RNA-sequencing identification and validation of genes differentially expressed in high-risk adenoma, advanced colorectal cancer, and normal controls.

Distinct gene expression patterns that occur during the adenoma-carcinoma sequence need to be determined to analyze the underlying mechanism in each step of colorectal cancer progression. Elucidation of biomarkers for colorectal polyps that harbor malignancy potential is important for prevention of colorectal cancer. Here, we use RNA sequencing to determine gene expression profile in patients with high-risk adenoma treated with endoscopic submucosal dissection by comparing with gene expression in patients with advanced colorectal cancer and normal controls. We collected 70 samples, which consisted of 27 colorectal polyps, 24 cancer tissues, and 19 normal colorectal mucosa. RNA sequencing was performed on an Illumina platform to select differentially expressed genes (DEGs) between colorectal polyps and cancer, polyps and controls, and cancer and normal controls. The Kyoto Gene and Genome Encyclopedia (KEGG) and gene ontology (GO) analysis, gene-concept network, GSEA, and a decision tree were used to evaluate the DEGs. We selected the most highly expressed genes in high-risk polyps and validated their expression using real-time PCR and immunohistochemistry. Compared to patients with colorectal cancer, 82 upregulated and 24 downregulated genes were detected in high-risk adenoma. In comparison with normal controls, 33 upregulated and 79 downregulated genes were found in high-risk adenoma. In total, six genes were retrieved as the highest and second highest expressed in advanced polyps and cancers among the three groups. Among the six genes, ANAX3 and CD44 expression in real-time PCR for validation was in good accordance with RNA sequencing. We identified differential expression of mRNAs among high-risk adenoma, advanced colorectal cancer, and normal controls, including that of CD44 and ANXA3, suggesting that this cluster of genes as a marker of high-risk colorectal adenoma.

Intestinal Epithelial Deletion of Sphk1 Prevents Colitis-Associated Cancer Development by Inhibition of Epithelial STAT3 Activation.

BACKGROUND AND AIMS: Colitis-associated cancer (CAC) is one of the most serious complications in patients with inflammatory bowel disease. Sphingosine kinase 1 (Sphk1) is a key enzyme in the sphingolipid pathway and has oncogene potential for inducing both initiation and progression of tumors. The aim of this work is to characterize the role of epithelial Sphk1 in mouse colitis and CAC models. METHODS: We investigated the roles of Sphk1 in CAC by conditional deletion of Sphk1 in intestinal epithelial cells (IECs). RESULTS: CAC was induced in both Sphk1ΔIEC/ApcMin/+ and Sphk1IEC/ApcMin/+ mice by administration of 2% dextran sodium sulfate (DSS) for 7 days. Genetic deletion of Sphk1 significantly reduced the number and size of tumors in ApcMin/+ mice. Histologic grade was more severe in Sphk1ΔIEC/ApcMin/+ mice compared with Sphk1IEC/ApcMin/+ mice (invasive carcinoma, 71% versus 13%, p < 0.05). Deletion of Sphk1 decreased mucosal proliferation and inhibited STAT3 activation and genetic expression of cyclin D1 and cMyc in tumor cells. Conditional deletion of Sphk1 using CRISPR-Cas9 in HCT 116 cells inhibited interleukin (IL)-6-mediated STAT3 activation. CONCLUSIONS: Epithelial conditional deletion of Sphk1 inhibits CAC in ApcMin/+-DSS models in mice by inhibiting STAT3 activation and its target signaling pathways.

PKA-dependent phosphorylation of IP3K-A at Ser119 regulates a binding affinity with EB3.

Microtubule-associated end-binding protein 3 (EB3) accumulates asymmetrically at the tip-end of growing microtubules, providing a central platform for linking various cellular components. EB3 orchestrates microtubule dynamics and targeting, enabling diverse processes within neurons. Inositol 1, 4, 5-trisphosphate 3-kinase A (IP3K-A; also known as ITPKA) is a neuron-enriched protein that binds to microtubules by PKA-dependent manners. In this study, we found that IP3K-A binds to EB3 and their binding affinity is precisely regulated by protein kinase A (PKA)-dependent phosphorylation of IP3K-A at Ser119 (pSer119). We also revealed that the complex of IP3K-A and EB3 dissociates and reassociates rapidly during chemically induced LTP (cLTP) condition. This dynamic rearrangement of IP3K-A and EB3 complex will contribute remodeling of microtubule cytoskeleton allowing effective structural plasticity in response to synaptic stimulations.

