Cell death pathways: molecular mechanisms and therapeutic targets for cancer

MedComm, Год журнала: 2024, Номер 5(9)

Опубликована: Сен. 1, 2024

Abstract Cell death regulation is essential for tissue homeostasis and its dysregulation often underlies cancer development. Understanding the different pathways of cell can provide novel therapeutic strategies battling cancer. This review explores several key mechanisms apoptosis, necroptosis, autophagic death, ferroptosis, pyroptosis. The research gap addressed involves a thorough analysis how these be precisely targeted therapy, considering tumor heterogeneity adaptation. It delves into genetic epigenetic factors signaling cascades like phosphatidylinositol 3‐kinase/protein kinase B/mammalian target rapamycin (PI3K/AKT/mTOR) mitogen‐activated protein kinase/extracellular signal‐regulated (MAPK/ERK) pathways, which are critical death. Additionally, interaction microenvironment with cells, particularly influence hypoxia, nutrient deprivation, immune cellular interactions, explored. Emphasizing strategies, this highlights emerging modulators inducers such as B lymphoma 2 (BCL2) homology domain 3 (BH3) mimetics, tumour necrosis factor‐related apoptosis‐inducing ligand (TRAIL), chloroquine, innovative approaches to induce ferroptosis provides insights therapy's future direction, focusing on multifaceted circumvent drug resistance. examination evolving underlines considerable clinical potential continuous necessity in‐depth exploration within scientific domain.

Язык: Английский

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The molecular code of kidney cancer: A path of discovery for gene mutation and precision therapy

Molecular Aspects of Medicine, Год журнала: 2025, Номер 101, С. 101335 - 101335

Опубликована: Янв. 1, 2025

Renal cell carcinoma (RCC) is a malignant tumor with highly heterogeneous and complex molecular mechanisms. Through systematic analysis of TCGA, COSMIC other databases, 24 mutated genes closely related to RCC were screened, including VHL, PBRM1, BAP1 SETD2, which play key roles in signaling pathway transduction, chromatin remodeling DNA repair. The PI3K/AKT/mTOR particularly important the pathogenesis RCC. Mutations such as PIK3CA, MTOR PTEN are associated metabolic abnormalities proliferation. Clinically, mTOR inhibitors VEGF-targeted drugs have shown significant efficacy personalized therapy. Abnormal regulation reprogramming, especially glycolysis glutamine pathways, provides cells continuous energy supply survival advantages, GLS1 promising results preclinical studies. This paper also explores potential immune checkpoint combination targeted drugs, well application nanotechnology drug delivery In addition, unique mechanisms revealed individualized therapeutic strategies explored for specific subtypes TFE3, TFEB rearrangement type SDHB mutant type. review summarizes common gene mutations their mechanisms, emphasizes diagnosis, treatment prognosis, looks forward prospects multi-pathway therapy, immunotherapy treatment, providing theoretical support clinical guidance new development.

Язык: Английский

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CRISPR/Cas systems for genomic Editing, biochemical Sensing, Bioanalysis, and diagnostics

Microchemical Journal, Год журнала: 2025, Номер unknown, С. 112638 - 112638

Опубликована: Янв. 1, 2025

Язык: Английский

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Low-cost inkjet-printed nanostructured biosensor based on CRISPR/Cas12a system for pathogen detection

Biosensors and Bioelectronics, Год журнала: 2024, Номер 258, С. 116340 - 116340

Опубликована: Апрель 25, 2024

The escalating global incidence of infectious diseases caused by pathogenic bacteria, especially in developing countries, emphasises the urgent need for rapid and portable pathogen detection devices. This study introduces a sensitive specific electrochemical biosensing platform utilising cost-effective electrodes fabricated inkjet-printing gold silver nanoparticles on plastic substrate. biosensor exploits CRISPR/Cas12a system detecting DNA sequence selected from genome target pathogen. Upon detection, trans-activity Cas12a/gRNA is triggered, leading to cleavage rationally designed single-strand reporters (linear hairpin) labelled with methylene blue (ssDNA-MB) bound electrode surface. In principle, this sensing mechanism can be adapted any bacterium choosing proper guide RNA its DNA. biosensor's performance was assessed two representative pathogens (a Gram-negative, Escherichia coli, Gram-positive, Staphylococcus aureus), results obtained inkjet-printed were compared those commercial screen-printed electrodes. Our show that use nanostructured electrodes, which provide large surface area, combination hairpin containing poly-T loop increase sensitivity assay corresponding signal variation 86%. targets amplified various clinically isolated have been tested demonstrate potential proposed point-of-need applications.

