Quercetin Mediated TET1 Expression Through MicroRNA-17 Induced Cell Apoptosis in Melanoma Cells.

A previous report suggested that the expression of ten-eleven translocation (TET) proteins is abnormal in certain cancers. Quercetin has been demonstrated as anti-cancer role in cancer development. In order to explore the inhibitory effect and mechanism of quercetin on uveal melanoma cells, the expression of TET proteins was analyzed in the present study. Our results suggest that the expression of TET1 was increased following treatment with quercetin in OCM-1, SK-MEL-1, and B16 cells. In addition, quercetin treatment induced apoptosis and inhibited migration and invasion. To further investigate the association of the expression of TET1 with cell growth, apoptosis, migration, and invasion, cell lines in which TET1 was knocked-down or overexpressed were constructed. The results showed that the increased expression of TET1-induced apoptosis, increased 5-hydroxymethylcytosine (5 hmC). and inhibited invasion. Our bioinformatics studies indicated that TET1 is a target gene of microRNA-17 (miR-17) Our results showed that inhibition of the expression of miR-17 resulted in increased TET1 expression in OCM-1 cells. Furthermore, our results indicated that quercetin treatment increased TET1 expression and inhibited melanoma growth in nude mice. Taken together, our results suggest that quercetin can regulate cell proliferation and apoptosis through TET1 via miR-17 in melanoma cells.

Baicalein Inhibits Proliferation Activity of Human Colorectal Cancer Cells HCT116 Through Downregulation of Ezrin.

BACKGROUND/AIMS: The present study was aimed at examining Ezrin expression in human colorectal cancer (CRC) tissues and elucidating the influence of baicalein on the proliferation of HCT116 cells. METHODS: The expression of Ezrin was determined by qRT-PCR and immunohistochemistry. HCT116 cells were divided into four groups－ baicalein groups with various concentrations, pcDNA3.1-Ezrin group, si-Ezrin group and dual inhibitory group (baicalein + si-Ezrin). CCK-8 assay and flow cytometry (FCM) were employed to assess cell proliferation and to detect the distribution of cell cycle respectively. The expression levels of Ezrin protein and cell cycle-associated proteins were detected by using western blot. The proliferation ability of CRC cells was also evaluated in vivo. RESULTS: Ezrin expression in CRC tissues was observably higher than that in adjacent colorectal tissues. With drug concentration and action time of baicalein increasing, the cell propagation capacity of HCT116 cells was decreased and the cell cycle progression was arrested. Ezrin expression was inhibited by the administration of baicalein in a dose-dependent way. The levels of CyclinD1 and CDK4 were also significantly decreased, but the expression of P53 pathway proteins P53 and P21 was markedly upregulated. CONCLUSION: Baicalein repressed proliferation of human colorectal cancer cells HCT116 and blocked cell cycle through downregulating Ezrin and upregulating P53 pathway-related proteins.

Correlation of bone morphogenetic protein-2 levels in serum and synovial fluid with disease severity of knee osteoarthritis.

BACKGROUND: This study aimed to investigate the bone morphogenetic protein-2 (BMP-2) levels in serum and synovial fluid (SF) of patients with primary knee osteoarthritis (OA) and to exam its correlation with radiographic and symptomatic severity of the disease. MATERIAL/METHODS: A total of 37 knee OA patients and 20 healthy controls were enrolled in this study. Knee OA radiographic grading was performed according to the Kellgren-Lawrence (KL) grading system by evaluating X-ray changes observed in anteroposterior knee radiography. Symptomatic severity of the disease was evaluated according to the Western Ontario McMaster University Osteoarthritis Index (WOMAC) scores. BMP-2 levels in serum and SF were determined using enzyme-linked immunosorbent assay. RESULTS: Serum BMP-2 level in patients with knee OA was higher than that in healthy controls. Knee OA patients with KL grade 4 showed significantly elevated BMP-2 levels in the serum and SF compared with those with KL grade 2 and 3. Knee OA patients with KL grade 3 had significant higher SF levels of BMP-2 than those with KL grade 2. BMP-2 levels in the serum and SF of knee OA patients were both positively correlated with KL grades and WOMAC scores. CONCLUSIONS: BMP2 levels in serum and SF were closely related to the radiographic and symptomatic severity of knee OA and may serve as an alternative biochemical parameter to determine disease severity of primary knee OA.