MW-PPG Sensor: An on-Chip Spectrometer Approach.

Multi-wavelength photoplethysmography (MW-PPG) sensing technology has been known to be superior to signal-wavelength photoplethysmography (SW-PPG) sensing technology. However, limited by the availability of sensing detectors, many prior studies can only use conventional bulky and pricy spectrometers as the detectors, and hence cannot bring the MW-PPG technology to daily-life applications. In this study we developed a chip-scale MW-PPG sensor using innovative on-chip spectrometers, aimed at wearable applications. Also in this paper we present signal processing methods for robustly extracting the PPG signals, in which an increase of up to 50% in the signal-to-noise ratio (S/N) was observed. Example measurements of saturation of peripheral blood oxygen (SpO2) and blood pressure were conducted.

CCR8 regulates contact hypersensitivity by restricting cutaneous dendritic cell migration to the draining lymph nodes.

Allergic contact dermatitis (ACD) is a typical occupational disease in industrialized countries. Although various cytokines and chemokines are suggested to be involved in the pathogenesis of ACD, the roles of these molecules remain to be elucidated. CC chemokine receptor 8 (CCR8) is one such molecule, of which expression is up-regulated in inflammatory sites of ACD patients. In this study, we found that Ccr8(-/-) mice developed severer contact hypersensitivity (CHS) responses to 2,4-dinitrofluorobenzene, a murine model of ACD, compared with wild-type mice. T cells from Ccr8(-/-) mice showed enhanced proliferative recall responses and Th1 and Th17 cell populations were expanded in these mice. However, CHS responses were similar between SCID mice adoptively transferred with Ccr8(-/-) and wild-type T cells, suggesting that CCR8 in T cells is not responsible for the exacerbation of CHS. Notably, skin-resident dendritic cells (DCs), such as Langerhans cells and dermal DCs, and inflammatory DCs were highly accumulated in lymph nodes (LNs) of Ccr8(-/-) mice after sensitization. Consistent with this, Ccr8(-/-) antigen-presenting cells readily migrated from the skin to the draining LNs after sensitization. These observations suggest that CCR8 negatively regulates migration of cutaneous DCs from the skin to the draining LNs in CHS by keeping these cells in the skin.

Inositol 1,4,5-trisphosphate 3-kinase A is a novel microtubule-associated protein: PKA-dependent phosphoregulation of microtubule binding affinity.

Inositol 1,4,5-trisphosphate 3-kinase A (IP(3)K-A) is a brain specific and F-actin-binding protein. We recently demonstrated that IP(3)K-A modulates a structural reorganization of dendritic spines through F-actin remodeling, which is required for synaptic plasticity and memory formation in brain. However, detailed functions of IP(3)K-A and its regulatory mechanisms involved in the neuronal cytoskeletal dynamics still remain unknown. In the present study, we identified tubulin as a candidate of IP(3)K-A-binding protein through proteomic screening. By various in vitro and in vivo approaches, we demonstrated that IP(3)K-A was a novel microtubule-associated protein (MAP), and the N terminus of IP(3)K-A was a critical region for direct binding to tubulin in dendritic shaft of hippocampal neurons. Moreover, PKA phosphorylated Ser-119 within IP(3)K-A, leading to a significant reduction of microtubule binding affinity. These results suggest that PKA-dependent phosphorylation and microtubule binding of IP(3)K-A are involved in its regulatory mechanism for activity-dependent neuronal events such as local calcium signaling and its synaptic targeting.

Effect of Chemical Agents on the Morphology and Chemical Structures of Microplastics.

