108 research outputs found
An intricate rewiring of cancer metabolism via alternative splicing
No full textAll human genes undergo alternative splicing leading to the diversity of the proteins. However, in some cases, abnormal regulation of alternative splicing can result in diseases that trigger defects in metabolism, reduced apoptosis, increased proliferation, and progression in almost all tumor types. Metabolic dysregulations and immune dysfunctions are crucial factors in cancer. In this respect, alternative splicing in tumors could be a potential target for therapeutic cancer strategies. Dysregulation of alternative splicing during mRNA maturation promotes carcinogenesis and drug resistance in many cancer types. Alternative splicing (changing the target mRNA 3'UTR binding site) can result in a protein with altered drug affinity, ultimately leading to drug resistance.. Here, we will highlight the function of various alternative splicing factors, how it regulates the reprogramming of cancer cell metabolism, and their contribution to tumor initiation and proliferation. Also, we will discuss emerging therapeutics for treating tumors via abnormal alternative splicing. Finally, we will discuss the challenges associated with these therapeutic strategies for clinical applications
Alternative Splicing: A Potential Therapeutic Target in Hematological Malignancies
No full textLeukemia represents the most prevalent malignancy in children, constituting 30% of childhood cancer cases, with acute lymphoblastic leukemia (ALL) being particularly heterogeneous. This paper explores the role of alternative splicing in leukemia, highlighting its significance in cancer development and progression. Aberrant splicing is often driven by mutations in splicing-factor genes, which can lead to the production of variant proteins that contribute to oncogenesis. The spliceosome, a complex of small nuclear RNAs and proteins, facilitates RNA splicing, a process critical for generating diverse mRNA and protein products from single genes. Mutations in splicing factors, such as U2AF1, SF3B1, SRSF2, ZRSR2, and HNRNPH1, are frequently observed across various hematological malignancies and are associated with poor prognosis and treatment resistance. This research underscores the necessity of understanding the mechanisms of RNA splicing dysregulation in order to develop targeted therapies to correct these aberrant processes, thereby improving outcomes for patients with leukemia and related disorders
P53: A key player in diverse cellular processes including nuclear stress and ribosome biogenesis, highlighting potential therapeutic compounds
No full textThe tumor suppressor proteins are key transcription factors involved in the regulation of various cellular processes,such as apoptosis, DNA repair, cell cycle, senescence, and metabolism. The tumor suppressor protein p53 responds to different type of stress signaling, such as hypoxia, DNA damage, nutrient deprivation, oncogene activation, by activating or repressing the expression of different genes that target processes mentioned earlier. p53 has the ability to modulate the activity of many other proteins and signaling pathway through protein–protein interaction, post-translational modifications, or non-coding RNAs. In many cancers the p53 is found to be mutated or inactivated, resulting in the loss of its tumor suppressor function and acquisition of new oncogenic properties. The tumor suppressor protein p53 also plays a role in the development of other metabolic disorders such as diabetes, obesity, and fatty liver disease. In this review, we will summarize the current data and knowledge on the molecular mechanisms and the functions of p53 in different pathways and processes at the cellular level and discuss the its implications for human health and disease
Advances in molecular function of UPF1 in Cancer
No full textIt is known that more than 10% of genetic diseases are caused by a mutation in protein-coding mRNA (premature termination codon; PTC). mRNAs with an early stop codon are degraded by the cellular surveillance process known as nonsense-mediated mRNA decay (NMD), which prevents the synthesis of C-terminally truncated proteins. Up-frameshift-1 (UPF1) has been reported to be involved in the downregulation of various cancers, and low expression of UPF1 was shown to correlate with poor prognosis. It is known that UPF1 is a master regulator of nonsense-mediated mRNA decay (NMD). UPF1 may also function as an E3 ligase and degrade target proteins without using mRNA decay mechanisms. Increasing evidence indicates that UPF1 could serve as a good biomarker for cancer diagnosis and treatment for future therapeutic applications. Long non-coding RNAs (lncRNAs) have the ability to bind different proteins and regulate gene expression; this role in cancer cells has already been identified by different studies. This article provides an overview of the aberrant expression of UPF1, its functional properties, and molecular processes during cancer for clinical applications in cancer. We also discussed the interactions of lncRNA with UPF1 for cell growth during tumorigenesis
