Indentation induces instantaneous nuclear stiffening and unfolding of nuclear envelope wrinkles.

The nuclear envelope (NE) separates genomic DNA from the cytoplasm and regulates transport between the cytosol and the nucleus in eukaryotes. Nuclear stiffening enables the cell nucleus to protect itself from extensive deformation, loss of NE integrity, and genome instability. It is known that the reorganization of actin, lamin, and chromatin can contribute to nuclear stiffening. In this work, we show that structural alteration of NE also contributes to instantaneous nuclear stiffening under indentation. In situ mechanical characterization of cell nuclei in intact cells shows that nuclear stiffening and unfolding of NE wrinkles occur simultaneously at the indentation site. A positive correlation between the initial state of NE wrinkles, the unfolding of NE wrinkles, and the stiffening ratio (stiffness fold-change) is found. Additionally, NE wrinkles unfold throughout the nucleus outside the indentation site. Finite element simulation, which involves the purely passive process of structural unfolding, shows that unfolding of NE wrinkles alone can lead to an increase in nuclear stiffness and a reduction in stress and strain levels. Together, these results provide a perspective on how cell nucleus adapts to mechanical stimuli through structural alteration of the NE.

Short- and long-term outcomes of Roux-en-Y and Billroth II with Braun reconstruction in total laparoscopic distal gastrectomy: a retrospective analysis.

BACKGROUND: The controversy surrounding Roux-en-Y (R-Y) and Billroth II with Braun (BII + B) reconstruction as an anti-bile reflux procedure after distal gastrectomy has persisted. Recent studies have demonstrated their efficacy, but the long-term outcomes and postoperative quality of life (QoL) among patients have yet to be evaluated. Therefore, we compared the short-term and long-term outcomes of the two procedures as well as QoL. METHODS: The clinical data of 151 patients who underwent total laparoscopic distal gastrectomy (TLDG) at the Gastrointestinal Surgery Department of the Second Hospital of Fujian Medical University from January 2016 to December 2019 were retrospectively analyzed. Of these, 57 cases with Roux-en-Y procedure (R-Y group) and 94 cases with Billroth II with Braun procedure were included (BII + B group). Operative and postoperative conditions, early and late complications, endoscopic outcomes at year 1 and year 3 after surgery, nutritional indicators, and quality of life scores at year 3 postoperatively were compared between the two groups. RESULTS: The R-Y group recorded a significantly longer operative time (194.65 ± 21.52 vs. 183.88 ± 18.02 min) and anastomotic time (36.96 ± 2.43 vs. 27.97 ± 3.74 min) compared to the BII + B group (p < 0.05). However, no other significant differences were observed in terms of perioperative variables, including blood loss (p > 0.05). Both groups showed comparable rates of early and late complications. Endoscopic findings indicated similar food residuals at years 1 and 3 post-surgery for both groups. The R-Y group had a lower occurrence of residual gastritis and bile reflux at year 1 and year 3 after surgery, with a statistically significant difference (p < 0.001). Reflux esophagitis was not significantly different between the R-Y and BII + B groups in year 1 after surgery (p = 0.820), but the R-Y group had a lower incidence than the BII + B group in year 3 after surgery (p = 0.023). Nutritional outcomes at 3 years after surgery did not differ significantly between the two groups (p > 0.05). Quality of life scores measured by the QLQ-C30 scale were not significantly different between the two groups. However, on the QLQ-STO22 scale, the reflux score was significantly lower in the R-Y group than in the BII + B group (0 [0, 0] vs. 5.56 [0, 11.11]) (p = 0.003). The rest of the scores were not significantly different (p > 0.05). CONCLUSION: Both R-Y and B II + B reconstructions are equally safe and efficient for TLDG. Nevertheless, the R-Y reconstruction reduces the incidence of residual gastritis, bile reflux, and reflux esophagitis, as well as postoperative reflux symptoms, and provides a better quality of life for patients. R-Y reconstruction is superior to BII + B reconstruction for TLDG.

Comparison of short-term and long-term clinical effects of modified overlap anastomosis and conventional incision-assisted anastomosis in laparoscopic total gastrectomy.

