Investigating underlying molecular mechanisms, signaling pathways, emerging therapeutic approaches in pancreatic cancer

Frontiers in Oncology, Год журнала: 2024, Номер 14

Опубликована: Июль 17, 2024

Pancreatic adenocarcinoma, a clinically challenging malignancy constitutes significant contributor to cancer-related mortality, characterized by an inherently poor prognosis. This review aims provide comprehensive understanding of pancreatic adenocarcinoma examining its multifaceted etiologies, including genetic mutations and environmental factors. The explains the complex molecular mechanisms underlying pathogenesis summarizes current therapeutic strategies, surgery, chemotherapy, emerging modalities such as immunotherapy. Critical pathways driving cancer development, KRAS, Notch, Hedgehog, are discussed. Current radiation, discussed, with emphasis on their limitations, particularly in terms postoperative relapse. Promising research areas, liquid biopsies, personalized medicine, gene editing, explored, demonstrating potential for enhancing diagnosis treatment. While immunotherapy presents promising prospects, it faces challenges related immune evasion mechanisms. Emerging directions, encompassing CRISPR/Cas9 genome computational intelligence applications, hold promise refining diagnostic approaches interventions. By integrating insights from genetic, molecular, clinical research, innovative strategies that improve patient outcomes can be developed. Ongoing these fields holds advancing treatment this formidable malignancy.

Язык: Английский

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Identification of a novel repressor encoded by the putative gene ctf1 for cellulase biosynthesis in Trichoderma reesei through artificial zinc finger engineering

Biotechnology and Bioengineering, Год журнала: 2020, Номер 117(6), С. 1747 - 1760

Опубликована: Март 3, 2020

Abstract Strains from Trichoderma reesei have been used for cellulase production with a long history. It has well known that biosynthesis by the fungal species is controlled through regulators, and elucidation of their regulation network great importance engineering T. robust production. However, progress in this regard still very limited. In study, RUT‐C30 was transformed an artificial zinc finger protein (AZFP) library, mutant M2 improved screened. Compared to its parent strain, filter paper activity endo‐β‐glucanase cellulases produced increased 67.2% 35.3%, respectively. Analysis quantitative reverse transcription polymerase chain reaction indicated significant downregulation putative gene ctf1 M2, deletion mutants were thus developed further studies. An increase 36.9% observed mutants, but when constitutively overexpressed under control strong pdc1 promoter, substantially compromised. Comparative transcriptomic analysis revealed upregulated encoding regulator VIB1, downregulated another RCE1, which consequently genes factors XYR1 ACE3 activation cellulolytic enzymes. As result, characterized as repressor RUT‐C30, elucidating molecular mechanism underlying rational design develop strains And meantime, AZFP transformation validated be effective strategy identifying functions genome .

Язык: Английский

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Role of CCCH-Type Zinc Finger Proteins in Human Adenovirus Infections

Viruses, Год журнала: 2020, Номер 12(11), С. 1322 - 1322

Опубликована: Ноя. 18, 2020

The zinc finger proteins make up a significant part of the proteome and perform huge variety functions in cell. CCCH-type have gained attention due to their unusual ability interact with RNA thereby control different steps metabolism. Since virus infections interfere metabolism, dynamic changes replication are expected happen. In present review, we will discuss how three proteins, ZC3H11A, MKRN1, U2AF1, human adenovirus replication. We summarize these cellular focus on potential pro- or anti-viral activities during lytic infection.

Язык: Английский

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Evolutionarily conserved transcription factors as regulators of longevity and targets for geroprotection

Physiological Reviews, Год журнала: 2022, Номер 102(3), С. 1449 - 1494

Опубликована: Март 28, 2022

Aging is the single largest risk factor for many debilitating conditions, including heart diseases, stroke, cancer, diabetes, and neurodegenerative disorders. Although far from understood in its full complexity, it scientifically well established that aging influenced by genetic environmental factors can be modulated various interventions. One of aging's early hallmarks aberrations transcriptional networks, controlling example metabolic homeostasis or response to stress. Evidence different model organisms abounds a number evolutionarily conserved transcription factors, which control such affect life span health across species. These thus potentially represent regulators longevity are emerging as important targets challenging quest develop treatments mitigate age-related possibly even slow itself. This review provides an overview impact diseases at least one multicellular organism (nematodes, flies, mice) and/or tentatively linked human aging. Discussed general evidence regulation disease, followed more detailed look selected families, common pathways involved, targeting strategy geroprotective

Язык: Английский

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Light-switchable transcription factors obtained by direct screening in mammalian cells

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Июнь 2, 2023

Abstract Optogenetic tools can provide fine spatial and temporal control over many biological processes. Yet the development of new light-switchable protein variants remains challenging, field still lacks general approaches to engineering or discovering with functions. Here, we adapt strategies for domain insertion mammalian-cell expression generate screen a library candidate optogenetic directly in mammalian cells. The approach is based on AsLOV2 photoswitchable at all possible positions interest, introduction into cells, light/dark selection activity. We demonstrate approach’s utility using Gal4-VP64 transcription factor as model system. Our resulting LightsOut exhibits > 150-fold change transcriptional activity between dark blue light conditions. show that function generalizes analogous sites two additional Cys6Zn2 C2H2 zinc finger domains, providing starting point regulation broad class factors. streamline identification single-protein switches, particularly cases where structural biochemical knowledge limited.

Язык: Английский

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