Identification of Pancreatic Metastasis Cells and Cell Spheroids by the Organelle-Targeting Sensor Array.

Pancreatic cancer is a highly malignant and metastatic cancer. Pancreatic cancer can lead to liver metastases, gallbladder metastases, and duodenum metastases. The identification of pancreatic cancer cells is essential for the diagnosis of metastatic cancer and exploration of carcinoma in situ. Organelles play an important role in maintaining the function of cells, the various cells show significant differences in organelle microenvironment. Herein, six probes are synthesized for targeting mitochondria, lysosomes, cell membranes, endoplasmic reticulum, Golgi apparatus, and lipid droplets. The six fluorescent probes form an organelles-targeted sensor array (OT-SA) to image pancreatic metastatic cancer cells and cell spheroids. The homology of metastatic cancer cells brings the challenge for identification of these cells. The residual network (ResNet) model has been proven to automatically extract and select image features, which can figure out a subtle difference among similar samples. Hence, OT-SA is developed to identify pancreatic metastasis cells and cell spheroids in combination with ResNet analysis. The identification accuracy for the pancreatic metastasis cells (> 99%) and pancreatic metastasis cell spheroids (> 99%) in the test set is successfully achieved respectively. The organelles-targeting sensor array provides a method for the identification of pancreatic cancer metastasis in cells and cell spheroids.

Organic peroxyl radicals from biacetyl accelerated the visible-light degradation of steroid estrogens in aqueous solution.

Indirect photodegradation is an important pathway for the reduction of steroid estrogens in sunlit surface waters. Nevertheless, the kinetics and mechanisms governing the interaction between coexisting carbonyl compounds and estrogens under visible light (Vis) remain unexplored. This study systematically investigates the Vis-induced photodegradation of 17ß-estradiol (E2) in the presence of five specific carbonyl compounds-biacetyl (BD), acetone, glyoxal, pyruvic acid, and benzoquinone. The results demonstrate that, among these compounds, only BD significantly enhanced the photodegradation of E2 under Vis irradiation (λ > 400 nm). The pseudo-first order photodegradation rate constants (k1) of E2 in the Vis/BD system were 0.025 min-1 and 0.076 min-1 in ultrapure water and river water, respectively. The enhancing effect of BD was found to be pH-dependent, increasing the pH from 3.0 to 11.0 resulted in a 76% reduction in the k1 value of E2 in the Vis/BD system. Furthermore, the presence of humic acid, NO3-, or HCO3- led to an increase of more than 35% in the k1 value of E2, while NO2- exerted a pronounced inhibitory effect, resulting in a 92% decrease. Peroxyacetyl and peroxymethyl radicals, derived from BD in a yield ratio of 9, played a crucial role in the degradation of E2. These peroxyl radicals primarily targeted electron-rich hydroxyl sites of E2, initiating hydroxylation and ring-opening reactions that culminated in the formation of acidic byproducts. Notably, toxicity evaluation indicates that these hydroxylated and acidic products exhibited lower toxicity than the parent compound E2. This study highlights the important role of peroxyl radicals in estrogen degradation within aquatic environment, and also helps to design efficient visible light-responsive photo-activators for the treatment of estrogen-contaminated waters.

Preclinical Short-term and Long-term Safety of Human Bone Marrow Mesenchymal Stem Cells.

Mesenchymal stem cells (MSCs) have become a promising therapeutic method. More safety data are needed to support clinical studies in more diseases. The aim of this study was to investigate the short- and long-term safety of human bone marrow-derived MSCs (hBMMSCs) in mice. In the present study, we injected control (saline infusion only), low (1.0 × 106/kg), medium (1.0 × 107/kg), and high (1.0 × 108/kg) concentrations of hBMMSCs into BALB/c mice. The safety of the treatment was evaluated by observing changes in the general condition, hematology, biochemical indices, pathology of vital organs, lymphocyte subsets, and immune factor levels on days 14 and 150. In the short-term toxicity test, no significant abnormalities were observed in the hematological and biochemical parameters between the groups injected with hBMMSCs, and no significant damage was observed in the major organs, such as the liver and lung. In addition, no significant differences were observed in the toxicity-related parameters among the groups in the long-term toxicity test. Our study also demonstrates that mice infused with different doses of hBMMSCs do not show abnormal immune responses in either short-term or long-term experiments. We confirmed that hBMMSCs are safe through a 150-day study, demonstrating that this is a safe and promising therapy and offering preliminary safety evidence to promote future clinical applications of hBMMSCs in different diseases.