Increased demand for plastics leads to a large amount of plastic manufacturing, which is accompanied by inappropriate disposal of plastics. The by-products of these waste plastics are microplastics (MPs; less than 5 nm in size), which are produced because of various environmental and physicochemical factors, posing hazardous effects to the ecosystem, such as the death of marine organisms due to the swallowing of plastic specks of no nutritional value. Therefore, the collection, preparation, identification, and recycling of these microsized plastics have become imperative. The pretreatment of MPs requires numerous chemical agents comprising strong acids, bases, and oxidizing agents. However, there is limited research on the chemical resistance of various MPs to these substances to date. In this study, the chemical resistance of five species of MPs (high-density polyethylene, low-density polyethylene, polystyrene, polyethylene terephthalate, and polypropylene) to sulfuric acid, hydrochloric acid, hydrogen peroxide, potassium hydroxide, and sodium hydroxide was studied. The MPs were reacted with these chemical reagents at preset temperatures and durations, and variations in morphology and chemical structures were detected when the MPs were reacted with mineral acids, such as sulfuric acid. The data pertaining to these changes in MP properties could be a significant reference for future studies on MP pretreatment with strong acids, bases, and oxidizing agents.

High Expression of Claudin-4 Is Associated with Synchronous Tumors in Patients with Early Gastric Cancer.

Claudin (CLDN) is a tight junction protein found in human epithelial cells and its altered expression is known to be associated with the progression of gastric cancer. We aimed to investigate the differential expression of CLDN-4 in early gastric cancer (EGC) according to its clinicopathological characteristics. We enrolled 53 patients with EGC who underwent surgical gastric resection from January 2007 to December 2018. The staining intensity of the tumor cells was scored as 0-3, and the percentage of staining was scored as 0-5; high expression was defined if the intensity plus percentage score was 7 or 8, and low expression was defined if the score was 0-6. Among the 53 patients, 16 (30.2%) showed low CLDN-4 expression, while 37 (69.8%) had high CLDN-4 expression. High CLDN-4 expression was significantly associated with intestinal-type EGC (low: 12.5% vs. high: 56.8%, p = 0.003), open-type atrophic change (low: 60.0% vs. high: 90.9%, p = 0.011), and the presence of synchronous tumors (0 vs. 32.4%, p = 0.010), and all 12 EGCs with synchronous tumors showed high CLDN-4 expression. However, expression of CLDN-3, a typical intestinal phenotype CLDN, was neither correlated with CLDN-4 expression nor associated with synchronous tumors. Taken together, high CLDN-4 expression may be considered as an auxiliary tool for screening synchronous tumors in patients with EGC.

Crosstalk between mucosal microbiota, host gene expression, and sociomedical factors in the progression of colorectal cancer.

Various omics-based biomarkers related to the occurrence, progression, and prognosis of colorectal cancer (CRC) have been identified. In this study, we attempted to identify gut microbiome-based biomarkers and detect their association with host gene expression in the initiation and progression of CRC by integrating analysis of the gut mucosal metagenome, RNA sequencing, and sociomedical factors. We performed metagenome and RNA sequencing on colonic mucosa samples from 13 patients with advanced CRC (ACRC), 10 patients with high-risk adenoma (HRA), and 7 normal control (NC) individuals. All participants completed a questionnaire on sociomedical factors. The interaction and correlation between changes in the microbiome and gene expression were assessed using bioinformatic analysis. When comparing HRA and NC samples, which can be considered to represent the process of tumor initiation, 28 genes and five microbiome species were analyzed with correlation plots. When comparing ACRC and HRA samples, which can be considered to represent the progression of CRC, seven bacterial species and 21 genes were analyzed. When comparing ACRC and NC samples, 16 genes and five bacterial species were analyzed, and four correlation plots were generated. A network visualizing the relationship between bacterial and host gene expression in the initiation and progression of CRC indicated that Clostridium spiroforme and Tyzzerella nexilis were hub bacteria in the development and progression of CRC. Our study revealed the interactions of and correlation between the colonic mucosal microbiome and host gene expression to identify potential roles of the microbiome in the initiation and progression of CRC. Our results provide gut microbiome-based biomarkers that may be potential diagnostic markers and therapeutic targets in patients with CRC.