Comparison between better and poorly differentiated locally advanced gastric cancer in preoperative chemotherapy: a retrospective, comparative study at a single tertiary care institute.

BACKGROUND: Gastric cancer is the third leading cause of cancer-related mortality in China, and the long-term survival for locally advanced gastric cancer is very poor. Simple surgery cannot yield an ideal result because of the high recurrence rate after tumor resection. Preoperative chemotherapy could help to reduce tumor volume, improve the R0 resection rate (no residual tumor after surgery), and decrease the risk of local tumor recurrence. The aim of this study was to evaluate the influence of pathological differentiation in the effect of preoperative chemotherapy for patients with locally advanced gastric cancer. METHODS: Patients with locally advanced gastric cancer (n = 32) received preoperative chemotherapy under the XELOX (capecitabine plus oxaliplatin) regimen. According to pathological examination, patients' tumors were classified into better (well and moderate) and poorly differentiated (lower differentiated and undifferentiated) groups, and the clinical response rate, type of gastrectomy, and negative tumor residual rate were compared between the two groups of patients. Morphological changes and toxic reactions were monitored after chemotherapy. RESULTS: The results showed that the clinical response rate in the better differentiated group was significantly higher than that in the poorly differentiated group (100% versus 25%, P = 0.000). The partial gastrectomy rate in the better differentiated group was significantly higher than that in the poorly differentiated group (87.5% versus 25% P = 0.000). A significant shrinking of tumor and necrosis of tumor tissues caused by chemotherapy could be observed. CONCLUSIONS: In conclusion, the better differentiated group with locally advanced gastric cancer is suitable for preoperative chemotherapy under the XELOX regimen, and as a result of effective preoperative chemotherapy, much more gastric tissue can be preserved for the better differentiated group.

Fast and Reliable Score-Based Generative Model for Parallel MRI.

The score-based generative model (SGM) can generate high-quality samples, which have been successfully adopted for magnetic resonance imaging (MRI) reconstruction. However, the recent SGMs may take thousands of steps to generate a high-quality image. Besides, SGMs neglect to exploit the redundancy in k space. To overcome the above two drawbacks, in this article, we propose a fast and reliable SGM (FRSGM). First, we propose deep ensemble denoisers (DEDs) consisting of SGM and the deep denoiser, which are used to solve the proximal problem of the implicit regularization term. Second, we propose a spatially adaptive self-consistency (SASC) term as the regularization term of the k -space data. We use the alternating direction method of multipliers (ADMM) algorithm to solve the minimization model of compressed sensing (CS)-MRI incorporating the image prior term and the SASC term, which is significantly faster than the related works based on SGM. Meanwhile, we can prove that the iterating sequence of the proposed algorithm has a unique fixed point. In addition, the DED and the SASC term can significantly improve the generalization ability of the algorithm. The features mentioned above make our algorithm reliable, including the fixed-point convergence guarantee, the exploitation of the k space, and the powerful generalization ability.

Changes in Tumor Immune Microenvironment after Radiotherapy Resistance in Colorectal Cancer: A Narrative Review.

BACKGROUND: Colorectal cancer (CRC) is a common digestive tract malignancy with high incidence and mortality rates. Radiotherapy is the most common anti-tumor therapeutic regime and is frequently used for treating CRC, especially rectal cancer. However, radiotherapy can lead to tumor resistance to treatment. While previous research on radiotherapy resistance in CRC has mostly focused on the tumor itself, recent advances, especially the emergence of immunotherapy, have led to a greater emphasis on the immune microenvironment of the tumor. SUMMARY: This review has summarized the recent literature on the role of the tumor immune microenvironment in CRC resistance to radiotherapy and provided new ideas for future anti-tumor treatment strategies. KEY MESSAGES: The proportion of immunosuppressive cells is greater than the numbers of cells associated with immune activation, leading to an overall state of immunosuppression; both the tumor and immunosuppressive cells secrete increased amounts of immunosuppressive regulatory factors, reduce the recognition and presentation of tumor antigens, inhibit immune cell's anti-tumor effect, and offset the non-targeted anti-tumor effect of radiotherapy.