Global trends in indocyanine green fluorescence navigation in the field of gastric cancer: bibliometrics and knowledge atlas analysis.

Background: Indocyanine green (ICG) fluorescence navigation can enhance the visualization of gastric cancer (GC) lesions, increase the lymph node detection rate, and reduce the incidence of anastomotic leakage in the treatment of GC. It thus holds considerable potential for application in GC clinical surgery and has attracted widespread research interest. The purpose of this study was to visualize the current topics and emerging trends in research regarding ICG in GC. Methods: We searched the Web of Science Core Collection (WoSCC) for articles relevant to the use of ICG in GC. The resulting information was then analyzed from a bibliometric and knowledge graph analysis perspective using CiteSpace, Scimago Graphica, and R Studio so that the key trends and hot spots in research within this field could be identified and visualized. Results: Ultimately, 1,385 papers from 58 countries or regions published from 1991 to 2022 were included in this study. The largest number of publications were from China, followed by Japan and the United States. High-yield institutions were concentrated in Asian countries, especially China. The top publication contributors were Shanghai Jiao Tong University. Li Y and Bang YJ ranked first among the top 10 most productive authors and top 10 most cocited authors, respectively. World Journal of Gastroenterology was the most productive academic journal on ICG in GC, while Cancer Research was the most commonly cocited journal. The keyword "indocyanine green" was among the top 5 keywords, and will likely remain a popular topic in future research. Furthermore, the emerging themes including surgery, biopsy, lymphadenectomy, dissection, and gastrectomy have attracted increasing attention. Conclusions: Current research hotspots in this area focus on the clinical implementation of ICG in precision surgery for GC. Given the imaging tracer characteristics of ICG and its utility in GC surgery, the optimization and application of ICG-guided precision surgery techniques for GC will be a research hot spot going forward.

Mesenchymal Stromal Cells Regulate M1/M2 Macrophage Polarization in Mice with Immune Thrombocytopenia.

Mesenchymal stromal cells have shown promising effects in the treatment of immune thrombocytopenia. However, the underlying mechanisms are not fully understood. In this study, we investigated the therapeutic effects of human bone marrow mesenchymal stromal cells (hBMSCs) and analyzed their unique role in regulating the M1/M2 macrophage ratio. We established a passive immune thrombocytopenia (ITP) mouse model and showed that there was a significant M1/M2 imbalance in ITP model mice by assessing the M1/M2 ratios in the liver, spleen, and bone marrow; we observed excessive activation of M1 cells and decreased M2 cell numbers in vivo. We have shown that systemic infusion of hBMSCs effectively elevated platelet levels after disease onset. Further analysis revealed that hBMSCs treatment significantly suppressed the number of proinflammatory M1 macrophages and enhanced the number of anti-inflammatory M2 macrophages; in addition, the levels of proinflammatory factors, such as interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α), were significantly decreased in vivo, while the levels of the anti-inflammatory factor interleukin-10 (IL-10) were increased. In conclusion, our data suggest that hBMSCs treatment can effectively increase platelet counts, and the mechanism is related to the induction of macrophage polarization toward the anti-inflammatory M2 phenotype and the decrease in proinflammatory cytokine production, which together ameliorate innate immune disorders.

Exploring Cancer Dependency Map genes and immune subtypes in colon cancer, in which TIGD1 contributes to colon cancer progression.

