PLXDC2 enhances invadopodium formation to promote invasion and metastasis of gastric cancer cells via interacting with PTP1B.

Plexin-domain containing 2 (PLXDC2) has been reported as an oncoprotein in several human malignancies. However, its expression and roles in gastric cancer remain largely unclear. In this study, we found that PLXDC2 was highly expressed in gastric cancer tissues, and the expression levels were positively correlated with clinicopathological features, but negatively with the patients' outcome. Cox regression analysis identified PLXDC2 as an independent prognostic indicator for the patients. Knockdown of PLXDC2 markedly suppressed the in vitro invasion and in vivo metastasis of gastric cancer cells, while overexpression of PLXDC2 resulted in opposite effects. Mechanistically, PLXDC2 enhanced the level of phosphorylated Cortactin (p-Cortactin) by physically interacting with protein tyrosine phosphatase 1B (PTP1B), an important dephosphorylase, to prevent its dephosphorylating of p-Cortactin, thereby promoting the formation of invadopodia. Collectively, our results indicate that PLXDC2 contributes to the invasion and metastasis of gastric cancer by inhibiting PTP1B to facilitate the invadopodium formation, and may serve as a potential prognostic biomarker and a therapeutic target for this disease.

Kir2.1 Interaction with Stk38 Promotes Invasion and Metastasis of Human Gastric Cancer by Enhancing MEKK2-MEK1/2-ERK1/2 Signaling.

Potassium ion channels are emerging as promalignant factors involved in cancer progression. In this study, we found that invading human gastric cancer cells express high levels of inwardly rectifying potassium channel 2.1 (Kir2.1). Silencing Kir2.1 markedly reduced the invasive and metastatic capabilities as well as the epithelial-mesenchymal transition (EMT) of gastric cancer cells. The promalignant nature of Kir2.1 in gastric cancer cells was independent of potassium permeation but relied on its interaction with serine/threonine-protein kinase 38 (Stk38) to inhibit ubiquitination and degradation of mitogen-activated protein kinase kinase kinase 2 (MEKK2). Degradation of MEKK2 was mediated by small mothers against decapentaplegic-specific E3 ubiquitin protein ligase 1 (Smurf1), which resulted in activation of the MEK1/2-ERK1/2-Snail pathway in gastric cancer cells. In human gastric cancer tissues, expression was high and positively correlated with invasion depth and metastatic status of the tumors as well as poor overall patient survival. Cox regression analysis identified Kir2.1 as an independent prognostic indicator for patients with gastric cancer. Our results suggest that Kir2.1 is an important regulator of gastric cancer malignancy and acts as a novel prognostic marker and a therapeutic target for gastric cancer.Significance: Kir2.1 contributes to invasion and metastasis by a noncanonical ion permeation-independent signaling pathway and may act as a novel prognostic marker and therapeutic target for gastric cancer. Cancer Res; 78(11); 3041-53. ©2018 AACR.

FPR2 promotes invasion and metastasis of gastric cancer cells and predicts the prognosis of patients.

Formyl peptide receptor 2 (FPR2), a classical chemoattractant receptor of G-protein-coupled receptors, is reported to be involved in invasion and metastasis of some cancers, but the role of FPR2 in gastric cancer (GC) has not yet been elucidated. In this study, we found that the levels of FPR2 expression in GC were positively correlated with invasion depth, lymph node metastasis and negatively correlated with the patients' overall survival. Multivariate analysis indicated that FPR2 expression was an independent prognostic marker for GC patients. FPR2-knockdown significantly abrogated the migration and invasion stimulated by Hp(2-20) and Ac(2-26), two well-characterized ligands for FPR2 in GC cells. FPR2 deletion also reduced the tumorigenic and metastatic capabilities of GC cells in vivo. Mechanistically, stimulation with FPR2 ligands resulted in down-regulation of E-cadherin and up-regulation of vimentin, which were reversed by FPR2 knock-down, implying the involvement of epithelial-mesenchymal transition (EMT). Moreover, the activation of FPR2 was accompanied with ERK1/2 phosphorylation, which could be attenuated by FPR2 silencing or treatment with MEK inhibitor, PD98059. Altogether, our results demonstrate that FPR2 is functionally involved in invasion and metastasis, and potentially acts as a novel prognostic marker as well as a potential therapeutic target in human GC.