The corrosion of 316L stainless steel induced by methanocossus mariplaudis through indirect electron transfer in seawater.

The effect of methanogenic archaea (Methanococcus maripaludis) on corrosion behavior of 316L stainless steel under different concentrations of organic electron donor (acetate) was investigated. The results showed that M. maripaludis can survive by utilizing 316L SS as an alternative energy source. The extracellular electron transfer from 316L SS relies on redox-active substances secreted by M. maripaludis. Corrosion of 316L SS is promoted along with decrease of acetate concentration. M. maripaludis causes severe pitting corrosion of 316L SS in the absence of acetate due to that more redox-active substances are secreted, which has little relationship with the M. maripaludis biofilm.

MicroRNA-543 controls pancreatic cancer development by LINC00847-microRNA-543-STK31 axis.

Background: Pancreatic cancer (PC) is one of the most malignant cancers of the gastrointestinal tract. However, the study of targeted therapy research in PC is not very thorough. Therefore, targeted molecular markers are needed to aid in the diagnosis and treatment of PC. Methods: In our research, we investigated the biological functions and molecular mechanism of microRNA-543 in PC. Western blotting (WB) and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to analyze the transcription and protein expression of microRNA-543, Serine/threonine kinase 31 (STK31), and LINC00847 in BxPC-3 and PANC-1 cells. Subsequently, Cell Counting Kit-8 (CCK-8), Transwell, colony formation, and flow cytometry (FCM) assays were utilized to evaluate cell growth, migration, invasion, and apoptosis. WB and fluorescence in-situ hybridization (FISH) were used to evaluate the epithelial-mesenchymal transition (EMT) process and subcellular localization. RNA immunoprecipitation (RIP), double luciferase reporter, and RNA-pull down assays were performed to determine the targeting relationship between microRNA-543 and STK31 or microRNA-543 and LINC00847. Results: While microRNA-543 expression was discovered to be low in PC, LINC00847 and STK31 were overexpressed at significant levels. MicroRNA-543 knockdown dramatically increased PC cell growth, invasion, metastasis, and EMT, as well as decreased apoptosis in functional studies. Furthermore, microRNA-543 and STK31 were found to be mutual targets. LINC00847 acted as a molecular sponge for microRNA-543 and a competitive endogenous RNA (ceRNA) for STK31, thereby increasing STK-31 transcription. Conclusions: Our results suggest that microRNA-543, through the LINC00847/microRNA-543/STK31 axis, plays a role in the development of PC as a tumor suppressor. As a result, microRNA-543 may prove to be an effective diagnostic and therapeutic target for PC.

The Role and Application of Exosomes in Gastric and Colorectal Cancer.

Gastric cancer and colorectal cancer are malignant tumors found in the human gastrointestinal tract. Bidirectional communication between tumor cells and their microenvironment can be realized through the transmission of exosomes-small, cell-derived vesicles containing complex RNA and proteins. Exosomes play an important role in the proliferation, metastasis, immune response, and drug resistance of cancer cells. In this review, we focus on the role and application of exosomes in gastric and colorectal cancer. We also summarize the role of exosomes secreted by different types of cells in tumor development and as drug carriers in cancer treatment.

Overexpression of Long Non-Coding RNA FGF14-AS2 Inhibits Colorectal Cancer Proliferation Via the RERG/Ras/ERK Signaling by Sponging microRNA-1288-3p.

