Jimenez-Lucena, Rosa;Camargo, Antonio;Alcala-Diaz, Juan Francisco;Romero-Baldonado, Cristina;Luque, Raul Miguel;van Ommen, Ben;Delgado-Lista, Javier;Ordovas, Jose Maria;Perez-Martinez, Pablo;Rangel-Zuniga, Oriol Alberto;Lopez-Miranda, Jose
Experimental and Molecular Medicine
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v.50
no.12
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pp.13.1-13.12
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2018
We aimed to explore whether changes in circulating levels of miRNAs according to type 2 diabetes mellitus (T2DM) or prediabetes status could be used as biomarkers to evaluate the risk of developing the disease. The study included 462 patients without T2DM at baseline from the CORDIOPREV trial. After a median follow-up of 60 months, 107 of the subjects developed T2DM, 30 developed prediabetes, 223 maintained prediabetes and 78 remained disease-free. Plasma levels of four miRNAs related to insulin signaling and beta-cell function were measured by RT-PCR. We analyzed the relationship between miRNAs levels and insulin signaling and release indexes at baseline and after the follow-up period. The risk of developing disease based on tertiles (T1-T2-T3) of baseline miRNAs levels was evaluated by COX analysis. Thus, we observed higher miR-150 and miR-30a-5p and lower miR-15a and miR-375 baseline levels in subjects with T2DM than in disease-free subjects. Patients with high miR-150 and miR-30a-5p baseline levels had lower disposition index (p = 0.047 and p = 0.007, respectively). The higher risk of disease was associated with high levels (T3) of miR-150 and miR-30a-5p ($HR_{T3-T1}=4.218$ and $HR_{T3-T1}=2.527$, respectively) and low levels (T1) of miR-15a and miR-375 ($HR_{T1-T3}=3.269$ and $HR_{T1-T3}=1.604$, respectively). In conclusion, our study showed that deregulated plasma levels of miR-150, miR-30a-5p, miR-15a, and miR-375 were observed years before the onset of T2DM and pre-DM and could be used to evaluate the risk of developing the disease, which may improve prediction and prevention among individuals at high risk for T2DM.
Two species of fishes of Genus Liobagrus that had been collected from three separate river systems in Korea were compared by their morphology and gel electrophoretic patterns of water soluble proteins. In morphology L. andersoni from Han River was distinctly different from L. mediadiposalis collected from both Gum River and Nagdong River. But L. andersoni collected from Gum River not only showed partial similarity for both groups of fishes above in their classifying characteristics but also had a unique ratio of body width/standard length. Comparable similarity and difference among the three groups were also noted in their protein patterns of SDS polyacrylamide gel electrophoresis of various tissues. The difference was clearer and more distinct in the gel run with muscle proteins. A couple of more distinctly different low molecular polypeptides were detected by two dimensional gel electrophoresis. Since the protein patterns shown in this study are not only agreeable with the morphological results but also provide detailed comparisons, fishes of Liobagrus from various water sources can be classified reliably by gel electrophoresis. On the bases of tghe findings above, L. andersoni like fishes collected from Gum River should no longer be classified as L. andersoni. Before naming them as an independent species, the possibility of natural hybrid between the two defined species, or of a varient of L. andersoni by geograpic isolation should be tested.