BACKGROUND: Tumour-dependent genes identified in CRISPR-Cas9 screens have been widely reported in Cancer Dependency Maps (CDMs). CDM-derived tumour-dependent genes play an important role in tumorigenesis and progression; however, they have not been investigated in colon cancer (CC). METHODS: CDM genes overexpressed in CC were identified from the TCGA-COAD dataset and CDM platform. A CDM signature and prognostic nomogram were constructed by Lasso Cox regression and multivariate Cox analyses. A weighted correlation network analysis (WGCNA) and consensus clustering were used to define coexpressed genes with CDM risk scores and to determine two new immune subtypes. A comprehensive investigation was performed between the two subtypes and immune regulation, the immune microenvironment and the impact of immunotherapy. RESULTS: First, 1304 overexpressed CDM genes were identified. Then, a CDM signature with five cancer-dependent genes (MMS19, NOP14, POLRMT, SNAPC5 and TIGD1) and a prognostic nomogram were constructed, and they demonstrated robust predictive performance and a close relationship with clinical characteristics in different CC datasets. Patients with high CDM risk scores showed worse survival outcome and weaker response to chemotherapy. Additionally, TIGD1 genes were oncogenes that affected the CC cell cycle, according to cell functional experiments that involved the suppression of the TIGD1 gene. Furthermore, WGCNA and consensus clustering were used to define coexpressed genes with CDM risk scores and to determine two new immune subtypes. Finally, systematic investigations were conducted with the relationship between the CDM subtypes and immune regulation. CONCLUSIONS: This study constructed a CDM signature consisting of five risk genes that predict survival in CC patients. In addition, the immune subtypes provided valuable insights into immunotherapy for CC patients. TIGD1, as an oncogene, is independent prognostic factors for CC, and contributes to CC progression.

Tyrosinase-activated Nanocomposites for Double-Modals Imaging Guided Photodynamic and Photothermal Synergistic Therapy.

Tyrosinase (TYR) is an important biomarker of melanoma. The exploration of fluorescent pr-obes-based composites is beneficial to build an integrative platform for the diagnosis and treatment of melanoma. Herein, a multifunctional nanocomposite IOBOH@BSA activated by TYR is developed for selective imaging and ablation of melanoma. The chemical structure of IOBOH enables the fluorescence (FL) imaging activated by TYR, photoacoustic (PA) imaging, and photodynamic-photothermal activity by regulating the balance between radiative decay and non-radiative decay. IOBOH combined with bovine serum albumin (IOBOH@BSA) presents the response to TYR and realizes FL imaging with mitochondria-targeting in melanoma. Moreover, IOBOH@BSA shows excellent photothermal ability and is applied for PA imaging. After IOBOH@BSA is activated by TYR, the singlet oxygen generation increases obviously. IOBOH@BSA can realize TYR-activated imaging and photodynamic-photothermal therapy of melanoma. The development of TYR-activated multifunctional nanocomposites promotes the precise imaging and improves the therapeutic effect of melanoma.

Quercetin induces autophagy-associated death in HL-60 cells through CaMKKß/AMPK/mTOR signal pathway.

Acute myeloid leukemia (AML) is one of the most common malignancies of the hematopoietic progenitor cell in adults. Quercetin has gained recognition over the years because of its anti-cancer effect with minimal toxicity. Herein, we aim to investigate the anti-leukemia mechanism of quercetin and to decipher the signaling pathway of quercetin in HL-60 leukemic cells. We observed that quercetin induces apoptosis and autophagic cell death, in which both pathways play an important role in suppressing the viability of leukemia cells. Phosphorylated AMPK (p-AMPK) protein expressions are lower in primary AML cells, HL-60 cells, KG-1 and THP-1 cells than in peripheral blood monocular cells. After quercetin treatment, the expression of p-AMPK is increased while the expression of p-mTOR is decreased in a dose-dependent manner. Mechanistically, compound C, an AMPK phosphorylation inhibitor, upregulates the phosphorylation of mTOR and inhibits autophagy and apoptosis in quercetin-induced HL-60 cells, while silencing of CaMKKß inhibits the quercetin-induced phosphorylation of AMPK, resulting in increased mTOR phosphorylation. Furthermore, silencing of CaMKKß inhibits the autophagy in HL-60 cells. Taken together, our data delineate that quercetin plays its anti-leukemia role by inhibiting cell viability and inducing apoptosis and autophagy in leukemia cells. Quercetin inhibits the phosphorylation of mTOR by regulating the activity of AMPK, thus playing a role in the regulation of autophagy and apoptosis. CaMKKß is a potential upstream molecule for AMPK/mTOR signaling pathway, through which quercetin induces autophagy in HL-60 cells.

Antifungal CoAl layered double hydroxide ultrathin nanosheets loaded with oregano essential oil for cereal preservation.