The mechanism of LPS-induced HIV type I activation in transgenic mouse macrophages.

In the course of the development of acquired immunodeficiency syndrome (AIDS), bacterial infection causes deleterious effects on the progression of the disease; bacterial LPS in the circulation activate immune cells, resulting in the acceleration of HIV replication. However, the precise HIV activation mechanisms in infected hosts remain largely unknown. Previously, we generated transgenic (Tg) mice carrying the HIV type I (HIV-1) genome and showed that LPS induces the activation of HIV-1 in splenocytes through the induction of tumor necrosis factor (TNF) and IL-1, although similarly induced IFN-gamma and IL-6 are not involved. In this study, we analyzed the mechanisms of HIV-1 activation in macrophages using these HIV-1 Tg mice, because macrophages are one of the major reservoirs of HIV-1. In contrast to splenocytes, direct Toll-like receptor (TLR) 4 signaling rather than TLR-induced pro-inflammatory cytokines was responsible for the LPS-induced activation of HIV-1 in macrophages, because the time course of HIV-1 activation was earlier than that observed in splenocytes and TNF neutralization did not inhibit the activation. p38 mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-kappaB) activation, but neither extracellular signal-regulated kinase nor c-Jun N-terminal kinase activation, were required for the activation, because only inhibitors for p38 MAPK and NF-kappaB suppressed activation of HIV-1. Furthermore, we showed that myeloid differentiation primary response gene (MyD) 88, rather than Toll/IL-1R domain-containing adaptor inducing IFN-beta (TRIF), was required as an adaptor molecule for this activation using Myd88(-/-) mice and Dynasore, a specific inhibitor for TRIF, and small interfering RNAs specific for Myd88 and Trif. These observations suggest that suppression of these molecules, which are involved in the TLR4-MyD88 pathway and the downstream p38 MAPK and NF-kappaB pathways, should be beneficial to prevent development of AIDS in HIV-1-infected people.

CXC chemokine ligand 12 promotes CCR7-dependent naive T cell trafficking to lymph nodes and Peyer's patches.

A number of chemokines, including CCL21, CCL19, CXCL12, and CXCL13, are coexpressed on the lumen or basal lamina of high endothelial venules (HEVs) in lymph nodes (LNs) and Peyer's patches (PPs), consistent with the idea that they might cooperate to regulate lymphocyte trafficking into these lymphoid tissues. In this study we report that CXCL12, acting through its receptor, CXCR4, cooperates with CCR7 ligands to promote T cell trafficking across HEVs. CXCL12 enhanced the CCR7-induced chemotaxis of wild-type but not CXCR4-deficient T cells in vitro at suboptimal concentrations of a CCR7 ligand, but without affecting the expression level or ligand-binding ability of CCR7. Real-time chemotaxis analysis showed that CXCL12 substantially shortened the lag time before cell migration began in vitro, but not the migration speed of T cells responding to suboptimal CCR7 ligand concentrations. In addition, CXCL12 augmented the CCR7 ligand-driven ERK phosphorylation and actin polymerization in T cells under the same conditions. In adoptive transfer experiments, CXCL12 promoted naive T cell trafficking to LNs and PPs in wild-type but not CCR7 ligand-deficient plt/plt recipient mice; this increased T cell trafficking was associated with enhanced binding of the T cells to HEVs and their subsequent migration into the LN parenchyma. Thus, CXCL12 synergizes with CCR7 ligands to promote T cell migration by sensitizing T cells through CXCR4, thus enabling them to respond to lower concentrations of CCR7 ligands. Such concerted action of chemokines provides an additional, previously unknown mechanism for efficient lymphocyte trafficking across HEVs into LNs and PPs.

CD8 T-cell activation in mice injected with a plasmid DNA vaccine encoding AMA-1 of the reemerging Korean Plasmodium vivax.