Siberian chipmunks, Tamias sibiricus, are one of several popular companion animals found in the pet shops of South Korea. At present, however, there have been no studies done in South Korea examining their origin even though they could be potential carriers of zoonotic diseases, and are a species of concern for efficient conservation and management strategies. Sequences of the mitochondrial cytochrome b gene (1140 bp) were determined to investigate the origin of Siberian chipmunks sold in four South Korean pet shops through comparison with sequence data from animals of known locality. Nine Siberian chipmunks were collected from pet shops in South Korea, which resulted in nine haplotypes. One (AR) of these coincided with the haplotype previously described. Phylogenetic and network analyses using 53 haplotypes including 45 haplotypes from GenBank showed three phylogenetic groups in South Korea, almost concordant to locality, designated as northern, central, and southern parts as described in a previous study. Of the nine individuals examined from the pet shops, eight were clustered into the northern phylogroup but one (cgrb9153) was grouped with the southern phylogroup, implying that at least the Siberian chipmunks examined in this study did not originate from other countries. It is likely that most individuals sold in the pet shops of Seoul were caught in the wild in Gyeonggi-do and Gangwon-do, or are maternal descendants of captive-bred individuals originating from the northern part of South Korea. It is recommended that conservation and management units of Korean chipmunks should be examined in further detail.
The discovery of nitric oxide (NO) as a major signaling molecule in a number of pathophysiological processes - vasodilation, immune response, platelet aggregation, wound repair, and cancer biology - has led to the development of various exogeneous NO delivery systems. However, the development of ideal delivery system for human body application is still left as a challenge due to its high reactivity and short half-life in physiological condition. In this article, an overview of several nano-structures as potential NO delivery system will be presented, along with their recent research results and biomedical applications. Nano-size delivery system has immense advantages compared to others due to its high surface-to-volume ratio and capability for surface modification; thus, it has been proven to be effective in delivering nitric oxide with enhanced performance. Through this novel nano-structure delivery system, we are expecting to achieve sustained release of nitric oxide within adequate range of concentration, which ensures desired drug effects at the target site. Among different nano-structures, in particular, nanoparticle, microemulsion and nanofilm will be reviewed and compared to each other in respect of nitric oxide release profile. The proposed nano-structures for exogeneous NO delivery have a biological significance in that it can be further utilized in diverse biomedical fields as a highly promising therapeutic method.
Thyroid cancer is the most common endocrine malignancy. Patients with well-differentiated thyroid cancers, such as papillary and follicular cancers, have a favorable prognosis. However, poorly differentiated thyroid cancers, such as medullary, squamous and anaplastic advanced thyroid cancers, are very aggressive and insensitive to radioiodine treatment. Thus, novel therapies that attenuate metastasis are urgently needed. We found that both PDGFC and PDGFRA are predominantly expressed in thyroid cancers and that the survival rate is significantly lower in patients with high PDGFRA expression. This finding indicates the important role of PDGF/PDGFR signaling in thyroid cancer development. Next, we established a SW579 squamous thyroid cancer cell line with 95.6% PDGFRA gene insertion and deletions (indels) through CRISPR/Cas9. Protein and invasion analysis showed a dramatic loss in EMT marker expression and metastatic ability. Furthermore, xenograft tumors derived from PDGFRA geneedited SW579 cells exhibited a minor decrease in tumor growth. However, distant lung metastasis was completely abolished upon PDGFRA gene editing, implying that PDGFRA could be an effective target to inhibit distant metastasis in advanced thyroid cancers. To translate this finding to the clinic, we used the most relevant multikinase inhibitor, imatinib, to inhibit PDGFRA signaling. The results showed that imatinib significantly suppressed cell growth, induced cell cycle arrest and cell death in SW579 cells. Our developed noninvasive apoptosis detection sensor (NIADS) indicated that imatinib induced cell apoptosis through caspase-3 activation. In conclusion, we believe that developing a specific and selective targeted therapy for PDGFRA would effectively suppress PDGFRA-mediated cancer aggressiveness in advanced thyroid cancers.
