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2022 ◽  
Vol 12 ◽  
Author(s):  
Eslam E. Abd El-Fattah ◽  
Sameh Saber ◽  
Mahmoud E. Youssef ◽  
Hanan Eissa ◽  
Eman El-Ahwany ◽  
...  

HIF-1α is a key factor promoting the development of hepatocellular carcinoma (HCC). As well, AKT-AMPKα-mTOR signaling is a promising target for cancer therapy. Yet, the AKT-AMPKα-mTOR-dependent activation of HIF-1α has not been studied in livers with HCC. In addition, the mechanisms underlying the potential antineoplastic effects of sitagliptin (STGPT), an antidiabetic agent, have not yet been elucidated. For that purpose, the N-nitrosodiethylamine (NDEA)-induced HCC mouse model was used in the present study using a dose of 100 mg/kg/week, i.p., for 8 weeks. NDEA-induced HCC mice received STGPT 20, 40, or 80 mg/kg starting on day 61 up to day 120. The present study revealed that STGPT inhibited HIF-1α activation via the interference with the AKT-AMPKα-mTOR axis and the interruption of IKKβ, P38α, and ERK1/2 signals as well. Accordingly, STGPT prolonged the survival, restored the histological features and improved liver function. Additionally, STGPT inhibited angiogenesis, as revealed by a significant downregulation in the VEGF and mRNA expression of CD309 with concomitant inhibition of tissue invasion was evident by an increased ratio of TIMP-1/MMP-2. STGPT exhibited apoptotic stimulatory effect as indicated upon calculating the BCL-2/Bax ratio and by the gene expression of p53. The decrease in AFP and liver index calculation, gene expression of Ki-67 confirmed the antiproliferative activity of STGPT. The anti-inflammatory potential was revealed by the decreased TNF-α level and the downregulation of MCP-1 gene expression. Moreover, an antifibrotic potential was supported by lower levels of TGF-β. These effects appear to be GLP1R-independent. The present study provides a potential basis for repurposing STGPT for the inhibition of HCC progression. Since STGPT is unlikely to cause hypoglycemia, it may be promising as monotherapy or adjuvant therapy to treat diabetic or even normoglycemic patients with HCC.


Dialog ◽  
2021 ◽  
Vol 44 (2) ◽  
pp. 178-189
Author(s):  
Krisharyanto Umbu Deta

This has been prevalent that the discourse of interreligious dialogue has been overwhelmingly dominated by the elites in the formal spheres. It even seems to be the only standard to examine the issues of interreligious relations, without taking into account the diverse modes of everyday engagements among the people. This then raises the recognition that there is actually no single pattern for interreligious engagement since it would be always contextual according to its distinctive context. It therefore implies the need to learn more from the localities to develop more contextual interreligious engagement. In this regard, this work will examine the interreligious engagement of Christianity and Marapu indigenous religion in Sumba. The data used in this work are based on the field research conducted in 2019 in Southwest Sumba. Observation and in depth interview with a number of Sumbanese Christians and Marapu are also conducted. The research finds that manawara (the teaching of love; compassion) as the potential basis for developing social engagement. The term manawara is used by Marapu people in their teaching, but since the term is a Sumbanese language, the Sumbanese Christians also translate their prominent teaching of love with that term. Manawara is then both scriptural-based for Christians, and oral-based for Marapu people. Using Lattu’s oral-based interreligious engagement and Knitter’s socially engaged dialogue as the theoretical frameworks, this work argues that manawara as a shared virtue is very potential to be developed, in realizing common liberation of the Sumbanese through mutual action. Keywords: interreligious engagement, manawara, orality, sumbanese christian, marapu indigenous rel   Wacana dialog antaragama selama ini telah didominasi sedemikian rupa oleh para elit dalam ruang-ruang formal. Hal itu bahkan menjadi seolah satu-satunya ukuran untuk membahas isu-isu hubungan antaragama, tanpa memperhitungkan keberagaman bentuk keterlibatan sehari-hari yang dihidupi secara nyata oleh orang-orang beragama yang merupakan subjek utama dalam topik tersebut. Dari sinilah kemudian muncul kesadaran bahwa sebenarnya tidak ada satu pola tertentu untuk keterlibatan antaragama karena ia akan selalu tergantung pada konteksnya yang unik. Hal ini menunjukkan bahwa penting untuk lebih banyak belajar dari lokalitas-lokalitas yang ada demi mengembangkan keterlibatan antaragama yang lebih kontekstual. Untuk itu, tulisan ini akan membahas keterlibatan antaragama Kristen dan Marapu di Sumba. Data yang digunakan dalam studi ini diperoleh dari sebuah penelitian lapangan pada tahun 2019 di Sumba Barat Daya yang dilakukan melalui observasi dan wawancara mendalam dengan sejumlah orang Sumba Kristen dan Marapu. Penelitian tersebut menemukan manawara (ajaran tentang kasih) sebagai basis potensial untuk mengembangkan keterlibatan yang ada. Istilah manawara digunakan oleh orang Marapu dalam ajaran mereka, namun karena istilah tersebut adalah sebuah kata dalam Bahasa Sumba, orang Sumba Kristen juga menerjemahkan ajaran kasih mereka dengan istilah manawara tersebut. Dengan demikian, manawara menjadi suatu ajaran yang basisnya skriptural, bagi orang Kristen, dan oral, bagi orang Marapu. Dengan menggunakan keterlibatan antaragama berbasis oral dari Lattu dan socially engaged dialogue dari Knitter sebagai kerangka teori, studi ini berargumen bahwa manawara sebagai sebuah kebajikan bersama sangatlah potensial untuk dikembangkan, dalam merealisasikan pembebasan bersama orang Sumba melalui aksi bersama. Kata Kunci: keterlibatan antaragama, manawara, kelisanan, orang Kristen Sumba, agama Marapu