BACKGROUND: To compare short-term and long-term clinical effects of modified overlap anastomosis and conventional incision-assisted anastomosis for laparoscopic total gastrectomy. METHODS: This retrospective cohort study included patients with gastric cancer admitted to the Second Affiliated Hospital of Fujian Medical University from January 2016 to March 2020. Quality of life, intraoperative and postoperative conditions were analyzed. RESULTS: Compared with the conventional assisted group, the modified overlap group showed a shorter auxiliary incision, milder postoperative pain, shorter time to the first postoperative anal exhaust, shorter time to the first postoperative liquid food intake, and shorter postoperative stay. There were no differences between the two groups regarding operation time, esophagus-jejunum anastomosis time, intraoperative blood loss, number of lymph nodes dissected, and length of the upper incision margin. There were no differences between the two groups regarding postoperative early and late complications. There were no differences between the two groups regarding the QLQ-C30 scale three years after the operation. The scores of the QLQ-STO22 scale 3 years after the operation showed significantly lower scores for dysphagia and feeding limit in the modified overlap group than those in the conventional assisted anastomosis group. There was no recurrence in the modified overlap group but one patient in the conventional assisted group. CONCLUSIONS: Patients undergoing totally laparoscopic total gastrectomy with modified overlap anastomosis have better minimal invasiveness and faster post-operative recovery than conventional incision-assisted anastomosis.

Chronic Intermittent Hypobaric Hypoxia Pretreatment Ameliorates Ischemia-Induced Cognitive Dysfunction Through Activation of ERK1/2-CREB-BDNF Pathway in Anesthetized Mice.

Chronic intermittent hypobaric hypoxia (CIHH) has protective effects on heart and brain against ischemia injury through mobilizing endogenous adaptive mechanisms. However, whether CIHH prevents against cognitive impairment was not elucidated. The present study aimed to investigate the effect and mechanism of CIHH treatment on ischemia/reperfusion (IR)-induced cognitive dysfunction. Mice were randomly divided into 8 groups: Control, Sham, CIHH (simulating 5000 m high-altitude for 28 days, 6 h per day), IR (three 16-min occlusions of bilateral common carotid arteries interrupted by two 10-min intervals), CIHH + IR, PD98059 (inhibitor of MEK1/2) + CIHH + IR, PD98059 + Sham and PD98059 + IR group. Morris water maze and step-down passive avoidance tests were performed to evaluate the capability of learning and memory 1 month after ischemia. Thionine dyeing was to examine histological manifestations of pyramidal neurons in hippocampus CA1 region. Western blotting assay was for measurement of the protein expressions in ERK1/2-CREB-BDNF signaling pathway. There were a shorter escape latency and a longer percentage of time retaining in the target quadrant in Morris water maze test, fewer times of errors in the step-down avoidance test and a higher neuronal density of the hippocampal CA1 subfield in CIHH + IR group than in IR group. CIHH upregulated the expressions of BDNF, phosphorylated CREB, ERK1/2 and TrkB with or without ischemia. The protective effects of CIHH were abolished by PD98059 administration 15 min before ischemia. CIHH ameliorated ischemia-induced cognitive dysfunction through activation of ERK1/2-CREB-BDNF signaling pathway.

Analysis of the safety and efficacy of the self-pulling and latter transected technique in modified overlap anastomosis in total laparoscopic total gastrectomy.