Fungal infestation of cereals seriously affects human health and the economy. Protecting cereals from fungal infestation is meaningful. Therefore, safe and economical antifungal agents must be explored. Oregano essential oil (OEO) has broad-spectrum antifungal activity but is unstable and poorly water-dispersible. CoAl-LDH ultrathin nanosheets (CoAl-LDH UNs) are a biosafe carrier with peroxidase-like activity and good water dispersibility. A new nanocomposite was constructed by integrating OEO and CoAl-LDH UNs named OEO/CoAl-LDH UNs. The antifungal activity of OEO was improved for the synergetic effect of OEO and CoAl-LDH UNs. OEO/CoAl-LDH UNs showed excellent antifungal activity against Fusarium moniliforme, Fusarium graminearum and Aspergillus flavus. A polyvinyl alcohol film containing OEO/CoAl-LDH UNs was prepared as a food package and effectively inhibited fungal infestation on cereals. This work can provide some insights for the exploration of other new antifungal materials. The good biosafety of this antifungal material can be effectively applied to food packaging.

The m7G-Related Long Noncoding RNA Signature Predicts Prognosis and Indicates Tumour Immune Infiltration in Colon Cancer.

With high morbidity and mortality, colon cancer (CC) is considered as one of the most often diagnosed cancers around the world. M7G-related lncRNA may provide a regulatory function in the formation of CC, but the principle of regulation is still unclear. The purpose of this research was to establish a novel signature that may be used to predict survival and tumour immunity in CC patients. Data about CC in TCGA was collected for analysis, coexpression analysis and univariate Cox analysis were used to screen prognostic m7G-related lncRNAs. A consensus clustering analysis based on prognostic m7G-related lncRNAs was applied, and a prognosis model based on least absolute shrinkage and selection operator (LASSO) regression analysis was established. Independent prognostic analysis, nomogram, PCA, clinicopathological correlation analysis, TMB, survival analysis, immune correlation analysis, qRT-PCR and clinical therapeutic compound prediction were also applied. 90 prognostic m7G-related lncRNAs were found, GO and KEGG analysis showed that prognostic m7G-related lncRNAs were mainly related to cell transcription and translation. The results of the consensus clustering analysis revealed substantial disparities in survival prognosis and tumour immune infiltration between two clusters. We built a risk model with 21 signature m7G-related lncRNAs, patients in the high-risk group had a considerably poorer prognosis than those in the low-risk group. Independent prognostic analysis confirmed that patients' prognosis was linked to their tumour stage and risk score. PCA, subgroups with distinct clinicopathological characteristics were studied for survival, multi-index ROC curve, c-index curve, the survival analysis of TMB, and model comparison tested the reliability of risk model. A tumour immunoassay revealed a substantial difference in immune infiltration between high-risk and low-risk individuals. Five chemicals were eliminated, and qRT-PCR indicated that the four lncRNAs were expressed differently. Overall, m7G-related lncRNA is closely related to colon cancer and the 21 signature lncRNAs risk model can efficiently evaluate the prognosis of CC patients, which has a possible positive consequence for the future diagnosis and therapy of CC.

Aggregation-Induced Emission (AIE) Photosensitizer Combined Polydopamine Nanomaterials for Organelle-Targeting Photodynamic and Photothermal Therapy by the Recognition of Sialic Acid.

The construction of organelle-targeting nanomaterials is an effective way to improve tumor imaging and treatment. Here, a new type of composite nanomaterial named as PTTPB is developed. PTTPB is composed of organelle-targeting aggregation-induced emission photosensitizer TTPB and polydopamine nanomaterials. With the functional modification of TTPB, PTTPB can recognize sialic acid on the cell membrane and present mitochondrial targeted capabilities. The intake of PTTPB in cancerous cells can be increased by the recognition process of cell membrane. PTTPB can generate singlet oxygen for photodynamic therapy (PDT), and present good photothermal conversion ability with irradiation. The PTTPB with organelle-targeting imaging-guided can realize the tumor ablation with the synergistic effect of PDT and photothermal therapy.

Retraction Notice to: Long Noncoding RNA UCA1 Regulates PRL-3 Expression by Sponging MicroRNA-495 to Promote the Progression of Gastric Cancer.

[This retracts the article DOI: 10.1016/j.omtn.2019.10.020.].

Macrophage mitochondrial fission improves cancer cell phagocytosis induced by therapeutic antibodies and is impaired by glutamine competition.