Transcription factor RUNX2 up-regulates chemokine receptor CXCR4 to promote invasive and metastatic potentials of human gastric cancer.

Runt-related transcription factor 2 (RUNX2) is a regulator of embryogenesis and development, but has also been implicated in the progression of certain human cancer. This study aimed to elucidate the role of RUNX2 in the invasive and metastatic potentials of human gastric cancer (GC) and the underlying mechanisms. We found that the levels of RUNX2 expression in gastric cancer tissues were correlated with the differentiation degrees, invasion depth and lymph node metastasis. COX regression analysis indicated that RUNX2 was an independent prognostic indicator for GC patients. RUNX2 significantly increased the migration and invasion ability of GC cells in vitro and enhanced the invasion and metastatic potential of GC cells in an orthotopic GC model of nude mice. Mechanistically, RUNX2 directly bound to the promoter region of the gene coding for the chemokine receptor CXCR4 to enhance its transcription. CXCR4 knockdown or treatment with AMD3100, a CXCR4 inhibitor, attenuated RUNX2-promoted invasion and metastasis. These results demonstrate that RUNX2 promotes the invasion and metastasis of human GC by transcriptionally up-regulating the chemokine receptor CXCR4. Therefore, the RUNX2-CXCR4 axis is a potential therapeutic target for GC.

Scinderin promotes the invasion and metastasis of gastric cancer cells and predicts the outcome of patients.

Invasion and metastasis are major malignant characteristics of human gastric cancer (GC), but the underlying molecular mechanisms are poorly understood. Recent studies have shown that scinderin (SCIN), an actin severing and capping protein that regulates the actin cytoskeleton, is involved in the proliferation and migration of certain cancer cells. Accordingly, this study aimed to investigate the potential role of SCIN in the invasion and metastasis of human GC cells and to evaluate its prognostic value for GC patients. We found that high levels of SCIN expression in GC tumors were correlated with poor overall survival of patients. Silencing of SCIN effectively suppressed the migratory and invasive capabilities of human GC cells in vitro and tumorigenicity and metastasis in vivo. Furthermore, knockdown of SCIN markedly inhibited the formation of filopodia, decreasing GC cell migration and the expression of Cdc42, an important regulator of filopodia by GC cells. These findings suggest that SCIN may be a novel prognostic marker and a potential therapeutic target in human GC.

Bidirectional regulation of acupuncture: a subgroup analysis of multicenter randomized controlled trial of acupuncture with / 中国针灸

OBJECTIVE@#To explore the bidirectional regulation of acupuncture based on a subgroup analysis of multicenter randomized controlled trial of acupuncture with @*METHODS@#A total of 519 patients were included in the analysis, including 137 patients with constipation type irritable bowel syndrome (IBS-C) (92 cases in the acupuncture group and 45 cases in the polyethylene glycol [PEG] group), and 382 patients with diarrhea type irritable bowel syndrome (IBS-D) (252 cases in the acupuncture group and 130 cases in the pinaverium group). The patients in the acupuncture group were given acupuncture at Baihui (GV 20), Yintang (GV 29), Tianshu (ST 25), Shangjuxu (ST 37), Zusanli (ST 36), Sanyinjiao (SP 6) and Taichong (LR 3) once every other day, 3 times a week. The patients in the PEG group received polyethylene glycol 4000 powder orally, and the pinaverium group received pinaverium bromide tablets orally. All were treated for 6 weeks. The IBS symptom severity score (IBS-SSS) was assessed at baseline, treatment period (2, 4, 6 weeks of treatment) and 12 weeks of follow-up, and the IBS quality of life (IBS-QOL) score was evaluated at the baseline period, 6 weeks of treatment and 12 weeks of follow-up.@*RESULTS@#The total IBS-SSS scores of the two groups of IBS-C patients at 2, 4, 6 weeks of treatment and follow-up of 12 weeks were lower than those in the baseline period (@*CONCLUSION@#Acupuncture with

Correlation between curative effect and 5-HTTLPR polymorphism in treatment of diarrhea-predominant irritable bowel syndrome with acupuncture for regulating / 中国针灸

OBJECTIVE@#To compare the curative effect on diarrhea-predominant irritable bowel syndrome (IBS-D) between acupuncture for regulating @*METHODS@#A total of 231 patients with IBS-D were randomized into an acupuncture group (154 cases) and a western medication group (77 cases) at the ratio of 2 to 1. In the acupuncture group, acupuncture was applied to acupoint regimen for regulating @*RESULTS@#After treatment and in follow-up, the total scores of IBS-SSS in the patients of the two groups were all reduced as compared with those before treatment (@*CONCLUSION@#Acupuncture for regulating

Identification and expression pattern analysis of Piwi genes during the spermiogenesis of Portunus trituberculatus.

