Comprehensive Analysis of CDK1-Associated ceRNA Network Revealing the Key Pathways LINC00460/LINC00525-Hsa-Mir-338-FAM111/ZWINT as Prognostic Biomarkers in Lung Adenocarcinoma Combined with Experiments.

Lung adenocarcinoma (LUAD) is the leading cause of cancer deaths worldwide, and effective biomarkers are still lacking for early detection and prognosis prediction. Here, based on gene expression profiles of LUAD patients from The Cancer Genome Atlas (TCGA), 806 long non-coding RNAs (lncRNAs), 122 microRNAs (miRNAs) and 1269 mRNAs associated with CDK1 were identified. The regulatory axis of LINC00460/LINC00525-hsa-mir-338-FAM111B/ZWINT was determined according to the correlation between gene expression and patient prognosis. The abnormal up-regulation of FAM111B/ZWINT in LUAD was related to hypomethylation. Furthermore, immune infiltration analysis suggested FAM111B/ZWINT could affect the development and prognosis of cancer by regulating the LUAD immune microenvironment. EMT feature analysis suggested that FAM111B/ZWINT promoted tumor spread through the EMT process. Functional analysis showed FAM111B/ZWINT was involved in cell cycle events such as DNA replication and chromosome separation. We analyzed the HERB and GSCALite databases to identify potential target medicines that may play a role in the treatment of LUAD. Finally, the expression of LINC00460/LINC00525-hsa-mir-338-FAM111B/ZWINT axis was verified in LUAD cells by RT-qPCR, and these results were consistent with bioinformatics analysis. Overall, we constructed a CDK1-related ceRNA network and revealed the LINC00460/LINC00525-hsa-mir-338-FAM111/ZWINT pathways as potential diagnostic biomarkers or therapeutic targets of LUAD.

Antibiotic Resistance Conferred by Class 1 Integron in Vibrio Cholerae Strains: A Meta-analysis.

Background: Class 1 integron is the most ubiquitous platform among antibiotic resistance bacterial populations, including Vibrio cholerae strains. This meta-analysis aimed to determine the antibiotic resistance conferred by class 1 integron conserved segments (CS); 3'-qacEΔ1 and sul1, and 5'-int1 in V. cholerae strains. Methods: An intensive literature search of electronic databases for relevant studies from their starting dates up to April 2019 was conducted by two independent investigators. The electronic databases included; PubMed, Ovid Medline and Google Scholar databases. Only studies that determined antibiotic resistance conferred by class 1 integron in V. cholerae strains isolated from clinical and/or environmental samples using Polymerase Chain Reaction (PCR) assay were included in this study. Results: The random-effects model was selected and performed for all the studies included in this meta-analysis. Fourteen studies consisting of both qacEΔ1 and sul1, and int1 in the class 1 integron of V. cholerae strains were included. The proportions of class 1 integron 3'-CS and 5'-CS were 70.4 % (95%CI: 37.5-94.4) and 52 % (95% CI: 6.3-95.7) respectively. Conclusions: The proportions of class 1 integron in V. cholerae strains significantly contributed to the antibiotic resistances, which are comparable to other gram-negative bacteria clinical isolates. Moreover, the 3'-CS qacEΔ1 and sul1 are highly involved in the antibiotic resistance in comparison to 5'-CS int1. Generally, the study findings provide a general view on antibiotic resistance conferred by class 1 integron in Vibrio cholerae strains.

Expression analysis of p16 and TOP2A protein biomarkers in cervical cancer lesions and their correlation with clinico-histopathological characteristics in a referral hospital, Tanzania.

INTRODUCTION: Biomarkers yield important information for early diagnosis of cervical cancer. However, they are rarely applied for prognosis of cervical cancer in Tanzania, where visual inspection assay with acetic acid or Lugol's iodine and Pap test are being used as the standard screening/ diagnostic methods. METHODS: This was a retrospective hospital-based cross-sectional study that was conducted to assess cyclin-dependent kinase inhibitor (p16) and topoisomerase II-alpha (TOP2A) proteins expression among women seeking cervical cancer care at Kilimanjaro Christian Medical Centre, Tanzania between May 1, 2017 and May 10, 2018. Immunohistochemistry technique was used to detect the expressions of p16 and TOP2A proteins from the retrieved formalin-fixed and paraffin-embedded (FFPE) cervical biopsies. RESULTS: A total of 145 patients, with a mean age of 52.1 ± 12.9 years, were included in this study. Upon immunohistochemistry staining, 103 (71.0%) and 90 (62.1%) were p16 and TOP2A positive respectively. There was a strong association between histopathological class and p16/TOP2A expression levels (Fisher's exact test, p<0.001). Moreover, there was a strong positive correlation between p16/TOP2A and cancerous cervical lesions (Spearman's rank correlation coefficients = 0.833 and 0.687, p = 0.006 and 0.005, respectively). The age-adjusted odds ratio for predicting cervical cancer lesions were independently significant for p16/TOP2A biomarkers in FFPE cervical tissues [p16: OR = 1.142 (95% CI: 1.059-1.232, p<0.001) and TOP2A: OR = 1.046 (95% CI: 1.008-1.085, p = 0.015)]. Importantly, the diagnostic performance of p16 was higher than that of TOP2A in the diagnosis of cancerous lesions from non-cancerous cervical lesions (sensitivity: 97.2% versus 77.6%, accuracy: 92.8% versus 87.8%, respectively). CONCLUSION: Our study has highlighted that over-expression of TOP2A is related to the grade of cervical intraepithelial neoplasia but does not predict prognosis in cervical cancer. Similarly, expression of p16 is related to degree of histological dysplasia and malignancy, suggesting its prognostic and predictive value in the management of cervical cancers. Further bigger studies are needed to validate their applications in the early diagnosis of cervical cancer.