In the present study, plant regeneration through adventitious shoot formation from hypocotyl segments of in vitro seedlings of groundcherry (Physalis angulata L.) was investigated to determine the optimum culture conditions for highly efficient regeneration of the species. Adventitious shoots in hypocotyl segments were efficiently induced on MS media with low concentrations of BAP, specifically, with 0.5-1.0 mg/L BAP singly or in combination with 0.1-0.5 mg/L NAA. The 1.0 mg/L BAP single treatment was most effective for forming multiple adventitious shoots. When the induced shoots were transferred to the root induction media, low concentrations of NAA, IBA, and IAA enhanced the development of adventitious roots from adventitious shoots, suggesting that low concentrations of auxins were optimal for producing regenerated plantlets. The number of roots per shoot was large (> 2.0), and the root length exceeded 8.0 cm. In particular, the development and the overall shape of the roots were ideal. Furthermore, the number and length of shoots exceeded 2 and 6.0 cm, respectively. When the regenerated plantlets were transferred to compost soil, the root and shoot systems had developed well to the point that all of the regenerated plantlets acclimated successfully, resulting in normal morphology and growth characteristics, similar to those of the mother plant. Therefore, plant regeneration via adventitious shoot formation is expected to be one of the main methods for producing groundcherry on a large scale for a stable supply of the raw materials.
International Journal of Computer Science & Network Security
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v.22
no.8
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pp.153-162
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2022
Relevance. Innovative activities in education should be aimed at ensuring the comprehensive development of the individual and professional development of students. The main idea of modular technology is that the student should learn by himself, and the teacher manages his learning activities. The advantage of modular technology is the ability of the teacher to design the study of the material in the most interesting and accessible forms for this part of the study group and at the same time achieve the best learning results. Innovative Moodle technology. it is gaining popularity every day, significantly expanding the space of teaching and learning, allowing students to study inter-faculty university programs in depth. The purpose of this study is to assess the quality of implementation of the e-learning system Moodle. The study was conducted at the South Ukrainian National Pedagogical University named after K. D. Ushinsky in order to identify barriers to the effective implementation of innovative distance learning technologies Moodle and introduce a new model that will have a positive impact on the development of e-learning. Methodology. The paper used a combination of theoretical and empirical research methods. These include: scientific analysis of sources on this issue, which allowed us to formulate the initial provisions of the study; analysis of the results of students 'educational activities; pedagogical experiment; questionnaires; monitoring of students' activities in practical classes. Results. This article evaluates the implementation of the principles of distance learning in the process of teaching and learning at the University in terms of quality. The experiment involved 1,250 students studying at the South Ukrainian National Pedagogical University named after K. D. Ushinsky. The survey helped to identify the main barriers to the effective implementation of modern distance learning technologies in the educational process of the University: the lack of readiness of teachers and parents, the lack of necessary skills in applying computer systems of online learning, the inability to interact with the teaching staff and teachers, the lack of a sufficient number of academic consultants online. In addition, internal problems are investigated: limited resources, unevenly distributed marketing advantages, inappropriate administrative structure, and lack of innovative physical capabilities. The article allows us to solve these problems by gradually implementing a distance learning model that is suitable for any university, regardless of its specialization. The Moodle-based e-learning system proposed in this paper was designed to eliminate the identified barriers. Models for implementing distance learning in the learning process were built according to the CAPDM methodology, which helps universities and other educational service providers develop and manage world-class online distance learning programs. Prospects for further research focus on evaluating students' knowledge and abilities over the next six months after the introduction of the proposed Moodle-based program.
Brugada syndrome (BS) is an autosomal dominant inheritance cardiac arrhythmia disorder associated with sudden death in young adults. Thailand has the highest prevalence of BS worldwide, and over 60% of patients with BS still have unclear disease etiology. Here, we performed a new viral metagenome analysis pipeline called VIRIN and validated it with whole genome sequencing (WGS) data of HeLa cell lines and hepatocellular carcinoma. Then the VIRIN pipeline was applied to identify viral integration positions from unmapped WGS data of Thai males, including 100 BS patients (case) and 100 controls. Even though the sample preparation had no viral enrichment step, we can identify several virus genes from our analysis pipeline. The predominance of human endogenous retrovirus K (HERV-K) viruses was found in both cases and controls by blastn and blastx analysis. This study is the first report on the full-length HERV-K assembled genomes in the Thai population. Furthermore, the HERV-K integration breakpoint positions were validated and compared between the case and control datasets. Interestingly, Brugada cases contained HERV-K integration breakpoints at promoters five times more often than controls. Overall, the highlight of this study is the BS-specific HERV-K breakpoint positions that were found at the gene coding region "NBPF11" (n = 9), "NBPF12" (n = 8) and long non-coding RNA (lncRNA) "PCAT14" (n = 4) region. The genes and the lncRNA have been reported to be associated with congenital heart and arterial diseases. These findings provide another aspect of the BS etiology associated with viral genome integrations within the human genome.