The Piwi genes have an important role in stem cell development, gametogenesis and RNA interference in diverse organisms. So far, most of the studies have focused on the function of Piwis in vertebrates, but their function during spermiogenesis in invertebrates still remains largely unclear. In order to investigate the function of Piwis during spermiogenesis in the crab Portunus trituberculatus, we use RT-PCR and RACE to identify three Piwi complete cDNA sequences from the total RNA of the testis in P. trituberculatus. The deduced amino acid sequences of P. trituberculatus Piwi-1, Piwi-2 and Piwi-3 showed that each contains a well-conserved PAZ domain and PIWI domain. RT-PCR analyzed the tissue expression pattern of P. trituberculatus Piwi-1, Piwi-2 and Piwi-3 in the testis, heart, muscle, hepatopancreas and gill. All of the Piwis are found in germ cells of adult testis in P. trituberculatus by in situ hybridization, suggesting that these genes may play function during spermiogenesis in this species.

Expression and function analysis of metallothionein in the testis of Portunus trituberculatus exposed to cadmium.

Metallothioneins (MTs) possess a unique molecular structure that provides metal-binding and redox capabilities. These capabilities include the maintenance of metal equilibria that protect against heavy metals (especially cadmium) and oxidative damage. Past studies have focused on the function of MTs in vertebrates. However, the functions of MTs during spermiogenesis in invertebrates remain unclear. In order to investigate the function of MTs during spermiogenesis in Portunus trituberculatus, we used RT-PCR and RACE to identify two MT complete cDNA sequences in the total RNA from the P. trituberculatus testis. The 450 bp MT-1 cDNA consists of a 77 bp 5' untranslated region, a 196 bp 3' untranslated region, and a 177 bp open reading frame that encodes 58 amino acids including 19 cysteines. The 581 bp MT-2 cDNA consists of 73 bp 5' untranslated region, a 328 bp 3' untranslated region, and a 180 bp open reading frame that encodes 59 amino acids including 18 cysteines. MT-1 and MT-2 of P. trituberculatus more closely resemble invertebrate (especially crab) MT homologues than vertebrate MT homologues as indicated by protein alignment comparisons and phylogenetic tree analysis. MT-1 and MT-2 were detected in the heart, testis, muscle, hepatopancreas, and gill of P. trituberculatus by tissue expression analysis. In addition, MT-1 and MT-2 are present during the entire process of spermiogenesis in P. trituberculatus as indicated by H&E staining and in situ hybridization. MT-1 and MT-2 expression levels significantly increase after cadmium (Cd) exposure as measured by real-time quantitative PCR analysis. Therefore, we suggest that MT-1 and MT-2 perform important functions in spermiogenesis and testis detoxification in P. trituberculatus.

[Effect of abdominal acupuncture on pain of pelvic cavity in patients with endometriosis].

