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The coronavirus disease 2019 (COVID-19) pandemic is ravaging the world. Many therapies have been explored to treat COVID-19. This report aimed to assess the global research trends for the development of COVID-19 therapies.We searched the relevant articles on COVID-19 therapies published from January 1, 2020, to May 25, 2022, in the Web of Science Core Collection Database (WOSCC). VOSviewer 1.6.18 software was used to assess data on the countries, institutions, authors, collaborations, keywords, and journals that were most implicated in COVID-19 pharmacological research. The latest research and changing trends in COVID-19-relevant pharmacological research were analyzed.After manually eliminating articles that do not meet the requirements, a total of 5,289 studies authored by 32,932 researchers were eventually included in the analyses, which comprised 95 randomized controlled trials. 3044 (57.6%) studies were published in 2021. The USA conducted the greatest number of studies, followed by China and India. The primary USA collaborators were China and England. The topics covered in the publications included: the general characteristics, the impact on pharmacists' work, the pharmacological research, broad-spectrum antiviral drug therapy and research, and promising targets or preventive measures, such as vaccine. The temporal diagram revealed that the current research hotspots focused on the vaccine, molecular docking, Mpro, and drug delivery keywords.Comprehensive bibliometric analysis can aid the rapid identification of the principal research topics, potential collaborators, and the direction of future research. Pharmacological research is critical for the development of therapeutic and preventive COVID-19-associated measures. This study may therefore provide valuable information for eradicating COVID-19.

According to the Correa model, the intestinal-type gastric cancer (GC) is preceded by premalignant lesions, including chronic gastritis, intestinal metaplasia and dysplasia. However, the dynamic change of innate and adaptive immune response during this process has not been studied comprehensively. In this study, we performed a comprehensive and trajectory analysis of circulating innate lymphoid cells (ILCs) and adaptive Th lymphocytes subtypes in patients spanning a cascade of gastric lesions. Increased circulating ILC2s frequency was found in the gastritis, premalignant stage and GC group, whereas further decreased ILC2s were detected in the GC group compared with the premalignant group. Moreover, ILC3s level was higher in both gastritis, premalignant lesion and GC stage, compared with healthy controls. Furthermore, up-regulated T follicular helper (Tfh) cell proportions were detected in the gastritis and premalignant process. In conclusion, by analyzing the circulating ILCs and Th cells frequency and the key cytokine production or immunoglobulin level, we demonstrated the potential involvement of ILC3 and Tfh in the gastric diseases. These findings will help to understand the immunologic mechanisms in both GC and the premalignant process and contribute to serve potential therapeutic targets to prevent the GC development.

Immunotherapy, especially immune checkpoint inhibitors, has been widely used in tumor therapy and have shown ideal clinical efficacy. However, some cancers still do not respond to PD-1/PD-L1 blockade therapy effectively. Helicobacter pylori infection might affect the curative effect of immunotherapy while it is rarely reported. We aimed to visualize the research hotspots and trends of H. pylori and immunotherapy using a bibliometric analysis to help understand the future development of basic and clinical research.The relevant publications on H. pylori and immunotherapy were searched on April 20, 2022, in the Web of Science Core Collection Database (WOSCC). The document types were limited to articles and reviews. The VOSviewer 1.6.16 software was used to assess the co-authorship, co-occurrence, citation of countries, institutions, authors, journals, and hotspot keywords. The research status and trend change of H. pylori and immunotherapy were analyzed by bibliometric analysis.A total of 95 studies authored by 561 researchers were eventually included in this study. The majority of the retrieved studies were 55 (58%) original research articles. China conducted the greatest number of studies, followed by USA and Italy. The related topics included the following three aspects: the relationship between microorganisms and cancer, the relationship between gastric cancer and immunity, and the relationship between H. pylori and immunotherapy, including purified/cloned components of H. pylori acting as efficient adjuvant to boost tumor responses and H. pylori infection which modulate host immune responses and impact on the efficacy of antitumor immunity initiated by immune checkpoint inhibitors. The timing diagram revealed that the current research hotspots focused on effects of microorganisms on immunotherapy.The effect of H. pylori on cancer immunotherapy is getting more and more attention in these years. It still remains uncertain, and more studies are needed in the future.

