The Multifaceted Biology of PCSK9

Endocrine Reviews, Год журнала: 2021, Номер 43(3), С. 558 - 582

Опубликована: Окт. 9, 2021

This article reviews the discovery of PCSK9, its structure-function characteristics, and presently known proposed novel biological functions. The major critical function PCSK9 deduced from human mouse studies, as well cellular structural analyses, is role in increasing levels circulating LDL-cholesterol (LDLc), via ability to enhance sorting escort cell surface LDL receptor (LDLR) lysosomes. implicates binding catalytic domain EGF-A LDLR. also requires presence C-terminal Cys/His-rich (CHRD), secreted cytosolic cyclase associated protein 1 (CAP-1), possibly another membrane-bound "protein X". Curiously, PCSK9-deficient mice, an alternative downregulation LDLR by taking place liver female mice a 17β-estradiol-dependent manner still unknown mechanism. Recent studies have extended our understanding functions namely implication septic shock, vascular inflammation, viral infections (Dengue; SARS-CoV-2) or immune checkpoint modulation cancer regulation T-cell MHC-I, which govern anti-tumoral activity CD8 + T cells. Because inhibition may be advantageous these processes, availability injectable safe inhibitors (PCSK9i) that reduces 50-60% LDLc above effect statins highly valuable. Indeed, mAb siRNA could added current immunotherapies cancer/metastasis.

Язык: Английский

---

Biotechnological methods to remove microplastics: a review

Environmental Chemistry Letters, Год журнала: 2023, Номер 21(3), С. 1787 - 1810

Опубликована: Фев. 8, 2023

Язык: Английский

---

AI-powered therapeutic target discovery

Trends in Pharmacological Sciences, Год журнала: 2023, Номер 44(9), С. 561 - 572

Опубликована: Июль 19, 2023

Disease modeling and target identification are the most crucial initial steps in drug discovery, influence probability of success at every step development. Traditional is a time-consuming process that takes years to decades usually starts an academic setting. Given its advantages analyzing large datasets intricate biological networks, artificial intelligence (AI) playing growing role modern identification. We review recent advances focusing on breakthroughs AI-driven therapeutic exploration. also discuss importance striking balance between novelty confidence selection. An increasing number AI-identified targets being validated through experiments several AI-derived drugs entering clinical trials; we highlight current limitations potential pathways for moving forward.

Язык: Английский

---

Current Scenario and Future Prospects of Endophytic Microbes: Promising Candidates for Abiotic and Biotic Stress Management for Agricultural and Environmental Sustainability

Microbial Ecology, Год журнала: 2023, Номер 86(3), С. 1455 - 1486

Опубликована: Март 14, 2023

Abstract Globally, substantial research into endophytic microbes is being conducted to increase agricultural and environmental sustainability. Endophytic such as bacteria, actinomycetes, fungi inhabit ubiquitously within the tissues of all plant species without causing any harm or disease. Endophytes form symbiotic relationships with diverse can regulate numerous host functions, including resistance abiotic biotic stresses, growth development, stimulating immune systems. Moreover, endophytes play a dominant role in nutrient cycling, biodegradation, bioremediation, are widely used many industries. have stronger predisposition for enhancing mineral metal solubility by cells through secretion organic acids low molecular weight metal-specific ligands (such siderophores) that alter soil pH boost binding activity. Finally, synthesize various bioactive compounds high competence promising candidates new drugs, antibiotics, medicines. Bioprospecting novel secondary metabolites has given momentum sustainable agriculture combating stresses. Biotechnological interventions aid played pivotal crop improvement mitigate stress conditions like drought, salinity, xenobiotic compounds, heavy metals. Identification putative genes from conferring tolerance diseases, apart those involved accumulation degradation contaminants, could open avenues development. Furthermore, detailed biochemical understanding endophyte entry colonization strategy would better help manipulating productivity under changing climatic conditions. Therefore, present review highlights current trends based on SCOPUS database, potential biotechnological microorganisms stresses influencing productivity, future opportunities improving tolerance, their contribution remediation hazardous contaminants. Graphical

Язык: Английский

---

CRISPR-Cas-mediated transcriptional modulation: The therapeutic promises of CRISPRa and CRISPRi

Molecular Therapy, Год журнала: 2023, Номер 31(7), С. 1920 - 1937

Опубликована: Март 24, 2023

The CRISPR-Cas system is commonly known for its ability to cleave DNA in a programmable manner, which has democratized gene editing and facilitated recent breakthroughs therapy. However, newer iterations of the technology using nuclease-disabled Cas enzymes have spurred variety different types genetic engineering platforms such as transcriptional modulation CRISPR activation (CRISPRa) interference (CRISPRi) systems. This review introduces creation these modulators, various methods delivery utilized systems, technological developments. CRISPRa CRISPRi also been implemented screens interrogating function discovering genes involved biological pathways. We describe compelling examples how tools become powerful means unravel networks uncovering important information about devastating diseases. Finally, we provide an overview preclinical studies used therapeutically, discuss potential future directions novel modalities.

