MicroRNAs as therapeutic targets in human diseases Jeyaseelan, Kandiah; Herath, Wishva B; Armugam, Arunmozhiarasi
Expert opinion on therapeutic targets,
08/2007, Letnik:
11, Številka:
8
Journal Article
Recenzirano
MicroRNAs (miRNAs) are important endogenous regulators of gene expression. The specific regulation at both the transcription and the translation level (inhibition or mRNA degradation) opens an avenue ...to use these small RNA molecules as potential targets for the development of novel drugs as well as for the diagnosis of several human diseases. Important information about the role of a miRNA in disease can be deduced by mimicking or inhibiting its activity and examining its impact on the phenotype/behaviour of the cell or organism. Modulating the activity of a miRNA is expected to lead to improvement in disease symptoms and this implies that the target miRNA plays an important role in the disease. It is also now possible to develop miRNA-based therapeutic products that can either increase or decrease the levels of proteins in pathophysiological conditions such as cancer, cardiovascular diseases, viral diseases, metabolic disorders and programmed cell death. The commercial potential of miRNA and related drugs is expected to exponentially increase within the next few years, yet there are several areas in miRNA biology and delivery that need to be extensively investigated.
The phenomenon of the emergence of the international terrorist group ISIS has succeeded in recruiting members from various countries in the world. This serious threat to national security is closely ...related to the issue of a person's citizenship status, either as a member or as a mere sympathizer. Several countries responded to the entry of their nationals into this international terrorist group with proposals to revoke their citizenship. On the one hand, international terrorism is a serious threat to state sovereignty, on the other hand the problem of denationalizing a former member or affiliated with ISIS is not an easy thing. Citizenship status is a human right that is protected, both in legal instruments in Indonesia and in international legal instruments. Citizenship law in Indonesia regulates in such a way regarding loss of citizenship. From an international perspective, international legal instruments strictly prevent member states from carrying out such denationalization efforts.
Badai ancaman terorisme masih terus mengintai dan tidak dapat dijadikan isapan jempol semata, tulisan ini bertujuan untuk menyoroti kembali tentang apa yang menjadi isu hangat pada pertengahan tahun ...2019-2020 lalu. Ya, wacana kembalinya simpatisan atau pendukung gerakan Islamic State of Iraq and Syria (ISIS) bagi mereka yang berasal dari Indonesia atau memiliki status kewarganegaraan WNI, agar dapat kembali ke tanah air. Ironis memang bila mengingat bahwa banyak yang berangkat dan menjadi simpatisan dengan keyakinan bahwa mereka telah memilih jalan yang benar, namun nyatanya masih memerlukan perhatian dari ibu Pertiwi. Terlepas dari pro dan kontra terhadap pemulangan eks-ISIS ini, penulis ingin menyoroti bagaimana sebenarnya isu pemulangan ini adalah hal yang kompleks, keputusan satu hari akan memberikan dampak kepada banyak hal, termasuk dalam kasus-kasus terorisme yang akan meningkat ke depannya, lalu apakah wacana pemulangan tersebut sudah tepat karena memperhatikan HAM dan sebagai tanggung jawab pihak Indonesia terhadap perilaku warga negaranya di negara lain atau justru menjadi sebuah potensi ancaman terhadap kesejahteraan dan keamanan negara itu sendiri.
Badai ancaman terorisme masih terus mengintai dan tidak dapat dijadikan isapan jempol semata, tulisan ini bertujuan untuk menyoroti kembali tentang apa yang menjadi isu hangat pada pertengahan tahun ...2019-2020 lalu. Ya, wacana kembalinya simpatisan atau pendukung gerakan Islamic State of Iraq and Syria (ISIS) bagi mereka yang berasal dari Indonesia atau memiliki status kewarganegaraan WNI, agar dapat kembali ke tanah air. Ironis memang bila mengingat bahwa banyak yang berangkat dan menjadi simpatisan dengan keyakinan bahwa mereka telah memilih jalan yang benar, namun nyatanya masih memerlukan perhatian dari ibu Pertiwi. Terlepas dari pro dan kontra terhadap pemulangan eks-ISIS ini, penulis ingin menyoroti bagaimana sebenarnya isu pemulangan ini adalah hal yang kompleks, keputusan satu hari akan memberikan dampak kepada banyak hal, termasuk dalam kasus-kasus terorisme yang akan meningkat ke depannya, lalu apakah wacana pemulangan tersebut sudah tepat karena memperhatikan HAM dan sebagai tanggung jawab pihak Indonesia terhadap perilaku warga negaranya di negara lain atau justru menjadi sebuah potensi ancaman terhadap kesejahteraan dan keamanan negara itu sendiri.