Soil salinization seriously affects crop yield and soil productivity. The application of bacteria and microalgae has been considered as a promising strategy to alleviate soil salinization. However, the effect of bacteria-microalgae symbiosis on saline-alkali land is still unclear. This study evaluated the effects of Azotobacter beijerinckii, Chlorella pyrenoidosa, and their combined application on the wheat growth and saline-alkali soil improvement. The results showed that, among all the treatments, A. beijerinckii + live C. pyrenoidosa combined inoculation group (BA) had the best effect on increasing wheat plant biomass, improving salt tolerance, and improving soil fertility. The dry weight of wheat plant in the BA group increased by 66.7%, 17.4%, and 35.0%, respectively, compared with the control group (CK), A. beijerinckii inoculation group (B), and live C. pyrenoidosa inoculation group (A). The total nitrogen content of wheat plant in the BA group increased by 69.5%, 76.7%, and 71.1%, compared with the CK, B, and A group. The proline content of wheat plant in the BA group was 100% higher than that in the CK group. The N/P ratio and K/Na ratio of wheat plant increased by 157% and 12.9% in the BA group compared with the CK group, respectively, which was more conducive to alleviating nitrogen limitation and salt stress. The A. beijerinckii + live C. pyrenoidosa inoculation treatment better reduced soil pH and improved the availability of phosphorus in soil. This study illustrated the comprehensive application prospects of bacteria-microalgae interactions on wheat growth promotion and soil improvement in saline-alkali land, and provided a new effective strategy for improving saline-alkali soil quality and increasing crop productivity.

Precisely identifying and killing tumor cells are diligent pursuits in oncotherapy. Synthesized gene circuits have emerged as an intelligent weapon to solve these problems. Gene circuits based on post-transcriptional regulation enable a faster response than systems based on transcriptional regulation, which requires transcription and translation, showing superior safety. In this study, synthetic-promoter-free gene circuits possessing two control layers were constructed to improve the specific recognition of tumor cells. Using split-TEV, we designed and verified the basic control layer of protein-protein interaction (PPI) sensing. Another orthogonal control layer was built to sense specific proteins. Two layers were integrated to generate gene circuits sensing both PPI and specific proteins, forming 10 logic gates. To demonstrate the utility of this system, the circuit was engineered to sense alpha-fetoprotein (AFP) expression and the PPI between YAP and 14-3-3σ, the matching profile of hepatocellular carcinoma (HCC). Gene-circuit-loaded cells distinguished HCC from other cells and released therapeutic antibodies, exhibiting in vitro and in vivo therapeutic effects., Graphical Abstract, This research used split TEV to design synthetic-promoter-free gene circuits for PPI sensing and specific protein sensing. Ten logic gates were formed to integrate the two sensing units. The circuit was utilized to distinguish HCC and release therapeutic antibodies in vitro and in vivo through sensing AFP expression and YAP/14-3-3σ interaction.

Owing to superior safety, the RNA-only delivery synthetic circuit is more suitable for cell-based medicine. Modules which possess matching inputs and outputs could be strung by daisy-chaining to compose RNA-only delivery synthetic gene circuits. In this study, we engineered well-characterized biological parts to construct composable modules, each of which could receive signals from the upstream module and transmit the processed signal to the next module using standard interfaces. Capsid-cNOT7, through which logic gates could be changed by merely changing the type of it, was used as the core element for logical process. Daisy chain topology was used to build RNA-only delivery mammalian synthetic circuits which possess validated functions such as fan out, protein sensing, drug sensing, light sensing, 2-input logic gate, 3-input logic gate, and volatile memory, providing a new method to simplify the design of RNA-only delivery synthetic circuits.

The tumor microenvironment and tumor immunity are crucially involved in tumor therapy. Immune checkpoint inhibitors targeting PD-1/PD-L1 signal transduction have been widely used in tumor therapy and have shown ideal clinical efficacy. However, some kinds of cancers still do not respond to PD-1/PD-L1 blockade therapy effectively, including gastric cancer. The related factors should be explored.This review summarizes the recent progression of understanding the influence of Helicobacter pylori infection on PD-1/PD-L1 blockade therapy. Current pieces of evidence have indicated that H. pylori infection might affect the curative effect of tumor therapy associating with the induced immunomodulation.It is necessary to understand the overall integration of PD-1/PD-L1 blockade therapy, the tumor microenvironment, and H. pylori infection. Much attention on the influence of H. pylori infection on the efficacy of tumor immunotherapy should be paid.