Background: Laparoscopic total gastrectomy plus lymph node dissection is an effective treatment method for patients with gastric cancer. With the development and popularization of laparoscopic techniques in recent years, surgeons have become more skilled in laparoscopic techniques. Totally laparoscopic total gastrectomy (TLTG) has been developed; however, digestive tract reconstruction remains difficult, especially with anastomosis of the esophagus and jejunum. Using the self-pulling and latter transection (SPLT) method combined with a linear stapler has effectively solved the problem of narrow space in esophagojejunostomy. Here, we examined the safety and effectiveness of the SPLT technique in TLTG compared with SPLT with traditional esophagojejunostomy overlap anastomosis. Methods: We retrospectively analyzed all patients with gastric cancer admitted to the Department of Gastrointestinal Surgery of the Second Affiliated Hospital of Fujian Medical University from September 2020 to September 2023. In total, 158 patients met the inclusion criteria and were included. Patients were grouped according to whether the lower esophagus was transected after self-pulling. Patient demographics, tumor characteristics, surgical conditions, and postoperative results between the two groups were statistically analyzed. Results: A total of 158 patients were included in the study. All patients underwent TLTG and completed intracavitary anastomosis. There were 70 cases (44%) in the SPLT-Overlap group and 88 cases (56%) in the traditional overlap group. There was no significant difference in demographic and oncological characteristics between the two groups. The operation time (P = 0.002) and esophageal jejunum anastomosis time (P<0.001) were significantly shorter in the SPLT-Overlap group compared with the traditional overlap group. The intraoperative blood loss of the SPLT-Overlap group was 80.29 ± 36.36 ml, and the intraoperative blood loss of the traditional overlap group was 101.40 ± 46.68 ml. The difference was statistically significant (P=0.003). The SPLT-Overlap group also achieved a higher upper cutting edge (P =0.03). There was no significant difference between the two groups in terms of the incision size, postoperative hospital stay, time to first flatus, time to first liquid intake, drainage tube removal time, and esophagojejunal anastomotic diameter. There were 15 and 19 cases of short-term postoperative complications in the SPLT-Overlap and traditional Overlap groups, respectively. All patients received R0 resection, and no secondary surgery or death occurred. Conclusion: We applied SPLT to overlap anastomosis. Short-term, SPLT has good safety and feasibility in TLTG. It can effectively shorten the time of digestive tract reconstruction, simplify the reconstruction procedure, and make the digestive tract reconstruction simple and fast; at the same time, a safe cutting edge can be obtained.

METTL3-mediated m6A methylation of PYGB facilitates pancreatic ductal adenocarcinoma progression through the activation of NF-κB signaling.

Brain Type Glycogen Phosphorylase (PYGB) has been revealed to participate in the progression of multiple human cancers. Nevertheless, the clinical significance and biological function of PYGB in pancreatic ductal adenocarcinoma (PAAD) remains unclarified. This study first analyzed the expression pattern, diagnostic value, and prognostic significance of PYGB in PAAD using the TCGA database. Subsequently, western blot assessed the protein expression of genes in PAAD cells. The viability, apoptosis, migration, and invasion of PAAD cells were assessed by CCK-8, TUNEL, and Transwell assays. Finally, in vivo experiment evaluated the effect of PYGB on PAAD tumor growth and metastasis. Through our investigation, it was revealed that PYGB had extremely high expression in PAAD and predicted a worse prognosis in patients with PAAD. Besides, the aggressiveness of PAAD cells could be suppressed or enhanced by depleting or supplementing PYGB. In addition, we demonstrated that METTL3 enhanced the translation of PYGB mRNA in an m6A-YTHDF1-dependent manner. Moreover, PYGB was revealed to regulate the malignant behaviors of PAAD cells by the mediation of the NF-κB signaling. Finally, PYGB depletion suppressed the growth and distant metastasis of PAAD in vivo. To conclude, our results indicated that METTL3-mediated m6A modification of PYGB exerted the tumor-promotive effect on PAAD through NF-κB signaling, suggesting PYGB is a potential therapeutic target in PAAD.

Formation of Ohmic contacts between ferromagnetic Cr2Ge2Te6and two-dimensional metals.