Quaternary ◽  
2021 ◽  
Vol 4 (4) ◽  
pp. 43
Author(s):  
Dmytro Hlavatskyi ◽  
Vladimir Bakhmutov

We present new palaeomagnetic and rock magnetic results with a stratigraphic interpretation of the late Early–Middle Pleistocene deposits exposed on the left bank of the River Danube at Dolynske, southern Ukraine. A thick succession of water-lain facies is succeeded by reddish-brown clayey soils, topped by a high-resolution loess–palaeosol sequence. These constitute one of the most complete recently discovered palaeoclimate archives in the Lower Danube Basin. The suggested stratigraphy is based on the position of the Matuyama–Brunhes boundary, rock magnetic, palaeopedological and sedimentological proxies, and it is confidently correlated with other loess records in the region (Roksolany and Kurortne), as well as with the marine isotope stratigraphy. The magnetic susceptibility records and palaeosol characteristics at Dolynske show an outstanding pattern that is transitional between eastern and south-eastern European loess records. Our data confirm that the well-developed S4 soil unit in Ukraine, and S5 units in Romania, Bulgaria and Serbia, correlate with the warm MIS 11. Furthermore, we suggest the correlation of rubified S6 palaeosols in Romania and Bulgaria and the V-S7–V-S8 double palaeosol in Serbia with S6 in Ukraine, a strong Mediterranean-type palaeosol which corresponds to MIS 15. Our new results do not support the hypothesis of a large magnetic lock-in depth like that previously interpreted for the Danube loess, and they prove that the Matuyama–Brunhes boundary is located within the palaeosol unit corresponding to MIS 19. The proposed stratigraphic correlation scheme may serve as a potential basis for further regional and global Pleistocene climatic reconstructions.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhichao Zhang ◽  
Shuai Yu ◽  
Jing Li ◽  
Yanbin Zhu ◽  
Siqi Jiang ◽  
...  

Abstract Background Genomic imprinting is an epigenetic phenomenon mainly occurs in endosperm of flowering plants. Genome-wide identification of imprinted genes have been completed in several dicot Cruciferous plant and monocot crops. Results Here, we analyzed global patterns of allelic gene expression in developing endosperm of sunflower which belongs to the composite family. Totally, 691 imprinted loci candidates were identified in 12 day-after-pollination sunflower endosperm including 79 maternally expressed genes (MEG) and 596 paternally expressed genes (PEG), 6 maternally expressed noncoding RNAs (MNC) and 10 paternally expressed noncoding RNAs (PNC). And a clear clustering of imprinted genes throughout the rapeseed genome was identified. Generally, imprinting in sunflower is conserved within a species, but intraspecific variation also was detected. Limited loci in sunflower are imprinted in other several different species. The DNA methylation pattern around imprinted genes were investigated in embryo and endosperm tissues. In CG context, the imprinted genes were significantly associated with differential methylated regions exhibiting hypomethylation in endosperm and hypermethylation in embryo, which indicated that the maternal demethylation in CG context potentially induce the genomic imprinting in endosperm. Conclusion Our study would be helpful for understanding of genomic imprinting in plants and provide potential basis for further research in imprinting in sunflower.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Taiyu Hui ◽  
Yuanyuan Zheng ◽  
Chang Yue ◽  
Yanru Wang ◽  
Zhixian Bai ◽  
...  