The Phosphatase and tensin homolog (PTEN) gene is one of the most important tumor suppressor genes, which acts through its unique protein phosphatase and lipid phosphatase activity. PTEN protein is widely distributed and exhibits complex biological functions and regulatory modes. It is involved in the regulation of cell morphology, proliferation, differentiation, adhesion, and migration through a variety of signaling pathways. The role of PTEN in malignant tumors of the digestive system is well documented. Recent studies have indicated that PTEN may be closely related to many other benign processes in digestive organs. Emerging evidence suggests that PTEN is a potential therapeutic target in the context of several non-neoplastic diseases of the digestive tract. The recent discovery of PTEN isoforms is expected to help unravel more biological effects of PTEN in non-neoplastic digestive diseases.

Histone deacetylase inhibitors (HDACis) are a new class of anticancer drugs confirmed to have good therapeutic effects against gastric cancer (GC) in preclinical experiments, but most HDACis are non-selective (pan-HDACis), with highly toxic side effects. Therefore, it is necessary to screen HDAC family members that play key roles in GC as therapeutic targets to reduce toxic side effects. In this study, we evaluated the targeting specificity of the HDACi suberoylanilide hydroxamic acid (SAHA) for GC via fluorescence molecular imaging (FMI). In vitro FMI results showed that SAHA had higher binding affinity for GC cells than for normal gastric cells. In vivo FMI of gastric tumor-bearing mice confirmed that SAHA can be enriched in GC tissues. However, there was also a high-concentration distribution in normal organs such as the stomach and lungs, suggesting potential side effects. In addition, we found that among the HDAC family members, HDAC9 was the most significantly upregulated in GC cells, and we verified this upregulation in GC tissues. Further experiments confirmed that knockdown of HDAC9 inhibits cell growth, reduces colony formation, and induces apoptosis and cell cycle arrest. These results suggest that HDAC9 has an oncogenic role in GC. Moreover, HDAC9 siRNA suppressed GC tumor growth and enhanced the antitumor efficacy of cisplatin in GC treatment by inhibiting the proliferation and inducing the apoptosis of GC cells in vitro and in vivo. Our findings suggest that the development of HDAC9-selective HDACis is a potential approach to improve the efficacy of chemotherapy and reduce systemic toxicity., Stomach cancer: identifying the right target Inhibiting histone deacetylase 9 (HDAC9), a protein that regulates gene expression, reduces stomach cancer cell growth. The efficacy of current treatments for stomach cancer is limited. Although HDACs have emerged as promising therapeutic targets, non-selective HDAC inhibitors can cause severe side effects. Shigang Ding at Peking University Third Hospital in Beijing, China, and colleagues found that human stomach cancer cells have significantly higher levels of HDAC9 than other members of the HDAC family and that high HDAC9 levels are associated with reduced patient survival. Interfering with the production of HDAC9 protein improved the efficacy of the chemotherapeutic drug cisplatin in mice with stomach cancer. The authors suggest that selective HDAC9 inhibitors could help to improve the survival of patients with this type of cancer.

Background Gastric cancer is still a common cancer worldwide. Investigation of potential plasma biomarkers for gastric cancer diagnosis is essential for prevention strategies and early intervention for gastric cancer-control planning. Objectives This study was aimed to explore the lncRNAs' promoter of CDKN1A antisense DNA-damage-activated RNA (PANDAR), FOXD2-AS1, and SMARCC2 as potential novel diagnostic biomarkers for gastric cancer. Method 109 gastric cancer patients and 106 healthy controls were involved in this study. Plasma lncRNAs PANDAR, FOXD2-AS1, and SMARCC2 were detected by real-time PCR. Student's t-test, Mann-Whitney U test, and Chi-square test were used to verify the differences of clinical variables between two groups. Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic value of every biomarker. Multivariable analysis of risk factors for gastric cancer was performed using logistic regression analysis. Results There were significant differences in age, gender, carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 153 between gastric cancer and healthy controls (P