Phagocytosis is required for the optimal efficacy of many approved and promising therapeutic antibodies for various malignancies. However, the factors that determine the response to therapies that rely on phagocytosis remain largely elusive. Here, we demonstrate that mitochondrial fission in macrophages induced by multiple antibodies is essential for phagocytosis of live tumor cells. Tumor cells resistant to phagocytosis inhibit mitochondrial fission of macrophages by overexpressing glutamine-fructose-6-phosphate transaminase 2 (GFPT2), which can be targeted to improve antibody efficacy. Mechanistically, increased cytosolic calcium by mitochondrial fission abrogates the phase transition of the Wiskott-Aldrich syndrome protein (WASP)-Wiskott-Aldrich syndrome interacting protein (WIP) complex and enables protein kinase C-θ (PKC-θ) to phosphorylate WIP during phagocytosis. GFPT2-mediated excessive use of glutamine by tumor cells impairs mitochondrial fission and prevents access of PKC-θ to compartmentalized WIP in macrophages. Our data suggest that mitochondrial dynamics dictate the phase transition of the phagocytic machinery and identify GFPT2 as a potential target to improve antibody therapy.

Comprehensive Analysis of Necroptosis-Related Long Noncoding RNA Immune Infiltration and Prediction of Prognosis in Patients With Colon Cancer.

Colon cancer (CC) is one of the most frequent malignancies in the world, with a high rate of morbidity and death. In CC, necroptosis and long noncoding RNA (lncRNAs) are crucial, but the mechanism is not completely clear. The goal of this study was to create a new signature that might predict patient survival and tumor immunity in patients with CC. Expression profiles of necroptosis-related lncRNAs in 473 patients with CC were retrieved from the TCGA database. A consensus clustering analysis based on differentially expressed (DE) genes and a prognostic model based on least absolute shrinkage and selection operator (LASSO) regression analysis were conducted. Clinicopathological correlation analysis, expression difference analysis, PCA, TMB, GO analysis, KEGG enrichment analysis, survival analysis, immune correlation analysis, prediction of clinical therapeutic compounds, and qRT-PCR were also conducted. Fifty-six necroptosis-related lncRNAs were found to be linked to the prognosis, and consensus clustering analysis was performed. There were substantial variations in survival, immune checkpoint expression, clinicopathological correlations, and tumor immunity among the different subgroups. Six lncRNAs were discovered, and patients were split into high-risk and low-risk groups based on a risk score generated using these six lncRNAs. The survival time of low-risk patients was considerably longer than that of high-risk patients, indicating that these lncRNAs are directly associated with survival. The risk score was associated with the tumor stage, infiltration depth, lymph node metastasis, and distant metastasis. After univariate and multivariate Cox regression analysis, the risk score and tumor stage remained significant. Cancer- and metabolism-related pathways were enriched by KEGG analyses. Immune infiltration was shown to differ significantly between high- and low-risk patients in a tumor immunoassay. Eight compounds were screened out, and qRT-PCR confirmed the differential expression of the six lncRNAs. Overall, in CC, necroptosis-related lncRNAs have an important function, and the prognosis of patients with CC can be predicted by these six necroptosis-related lncRNAs. They may be useful in the future for customized cancer therapy.

Artificial intelligence applicated in gastric cancer: A bibliometric and visual analysis via CiteSpace.

Objective: This study aimed to analyze and visualize the current research focus, research frontiers, evolutionary processes, and trends of artificial intelligence (AI) in the field of gastric cancer using a bibliometric analysis. Methods: The Web of Science Core Collection database was selected as the data source for this study to retrieve and obtain articles and reviews related to AI in gastric cancer. All the information extracted from the articles was imported to CiteSpace to conduct the bibliometric and knowledge map analysis, allowing us to clearly visualize the research hotspots and trends in this field. Results: A total of 183 articles published between 2017 and 2022 were included, contributed by 201 authors from 33 countries/regions. Among them, China (47.54%), Japan (21.86%), and the USA (13.11%) have made outstanding contributions in this field, accounting fsor 82.51% of the total publications. The primary research institutions were Wuhan University, Tokyo University, and Tada Tomohiro Inst Gastroenterol and Proctol. Tada (n = 12) and Hirasawa (n = 90) were ranked first in the top 10 authors and co-cited authors, respectively. Gastrointestinal Endoscopy (21 publications; IF 2022, 9.189; Q1) was the most published journal, while Gastric Cancer (133 citations; IF 2022, 8.171; Q1) was the most co-cited journal. Nevertheless, the cooperation between different countries and institutions should be further strengthened. The most common keywords were AI, gastric cancer, and convolutional neural network. The "deep-learning algorithm" started to burst in 2020 and continues till now, which indicated that this research topic has attracted continuous attention in recent years and would be the trend of research on AI application in GC. Conclusions: Research related to AI in gastric cancer is increasing exponentially. Current research hotspots focus on the application of AI in gastric cancer, represented by convolutional neural networks and deep learning, in diagnosis and differential diagnosis and staging. Considering the great potential and clinical application prospects, the related area of AI applications in gastric cancer will remain a research hotspot in the future.

