as the possible cause of sperm DNA damage. Eighty-three human studies were identified after an extensive literature search involving the role of varicoceles in sperm DNA damage. Of the 83 studies, 12 were selected that measured similar types of reactive sperm DNA damage by a similar method. Seven studies determined the damage of sperm DNA in varicocele-associated patients and six studies evaluated the efficacy of varicocelectomy. One study was a duplicate because both outcomes were included. The data were then entered in the RevMan software for analysis. The overall estimate showed that patients with varicoceles have significantly higher sperm DNA damage than controls, with a mean difference of 9.84% (95% CI 9.19 to 10.49; P<0.00001). A varicocelectomy can improve sperm DNA integrity, with a mean difference of -3.37% (95% CI -4.09 to -2.65; P<0.00001). Based on the results, it can be concluded that there is increased sperm DNA damage in patients with varicoceles and that varicocelectomy may be a possible treatment; however, more studies with appropriate controls are needed to confirm this finding.

[In vivo HSV-TK gene transfer and the therapeutic effects of ganciclovir on bladder cancer in mice with HSV-TK gene transfer].

OBJECTIVE: To explore an effective method for in vivo HSV-TK gene transfer and observe the therapeutic effect of ganciclovir (GCV) on bladder cancer in mice after receiving such gene transfer therapy. METHODS: Mice models bearing subcutaneous tumors of bladder cancer were established in 24 syngeneic mice, and HSV-TK gene transfer was performed by means of naked DNA plasmids, DNA-liposome complex or retroviral mediators respectively. GCV treatment was administered in all the mice and its effect on the growth of the tumor was subsequently observed. RESULTS: Gene transfer therapies by DNA-liposome complex and retroviral mediators both significantly inhibited the growth of the tumor by 54% and 68% respectively, and the survival of the mice was prolonged by 28.81% and 44.16% (P<0.05). The effect of gene transfer by naked DNA plasmids was not obvious (P>0.05). CONCLUSION: Gene transfer therapies by DNA-liposome complex and retroviral vectors supplemented by GCV treatment are effective therapeutic modalities against bladder cancer.