Helicobacter pylori is a major cause of gastric cancer. This study was aimed to explore the characteristic of DNA damage induced by H. pylori infection in gastric cancer AGS cells. After infection with H. pylori, the reactive oxygen species (ROS) levels in AGS cells were significantly higher than those in the uninfected cells. Cells with longer comet tails were detected after infection with H. pylori. The number of apurinic/apyrimidinic endonuclease 1- and phosphorylated H2AX-positive cells was significantly increased compared with the number of negative control cells. The expression of pChk1 and pChk2 was significantly upregulated by H. pylori infection. Cell growth was inhibited after H. pylori infection. All these results were dose dependent. The cell alterations were more significant upon infection with H. pylori at a multiplicity of infection (MOI) of 100:1 than at an MOI of 50:1. H. pylori infection can induce DNA single-strand breaks, DNA double-strand breaks, and cell cycle checkpoint activation after ROS generation in the gastric cancer cell line AGS, which is a potential driver for gastric cancer.

Goals The main aim of this study was to investigate the significance of a pale area via flexible spectral imaging color enhancement (FICE) in the diagnosis of esophageal dysplasia and cancer. Background The early diagnosis of esophageal squamous cancer is challenging, and the indication of Lugol's chromoendoscopy has not yet been well established. Study The esophageal mucosa of patients at our endoscopic center were sequentially evaluated with white-light endoscopy and FICE during insertion of the endoscope, followed by staining with Lugol's solution during withdrawal. Patients were divided into 2 groups depending on whether esophageal leukoplakia was detected by white-light endoscopy and 2 groups depending on whether a pale area was detected by FICE. We compared cases of patients with abnormal iodine staining, and cases of dysplasia or cancer in esophageal leukoplakia-or pale area-positive and negative groups. Results Cases of abnormal staining in the esophageal leukoplakia-or pale area-positive group were far more numerous than cases without esophageal leukoplakia or pale area, respectively (P=0.000). Cases of esophageal dysplasia and cancer in the esophageal leukoplakia-or pale area-positive group were far more numerous than cases without esophageal leukoplakia or pale area, respectively (P=0.000). Conclusions Iodine staining should be performed in patients with esophageal leukoplakia or pale areas. Esophageal dysplasia and early-stage cancer were more easily detected in those with esophageal leukoplakia or pale areas.

Optical imaging technologies improve clinical diagnostic accuracy of early gastric cancer (EGC). However, there was a lack of imaging agents exhibiting molecular specificity for EGCs. Here, we employed the dye labeled human heavy-chain ferritin (HFn) as imaging nanoprobe, which recognizes tumor biomarker transferrin receptor 1 (TfR1), to enable specific EGC imaging using confocal laser endomicroscopy (CLE). TfR1 expression was initially examined in vitro in gastric tumor cells and in vivo through whole-body fluorescence and CLE imaging in tumor-bearing mice. Subsequently, dye labeled HFn was topically applied to resected human tissues for EGC detection. CLE analysis of TfR1-targeted fluorescence imaging allowed distinction of neoplastic from non-neoplastic tissues (P 0.0001), and TfR1 expression level was found to correlate with EGC differentiation degrees (P 0.0001). Notably, the CLE evaluation correlated well with the immunohistochemical findings (κ-coefficient: 0.8023). Our HFn-nanoprobe-based CLE increases the accuracy of EGC detection and enables visualization of tumor margins and endoscopic resection.

Helicobacter pylori infection is related to the development of gastric diseases. Our previous studies showed that high thioredoxin-1 (Trx1) expression in H. pylori can promote gastric carcinogenesis. To explore the underlying molecular mechanisms, we performed an isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomic analysis of stomach tissues from Mongolian gerbil infected with H. pylori expressing high and low Trx1. Differences in the profiles of the expressed proteins were analyzed by bioinformatics and verified using Western blot analysis. We found three candidate proteins, 14-3-3α/β, glutathione-S-transferase (GST), and heat shock protein 70 (HSP70), in high Trx1 tissues compared with low Trx1 tissues and concluded that cellular stress and redox activity-related proteins were involved in the pathogenesis of gastric cancer associated with H. pylori Trx1.

The survival rate of early gastric cancer and esophageal cancer is more than 90%. Confocal endoscopy can detect cell morphology and mucosal glandular structure (depth about 500 μm), presenting a cross-sectional microscopic image unfamiliar to both endoscopists and pathologists. Therefore, using computer-aided diagnosis technology to complete real-time artificial intelligence diagnosis of early esophageal and gastric cancer is of great significance for early detection and early treatment of cancer patients. ResNet convolution neural network based image classification model, the introduction of attention mechanism based on CBAM module to improve the performance of the model, to achieve intelligent diagnosis of confocal endoscopy images.