As a ferromagnetic semiconductor, two-dimensional (2D) Cr2Ge2Te6holds significant implications for electronic and spintronic devices. To achieve 2D electronics, it is essential to integrate Cr2Ge2Te6with 2D electrodes to form Schottky-barrier-free Ohmic contacts with enhanced carrier injection efficiency. Herein, by using first-principles calculations based on density-functional theory, we systematically investigate the structural, energetic, electronic and magnetic properties of 2D heterojunctions by combining Cr2Ge2Te6with a series of 2D metals, including graphene, ZrCl, NbS2, TaS2, TaSe2, Zn3C2, Hg3C2, and Zr2N. Results show that NbS2, TaS2, TaSe2, Zn3C2, Hg3C2, and Zr2N form Ohmic contacts with Cr2Ge2Te6, in contrast to graphene and ZrCl that exhibit a finite Schottky barrier. By examining the tunneling barriers and Fermi level shift, we reveal that the heterojunctions with Zn3C2and Hg3C2as electrodes exhibit advantages of both high electron injection efficiency and spin injection efficiency, for which an apparent decrease of the magnetic moment of Cr atoms in Cr2Ge2Te6can be observed. These findings not only provide physical insights into the role of interfacial interaction in regulating the physical properties of 2D heterojunctions, but also pave way for the development of high-performance spintronic nanodevices for practical implementation.

Mechanical nanosurgery of chemoresistant glioblastoma using magnetically controlled carbon nanotubes.

Glioblastoma (GBM) is the most common and aggressive primary brain cancer. Despite multimodal treatment including surgery, radiotherapy, and chemotherapy, median patient survival has remained at ~15 months for decades. This situation demands an outside-the-box treatment approach. Using magnetic carbon nanotubes (mCNTs) and precision magnetic field control, we report a mechanical approach to treat chemoresistant GBM. We show that GBM cells internalize mCNTs, the mobilization of which by rotating magnetic field results in cell death. Spatiotemporally controlled mobilization of intratumorally delivered mCNTs suppresses GBM growth in vivo. Functionalization of mCNTs with anti-CD44 antibody, which recognizes GBM cell surface-enriched antigen CD44, increases mCNT recognition of cancer cells, prolongs mCNT enrichment within the tumor, and enhances therapeutic efficacy. Using mouse models of GBM with upfront or therapy-induced resistance to temozolomide, we show that mCNT treatment is effective in treating chemoresistant GBM. Together, we establish mCNT-based mechanical nanosurgery as a treatment option for GBM.

Construction of Macroporous Co2SnO4 with Hollow Skeletons as Anodes for Lithium-Ion Batteries.

Increasing the energy density of lithium-ion batteries (LIBs) can broaden their applications in energy storage but remains a formidable challenge. Herein, with polyacrylic acid (PAA) as phase separation agent, macroporous Co2SnO4 with hollow skeletons was prepared by sol-gel method combined with phase separation. As the anode of LIBs, the macroporous Co2SnO4 demonstrates high capacity retention (115.5% at 200 mA·g-1 after 300 cycles), affording an ultrahigh specific capacity (921.8 mA h·g-1 at 1 A·g-1). The present contribution provides insight into engineering porous tin-based materials for energy storage.

Preparation of a novel double crosslinked chitin aerogel via etherification with high strength.

In this study, we introduced a novel double crosslinked chitin aerogel via etherification with EGDE for mechanical reinforcement. Samples with different EGDE: chitin weight ratios from 0 to 1.5:1 were fabricated through chitin dissolution in KOH/urea aqueous solution, ethanol neutralization and washing, and supercritical CO2 drying. Both the physical and chemical crosslinking maintained the high porosity and light weight of chitin aerogels. The morphology under SEM has shown the close-ended and denser fibrils alignment for EGDE crosslinked aerogels and the mesoporous and macroporous structure induced by emulsion effect from excessive EGDE. FTIR characterization was conducted for chemical structure analysis. Compressive testing showed an increase of 247 % compressive strength at 10 % strain and 243 % modulus could be achieved at 1.0 EGDE samples. TGA results revealed a delayed thermal degradation for the chemically crosslinked samples. This study demonstrates EGDE an effective chemical crosslinker for reinforced chitin aerogels.

Prognostic and immunological value of ATP6AP1 in breast cancer: implications for SARS-CoV-2.