[Effects of HMGB1 on Proliferation and Secretion of Human Bone Marrow Mesenchymal Stem Cells].

OBJECTIVE: To investigate the effect of high mobility group protein 1(HMGB1) on the proliferation and cytokine expression of human bone marrow mesenchymal stem cells (MSC). METHODS: Different concentrations of recombinant human HMGB1 protein (100, 200, 400, 800 and 1000 ng/ml) were incubated with MSC for 24, 48, 72 h and the proliferation of MSC were detected respectively by using the CCK-8 method and flow cytometry. The best concentrations of HMGB1 incubated with MSC was determined (200 ng/ml, 1000 ng/ml), and the flow cytomerty was used to determine the effect of HMGB1 on the proliferation of MSC. The mRNA expression levels of IL-10, TGF- ß1, TSG-6 and IFN-γ in MSC incubated with HMGB1 protein were detected by real-time quantitative PCR and ELISA. RESULTS: The result of MSC identification and flow cytometry showed that the CD105, CD73 and CD90 were expressed, but did not expression CD45, CD34, CD11b, CD19 and HLA-DR; CCK-8 showed that HMGB1 at the concentrations of 100 ng/ml, 200 ng/ml and 400 ng/ml could promote the proliferation of MSC incubated for 24, 48 and 72 h as compared with the control group (P<0.05), and the most effective concentration was 200 ng/ml; flow cytometry showed that the compared with the control group, HMGB1 200 ng/ml could induce MSC from G1 phase to S phase to promote the proliferation of MSC; QPCR showed that the mRNA expression of MSC cytokines IL-10, TGF-ß1, TSG-6 increased while IFN-γ decreased at the concentration of 200 ng/ml HMGB1 as compared with the control group. ELISA experiments showed that the HMGB1 200 ng/ml acting on MSC for 48 h could significantly promoted the secretion of IL-10, TGF-ß 1 and TSG-6(P<0．05), while IFN-γ showed no significant difference as compared with control group. CONCLUSION: Recombinant human HMGB1 can promote the proliferation and secretion of MSC in healthy people.

Long Noncoding RNA UCA1 Regulates PRL-3 Expression by Sponging MicroRNA-495 to Promote the Progression of Gastric Cancer.

Gastric cancer (GC) is among the most frequently occurring malignancies worldwide. In recent years, long noncoding RNAs (lncRNAs) have been widely studied because of their ability to regulate the cellular processes involved with tumorigenesis. The present study aims to investigate the underlying molecular mechanism by which lncRNA urothelial carcinoma-associated 1 (UCA1) influences the progression of GC. Differentially expressed lncRNA UCA1 was initially identified by microarray-based analysis, after which a high expression of UCA1 was determined in GC tissues and cells. It is important to note that UCA1 could upregulate the expression of phosphatase of regenerating liver-3 (PRL-3) by sponging miR-495. The expression of UCA1 and miR-495 was altered in human GC cells to evaluate cell activity in vitro, as well as peritoneal metastasis and tumor formation ability in vivo. Results suggested that increased expression of UCA1 promoted cell proliferation, migration, and invasion, accompanied by suppressed cell apoptosis, as well as enhanced peritoneal metastasis and tumorigenesis of GC cells. Meanwhile, the upregulated expression of miR-495 could reverse the promotive effects exerted by UCA1. Taken conjointly, UCA1, as a competing endogenous RNA (ceRNA) of miR-495, could accelerate the development of GC by upregulating PRL-3, highlighting a potentially promising basis for the targeted intervention treatment of GC.

CENPO expression regulates gastric cancer cell proliferation and is associated with poor patient prognosis.

