7 research outputs found
Exosome-mediated PROTAC delivery for treatment of RNA viral infections and zoonosis
The increase in diseases caused by RNA viruses, such as influenza, severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome (MERS), and Ebola, presents a growing global health challenge as well as the threat of zoonosis. Traditional antiviral treatments are often undermined by fast-mutating viruses, drug resistance, and newly emerging pathogens. Here, we explore proteolysis-targeting chimeras (PROTACs), a novel protein degradation machinery that has the potential to reshape the way in which RNA viral infections can be managed. PROTACs excel at specifically degrading pathogenic proteins, offering a targeted and efficient antiviral strategy. We also investigate the potential of exosome-based diagnostic technologies, which harness cell-derived nanovesicles for non-invasive sampling and early viral infection detection. Addressing the challenge of PROTAC delivery, we introduce a groundbreaking strategy utilizing exosomes to deliver PROTACs with improved precision and as a targeted delivery vehicle. Integrating these innovative strategies provides a novel approach to combat RNA zoonotic viral diseases, paving the way for a new era in antiviral therapy.</p
Revolutionizing human papillomavirus (HPV)ârelated cancer therapies: unveiling the promise of proteolysis targeting chimeras (PROTACs) and proteolysis targeting antibodies (PROTABs) in cancer nanoâvaccines
Personalized cancer immunotherapies, combined with nanotechnology (nanoâ vaccines), are revolutionizing cancer treatment strategies, explicitly targeting Human papilloma virus (HPV)ârelated cancers. Despite the availability of preventive vaccines, HPVârelated cancers remain a global concern. Personalized cancer nanoâvaccines, tailored to an individual's tumor genetic mutations, offer a unique and promising solution. Nanotechnology plays a critical role in these vaccines by efficiently delivering tumorâspecific antigens, enhancing immune responses, and paving the way for precise and targeted therapies. Recent advancements in preclinical models have demonstrated the potential of polymeric nanoparticles and highâdensity lipoproteinâmimicking nanoâdiscs in augmenting the efficacy of personalized cancer vaccines. However, challenges related to optimizing the nanoâcarrier system and ensuring safety in human trials persist. Excitingly, the integration of nanotechnology with Proteolysisâ Targeting Chimeras (PROTACs) provides an additional avenue to enhance the effectiveness of personalized cancer treatment. PROTACs selectively degrade diseaseâcausing proteins, amplifying the impact of nanotechnologyâbased therapies. Overcoming these challenges and leveraging the synergistic potential of nanotechnology, PROTACs, and ProteolysisâTargeting Antibodies hold great promise in pursuing novel and effective therapeutic solutions for individuals affected by HPVârelated cancers.</p
Exosomes in liquid biopsy and oncology: Nanotechnological interplay and the quest to overcome cancer drug resistance
Exosomes, small extracellular vesicles of endocytic origin, have emerged as pivotal mediators in intercellular communication, driving transformative advancements across diverse fields of biology and medicine. This comprehensive review delves into the multifaceted roles of exosomes in health and disease, elucidating their biogenesis, cargo composition, and far-reaching implications. Exosomes, secreted by virtually all cell types, encapsulate a cargo comprising proteins, lipids, and nucleic acids, reflecting their cellular origin. Their molecular cargo modulates cellular processes, facilitating complex signalling cascades and contributing to the pathogenesis of various diseases, including cancer, neurodegenerative disorders, and infectious diseases. In cancer, exosomes serve as messengers of tumorigenesis and metastasis, orchestrating critical events within the tumor micro environment. Furthermore, exosomes participate in drug resistance mechanisms, presenting significant challenges in cancer therapy. The diagnostic potential of exosomes, particularly in the context of liquid biopsy, is underscored by their presence in various biofluids. This offers non-invasive disease monitoring and biomarker discovery, revolutionizing early detection and monitoring strategies. Additionally, exosomes have gained recognition as therapeutic vehicles, holding promise for targeted drug delivery, immunomodulation, and regenerative medicine. This review comprehensively explores the ever-expanding landscape of exosome biology, emphasizing their roles in health and disease. It underscores the transformative potential of exosomes in liquid biopsy-based diagnostics and therapeutics while acknowledging the complexities and challenges that lie ahead in harnessing their full clinical utility.</p
Harnessing PROTACs to combat H5N1 influenza: A new frontier in viral destruction
H5N1, a highly pathogenic avian influenza virus, poses an ongoing and significant threat to global public health, primarily due to its potential to cause severe respiratory illness and high mortality rates in humans. Despite extensive efforts in vaccination and antiviral therapy, H5N1 continues to exhibit high mutation rates, resulting in recurrent outbreaks and the emergence of drugâresistant strains. Traditional antiviral therapies, such as neuraminidase inhibitors and M2 ion channel blockers, have demonstrated limited efficacy, necessitating the exploration of innovative therapeutic strategies. Proteolysisâ targeting chimeras (PROTACs) emerge as a novel and promising approach, leveraging the ubiquitinâproteasome system to selectively degrade pathogenic proteins. Unlike conventional inhibitors that only block protein function, PROTACs eliminate the target protein, providing a sustained therapeutic effect and potentially reducing the development of resistance. This paper offers a comprehensive examination of the current landscape of H5N1 infections, detailing the pathogenesis and challenges associated with existing treatments. It further explores the mechanism of action, design, and therapeutic potential of PROTACs in inhibiting H5N1. By targeting essential viral proteins, such as hemagglutinin and the RNAâdependent RNA polymerase complex, PROTACs hold the potential to revolutionize the treatment of H5N1 infections, offering a new frontier in antiviral therapy</p