Abnormal ATPase H+ Transporting Accessory Protein 1 (ATP6AP1) expression may promote carcinogenesis. We investigated the association of ATP6AP1 with breast cancer (BC) and COVID-19. The Oncomine, Gene Expression Profiling Interactive Analysis, Human Protein Atlas and Kaplan-Meier plotter databases were used to evaluate the expression and prognostic value of ATP6AP1 in BC. ATP6AP1 was upregulated in BC tissues, and higher ATP6AP1 expression was associated with poorer outcomes. Data from the Tumor Immune Estimation Resource, Tumor-Immune System Interaction Database and Kaplan-Meier plotter indicated that ATP6AP1 expression correlated with immune infiltration, and that its prognostic effects in BC depended on tumor-infiltrating immune cell subtype levels. Multiple databases were used to evaluate the association of ATP6AP1 with clinicopathological factors, assess the mutation and methylation of ATP6AP1, and analyze gene co-expression and enrichment. The ATP6AP1 promoter was hypomethylated in BC tissues and differentially methylated between different disease stages and subtypes. Data from the Gene Expression Omnibus indicated that ATP6AP1 levels in certain cell types were reduced after SARS-CoV-2 infections. Ultimately, higher ATP6AP1 expression was associated with a poorer prognosis and with higher or lower infiltration of particular immune cells in BC. BC patients may be particularly susceptible to SARS-CoV-2 infections, which may alter their prognoses.

Comprehensive Genomic and Epigenomic Analyses on Transcriptomic Regulation in Stomach Adenocarcinoma.

Background: DNA methylation (MET)-mediated transcriptomic disturbance and copy number variations (CNVs) exert a significant influence in stimulating the heterogeneous progression of stomach adenocarcinoma (STAD). Nevertheless, the relation of DNA MET with CNVs, together with its impact on tumor occurrence, is still unclear. Methods: The messenger RNA (mRNA) expression (EXP) profiles, DNA MET, and DNA copy numbers, together with STAD mutation data, were collected from the TCGA official data portal. We employed circular binary segmentation algorithm in "DNAcopy." library of R package for mapping DNA CNV data at genetic level for all samples based on the segmented CNV data. Stable clusters of samples were recognized using negative matrix factorization cluster analysis based on 50 iterations and the "brunet" method using the MET-correlated (METcor) and CNV-correlated (CNVcor) genes. The R package "iCluster" method was utilized to comprehensively analyze the EXP, MET, and DNA CNV profiles. Results: A total of 313 STAD samples were isolated for checking DNA copy numbers and MET and for measuring EXP. In accordance with our results, we discovered obvious co-regulation of CNVcor genes and METcor counterparts. Apart from that, these genes were subject to multi-omics integration. Meanwhile, three subtypes of STAD were detected and confirmed based on independent data. Among them, the subtype with increased aggressiveness was related to decreased mutation frequencies of ARID1A, PIK3CA, ZFHX3, SPECC1, OBSCN, KMT2D, FSIP2, ZBTB20, TTN, and RANBP2, together with the abnormal levels of JPH3, KCNB1, and PLCXD3. Conclusion: According to the results, these aforementioned genes exerted crucial roles in the development of invasive STAD. Our findings on transcriptomic regulation genomically and epigenetically facilitate the understanding of the STAD pathology from different aspects, which help to develop efficient anti-STAD therapy.

The beneficial role of Asian-based RecurIndex test in the prognostic prediction in Chinese male breast cancer patients.

RecurIndex, a multigene profiling assay, can predict the risk of local recurrence and distant metastasis in female breast cancer (FBC), but its role in male breast cancer (MBC) remains unclear. In this study, the clinicopathological data of 43 consecutive MBC patients undergoing surgeries between 2009 and 2018 were retrospectively analysed. Their paraffin-embedded tissue sections were examined by RecurIndex test which comprised 2 models: recurrence index for local recurrence (RI-LR) and recurrence index for distant recurrence (RI-DR). Of 43 patients, there were 26 low-risk and 17 high-risk patients assessed by RI-LR, while 17 low-risk and 26 high-risk patients by RI-DR. For RI-LR, tumor N stage showed statistically significant (P < 0.001) between low- and high-risk patients; for RI-DR, differences were pronounced in tumor grade (P = 0.033), T stage (P = 0.043) and N stage (P = 0.003). In terms of clinical outcomes, the overall survival (OS) of low- and high-risk patients stratified by RI-LR showed no statistically significant differences (P = 0.460), while high-risk patients identified by RI-DR had a significantly worse distant recurrence-free survival (DRFS) (P = 0.035), progression-free survival (PFS) (P = 0.019) and OS (P = 0.044) than low-risk patients. Overall, RI-DR can effectively predict the DRFS, PFS and OS of MBC patients and identify those at low risk of recurrence, which may serve as a potential prognostic tool for MBC.