Gastric cancer (GC) is one of the most common malignancies worldwide; however, understanding of its development and carcinogenesis is currently limited. Centromere protein O (CENPO), is a newly discovered constitutive centromeric protein, associated with cell death. The expression of CENPO in human cancers, including GC, is currently unknown. The aim of the present study was to investigate the clinical association between CENPO and GC, and to elucidate the potential mechanisms of CENPO in the process of GC progression. The results demonstrated that CENPO was expressed at high levels in GC and was correlated with p­TNM stage. In addition, CENPO was observed to be a marker of poor prognosis in patients with GC. Knockdown of CENPO contributed to GC cell growth inhibition and apoptosis induction. In addition, downregulation of CENPO expression suppressed GC cell growth in vivo. Furthermore, CENPO knockdown decreased ataxia telangiectasia mutated (ATM), cyclin D1 and c­Jun expression, indicating that the ATM signaling pathway may be involved in CENPO­mediated regulation of GC cell growth. In conclusion, increased CENPO expression may be associated with the aggressive tumor biology of GC and CENPO may present a novel therapeutic target and prognostic biomarker for patients with GC.

Mesenchymal stem cells improve platelet counts in mice with immune thrombocytopenia.

Immune thrombocytopenia (ITP) is a common autoimmune bleeding disorder. The breakdown of immune tolerance (regulatory T [Treg] cells and suppressor cytokines) plays an important role in ITP pathophysiology, especially in refractory ITP. Bone marrow-derived mesenchymal stem cells (BM-MSCs) show immunomodulatory properties and have been extensively utilized for autoimmune diseases. However, it has not been fully elucidated how BM-MSCs affect ITP. In this study, we explore the therapeutic mechanism of BM-MSCs on ITP in mice. Dose-escalation passive ITP mice were inducted by injection of MWReg30. BALB/c mice were randomly divided into two groups: ITP with BM-MSC transplantation and ITP controls. The serum levels of cytokines (interleukin 10 [IL-10] and transforming growth factor-ß1 [TGF-ß1]) were examined by enzyme-linked immunosorbent assays. The frequency of Treg cells in both peripheral blood and spleen mononuclear cells was analyzed by flow cytometry, and the forkhead box P3 (Foxp3) messenger RNA (mRNA) level was measured by real-time polymerase chain reaction. After BM-MSC treatment, the platelet (PLT) counts were significantly elevated. Meanwhile, cytokines (TGF-ß1 and IL-10), the ratios of Treg cells, and the Foxp3 mRNA expression level were significantly higher in the BM-MSC group. Our results show that BM-MSCs can improve PLT counts mainly by secreting suppressive cytokines and upregulating Tregs, which may provide new therapeutic potential for human ITP.

PRL-3 promotes gastric cancer peritoneal metastasis via the PI3K/AKT signaling pathway in vitro and in vivo.

The peritoneal metastasis-associated phosphatase of regenerating liver-3 (PRL-3) is upregulated in gastric cancer. The phosphatidylinositol 3-kinase (PI3K)/RAC serine/threonine-protein kinase (AKT) signaling pathway acts downstream of PRL-3 in gastric cancer. However, the exact PRL-3 signaling mechanisms are poorly understood. The present study investigated whether PRL-3 facilitates the peritoneal metastasis of gastric cancer via the PI3K/AKT pathway in vivo and in vitro. Nude mouse models of peritoneal metastasis were established using SGC7901/PRL-3 cell lines. The results confirmed that the invasion and migration abilities of SGC7901/PRL-3 cells were significantly increased in these models. Furthermore, western blotting demonstrated that the expression of p-AKT, matrix metallopeptidase-2 (MMP-2) and -9 proteins increased in SGC7901/PRL-3 cells. These effects were suppressed in SGC7901 cell lines when PI3K was inhibited by LY294002. Furthermore, tumors derived from the peritoneal injection of SGC7901/PRL-3 cells were significantly smaller when the cells were grown in the presence of LY249002, compared with cells grown in its absence. These results indicated that targeted inhibition of the PI3K/AKT signaling pathway decreased the effects of PRL-3 on metastasis in vivo. Collectively, the results of the present study indicated that PRL-3 acts via the PI3K/AKT pathway to promote peritoneal metastasis and invasion of gastric cancer cells in vitro and in vivo.