MiR-9-1 Suppresses Cell Proliferation and Promotes Apoptosis by Targeting UHRF1 in Lung Cancer.

Lung cancer is listed as the most common reason for cancer-related death all over the world despite diagnostic improvements and the development of chemotherapy and targeted therapies. MicroRNAs control both physiological and pathological processes including development and cancer. A microRNA-9 to 1 (miR-9 to 1) overexpression model in lung cancer cell lines was established and miR-9 to 1 was found to significantly suppress the proliferation rate in lung cancer cell lines, colony formation in vitro, and tumorigenicity in nude mice of A549 cells. Ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) was then identified to direct target of miR-9 to 1. The inhibition of UHRF1 by miR-9 to 1 causes G1 arrest and p15, p16, and p21 were re-expressed in miR-9 to 1 group in mRNA level and protein level. Silence of UHRF1 expression in A549 cells resulted in the similar re-expression of p15, p16, p21 which is similar with miR-9 to 1 infection. Therefore, we concluded that UHRF1 is a new target for miR-9 to 1 to suppress cell proliferation by re-expression of tumor suppressors p15, p16, and p21 mediated by UHRF1.

Biosafety risk assessment of nanoparticles: Evidence from food case studies.

Nanotechnology provides a wide range of benefits in the food industry in improving food tastes, textures, sensations, quality, shelf life, and food safety. Recently, potential adverse effects such as toxicity and safety concerns have been associated with the increasing use of engineered nanoparticles in food industry. Additionally, very limited information is known concerning the behavior, properties and effects of food nano-materials in the gastrointestinal tract. There is explores the current advances and provides insights of the potential risks of nanoparticles in the food industry. Specifically, characteristics of food nanoparticles and their absorption in the gastrointestinal tract, the effects of food nanoparticles against the gastrointestinal microflora, and the potential toxicity mechanisms in different organs and body systems are discussed. This review would provide references for further investigation of nano-materials toxicity effect in foods and their molecular mechanisms. It will help to develop safer foods and expand nano-materials applications in safe manner.

WT1-AS/IGF2BP2 Axis Is a Potential Diagnostic and Prognostic Biomarker for Lung Adenocarcinoma According to ceRNA Network Comprehensive Analysis Combined with Experiments.

Lung adenocarcinoma (LUAD) is one of the most common malignancies, and there is still a lack of effective biomarkers for early detection and prognostic prediction. Here, we comprehensively analyze the characteristics of. an RNA sequencing data set of LUAD samples. In total, 395 long non-coding RNAs (lncRNAs), 89 microRNAs (miRNAs), and 872 mRNAs associated with c-Myc were identified, which were differentially expressed between tumor and normal tissues. The most relevant pathway was found to be WT1-AS-miR-200a-3p-IGF2BP2 according to the rules of competitive endogenous RNA (ceRNA) regulation. WT1-AS and IGF2BP2 expression were positively correlated and increased in LUAD samples, while miR-200a-3p had relatively low expression. The high expression of WT1-AS and IGF2BP2 was associated with poor prognosis in LUAD patients, while low expression of miR-200a-3p predicted reduced survival (p < 0.05). The analysis of the multi-gene regulation model indicated that the WT1-AS (downregulation)-miR-200a-3p (upregulation)-IGF2BP2 (downregulation) pattern significantly improved the survival of LUAD patients. Finally, reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were detected in LUAD cells, and the results are consistent with the bioinformatics analysis. In summary, the WT1-AS/IGF2BP2 axis is a potential prognostic biomarker in LUAD and is expected to become an effective target for diagnosis and treatment.

Insulin-delivery methods for children and adolescents with type 1 diabetes.