Ionic liquids facilitated dispersion of chitin nanowhiskers for reinforced epoxy composites.

In this work, we propose a novel approach to produce a high-strength epoxy nanocomposite using ionic liquids facilitated dispersion of chitin nanowhiskers (CNWs). Samples with 0-3 wt% CNWs and 1 wt% of [Emim][OAc] were fabricated by mixing, casting, and curing. The morphological observations of the ethanol/ionic liquid suspensions by TEM indicated that [Emim][OAc] helped in dispersing the CNWs. The tensile, impact, dynamical mechanical properties, and thermal stability of the composites were further evaluated to access the reinforcing effect of CNWs. Increase of 35 % tensile strength, 175 % toughness and 90 % impact strength were observed upon addition of 2 wt% of CNWs. Thermal stability of the epoxy was not affected by the addition of CNWs. The SEM observations of the composites evidenced that the fracture mechanisms had changed upon CNWs addition. This work shows the advantage of the novel approach using ionic liquids as nanofiller dispersant in fabricating CNWs nanocomposites.

Construction and Transition Metal Oxide Loading of Hierarchically Porous Carbon Aerogels.

Hierarchically porous carbon aerogels (CAs) were prepared by organic condensation gelation method combined with atmospheric drying and pore-formation technology, followed by a carbonization process. With as-prepared CAs as substrate, the transition metal oxide nanoparticles loaded CAs composites (MnO2/Mn2O3@CA and Ni/NiO@CA) were achieved by means of liquid etching method combined with heat treatment, respectively. The catalyst, pore-forming agent and etching have important roles on the apparent density and pore structure of CAs. The hydrochloric acid (catalyst) significantly accelerates the gelation process and influences the size and distribution of macropores, whereas the addition of PEG2000 (pore-forming agent) and the etching of liquid solution leads to the formation of mesopore structure in CAs. Appropriate amounts of hydrochloric acid and PEG2000 allow the formation of hierarchically porous CAs with a BET surface area of 482.9 m2·g-1 and a macropore size of 11.3 µm. After etching and loading, the framework of CAs is etched to become a mesoporous structure, and the transition metal oxide nanoparticles can be uniformly loaded in CAs. These resultant composites have promising application in super capacitor, electrocatalysis, batteries and other fields.

Flexible, Reconfigurable, and Self-Healing TPU/Vitrimer Polymer Blend with Copolymerization Triggered by Bond Exchange Reaction.

In recent decades, flexible, reconfigurable, and fast-response self-healing polymers have attracted considerable attention for both industrial field and scientific research. Mechanical blending remains the most mature, economical, effective, and the simplest approach to produce polymer blends, which can combine several distinctive advantages from different thermoplastic materials. However, such a process cannot be simply applied to thermosetting materials due to their permanent molecular structures. The synthesis of high-performance polymer blends connected by covalent cross-links remains a big challenge for the present industrial system. In this paper, we proposed a novel approach to synthesize polymer blends via blending thermosetting vitrimer containing dynamic covalent networks with thermoplastic polymers. It is demonstrated that the intrinsic relationship could be established by controlling the bond exchange reactions between the thermoset and the thermoplastic, thus triggering copolymerization. Due to the highly controlled processing conditions, the synthesized polymer is highly flexible, recyclable, and reprocessable, and possesses self-healing behavior at the same time. In addition, it shows potential applications in adhesive film and wearable electronics. This new technology opens a new way to reprocess thermoset in a fashion similar to thermoplastic in the current polymer industry.