Ribosome-directed therapies in cancer
No full textThe human ribosomes are the cellular machines that participate in protein synthesis, which is deeply affected during cancer transformation by different oncoproteins and is shown to provide cancer cell proliferation and therefore biomass. Cancer diseases are associated with an increase in ribosome biogenesis and mutation of ribosomal proteins. The ribosome represents an attractive anti-cancer therapy target and several strategies are used to identify specific drugs. Here we review the role of different drugs that may decrease ribosome biogenesis and cancer cell proliferation
Role of community health workers in addressing dementia: A global perspective
No full textThe current increase in dementia prevalence suggests a need for public health intervention. While prevention is crucial, lack of awareness, limited access to healthcare system and shortage of health workforce are significant shortcomings. Therefore, adopting a process that increases utilization of community health workers (CHWs) is a promising strategy. This review synthesizes existing research on roles of CHWs in dementia related services to improve dementia care. PubMed, CINAHL, Scopus, CABI Global Health, Web of Science, PsycINFO, and Cochrane Library were searched for specific keywords. A cited reference search and reference list search were also conducted. Among the ten eligible articles, six cross-sectional, two pre-post, one longitudinal and one qualitative study were found. Four broad aspects emerged as potential roles of CHWs. Four studies focused on screening for dementia, two on screening for HIV-associated dementia (HIV-D), three on dementia education and one on advance care planning (ACP) conversations. The dementia education intervention was conducted among the underrepresented and culturally and linguistically diverse (CALD) communities. Nine of the ten studies (90%) found the CHWs to be efficient in performing the interventions. The CHWs were trained and results were evaluated. CHWs were influential in bridging the community and the healthcare system and addressed dementia through cost effective approaches. Their engagement in multiple wide-ranging programs in future may help to prevent, screen and manage dementia.Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2022-05-01The student, Rifat Alam, accepted the attached license on 2020-05-13 at 13:19.The student, Rifat Alam, submitted this Thesis for approval on 2020-05-13 at 13:45.This Thesis was approved for publication on 2020-05-13 at 15:03.DSpace SAF Submission Ingestion Package generated from Vireo submission #15383 on 2020-08-25 at 17:44:27Made available in DSpace on 2020-08-27T00:51:34Z (GMT). No. of bitstreams: 2
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A study on strengthening of reinforced concrete frames using precast concrete panels
No full textThis study describes the effectiveness of the behavior resulting from strengthening infill walls in existing reinforced concrete frame systems with low resistance against earthquake effects using precast concrete panels. In this study, a strengthening method that can be applied without building occupants having to leave the building was investigated. For this purpose, six 1/2 scale, two-story and single span test specimens with brick infill walls and low earthquake resistance, which have common errors seen in existing reinforced concrete buildings, were generated. The first of test frames with equivalent properties was tested as the reference specimen under reversible repeatable lateral loads. Others were tested after high-strength concrete panels produced in different geometric shapes were strengthened by bonding them onto existing frame infill walls. Brick infill walls strengthened using concrete panels were modeled as shell elements by SAP2000 software package and the accuracy of experimental studies were compared with analytical results. Experimental and analytical studies demonstrated that the reinforcement method significantly improved properties, such as resistance to lateral loads, energy dissipation capacity, of brick infill reinforced concrete frames.S.U.-BAPSelcuk University [13701617]This study was supported financially by S.U.-BAP (13701617). This study was prepared by using PhD thesis of Arife Akin. The author also thank Dr. Rifat Sezer for his valuable help
Investigation of precast new diagonal concrete panels in strengthened the infilled reinforced concrete frames