Targeted therapies for HPVâassociated cervical cancer: harnessing the potential of exosomeâbased chipsets in combating leukemia and HPVâmediated cervical cancer
Exosomes play a crucial role in intercellular communication and have emerged as significant vehicles for transporting diseaseâspecific biomarkers. This feature provides profound insights into the progression of diseases and the responses of patients to treatments. For example, in leukemia, exosomes convey critical information through the carriage of specific proteins and nucleic acids. In the case of human papillomavirus (HPV)âmediated cervical cancer, exosomes are particularly useful for noninvasive detection as they transport highârisk HPV DNA and specific biomolecules, which can be indicators of the disease. Despite their vast potential, there are several challenges associated with the use of exosomes in medical diagnostics. These include their inherent heterogeneity, the need for enhanced sensitivity in detection methods, the establishment of standardization protocols, and the requirement for costâeffective scalability in their application. Addressing these challenges is crucial for the effective implementation of exosomeâbased diagnostics. Future research and development are geared towards overcoming these obstacles. Efforts are concentrated on refining the processes of biomarker discovery, establishing comprehensive regulatory frameworks, developing convenient pointâofâcare devices, exploring methods for multimodal detection, and conducting extensive clinical trials. The ultimate goal of these efforts is to inaugurate a new era of precision diagnostics within healthcare. This would significantly improve patient outcomes and reduce the burden of diseases such as leukemia and HPVâmediated cervical cancer. The integration of exosomes with cuttingâedge technology holds the promise of significantly reinforcing the foundations of healthcare, leading to enhanced diagnostic accuracy, better disease monitoring, and more personalized therapeutic approaches.</p
Unlocking exosome-based theragnostic signatures: deciphering secrets of ovarian cancer metastasis
Ovarian cancer (OC) is a common gynecological cancer worldwide. Unfortunately, the lack of early detection methods translates into a substantial cohort of women grappling with the pressing health crisis. The discovery of extracellular vesicles (EVs) (their major subpopulation exosomes, microvesicles, and apoptotic bodies) has provided new insights into the understanding of cancer. Exosomes, a subpopulation of EVs, play a crucial role in cellular communication and reflect the cellular status under both healthy and pathological conditions. Tumor-derived exosomes (TEXs) dynamically influence ovarian cancer progression by regulating uncontrolled cell growth, immune suppression, angiogenesis, metastasis, and the development of drug and therapeutic resistance. In the field of OC diagnostics, TEXs offer potential biomarkers in various body fluids. On the other hand, exosomes have also shown promising abilities to cure ovarian cancer. In this review, we address the interlink between exosomes and ovarian cancer and explore their theragnostic signature. Finally, we highlight future directions of exosome-based ovarian cancer research.</p
Data_Sheet_1_Recognizing novel drugs against Keap1 in Alzheimerâs disease using machine learning grounded computational studies.xlsx
Alzheimerâs disease (AD) is the most common neurodegenerative disorder in the world, affecting an estimated 50 million individuals. The nerve cells become impaired and die due to the formation of amyloid-beta (AÎČ) plaques and neurofibrillary tangles (NFTs). Dementia is one of the most common symptoms seen in people with AD. Genes, lifestyle, mitochondrial dysfunction, oxidative stress, obesity, infections, and head injuries are some of the factors that can contribute to the development and progression of AD. There are just a few FDA-approved treatments without side effects in the market, and their efficacy is restricted due to their narrow target in the etiology of AD. Therefore, our aim is to identify a safe and potent treatment for Alzheimerâs disease. We chose the ursolic acid (UA) and its similar compounds as a compoundsâ library. And the ChEMBL database was adopted to obtain the active and inactive chemicals against Keap1. The best Quantitative structure-activity relationship (QSAR) model was created by evaluating standard machine learning techniques, and the best model has the lowest RMSE and greatest R2 (Random Forest Regressor). We chose pIC50 of 6.5 as threshold, where the top five potent medicines (DB06841, DB04310, DB11784, DB12730, and DB12677) with the highest predicted pIC50 (7.091184, 6.900866, 6.800155, 6.768965, and 6.756439) based on QSAR analysis. Furthermore, the top five medicines utilize as ligand molecules were docked in Keap1âs binding region. The structural stability of the nominated medications was then evaluated using molecular dynamics simulations, RMSD, RMSF, Rg, and hydrogen bonding. All models are stable at 20 ns during simulation, with no major fluctuations observed. Finally, the top five medications are shown as prospective inhibitors of Keap1 and are the most promising to battle AD.</p