OBJECTIVE: To compare the effect of abdominal acupuncture and Chinese medicine on pain relieving in pelvic cavity in patients with endometriosis. METHODS: Fifty-eight cases were randomly divided into 2 groups. Thirty cases were in abdominal acupuncture group and 28 cases in Chinese medicine group. Abdominal acupuncture points such as Zhongwan (CV 12), Xiawan (CV 10) and Qihai (CV 6), etc. were adopted for the abdominal acupuncture group, and Tianqi Tongjing Capsule (radix notoginseng capsule for dysmenorrhea) was taken by the Chinese medicine group. After a 3-month treatment, the scores of McGill pain questionaire, level of serum CA125, average value of the radial line of endometrial cyst of ovary and the sum of 3 radial lines of the uterus of patients with adenomyosis as the complication of both groups were observed before and after treatment. RESULTS: The McGill estimation of 6 items for both groups improved obviously after treatment (all P < 0.01, except numbers of selected deseriptors in Chinese medicine group). The differences of the result of McGill estimation of 6 items after treatment had statistical significance, the scores in the abdominal acupuncture group were obviously better than those in the Chinese medicine group (all P < 0.01). The differences of CA125 levels within one group or between 2 groups had statistical significance (P < 0.01, P < 0.05). The difference of the radial lines of patients with endometrial cyst of ovary within one group or between 2 groups after treatment had not statistical significance (all P > 0.05). For the value of 3 radial lines of the uterus of patients with adenomyosis within one group before and after treatment, only the difference in the abdominal acupuncture group had statistical significance (P < 0.01). The differences before and after treatment in the Chinese medicine group and the difference between 2 groups after treatment had no statistical significance (all P > 0.05). CONCLUSION: Effect of abdominal acupuncture on relieving pain of pelvic cavity caused by endometriosis, reducing the level of serum CA125 is obverious than Tianqi Tongjing Capsule (radix notoginseng capsule for dysmenorrhea). However, the effects on reducing the size of the ovarian endometrial cyst and the size of uterus with adenomyosis are not significant. Therefore, it is concluded that abdominal acupuncture is a better choice for endometriosis with pain as the chief complaints.

Progress on epigenetics applications in forensic science / 法医学杂志

Epigenetics is the study of heritable changes in gene expression other than changes in the underlying DNA sequence. Such changes include DNA methylation, histone modification, chromatin remodeling, genomic imprinting, X chromosome inactivation and non-coding RNA regulation. Recent progresses on epigenetics open new possibilities in tackling these challenging problems in forensic science, including identification of fetal paternity testing in embryonic period, determination of the necessary allele in paternity testing, discrimination of identical twins, origination analysis of micro tissue, verification of forged DNA. This review focuses on epigenetics concept and its latest application in the field of paternity testing, age estimation, discrimination between the twins, identification of tissue of origin, and estimation of postmortem interval.

A correlation analysis of HBV-DNA load levels between in perinatal mother's serum and neonatal cord blood / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate the correlations of hepatitis B virus markers and hepatitis B virus -DNA vectors in blood between women in perinatal period and cord blood, and to assess the risk of HBV infections status in pregnant women to intrauterine fetal infective.</p><p><b>METHODS</b>We selected 612 pregnant women who decided to delivery in hospital, in compliance with the principles of informed consent. According the difference of hepatitis virus serological markers existing in pregnant women, samples were divided into six groups. We used enzyme-linked immunosorbent assay to detect hepatitis virus serological markers, existing in serum of mother and cord blood. Real-time fluorescence quantitative PCR was supplied to test HBV-DNA load levels in these two kinds of biological specimen.</p><p><b>RESULTS</b>In group A, hepatitis B virus "big 3 positives" or 1,3 positive 149 lying-in woman examples, two positive rates of HBV-DNA about pregnant women and cord blood are 99.33% and 32.21%; in group B, positive rates of HBV-DNA in two kinds of specimen are 20.00% and 3.08%; in group C and D, two positive rates are and the average contents of HBV-DNA, the results as mentioned in each group respectively are 65.52%, 12.07% and 13.56%, 1.69% respectively. Control group is group E, 86 lying-in woman examples and the detecting results orderly are 1.16%, 0. There was a significant difference in positive rate of HBV-DNA in cord blood between group A and group B subgroups (chi2 = 54.09, P < 0.01). There is significant positive correlation between HBV-DNA vectors existing in mother's serum and the positive rate of HBV-DNA in cord blood. Hepatitis B virus the mother blood " big 3 positives " is the umbilicus blood HBV-DNA 6345 times that carries quantity in average.</p><p><b>CONCLUSION</b>(1) During the perinatal period, along with the HBV-DNA load levels arising of pregnant women, the risk of HBV infections status in pregnant women to intrauterine fetal infective increased. (2) Suggested to develop the compound pattern human hepatitis B immunoglobulin: Increase the composition of efficient price HBeAb-can be combinated HBeAg, HBsAb can be combinated HBsAg, strengthen the hinderance and break hepatitis B virus disseminate. (3) Our government should strengthen the propaganda of hepatitis B virus education. Establish and perfect to surround and produce the system of health protection.</p>