AbstractCompetitive endogenous RNA (ceRNA) is a transcript that can be mutually regulated at the post-transcriptional level by competing shared miRNAs. The ceRNA network connects the function of protein-encoded mRNA with the function of non-coding RNA, such as microRNA (miRNA), long non-coding RNA (lncRNA), and circular RNA (circRNA). However, compared with the ceRNA, the identification and combined analysis of lncRNAs, mRNAs, miRNAs, and circRNAs in the cashmere fineness have not been completed. Using RNA-seq technology, we first identified the miRNAs presented in Liaoning Cashmere Goat (LCG) skin, and then analyzed the mRNAs, lncRNAs, circRNAs expressed in LCG and Inner Mongolia cashmere goat (MCG) skin. As a result, 464 known and 45 new miRNAs were identified in LCG skin. In LCG and MCG skin, 1222 differentially expressed mRNAs were identified, 170 differentially expressed lncRNAs and 32 differentially expressed circRNAs were obtained. Then, qRT-PCR was used to confirm further the representative lncRNAs, mRNAs, circRNAs and miRNAs. In addition, miRanda predicted the relationships of ceRNA regulatory network among lncRNAs, circRNAs, miRNAs and mRNAs, the potential regulatory effects were investigated by Go and KEGG analysis. Through the screening and analysis of the results, the ceRNA network regulating cashmere fineness was constructed. LncRNA MSTRG14109.1 and circRNA452 were competed with miRNA-2330 to regulated the expression of TCHH, KRT35 and JUNB, which may provide a potential basis for further research on the process of regulating the cashmere fineness.


EMJ Diabetes ◽  
2021 ◽  
pp. 80-83
Author(s):  
Pablo Millares Martin ◽  
Rosa Bobet Reyes

Background: Heart failure (HF) is underdiagnosed among patients with diabetes. Awareness is required to improve its management and to reduce its impact. Objectives: To suggest a risk assessment tool that could facilitate the early diagnosis of HF and even reduce its incidence by facilitating individualised management plans. Methods: Assess current medical literature, searching for parameters that indicate a higher risk of HF among the diabetic population. Results: Twenty-four parameters were found that could be the potential basis for a risk stratification tool. Conclusion: The concept of a risk stratification tool is presented. Work on validating will be required. It has the potential to affect the future management of patients with diabetes and to reduce the incidence and prevalence of HF in this population.


2021 ◽  
pp. 201-229
Author(s):  
Channa Samkalden

Channa Samkalden reviews the position in the Netherlands regarding the imposition of liability on multinationals for human rights abuses overseas. She explains the potential basis for, the process, and the advantages of seeking corporate criminal liability under the provisions of the Criminal Code. Regarding civil liability, she outlines the rules on jurisdiction, applicable law and the interplay with the Dutch Code of Civil Procedure, including forum necessitates. She outlines jurisdictional decisions in Milieudefensie v. Shell and Kiobel v. Shell and the principle for establishing foreign direct civil liability on a parent company based on the breach of a tort law duty of care and alternative grounds and the potential relevance of soft law and the European Convention on Human Rights. She outlines the rules on admissibility of claims by representative organisations, collective actions, limitation, assessment of damages, discovery, witness protection, and costs and funding.


2021 ◽  
Author(s):  
Е. Янковская ◽  
◽  
Дмитрий Войтка ◽  
М. Федорович ◽  
А. Михнюк ◽  
...  

The researches on evaluation the influence of entomopathogenic fungi of the genuses Beauveria, Isaria and Lecanicillium influence on phytopathogenic microorganisms Alternaria solani, Botrytis ciner-ea, Sclerotinia sclerotiorum, Rhizoctonia solani, Fusarium solani, Phytophtora alni are presented. The antifungal peculiarities of tested strains – a potential basis of complex action biological preparations for plant protection are shown in vitro. The highest level of antagonistic activity has been revealed in strains Beauveria brongniartii МХ, Lecanicillium sp. аph and Isaria fumosorosea 21-2.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yaojun Tong ◽  
Tue S. Jørgensen ◽  
Christopher M. Whitford ◽  
Tilmann Weber ◽  
Sang Yup Lee

AbstractCRISPR base editing is a powerful method to engineer bacterial genomes. However, it restricts editing to single-nucleotide substitutions. Here, to address this challenge, we adapt a CRISPR-Prime Editing-based, DSB-free, versatile, and single-nucleotide resolution genetic manipulation toolkit for prokaryotes. It can introduce substitutions, deletions, insertions, and the combination thereof, both in plasmids and the chromosome of E. coli with high fidelity. Notably, under optimal conditions, the efficiency of 1-bp deletions reach up to 40%. Moreover, deletions of up to 97 bp and insertions up to 33 bp were successful with the toolkit in E. coli, however, efficiencies dropped sharply with increased fragment sizes. With a second guide RNA, our toolkit can achieve multiplexed editing albeit with low efficiency. Here we report not only a useful addition to the genome engineering arsenal for E. coli, but also a potential basis for the development of similar toolkits for other bacteria.


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