Язык: Английский

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Mechanisms and Strategies of Immunosenescence Effects on Non-Small Cell Lung Cancer (NSCLC) Treatment: A Comprehensive Analysis and Future Directions

Seminars in Cancer Biology, Год журнала: 2025, Номер 109, С. 44 - 66

Опубликована: Янв. 9, 2025

Язык: Английский

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Insight into crRNA Processing in Streptococcus mutans P42S and Application of SmutCas9 in Genome Editing

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(5), С. 2005 - 2005

Опубликована: Фев. 25, 2025

CRISPR-Cas is an adaptive immune system found in bacteria and archaea that provides resistance against invading nucleic acids. Elements of this natural have been harnessed to develop several genome editing tools, including CRISPR-Cas9. This technology relies on the ability nuclease Cas9 cut DNA at specific locations directed by a guide RNA. In addition, activity requires presence short nucleotide motif (5'-NGG-3' for from Streptococcus pyogenes) called PAM, flanking targeted region. As reliance PAM typically strict, diverse variants recognising different motifs studied target broader range genomic sites. study, we assessed potential mutans strain P42S (SmutCas9) gene editing. SmutCas9 recognises rarely 5'-NAA-3' 5'-NGAA-3' PAMs. To test its efficacy, two genes virulent lactococcal phage p2 were edited, thereby demonstrating purposes, particularly AT-rich genomes. Sequencing total RNA also revealed components system, allowing further molecular characterisation type II-A S. mutans.

Язык: Английский

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Nanotechnology in Gene Editing: Pioneering CRISPR‐Cas Delivery Systems to Tackle Antibiotic Resistance

Advanced Therapeutics, Год журнала: 2025, Номер unknown

Опубликована: Март 3, 2025

Abstract The rise of antibiotic‐resistant bacteria, driven by antibiotic misuse, is a major global health threat. Addressing this issue requires understanding resistance mechanisms and developing innovative solutions. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)‐associated systems (Cas), genome‐editing tool derived from prokaryotic defense mechanisms, offers precise targeting genes. By reprogramming CRISPR‐Cas, bacteria can be killed or resensitized to antibiotics through plasmid curing. However, clinical applications face challenges, particularly in delivering CRISPR‐Cas components effectively. Nanotechnology has emerged as promising approach for targeted delivery tissues cells. This paper explores the molecular resistance, emphasizing structure function their mechanisms. It highlights use nanoparticles (NPs) nanoscale carriers deliver components, reviewing recent studies that combine NPs CRISPR target Additionally, discusses current challenges future prospects field, underscoring potential nanotechnology combat resistance.

Язык: Английский

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Transgenesis in Drug Discovery: Enhancing Target Identification and Validation

Molecular Biotechnology, Год журнала: 2025, Номер unknown

Опубликована: Март 27, 2025

Язык: Английский

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Ultrasensitive CRISPR/Cas12a-Based System for Detection of BlaOXA-1 Gene in Antibiotic-Resistant Microorganisms

Current Issues in Molecular Biology, Год журнала: 2025, Номер 47(4), С. 238 - 238

Опубликована: Март 29, 2025

The blaOXA-1 gene encodes an oxacillin-hydrolyzing beta-lactamase of extended-spectrum (ESBL)-producing microorganisms. is found in the resistomes some Enterobacteriaceae, Morganellaceae, Pasteurellaceae, Moraxellaceae, Aeromonadaceae, Pseudomonadaceae, Yersiniaceae, and Vibrionaceae. Most ESBL detection methods, including those to detect OXA-1-producing microorganisms, are time-consuming, require specialized equipment qualified personnel. Here, we report a new CRISPR(Clustered Regularly Interspaced Short Palindromic Repeats)/Cas12a-based assay coupled with polymerase chain reaction (PCR) sensitively OXA-1-bearing PCR-coupled CRISPR/Cas12a-based fluorescence includes (i) pre-amplification step (ii) nucleic acid step. based on commonly used PCR, CRISPR/Cas12a property nonspecifically hydrolyze single-stranded DNA fluorescent reporter molecules. takes 65 min, shortened only 5 min. developed can easily single (1.25) copies efficient not model matrix but also blaOXA-1-positive We hope that our has potential improve monitoring microorganisms therefore contribute mitigating deadly global threat antibiotic-resistant

Язык: Английский

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Landscape of NRXN1 Gene Variants in Phenotypic Manifestations of Autism Spectrum Disorder: A Systematic Review

Journal of Clinical Medicine, Год журнала: 2024, Номер 13(7), С. 2067 - 2067

Опубликована: Апрель 2, 2024

Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by social communication challenges and repetitive behaviors. Recent research has increasingly focused on the genetic underpinnings of ASD, with Neurexin 1 (NRXN1) gene emerging as key player. This comprehensive systematic review elucidates contribution NRXN1 variants in pathophysiology ASD. Methods: The protocol for this was designed priori registered PROSPERO database (CRD42023450418). A risk bias analysis conducted using Joanna Briggs Institute (JBI) critical appraisal tool. We examined various studies that link disruptions discussing both genotypic variability resulting phenotypic expressions. Results: Within review, there marked heterogeneity observed ASD manifestations among individuals mutations. presence mutations population emphasizes gene’s role synaptic function neural connectivity. Conclusion: not only highlights but also need further to unravel disorder. better knowledge about multifaceted can provide crucial insights into neurobiological foundations autism pave way novel therapeutic strategies.

Язык: Английский

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