Beyond Nutrition: The Emerging Therapeutic Potential Landscape of Breast Milk-Derived Extracellular Vesicles

Nutrition Research, Journal Year: 2025, Volume and Issue: 135, P. 42 - 51

Published: Jan. 14, 2025

Breastfeeding is widely recognized for its essential nutritional benefits and broader biological impacts. Beyond providing infants with a balanced mix of vitamins, proteins, fats critical growth development, breast milk contains bioactive extracellular vesicles (BMEVs). These membrane-bound particles, rich in lipids, nucleic acids, play pivotal role immune modulation, intercellular communication, the overall development infant's system. This review explores emerging therapeutic potential BMEVs, highlighting their capacity to modulate recipient cell functions, influence responses, contribute infant health. Preclinical evidence suggests that these can prevent manage conditions such as necrotizing enterocolitis, allergies, viral infections, which are common early childhood. Furthermore, BMEVs offer promise vehicles targeted drug delivery, enhancing efficacy interventions. Despite growing body evidence, challenges need standardized isolation methods, characterization techniques, larger-scale clinical studies persist, hindering translation this research into practice. addresses discusses future directions, emphasizing comprehensive mechanistic fully realize novel agents biomarkers Ultimately, represent promising frontier maternal child health, applications extending far beyond traditional nutrition. By harnessing unique properties, could revolutionize care, offering new strategies disease prevention innovative interventions enhance health outcomes.

Language: Английский

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Harnessing antiviral RNAi therapeutics for pandemic viruses: SARS-CoV-2 and HIV

Drug Delivery and Translational Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 20, 2025

Abstract Using the knowledge from decades of research into RNA-based therapies, COVID-19 pandemic response saw rapid design, testing and production first ever mRNA vaccines approved for human use in clinic. This breakthrough has been a significant milestone RNA therapeutics vaccines, driving an exponential growth field. The development novel targeting high-threat pathogens, that pose substantial risk to global health, could transform future health delivery. In this review, we provide detailed overview two interference (RNAi) pathways how antiviral RNAi therapies can be used treat acute or chronic diseases caused by viruses SARS-CoV-2 HIV, respectively. We also insights short-interfering (siRNA) delivery systems, with focus on lipid nanoparticles functionalized achieve targeted specific sites disease. review will current developments HIV siRNAs, highlighting strategies advance progression siRNA along clinical pathway. Graphical

Language: Английский

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Identification of the Inducible HIV reservoir in Tonsillar, Intestinal and Cervical Tissue Models of HIV Latency

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 12, 2025

Abstract HIV persists in diverse tissues, with distinct cellular reservoirs presenting a major barrier to cure and requiring targeted therapeutic strategies address this heterogeneity. Here, we developed tissue models of latency using human tonsillar, intestinal cervicovaginal tissues. These revealed differential infection across CD4 + T cell subpopulations, ART partially restoring cells reducing intact DNA. follicular helper (T FH CD69+ CCR7- ) were the primary inducible reservoir tonsils, while tissue-resident memory RM CD49a+ dominated intestine. Identification markers for that CD69, CD45RO, PD-1 shared CXCR5 tonsils CD49a intestine served as tissue-specific markers. Furthermore, different reversal agents (LRAs) found Histone Deacetylase Inhibitors (HDACis) failed induce any tissue, SMAC mimetic AZD5582 was effective only resident-memory subpopulation intestine, IL15 exhibited broadest reactivation potential tissues subsets. recapitulate key aspects providing insights into reservoir’s composition informing its elimination.

Language: Английский

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Application and Development of Gene Therapy in HIV-Treatment

Highlights in Science Engineering and Technology, Journal Year: 2025, Volume and Issue: 129, P. 33 - 41

Published: March 3, 2025

As an emerging treatment strategy, HIV gene therapy has shown potential breakthrough results. Existing technologies such as CRISPR-Cas9, ZFN, and CAR-T cells have made significant progress in laboratory early clinical trials by targeting viral genomes or host receptors, the CCR5 gene, enhancing ability of immune to recognize eliminate infected cells. These methods aim overcome limitations traditional antiretroviral (ART), especially inability ART latent pool dependence on lifelong medication. However, widespread application still faces challenges, including high variability HIV, off target effects editing technology, safety delivery tools, related ethical issues. Future research directions will focus multi-target safe efficient tools non-viral vectors, reconstruction, combined with vaccines therapies, order improve efficacy achieve functional cure. For example, after stimulate system, edited T can more effectively clear reduce risk virus rebound. Through multi-level combination therapy, not only medication be reduced, but it also provides new possibilities for complete cure HIV. Despite numerous prospects are broad, is expected bring benefits patients continuous technological international cooperation.