Background and study aims Endoscopy plays a crucial role in diagnosis of gastritis. Endoscopists have low accuracy in diagnosing atrophic gastritis with white-light endoscopy (WLE). High-risk factors (such as atrophic gastritis [AG]) for carcinogenesis demand early detection. Deep learning (DL)-based gastritis classification with WLE rarely has been reported. We built a system for improving the accuracy of diagnosis of AG with WLE to assist with this common gastritis diagnosis and help lessen endoscopist fatigue. Methods We collected a total of 8141 endoscopic images of common gastritis, other gastritis, and non-gastritis in 4587 cases and built a DL -based system constructed with UNet + + and Resnet-50. A system was developed to sort common gastritis images layer by layer: The first layer included non-gastritis/common gastritis/other gastritis, the second layer contained AG/non-atrophic gastritis, and the third layer included atrophy/intestinal metaplasia and erosion/hemorrhage. The convolutional neural networks were tested with three separate test sets. Results Rates of accuracy for classifying non-atrophic gastritis/AG, atrophy/intestinal metaplasia, and erosion/hemorrhage were 88.78 %, 87.40 %, and 93.67 % in internal test set, 91.23 %, 85.81 %, and 92.70 % in the external test set ,and 95.00 %, 92.86 %, and 94.74 % in the video set, respectively. The hit ratio with the segmentation model was 99.29 %. The accuracy for detection of non-gastritis/common gastritis/other gastritis was 93.6 %. Conclusions The system had decent specificity and accuracy in classification of gastritis lesions. DL has great potential in WLE gastritis classification for assisting with achieving accurate diagnoses after endoscopic procedures.

Background Abnormal DNA methylation is a hallmark of human cancers and may be a promising biomarker for early diagnosis of human cancers. However, the majority of DNA methylation biomarkers that have been identified are based on the hypothesis that early differential methylation regions (DMRs) are maintained throughout carcinogenesis and could be detected at all stages of cancer. Methods In this study, we identified potential early biomarkers of colorectal cancer (CRC) development by genome-wide DNA methylation assay (Illumina infinium450, 450 K) of normal (N = 20) and pre-colorectal cancer samples including 18 low-grade adenoma (LGA) and 22 high-grade adenoma (HGA), integrated with GEO and ArrayExpress datasets (N = 833). Results We identified 209 and 8692 CpG sites that were significantly hyper-methylated in LGA and HGA, respectively. Pathway analysis identified nervous system-related methylation changes that are significantly associated with early adenoma development. Integration analysis revealed that DNA methylation in the promoter region of ADHFE1 has the most potential for being an early diagnostic biomarker for colorectal adenoma and cancer (sensitivity = 0.96, specificity = 0.95, area under the curve = 0.97). Conclusions Overall, we demonstrated that DNA methylation have been shown significant changes in the stage of LGA and HGA in the development of colon cancer. Genome-wide DNA methylation to LGA and HGA provided an important proxy to identify promising early diagnosis biomarkers for colorectal cancer.

Additional file 1. Supplementary figures and tables

Background and Aims: The poor outcomes of hepatocellular carcinoma (HCC) patients may be due to not only malignant tumors but also limited liver function. Therefore, as stated in major guidelines, only patients with relatively normal liver function (Child-Pugh A) would be referred for curative hepatectomy. Even so, the postsurgery survival rate of patients is still extremely poor. Direct curative resection may benefit most patients. This study aimed to improve the prognosis predicting accuracy of the Child-Pugh scoring system. Methods: This study included two cohorts: cohort A being composed of 613 HCC patients, with a 23-month median postsurgery follow-up time; and cohort B being composed of 554 tumor-free chronic liver disease patients. Kaplan–Meier test and Cox model were used for survival analysis. Independent-samples t test or one-way ANOVA was used to test the differences between different groups. Results: Serum prealbumin levels were found inversely correlated with worsening of fibrotic scores (r = −0.482, p < 0.001). Lower levels of presurgery prealbumin was an independent factor of poor postsurgery prognosis in Child-Pugh A patients, with a hazard ratio of 0.731 (p = 0.001). By integrating prealbumin together with total bilirubin level, serum albumin concentration and prothrombin time, a modified liver disease prognosis scoring system was developed to define traditional Child-Pugh A HCC patients as Modified Child-Pugh MCP-1, MCP-2 and MCP-3, with median postsurgery overall survival times of 44.00, 28.00 and 11.00 months respectively. Conclusions: Preoperative serum prealbumin is a valuable prognosis predicting biomarker for Child-Pugh A HCC patients who may be under consideration for curative resection. With serum prealbumin included as one of the parameters, the MCP scoring system might improve the postsurgery survival predicting accuracy for HCC patients.