Colorectal cancer remains one of most common cancer types with poor prognosis globally. Recent years, numerous studies depicted pivotal roles of lncRNAs in colorectal cancer progression. This study aimed to investigate the role of FGF14-AS2 in colorectal cancer development. FGF14-AS2 was found as a significantly downregulated lncRNA in TCGA dataset. Via RT-qPCR, we confirmed the downregulation of FGF14-AS2 in collected colorectal carcinoma samples. Transfection of plasmid containing full length of FGF14-AS2 repressed cell proliferation and induced elevation of cell apoptosis in colorectal cancer cells. In addition, FGF14-AS2 overexpression inactivated MAPK/ERK signaling in cells. Bioinformatic analysis and subsequent cell-based assays showed that FGF14-AS2 sponging miR-1288-3p, an oncogenic miRNA in colorectal cancer. RERG, the regulator of Ras/ERK pathway, was predicted and verified as target gene of miR-1288. Via downregulation of miR-1288, FGF14-AS2 elevated RERG expression in colorectal cancer cells. Rescue assays indicated that FGF14-AS2 relied on regulation of RERG to control cell proliferation and apoptosis in colorectal cancer. Taken together, the current study demonstrated FGF14-AS2 as a regulator of colorectal cancer development via downregulation of miR-1288-3p and inactivation of Ras/ERK signaling.

Building an Open Resources Repository for COVID-19 Research.

The COVID-19 outbreak is a global pandemic declared by the World Health Organization, with rapidly increasing cases in most countries. A wide range of research is urgently needed for understanding the COVID-19 pandemic, such as transmissibility, geographic spreading, risk factors for infections, and economic impacts. Reliable data archive and sharing are essential to jump-start innovative research to combat COVID-19. This research is a collaborative and innovative effort in building such an archive, including the collection of various data resources relevant to COVID-19 research, such as daily cases, social media, population mobility, health facilities, climate, socioeconomic data, research articles, policy and regulation, and global news. Due to the heterogeneity between data sources, our effort also includes processing and integrating different datasets based on GIS (Geographic Information System) base maps to make them relatable and comparable. To keep the data files permanent, we published all open data to the Harvard Dataverse (https://dataverse.harvard.edu/dataverse/2019ncov), an online data management and sharing platform with a permanent Digital Object Identifier number for each dataset. Finally, preliminary studies are conducted based on the shared COVID-19 datasets and revealed different spatial transmission patterns among mainland China, Italy, and the United States.

Polydopamine-coated Au-Ag nanoparticle-guided photothermal colorectal cancer therapy through multiple cell death pathways.

Nanoparticles are emerging as a new therapeutic modality due to their high stability, precise targeting, and high biocompatibility. Branched Au-Ag nanoparticles with polydopamine coating (Au-Ag@PDA) have strong near-infrared absorbance and no cytotoxicity but high photothermal conversion efficiency. However, the photothermal activity of Au-Ag@PDA in vivo and in vitro has not been reported yet, and the mechanism underlying the effects of photothermal nanomaterials is not clear. Therefore, in this study, the colorectal cancer cell line HCT-116 and nude mice xenografts were used to observe the photothermal effects of Au-Ag@PDA in vivo and in vitro. The results suggest that Au-Ag@PDA NPs significantly inhibited cell proliferation and induced apoptosis in colorectal cancer cells. Moreover, Au-Ag@PDA NP-mediated photothermal therapy inhibited the growth of tumors at doses of 50 and 100 µg in vivo. The mechanisms through which Au-Ag@PDA NPs induced colorectal cancer cell death involved multiple pathways, including caspase-dependent and -independent apoptosis, mitochondrial damage, lysosomal membrane permeability, and autophagy. Thus, our findings suggest that Au-Ag@PDA NPs could be used as potential antitumor agents for photothermal ablation of colorectal cancer cells.

miR-613 inhibits gastric cancer progression through repressing brain derived neurotrophic factor.