Язык: Английский

---

Principles of CRISPR-Cas9 technology: Advancements in genome editing and emerging trends in drug delivery

Journal of Drug Delivery Science and Technology, Год журнала: 2024, Номер 92, С. 105338 - 105338

Опубликована: Янв. 6, 2024

The rapid advancement of CRISPR-Cas9 technology has instigated a profound transformation in genome editing with significant implications for fields like health, agriculture, and biotechnology. This abstract provides an overview the historical significance fundamental components CRISPR-Cas9, notably Cas9 protein guide RNA, underscoring its pivotal role genetic manipulation. It emphasizes CRISPR-Cas9's preeminence domain precise editing, driving breakthroughs personalized medicine, gene therapy, agriculture. Of paramount importance is integration nanomaterials, encompassing lipid-based polymeric nanoparticles, alongside viral vectors, serving as potent vehicles augmenting delivery efficiency precision. We explore strategies aimed at enhancing through while also addressing ethical regulatory considerations. In expert opinion section, we offer nuanced perspective on present state field, highlighting potential transformative progress research therapy. stands brink unlocking new possibilities providing innovative solutions to address pressing global challenges.

Язык: Английский

---

Smartphone-assisted self-powered dual-mode biosensor designed on binary 3D DNA Walkers mediated CRISPR/Cas12a system

Chemical Engineering Journal, Год журнала: 2024, Номер 483, С. 149231 - 149231

Опубликована: Янв. 30, 2024

Язык: Английский

---

CRISPR/Cas12a-based biosensors for environmental monitoring and diagnostics

Environmental Technology & Innovation, Год журнала: 2024, Номер 34, С. 103625 - 103625

Опубликована: Апрель 4, 2024

Contaminants, such as nucleic acids or toxic small molecules, threaten both human health and ecosystems when they infiltrate the environment. The precise highly sensitive identification of contaminants holds paramount importance across diverse domains, including safeguarding food integrity, facilitating clinical diagnostics, monitoring environmental conditions. Traditional methodologies, encompassing spectroscopy, chromatography, sequencing, metagenomics, have conventionally served pivotal roles in detection processes. Nevertheless, these methods encountered recurring challenges related to sensitivity, specificity, portability. This review focuses on groundbreaking CRISPR/Cas12-based biosensors. These biosensors leverage incredible precision programmability CRISPR/Cas system recognize specific targets. Here, we comprehensively assess fundamental mechanisms that enable detection, ranging from guide RNA design collateral cleavage. versatility CRISPR/Cas12 becomes evident through their applications. applications encompass medical safety, monitoring. transition conventional ultimately represents a significant milestone contaminant detection. By incorporating molecular biology, nanotechnology, bioinformatics, potential reshape landscape water CRIPSR-Cas diagnostics is transformative technology paves way for safer healthier future environment life.

Язык: Английский

---

New Frontiers in CRISPR: Addressing Antimicrobial Resistance with Cas9, Cas12, Cas13, and Cas14

Heliyon, Год журнала: 2025, Номер 11(2), С. e42013 - e42013

Опубликована: Янв. 1, 2025

The issue of antimicrobial resistance (AMR) poses a major challenge to global health, evidenced by alarming mortality predictions and the diminishing efficiency conventional drugs. CRISPR-Cas system has proven be powerful tool in addressing this challenge. It originated from bacterial adaptive immune mechanisms gained significant recognition scientific community. This review aims explore applications technologies combating AMR, evaluating their effectiveness, challenges, potential for integration into current strategies. We conducted comprehensive recent literature databases such as PubMed Web Science, focusing on studies that employ against AMR. offer transformative approach combat with extend beyond traditional Integrating these existing methods could significantly enhance our ability manage potentially reverse growing problem resistance. Future research should address technical ethical barriers facilitate safe effective clinical environmental applications. underscores necessity interdisciplinary collaboration international cooperation harness full fight superbugs.

Язык: Английский

---

Exosome/Liposome-like Nanoparticles: New Carriers for CRISPR Genome Editing in Plants

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(14), С. 7456 - 7456

Опубликована: Июль 12, 2021

Rapid developments in the field of plant genome editing using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) systems necessitate more detailed consideration delivery CRISPR system into plants. Successful and safe genomes is partly based on efficient system. Along with use plasmids viral vectors as cargo material for editing, non-viral have also been considered purposes. These can be made a variety materials, including inorganic nanoparticles, carbon nanotubes, liposomes, protein- peptide-based well nanoscale polymeric materials. They decreased immune response, an advantage over vectors, offer additional flexibility their design, allowing them to functionalized targeted specific sites biological low cytotoxicity. This review dedicated describing methods plants emphasis vectors.

Язык: Английский

---