Background Recent studies have shown that gastrokine 1 (GKN1), an important tumor suppressor gene, is downregulated in Helicobacter pylori (H. pylori) infected gastric mucosa and gastric cancer. However, the underlying mechanism is poorly understood. Herein, we investigated the potential mechanism of H. pylori-induced GKN1 downregulation. Materials and methods GKN1 and AU-rich element RNA-binding factor 1 (AUF1) expressions were assessed by quantitative real-time PCR, Western blot, or immunohistochemistry in H. pylori-infected tissues and H. pylori co-cultured cell lines. The regulation of AUF1 on GKN1 was determined by RNA pulldown assay, RNA immunoprecipitation, mRNA turnover, and luciferase activity assays. The involvement of phosphorylated extra-cellular signal-regulated kinase (p-ERK) or CagA in H. pylori-induced AUF1 expression was verified using p-ERK inhibitor or CagA knockout H. pylori. In addition, the cell proliferation and migration capacities of AUF1-knockdown cells were investigated. Results GKN1 expression progressively decreased from H. pylori-infected gastritis to gastric cancer tissues. H. pylori co-culture also induced significant GKN1 reduction in GES-1 and BGC-823 cells. Besides, the mRNA level of GKN1 and AUF1 in human gastric mucosa showed negative correlation significantly. AUF1 knockdown resulted in upregulation of GKN1 expression and promoted GKN1 mRNA decay by binding the 3' untranslated region of GKN1 mRNA H. pylori-induced AUF1 expression was associated with p-ERK activation and CagA. Furthermore, knockdown of AUF1 significantly inhibited cell viability, migration ability, and arrested fewer cells in S-phase. Conclusion Our data demonstrated that H. pylori infection downregulated GKN1 expression via the CagA/p-ERK/AUF1 pathway. AUF1 promoted gastric cancer at least partly through downregulating GKN1, which presented a novel potential target for the treatment of gastric cancer.

Current endoscopy techniques have difficulties to provide both high resolution and large imaging depth, which significantly hinders the early diagnosis of gastric cancer. Here, we developed a label-free, large-depth, three-dimensional (3D) chromatic reflectance confocal endomicroscopy. In order to solve the problem of insufficient imaging depth of traditional chromatic confocal microscopy, a customized miniature objective lens both with large chromatic focal shift and correction for spherical aberration was used to focus light of different wavelengths at different depths of the sample simultaneously, and a fiber bundle containing 50000 single-mode cores was used to collect the confocal reflectance signal. To acquire detailed information along the axial direction at a faster speed, a high-speed multi-pixel spectrometer was used to realize simultaneous detection of multi-depth signals. Specifically, we have built up a label-free fiber-optic 3D chromatic reflectance confocal endomicroscopy, with 2.3 µm lateral resolution, imaging depth of 570 µm in 3D phantom and 220 µm in tissue, and 1.5 Hz 3D volumetric frame rate. We have demonstrated that the fiber-optic 3D chromatic confocal endomicroscopy can be used to image human gastric tissues ex vivo, and provide important morphological information for diagnosis without labeling. These results show the great potential of the fiber-optic 3D chromatic confocal endomicroscopy for gastric cancer diagnosis.

Gastric cancer is an important cause of death worldwide with Helicobacter pylori (H. pylori) considered a leading and known risk factor for its development. More particularly and despite the underlying mechanisms not being very clear, studies have revealed that the H. pylori cytotoxin-associated gene A (CagA) protein plays a key role in this process. In this study it was found that H. pylori increased the expression of miR-543 in human gastric cancer tissue when compared with H. pylori-negative gastric cancer tissue samples. In vitro experiments showed that increased expression of miR-543 induced by CagA is a strong promoter of cell proliferation, migration, and invasion. Conversely, a miR-543 inhibitor suppressed or reversed these effects. It was furthermore found that silencing miR-543 inhibited autophagy and led to epithelial–mesenchymal transition (EMT) under in vitro. The mechanisms by which miR-543 targets SIRT1 to downregulate autophagy was also described. The results suggest that in the progression of H. pylori-associated gastric cancer, CagA induces overexpression of miR-543, which subsequently targets SIRT1 to suppress autophagy. This may be followed by increased expression of EMT causing cell migration and invasion. Consequently, miR-543 might be considered a therapeutic target for H. pylori-associated gastric cancer.