Relatively little has been studied on the AMA-1 vaccine against Plasmodium vivax and on the plasmid DNA vaccine encoding P. vivax AMA-1 (PvAMA-1). In the present study, a plasmid DNA vaccine encoding AMA-1 of the reemerging Korean P. vivax has been constructed and a preliminary study was done on its cellular immunogenicity to recipient BALB/c mice. The PvAMA-1 gene was cloned and expressed in the plasmid vector UBpcAMA-1, and a protein band of approximately 56.8 kDa was obtained from the transfected COS7 cells. BALB/c mice were immunized intramuscularly or using a gene gun 4 times with the vaccine, and the proportions of splenic T-cell subsets were examined by fluorocytometry at week 2 after the last injection. The spleen cells from intramuscularly injected mice revealed no significant changes in the proportions of CD8(+) T-cells and CD4(+) T-cells. However, in mice immunized using a gene gun, significantly higher (P<0.05) proportions of CD8(+) cells were observed compared to UB vector-injected control mice. The results indicated that cellular immunogenicity of the plasmid DNA vaccine encoding AMA-1 of the reemerging Korean P. vivax was weak when it was injected intramuscularly; however, a promising effect was observed using the gene gun injection technique.

PARK7 maintains the stemness of glioblastoma stem cells by stabilizing epidermal growth factor receptor variant III.

PARK7 is involved in many key cellular processes, including cell proliferation, transcriptional regulation, cellular differentiation, oxidative stress protection, and mitochondrial function maintenance. Deregulation of PARK7 has been implicated in the pathogenesis of various human diseases, including cancer. Here, we aimed to clarify the effect of PARK7 on stemness and radioresistance of glioblastoma stem cells (GSCs). Serum differentiation and magnetic cell sorting of GSCs revealed that PARK7 was preferentially expressed in GSCs rather than differentiated GSCs. Immunohistochemical staining showed enhanced expression of PARK7 in glioma tissues compared to that in normal brain tissues. shRNA-mediated knockdown of PARK7 inhibited the self-renewal activity of GSCs in vitro, as evidenced by the results of neurosphere formation, limiting dilution, and soft-agar clonogenic assays. In addition, PARK7 knockdown suppressed GSC invasion and enhanced GSC sensitivity to ionizing radiation (IR). PARK7 knockdown suppressed expression of GSC signatures including nestin, epidermal growth factor receptor variant III (EGFRvIII), SOX2, NOTCH1, and OCT4. Contrarily, overexpression of PARK7 in CD133- non-GSCs increased self-renewal activities, migration, and IR resistance, and rescued the reduction of GSC factors under shPARK7-transfected and serum-differentiation conditions. Intriguingly, PARK7 acted as a co-chaperone of HSP90 by binding to it, protecting EGFRvIII from proteasomal degradation. Knockdown of PARK7 increased the production of reactive oxygen species, inducing partial apoptosis and enhancing IR sensitivity in GSCs. Finally, PARK7 knockdown increased mouse survival and IR sensitivity in vivo. Based on these data, we propose that PARK7 plays a pivotal role in the maintenance of stemness and therapeutic resistance in GSCs.

Detection of Microsatellite Instability in Colorectal Cancer Patients With a Plasma-Based Real-Time PCR Analysis.

A microsatellite instability (MSI) test is crucial for screening for HNPCC (Hereditary nonpolyposis colorectal cancer; Lynch syndrome) and optimization of colorectal cancer (CRC) treatment. Mismatch repair (MMR) deficiency is a predictor for good response of immune checkpoint inhibitors in various malignancies. In this study, we evaluated the results of a newly developed plasma-based real-time PCR kit for the detection of MSI in CRC patients. We assessed a peptide nucleotide acid (PNA) probe-mediated real-time PCR test (U-TOP MSI Detection Kit Plus) that determines MSI status by using amplicon melting analysis of five markers (NR21, NR24, NR27, BAT25, and BAT26) from plasma. Eighty-four CRC patients (46 dMMR and 38 pMMR) with colorectal cancer were analyzed. The concordance rate of MSI status assessment between the plasma kit and IHC was 63.0% in dMMR patients (29/46), but in the pMMR evaluation, a 100% (38/38) concordance rate was observed. In the evaluation of the performance of a custom tissue U-TOP MSI Detection Kit and plasma kit in 28 patients, sensitivity, specificity, PPV (positive predictive value) and NPV (negative predictive value) of plasma kit were 68.4, 100, 100, and 44.4%, respectively, with the tissue U-TOP MSI Detection Kit. Our results demonstrate the feasibility of a non-invasive and rapid plasma-based real-time PCR kit (U-TOP MSI Detection Kit Plus) for the detection of MSI in colorectal cancer.