Spinal muscular atrophy (SMA) is one of the leading genetic diseases of children and infants. SMA is caused by deletions or mutations of
(
) gene.
, a nearly identical copy of
, cannot compensate for ...the loss of
due to predominant skipping of exon 7. While various regulatory elements that modulate
exon 7 splicing have been proposed, intronic splicing silencer N1 (ISS-N1) has emerged as the most promising target thus far for antisense oligonucleotide-mediated splicing correction in SMA. Upon procuring exclusive license from the University of Massachussets Medical School in 2010, Ionis Pharmaceuticals (formerly ISIS Pharamaceuticals) began clinical development of Spinraza
(synonyms: Nusinersen, IONIS-SMN
, ISIS-SMN
), an antisense drug based on ISS-N1 target. Spinraza
showed very promising results at all steps of the clinical development and was approved by US Food and Drug Administration (FDA) on December 23, 2016. Spinraza
is the first FDA-approved treatment for SMA and the first antisense drug to restore expression of a fully functional protein via splicing correction. The success of Spinraza
underscores the potential of intronic sequences as promising therapeutic targets and sets the stage for further improvement of antisense drugs based on advanced oligonucleotide chemistries and delivery protocols.
This article compares two universes of official Islamic State media that were compiled 18 months apart. It explores the nuances of the group's worldview and illustrates the extent to which external ...and internal situational exigencies impacted the Islamic State's brand during its formative years as caliphate. It finds that the organization's media infrastructure was about half as productive in early 2017 as it had been in mid-2015. The data also show that, even though the group had internationalized its theater of terrorist operations during the time period in question, the brand itself actually contracted to become markedly less globalized in 2016. Finally, the data indicate a substantial thematic rearrangement in the organization's propaganda, one that saw its story shifting away from the millenarian "utopia" towards military denialism. In sum, the data indicate that the Islamic State propagandists were far less productive by January 2017, and that their aggregate product was less international and less utopian but more militant and more defiant, a shift that suggested a new phase in their political marketing operations, one focused on framing the caliphate as an embattled but still defiant pseudo-state struggling to maintain past momentum.
Indonesian Government confronts a multifaceted challenge in repatriating former ISIS members, necessitating a delicate equilibrium between advocacy, citizenship status, and human rights principles. ...International conventions uphold the fundamental right to nationality, articulated in Article 15 of the Universal Declaration of Human Rights, yet over 500 former ISIS members from Indonesia remain stranded in Syria, having illegally departed and destroyed their official documentation. While several countries in Southeast Asia and Europe have undertaken repatriation efforts under rigorous conditions, Indonesia faces a quandary. These individuals do not qualify as People with Social Welfare Problems under domestic law, complicating their reintegration. This classification divergence conflicts with international obligations requiring nations to accept and restore nationality to their citizens, notwithstanding their affiliation with extremist groups not recognized as refugees by the UNHCR. This paper delves into the legal and humanitarian imperatives compelling Indonesia to address this issue. It examines international frameworks and national legislation to argue for the necessity of repatriation, while also exploring the preventive and repressive measures Indonesia employs. Balancing the imperative to safeguard human rights with national security concerns presents a formidable task, demanding a nuanced approach that ensures compliance with international standards while safeguarding domestic stability and security.
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•An uncommon spiroketal steroid, 24-dehydrohippuristaol (1), was isolated from Isis hippuris.•24-Dehydrohippuristaol is the first Δ24(28)-hippuristanol ...derivative.•24-Dehydrohippuristaol showed cytotoxicity towards DLD-1 and LoVo cells.
Chemical screening of a Formosan sea bamboo octocoral Isis hippuris have led to the isolation of nine spiroketal steroids, including a new metabolite, 24-dehydrohippuristanol (1), a new natural product, hippuristanol 11-one (2), as well as seven known analogs, hippuristanol (3), 22-epi-hippuristanol (4), hippurin-1 (5), 22-epi-hippurin-1 (6), 3-acetyl-22-epi-hippurin-1 (7), 3α-acetoxy-11β-hydroxy-24-methyl-22,25-epoxy-5α-furostan-18,20β-lactone (8) and (22S)-3α-acetoxy-11β,18α-dihydroxy-24-methyl-18,20β;22,25-diepoxy-5α-furostane (9). The structures of steroids 1–9 were corroborated by 2D NMR experiments and comparison with literature data. The configurations of steroids 3, 4, 6 and 9, obtained in previous studies, were reported for the first time in this study by single-crystal X-ray diffraction analysis. Steroid 1 exhibited cytotoxic effects against DLD-1 and LoVo cancer cells with IC50 values of 5.54 and 6.89 μM, respectively.
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