CMTM4 (CKLF-like MARVEL transmembrane domain containing 4), a potential tumor suppressor gene, is involved in several types of malignancies. It has been reported to be downregulated and exhibit anti-tumorigenic activities by regulating cell growth and cell cycle in clear cell renal cell carcinoma. It has also been identified as a tumor suppressor in hepatocellular carcinoma (HCC), and its negative expression is a risk factor for poor prognosis of HCC patients. In the present study, an integrated bioinformatics analysis based on The Cancer Genome Atlas (TCGA) database showed that CMTM4 was frequently reduced in colorectal cancer (CRC) and high expression of CMTM4 was associated with increased overall survival rates. Based on these findings, we adopted gain-of-function and lost-of-function strategies using SW480 and HT29 CRC cell lines which have relatively low and high endogenous CMTM4 levels, respectively. We observed impeded cell proliferation and migration upon overexpression of CMTM4 in SW480 cells, and the opposite effects were observed upon knockdown of CMTM4 in HT-29 cells. Cell signaling pathways essential for CRC progression were then examined, and the phosphorylation levels of AKT, ERK1/2, and STAT3 were found to be decreased by CMTM4 overexpression in SW480 cells and elevated by CMTM4 silencing in HT29 cells. Their inhibitors were used to validate that the three signaling pathways contributed to the inhibitory effects of CMTM4 on CRC cells. Taken together, our results suggest that CMTM4 plays a tumor suppressive role in CRC.

Basal-like breast cancer with a luminal progenitor gene expression profile is an aggressive subtype of breast cancer with a poorer prognosis compared with other subtypes. However, genes that specifically promote basal-like breast cancer development remain largely unknown. Here, we report that a novel gene C1orf106 plays an important role in maintaining the feature of basal-like/luminal progenitors. C1orf106 is frequently amplified and overexpressed in basal-like breast cancer and is associated with a poor outcome in patients. In human TCGA database, C1orf106 expression was correlated with upregulation of ELF5 and downregulation of GATA3, two transcription factors that regulate mammary gland stem cell fate. Enhanced expression of C1orf106 promotes tumor progression and expression of basal-like/luminal progenitor marker ELF5; depletion of C1orf106 suppresses tumorigenesis and expression of basal-like/luminal progenitor marker GATA3. These findings suggest that C1orf106 maintains the basal-like/luminal progenitor character through balancing the expression of ELF5 and GATA3. Taken together, we demonstrated that C1orf106 is an important regulator for basal-like/luminal progenitors and targeting C1orf106 is of therapeutic value for breast cancer.

Background and objective Gastric cancer is one of the most common cancers worldwide. However, the mechanisms associated with this disease are still not clear. Malic enzyme 1 (ME1) is a metabolic enzyme that is overexpressed in various cancers. Here, we examined whether it is involved in gastric cancer. Methods ME1 expression was knocked down in the gastric cancer cell line SGC7901. Cell growth and migration were measured using a real-time microelectronic cell sensor system. Cell invasion was measured using a Transwell assay. Cell cycle analysis was also performed to examine cell cycle arrest. A gastric cancer tissue microarray of gastric cancer was stained using immunohistochemistry. ME1 expression levels were also statistically analysed. Results ME1 knockdown in gastric cancer SGC7901 cells significantly inhibited cell proliferation, migration, and invasion. Cell cycle arrest was induced in the G2 phase. Further, ME1 expression was significantly correlated with gastric cancer patient prognosis based on both univariable and multivariable survival analysis. No significant difference was found between ME1 expression in gastric cancer tissues and that in adjacent tissues. Conclusion Our results provide evidence that ME1 is a key factor for gastric cancer. ME1 might be pro-oncogenic during both the development and migration of gastric cancer; it also might be related to gastric cancer patient survival.