Indian spices are well known for their numerous health benefits, flavour, taste, and colour. Recent Advancements in chemical technology have led to better extraction and identification of bioactive molecules (phytochemicals) from spices. The therapeutic effects of spices against diabetes, cardiac problems, and various cancers has been well established. The present in silico study aims to investigate the binding affinity of 29 phytochemicals from 11 Indian spices with two prominent proteins, BCL3 and CXCL10 involved in invasiveness and bone metastasis of breast cancer. The three-dimensional structures of 29 phytochemicals were extracted from PubChem database. Protein Data Bank was used to retrieve the 3D structures of BCL3 and CXCL10 proteins. The drug-likeness and other properties of compounds were analysed by ADME and Lipinski rule of five (RO5). All computational simulations were carried out using Autodock 4.0 on Windows platform. The proteins were set to be rigid and compounds were kept free to rotate. In-silico study demonstrated a strong complex formation (positive binding constants and negative binding energy ΔG) between all phytochemicals and target proteins. However, piperine and sesamolin demonstrated high binding constants with BCL3 (50.681 × 103 mol-1, 137.76 × 103 mol-1) and CXCL10 (98.71 × 103 mol-1, 861.7 × 103 mol-1), respectively. The potential of these two phytochemicals as a drug candidate was highlighted by their binding energy of -6.5 kcal mol-1, -7.1 kcal mol-1 with BCL3 and -6.9 kcal mol-1, -8.2 kcal mol-1 with CXCL10, respectively coupled with their favourable drug likeliness and pharmacokinetics properties. These findings underscore the potential of piperine and sesamolin as drug candidates for inhibiting invasiveness and regulating breast cancer metastasis. However, further validation through in vitro and in vivo studies is necessary to confirm the in silico results and evaluate their clinical potential.
Cellobiose dehydrogenases (CDHs) are a group of enzymes belonging to the hemoflavoenzyme group, which are mostly found in fungi. They play an important role in the production of acid sugar. In this research, CDH annotated from the actinobacterium Cellulomonas palmilytica EW123 (CpCDH) was cloned and characterized. The CpCDH exhibited a domain architecture resembling class-I CDH found in Basidiomycota. The cytochrome c and flavin-containing dehydrogenase domains in CpCDH showed an extra-long evolutionary distance compared to fungal CDH. The amino acid sequence of CpCDH revealed conservative catalytic amino acids and a distinct flavin adenine dinucleotide region specific to CDH, setting it apart from closely related sequences. The physicochemical properties of CpCDH displayed optimal pH conditions similar to those of CDHs but differed in terms of optimal temperature. The CpCDH displayed excellent enzymatic activity at low temperatures (below 30℃), unlike other CDHs. Moreover, CpCDH showed the highest substrate specificity for disaccharides such as cellobiose and lactose, which contain a glucose molecule at the non-reducing end. The catalytic efficiency of CpCDH for cellobiose and lactose were 2.05 × 105 and 9.06 × 104 (M-1 s-1), respectively. The result from the Fourier-transform infrared spectroscopy (FT-IR) spectra confirmed the presence of cellobionic and lactobionic acids as the oxidative products of CpCDH. This study establishes CpCDH as a novel and attractive bacterial CDH, representing the first report of its kind in the Cellulomonas genus.
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