Efforts directed toward restoring normal metabolic levels by mimicking the physiological insulin secretion, thereby ensuring safety, efficacy, minimal invasiveness and conveniences, are of great significance in the management of type 1 diabetes among children and adolescents. Regardless of the various technologies being discovered in addressing invasiveness and enhancing medication adherence in the management of type 1 diabetes, yet limited success had been observed among children and adolescents. The multiple daily subcutaneous insulin injections route using vial and syringe, and occasionally insulin pens, remain the most predictable route for insulin administration among children and adolescents. However, this route has been associated with compromised patient compliance, fear of injections and unacceptability, resulting in poor glycemic control, which promote the demand for alternative routes of insulin administration. Alternative routes for delivering insulin are being investigated in children and adolescents with type 1 diabetes; these include the hybrid closed-loop 'artificial pancreas' system, oral, inhalation, intranasal routes, and others. This review article explores the current advances in insulin-delivery methods that address the needs of children and adolescents in the treatment of type 1 diabetes.

Linking rhizosphere bacterial diversity and soil fertility in tobacco plants under different soil types and cropping pattern in Tanzania: A pilot study.

Tobacco (Nicotiana tabacum L.), one of the major crop plants in Tanzania, cropping affects the level of soil fertility, but the reason has not been known. Plant rhizosphere plays an important role in affecting soil fertility through changing microbial composition. We planned a pilot study to understand the changes in microbial composition and soil nutrients in the rhizosphere soils of tobacco in three agro-ecological zone, namely Sikonge, Tabora and Urambo in Tanzania. This study assessed bacteriota composition using 16S rRNA sequencing and soil fertility in the rhizosphere of tobacco plants. The results showed that bacterial diversity in tobacco rhizosphere soils belonged to Proteobacteria phyla, associated significantly (p < 0.05) with solubilization of insoluble P, K and S. The solubilization of P, K and S in soils facilitates the availability of these nutrients to the tobacco plants (a heavy feeder crop) allows low levels of these nutrients in the soils for the subsequent crop. The Proteobacteria phyla also associated with an increase in soil N content through fixation. Therefore, bacteria diversity in tobacco rhizosphere influence solubilities of macronutrients (P, K, S) and quickly up taken by the tobacco plant and reduces their levels in soils, some bacteria involved in fixing N and increases total N in the soil.

MicroRNA Response and Toxicity of Potential Pathways in Human Colon Cancer Cells Exposed to Titanium Dioxide Nanoparticles.

Titanium dioxide nanoparticles (TiO2-NPs) are widely used for biomedical and food applications, the toxicity of TiO2-NPs in vivo and in vitro has been elucidated, but the underlying cytotoxicity of TiO2-NPs against microRNA remains largely unknown. The purpose of this study was to analyze microRNA profiling induced by TiO2-NPs against NCM460 and HCT116 cell lines. Comparative analysis identified 34 and 24 microRNAs were significantly altered in the TiO2-NPs treated cells at concentrations of 3 and 30 µg/mL, respectively. Functional classification demonstrated that a large proportion of genes involved in metabolism, human disease, and environmental information process were significantly upregulated by TiO2-NPs. Bioinformatics analysis suggested that microRNA 378 might be an early indicator of cellular response to exogenous stimuli with apoptotic signals. Furthermore, TiO2-NPs significantly altered the expression of microRNA 378b and 378g in HCT116 and NCM460 cell lines at different concentrations from 3 to 6 µg/mL. These concentrations elicit high-sensitivity of stimuli response in colon cancer cells when exposed to the slight doses of TiO2-NPs. Our study indicated that microRNAs 378b and 378g may play an important role in TiO2-NPs-mediated colonic cytotoxicity, which may provide a valuable insight into the molecular mechanisms of potential risks in colitis and colon cancer.

Rapid recognition and determination of tryptophan by carbon nanotubes and molecularly imprinted polymer-modified glassy carbon electrode.

A tryptophan (Trp) molecularly imprinted electrochemical sensor was fabricated by drop-coating an imprinted chitosan film on the surface of a glassy carbon electrode modified with multi-walled carbon nanotubes (MIP-MWCNTs/GCE). The surface morphology and electrochemical properties of the MIP-MWCNTs/GCE were characterized by scanning electron microscopy (SEM) and cyclic voltammetry (CV), respectively. The formation of hydrogen bonds between the functional polymer and the template molecule was confirmed by infrared spectroscopy. The electrochemical performance of the MIP-MWCNTs/GCE with Trp showed that the signal of the oxidation current of Trp obtained with MIP-MWCNTs/GCE was significantly enhanced relative to that of the uncovered GCE, indicating that the modified electrode can accelerate electron transfer and has strong selectivity for Trp. The experimental conditions were optimized in parallel, and under the optimal conditions, the MIP-MWCNTs/GCE showed a good linear relationship between the Trp oxidation peak current and Trp concentrations in the ranges of 2.0 nM-0.2 µM, 0.2 µM-10 µM and 10 µM-100 µM The limit of detection (LOD) was 1.0 nM (S/N = 3), and the modified electrode had good reproducibility and stability. Finally, the MIP-MWCNTs/GCE was successfully applied to the determination of Trp in the human serum samples.