Comment on 'Fabrication of uniform core-shell structural calcium and titanium precipitation particles and enhanced electrorheological activities'.

This comment is an analysis of the static yield stress of core-shell structured SiO(2)-calcium-titanium precipitation (CTP) particle-based electrorheological (ER) suspensions under various applied electric field strengths. We find that our previously published universal yield stress equation covers both polarization and conduction regions while the polar-molecule-based linearity mechanism becomes dominant for the giant ER fluid beyond the second critical electric field strength.

Ultralow Water Permeation Barrier Films of Triad a-SiNx:H/n-SiOxNy/h-SiOx Structure for Organic Light-Emitting Diodes.

Organic electronic devices such as organic light-emitting diodes (OLEDs), quantum dot LEDs, and organic photovoltaics are promising technologies for future electronics. However, achieving long-term stability of organic-based optoelectronic devices has been regarded as a crucial problem to be solved. In this work, a simple and reproducible fabrication method for ultralow water permeation barrier films having a triple-layered (triad) hydrogenated silicon nitride (a-SiNx:H)/nanosilicon oxynitride (n-SiOxNy)/hybrid silicon oxide (h-SiOx) multistructure is presented. Two triad (a-SiNx:H/n-SiOxNy/h-SiOx)n=2 multistructure barrier films are deposited on both sides of a poly(ethylene terephthalate) substrate using a combination of low-pressure plasma-enhanced chemical vapor deposition and dip coating. The deposited films show a high average transmittance (400-700 nm) of 84% and an ultralow water vapor transmission rate of 2 × 10-6 g/m2/day. In the electroluminescence characteristics of OLEDs encapsulated with two triad barrier films, the operational lifetime (T50) of OLEDs is 1584 h, which is almost similar to that (1416 h) of OLEDs encapsulated with a glass lid.

Regulation of AHI1 expression in adult rat brain: Implication in hypothalamic feeding control.

Recent studies revealed that Abelson helper integration site 1 (AHI1) plays a role in brain development. However, little is known about the role of AHI1 in adult brain. To directly assess the role of AHI1 in the adult brain, we cloned full-length cDNA of rat AHI1 and observed prominent expression of AHI1 in the hypothalamus, which contributes mainly to the control of energy homeostasis. Furthermore, we demonstrated that food deprivation caused induction of AHI1 in the hypothalamus and subsequent re-feeding down-regulated AHI1 expression, suggesting the involvement of AHI1 in feeding control. Moreover, the expression of AHI1 was increased in serum-depleted Neuro2A cells and restored by subsequent insulin treatment. Furthermore, treatment in food-deprived rat with intraperitoneal glucose also reduced the increased AHI1 expression. These results demonstrate that AHI1 expression can be regulated through diet and suggest the novel role of AHI1 in feeding behavior.

Early differentiation of long-standing persistent atrial fibrillation using the characteristics of fibrillatory waves in surface ECG multi-leads.

We characterized the f-waves in atrial fibrillation (AF) in the surface ECG by quantifying the amplitude, irregularity, and dominant rate of the f-waves in leads II, aVL, and V1, and investigated whether those parameters of the f-waves could discriminate long-standing persistent AF (LPeAF) from non-LPeAF. A total of 224 AF patients were enrolled: 112 with PAF (87 males), 48 with PeAF (38 males), and 64 with LPeAF (47 males). The f-waves in surface ECG leads V1, aVL, and II, which reflect well electrical activity in the right atrium (RA), the left atrium (LA), and both atria, respectively, were analyzed. The f-waves for LPeAF had lower amplitudes in II and aVL, increased irregularity and a higher dominant rate in II and V1 compared to PAF and PeAF (all p < 0.02). In a multivariate analysis, a low amplitude in lead II (<34.6 uV) and high dominant rate in lead V1 (≧390/min) (p < 0.001) independently discriminated LPeAF from the other AF types. The f-waves combined with both a low amplitude in lead II and high dominant rate in lead V1 were significantly associated with LPeAF (OR 6.27, p < 0.001). Characteristics of the f-waves on the surface ECG could discriminate LPeAF from other types of AF.