Chitin nano-whiskers (CNWs) as a bio-based bio-degradable reinforcement for epoxy: evaluation of the impact of CNWs on the morphological, fracture, mechanical, dynamic mechanical, and thermal characteristics of DGEBA epoxy resin.

Chitin nano-whiskers (CNWs) are high performance nanomaterials that can be extracted from chitin, which is one of the most widely available bio-resources. Herein we investigate the effect of CNWs on the morphological, mechanical, dynamic mechanical and thermal properties of DGEBA epoxy. Optically transparent, bulk epoxy nano-composites with 0.25 wt%, 0.5 wt% and 0.75 wt% CNWs were evaluated in addition to neat epoxy. The composites were prepared based on a modified slurry compounding method. CNWs appear to be well dispersed within the epoxy matrix with increasing tendency for clustering as the CNW content is increased. The addition of 0.25 wt% CNWs to neat epoxy results in a decrease in the glass transition temperature and an increase in the tensile strength, modulus, damping and thermal degradation temperature. All the composites evaluated with CNWs showed distinct crack arrest events upon initiation of the first major crack growth during fracture toughness testing. Composites with 0.75 wt% CNWs showed the highest damping and an increase in the fracture toughness and resilience over neat epoxy.

Reduced miR-203 predicts metastasis and poor survival in esophageal carcinoma.

We analyzed data from two non-coding RNA profiling arrays made available by the Gene Expression Omnibus (GEO) and found 17 miRNAs with remarkable differential expression between malignant and normal esophageal tissue. Correlation analysis between expression of these 17 miRNAs and patients' clinicopathological characteristics showed that miR-203 was down-regulated in esophageal carcinoma (EC) tissues and was significantly associated with lymph node metastasis and poor overall survival. Overexpression of miR-203 significantly attenuated cellular proliferation, migration and invasion by EC cells in culture. Additionally, gene expression profiles and bioinformatics analysis revealed KIF5C to be a direct target of miR-203, and KIF5C overexpression partially counteracted the tumor inhibitory effects of miR-203 on EC cells. We also observed that miR-203, reduced KIFC5 protein levels, promoted cytoplasmic accumulation of Axin2, and reversed the invasive phenotype of EC cells. Taken together, these data demonstrate that miR-203 is a tumor suppressor in EC cells and its expression level could potentially be used as a prognostic indicator for EC patient outcomes.

DNA Methylation of miR-122 Aggravates Oxidative Stress in Colitis Targeting SELENBP1 Partially by p65NF-κB Signaling.

Aberrant microRNA (miRNA) expressions contribute to the development and progression of various diseases, including Crohn's disease (CD). However, the accurate mechanisms of miRNAs in CD are definitely unclear. We employed colonic tissue samples from normal volunteers and CD patients, an acute mice colitis model induced by 2,4,6-trinitro-benzene-sulfonic acid (TNBS), and a cellular oxidative stress model induced by H2O2 in HT-29 cells to determine the effects of oxidative stress on expressions of miR-122, selenium-binding protein 1 (SELENBP1, SBP1), p65 nuclear factor κB (p65NF-κB) signaling, and DNA methylation. We found that SBP1 was mainly located on epithelial cells and was significantly increased in patients with active CD. SBP1 was the target gene of miR-122. miR-122 expression was downregulated while SBP1 expression was upregulated under TNBS-induced colitis or oxidative stress. Pre-miR-122 or siRNA SBP1 (si-SBP1) treatment ameliorated acute TNBS-induced colitis and H2O2-induced oxidative stress. Cotreatment of pre-miR-122 and si-SBP1 enhanced these effects. Besides, pre-miR-122 and si-SBP1 obviously activated the p65NF-κB signaling by phosphorylation of IκBα. Bisulfite sequencing of the CpG islands in the promoter region of miR-122 showed that CpG methylation was significantly increased under oxidative stress. Treating cells with 5'-AZA which was well known as a DNA-demethylating agent significantly increased miR-122 expression. Our results suggest that oxidative stress-induced DNA methylation of miR-122 aggravates colitis targeting SELENBP1 partially by p65NF-κB signaling and may promote the progression of CD.