No full textMajor part of the structural stock in Turkey doesn't have sufficient endurance, rigidity and ductility against possible large earthquakes. Strengthening of structures against earthquakes always appears on the agenda and structures are being strengthened by using different techniques. In this context, cast in place reinforced concrete shear walls is a highly effective and reliable method for improving the system behavior. However, construction work takes long time in this method, so the structure is required to be emptied before the practice. For this reason, it is required to develop the strengthening methods which facilitates lives of people and which is economic and effective in terms of structure. The principle of the technique recommended in this study is to convert plastered hollow brick walls of the structure to shear walls equivalent to reinforced concretes (RC) by strengthening them with high-strength precast new diagonal concrete panels. For this purpose, a reinforced concrete frame, which is 1/3 scaled, low-strengthened against earthquake, has two-story and single span unreinforced brick infilling wall, has been produced with failures frequently seen especially in concrete buildings of our country as reference sample. Moreover, strengthening three reinforced concrete infilled frame wall having same features with reference sample by new diagonal concrete panels which are precast, high strengths in different shapes used for the first time in the literature, their behaviors under reversible-repeatable horizontal loading simulating earthquake effect have been tested. Results of the experiment have been compared with the analytic study and it has been observed that applied technique has increased the energy dissipation capacity of test elements and improved the earthquake behaviors.S.U. OYP [2014-OYP-104]; TUBITAK-3001 [215M375]This study was supported financially by S.U. OYP (2014-OYP-104) and TUBITAK-3001 (215M375). This study was prepared by using Ph. D. thesis of Ceyhun AKSOYLU. The author also thanks Dr. Rifat Sezer and Dr. Nail Kara
Irréformable Russie
No full textAnalysing the Gorbachev / Yeltsin era, the author addresses a fundamental question : why is it that in Russia liberalising social and economic reforms always fail ? There are several answers to this question :
1 . The reformer(s) fail to take into account the hopes and aspirations of the people themselves.
2. They have no faith in society's creative ability. Hopeless dreamers and ardent idealists, they have, generation after generation (Peter the Great, Catherine the Great, Alexander II, Lenin, Gorbachev, Yeltsin / Gaidar) either been unaware of, or chosen to ignore, their people. They have posed as saviours, deserving, as they saw it, of the people's eternal gratitude. The frequently catastrophic results of their reforms force them (or their successor) to throw the reform movement violently into reverse.
3. In terms of the State's presence in the daily lives of its citizens, Russia belongs more to Asia than to Europe. This is a State that has grown too big, owns vast tracts of land, has huge industrial interests, and innovates in many areas. Its leaders very quickly realised that as the free market developed, so their power would wither away.
4. The Russian mentality (its values and behaviours) is imbued with the collecti- vist, "solidarity" ethic, as shown by the results of a study carried out in Novosibirsk in 1997. The Orthodox Church and its anti-free market stance is a further problem. As a result, the author is highly sceptical as to the prospects for the emergence of a market economy and democracy in Russia. "In our country", he pessimistically concludes, "the market economy is the end, and the means of achieving this end is to make people suffer."Gousseïnov Rifat, Daniaud Élise, Jobert Véronique, Comte Philippe. Irréformable Russie. In: Revue Russe n°38, 2012. La perestroïka de Gorbatchev : piteuse déconfiture ou réussite historique ? pp. 11-24
Ribosome biogenesis and ribosome therapy in cancer cells
No full textIntroduction: The process of protein synthesis is a vital process for all kingdoms of life. The ribosome is a ribonucleoprotein complex that reads the genetic code, from messenger RNA (mRNA) to produce proteins and to tightly regulate and ensure cells growth. The fact that numerous diseases are caused by defect during the ribosome biogenesis is important to understand this pathway. Materials and methods: We have analyzed the literature for ribosome biogenesis and its links with different diseases which have been found. Results and discussion: We have discussed the key aspect of human ribosome biogenesis and its links to diseases. We have also proposed the potential of applying this knowledge to the development of a ribosomal stress-based cancer therapy. Conclusion: Major challenges in the future will be to determine factors which play a pivotal role during ribosome biogenesis. Therefore, more anti-cancer drugs and gene therapy for genetic diseases will be developed against ribosomal biogenesis in the coming years. Graphical abstract
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