MicroRNA (miR)-613 has been reported to function as a tumor suppressor in several types of cancer. However, the biological function and underlying mechanism in gastric cancer (GC) has remained elusive. Therefore, the aim of the present study was to assess the expression and biological role of miR-613 in GC tissues and cell lines. miR-613 expression was found to be downregulated in 38 GC tissue samples compared to that in their adjacent non-cancerous tissues, and low expression of miR-613 was associated with lymph node metastasis and advanced tumor-nodes-metastasis stage. A gain-of-function assay demonstrated that miR-613 overexpression reduced tumor cell proliferation, migration and invasion of SGC-7901 cells, as determined by MTT and Transwell assays. Furthermore, brain-derived neutrophic factor (BDNF) was identified as a direct target of miR-613 in GC cells by a luciferase reporter assay. BDNF expression was upregulated and inversely correlated with miR-613 levels in GC tissues. In addition, knockdown of BDNF expression mimicked the tumor suppressive effect of miR-613 in GC cells. In conclusion, these findings demonstrated that miR-613 functions as a tumor suppressor in GC by targeting BDNF. Thus, miR-613 is a potential therapeutic target for GC.

Clinical benefits of combined chemotherapy with S-1, oxaliplatin, and docetaxel in advanced gastric cancer patients with palliative surgery.

BACKGROUND AND AIM: Advanced gastric cancer accounts for a substantial portion of cancer-related mortality worldwide. Surgical intervention is the curative therapeutic approach, but patients with advanced gastric cancer are not eligible for the radical resection. The present work aimed to investigate the efficacy and safety of palliative surgery combined with S-1, oxaliplatin, and docetaxel chemotherapy in the treatment of patients with advanced gastric cancer. METHOD: A total of 20 patients who underwent palliative resection of gastric cancer in China-Japan Union Hospital of Jilin University from 2010 to 2011 were evaluated. Days 20-30 postoperative, these patients started to receive chemotherapy of S-1 (40 mg/m(2), oral intake twice a day) and intravenous infusion of oxaliplatin (135 mg/m(2)) and docetaxel (75 mg/m(2)). After three cycles of chemotherapy (21 days/cycle), patients were evaluated, and only those who responded toward the treatment continued to receive six to eight cycles of the treatment and were included in end point evaluation. Patients' survival time and adverse reactions observed along the treatment were compared with those treated with FOLFOX. RESULTS: Out of 20 patients evaluated, there was one case of complete response, nine cases of partial response, six cases of stable disease, and four cases of progressive disease. The total efficacy (complete response + partial response) and clinical benefit rates were 50% and 80%, respectively. Of importance, the treatment achieved a significantly longer survival time compared to FOLFOX, despite the fact that both regimens shared common adverse reactions. The adverse reactions were gastrointestinal reaction, reduction in white blood cells, and peripheral neurotoxicity. All of them were mild, having no impact on the treatment. CONCLUSION: Combination therapy of S-1, oxaliplatin, and docetaxel improves the survival of gastric cancer patients treated with palliative resection, with adverse reactions being tolerated. The clinical application of the chemotherapy warrants further investigation.

Association of single nucleotide polymorphisms of ERCC1 and XPF with colorectal cancer risk and interaction with tobacco use.

We investigated the association between polymorphisms in excision repair cross-complementation group 1 (ERCC1) (rs3212986, rs2298881 and rs11615) and xeroderma pigmentosum-complementation group F (XPF) (rs2276466 and rs6498486) and risk of colorectal cancer. A 1:1 matched case-control study was conducted. Conditional regression analysis indicated that individuals carrying the ERCC1 rs3212986 TT genotype and T allele had a marginally increased risk of colorectal cancer when compared with subjects with the GG genotype. Similarly, subjects carrying the rs11615 TT genotype and T allele had a marginally increased risk of colorectal cancer when compared with those with the CC genotype. Stratified analysis revealed that individuals with rs3212986 TT who were current or former smokers had a significantly increased risk of colorectal cancer, and a significant interaction was found between this SNP and cigarette smoking. In conclusion, our study suggests that rs3212986 and rs11615 polymorphisms are associated with risk of colorectal cancer in a Chinese population, particularly in smokers. This finding could be useful in revealing the genetic characteristics of colorectal cancer, and suggests more effective strategies for prevention and treatment.