Inhibition of STAT3 in gastric cancer: role of pantoprazole as SHP-1 inducer.

BACKGROUND: We investigated the inhibitory effect of pantoprazole on signal transducer and activator of transcription 3 (STAT3) activity and invasiveness of gastric adenocarcinoma cells, and the role of SH2-containing protein tyrosine phosphatase 1 (SHP-1) in mediating role. METHODS: We used AGS and MKN-28 cells because of reduced SHP-1 and preserved p-STAT3 expression. Western blot, wound closure assay, Matrigel invasion assay and 3-D culture invasion assay were performed. Pharmacologic inhibitor of SHP-1 and siRNA were used for validation of the role of SHP-1. RESULTS: We observed that pantoprazole at 40, 80, and 160 µg/ml upregulated SHP-1 and downregulated p-STAT3 expression in a dose-dependent manner in AGS and MKN-28 cells. Furthermore, pantoprazole significantly downregulated mesenchymal markers (Snail1 and vimentin), upregulated epithelial marker (E-cadherin), and inhibited migration and invasion of AGS and MKN-28 cells. To validate the role of SHP-1 in inhibition of STAT3 activity by pantoprazole in gastric cancer cells, we performed pharmacologic inhibition (pervanadate) or knockdown of SHP-1 before pantoprazole treatment, which significantly attenuated the suppression of p-STAT3 and anti-migration and invasion effect by pantoprazole in AGS cells. In xenograft tumor model, tumor volume was significantly reduced by intraperitoneal injection of pantoprazole, with upregulation of SHP-1 and downregulation of p-STAT3, which were attenuated by concomitant injection of pervanadate. CONCLUSION: Our data suggest that the inhibitory effect of pantoprazole on cellular migration and invasion might be through inducing SHP-1 in gastric cancer cells.

Efficacy and safety of thread embedding acupuncture for chronic low back pain: a randomized controlled pilot trial.

BACKGROUND: We investigated the efficacy and safety of thread-embedding acupuncture (TEA) for chronic low back pain (LBP) in a randomized controlled pilot trial with the aim of laying the foundation for a large-scale randomized controlled trial on this topic. METHODS: Forty participants were recruited for this two-arm, assessor-blinded randomized controlled pilot trial. The participants were randomly allocated to a TEA group (experimental group) or an acupuncture group (control group). The TEA group received TEA once every 2 weeks for 8 weeks (four sessions in total), while the acupuncture group received acupuncture twice per week for 8 weeks (16 sessions in total). The primary outcome was the visual analog scale (VAS) score for pain and the secondary outcomes were short-form McGill Pain Questionnaire (SF-MPQ) and Oswestry Disability Index (ODI) scores. Assessments were performed at screening and at 2, 4, 6, 8, and 10 weeks after treatment initiation (the 10-week assessment was conducted at 2 weeks after treatment cessation). RESULTS: Of the 40 participants, 36 completed the study and four dropped out. Both the TEA group and the acupuncture group showed significant improvements in VAS, SF-MPQ, and ODI scores in a time-dependent manner. Furthermore, with regard to ODI, a significant interaction between group and time was observed, with the two groups exhibiting a different pattern of change at 8 weeks according to contrast analysis with Bonferroni's correction. No serious adverse event occurred, and hematological and biochemical test findings were within normal limits. CONCLUSION: This pilot study has provided basic data for a larger clinical trial to demonstrate the efficacy and safety of TEA for chronic LBP. TRIAL REGISTRATION: Clinical Research Information Service of the Korea National Institute of Health, ID: KCT0001819 . Registered on 15 February 2016.