Language: Английский

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CD3+ T-cell: CD14+ monocyte complexes are dynamic and increased with HIV and glucose intolerance

The Journal of Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 28, 2025

Persistent systemic inflammation is associated with an elevated risk of cardiometabolic diseases. However, the characteristics innate and adaptive immune systems in individuals who develop these conditions remain poorly defined. Doublets, or cell-cell complexes, are routinely eliminated from flow cytometric other phenotyping analyses, which limits our understanding their relationship to disease states. Using well-characterized clinical cohorts, including participants controlled human immunodeficiency virus (HIV) as a model for chronic increased cell interactions, we show that circulating CD14+ monocytes complexed CD3+ T cells dynamic, biologically relevant, diabetes after adjusting confounding factors. The complexes form functional synapses expression proinflammatory cytokines greater glucose utilization. Furthermore, persons HIV, cell: monocyte had more HIV copies compared matched CD4+ alone. Our results demonstrate T-cell: pairs represent dynamic cellular interactions may contribute pathogenesis. originate be maintained, part, by viral infections. These findings provide foundation future studies investigating mechanisms linking cell-monocyte developing immune-mediated diseases, diabetes.

Language: Английский

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Deep Thought on the HIV Cured Cases: Where Have We Been and What Lies Ahead?

Biomolecules, Journal Year: 2025, Volume and Issue: 15(3), P. 378 - 378

Published: March 5, 2025

Antiretroviral therapy (ART) can effectively suppress the replication of human immunodeficiency virus (HIV), but it cannot completely eradicate virus. The persistent existence HIV reservoir is a major obstacle in quest for cure. To date, there have been total seven cured cases worldwide. These patients all cleared while undergoing allogeneic stem cell transplantation (allo-HSCT) hematological malignancies. However, these cases, specific mechanism by which allo-HSCT leads to eradication remains unclear, so necessary conduct an in-depth analysis. Due difficulty obtaining donors and risks associated with transplantation, this treatment method not applicable patients. There still need explore new strategies. In recent years, emerging therapies such as neutralizing antibody immunotherapy, chimeric antigen receptor T (CAR-T) therapy, gene editing, antiviral targeting attracted wide attention due their ability inhibit replication. This article first elaborates on nature reservoir, then deeply explores modalities potential success factors finally discusses current novel methods, hoping provide comprehensive feasible strategies achieving cure HIV.

Language: Английский

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High concordance of human immunodeficiency virus-1 genotypic drug resistance generated from paired cerebrospinal fluid and plasma in antiretroviral therapy -naive or -experienced patients

Frontiers in Microbiology, Journal Year: 2025, Volume and Issue: 16

Published: March 26, 2025

Background The development of human immunodeficiency virus (HIV) drug resistance significantly impairs patients’ quality life. However, the HIV-1 patterns in central nervous system (CNS) have been poorly studied. Objective We aimed to compare genotypes and mutations (DRMs) derived from cerebrospinal fluid (CSF) plasma antiretroviral therapy (ART)-naive or -experienced patients. Methods matched CSF samples 59 patients with HIV were subjected proteinase (PR), reverse transcriptase (RT), integrase (IN) gene sequencing. To determine genotypes, sequences assessed Context-based Modelling for Expeditious Typing (COMET) tool, neighbour-joining (NJ) phylogenetic tree was used confirm results. Quality control based on genotype analysis conducted assess potential sequence contamination during detection process. database Stanford University identify DRMs sensitivity four classes [protease inhibitors (PIs), nucleoside (NRTIs), nonnucleoside (NNRTIs), strand transfer (INSTIs)]. Results Of samples, 37 included study after excluding that failed be successfully amplified. CRF01_AE most frequently occurring genotype, a frequency 46.0% (17/37), followed by CRF07_BC (27.0%, 10/37) CRF55_01B (10.8%, 4/37). Among patients, 37.8% (14/37) carried at least one DRM, mutation sites consistent both plasma, except one. NNRTI-related predominant DRMs, particularly V179D/E, present 71.4% (10/14) DRM sites, primarily ART-naive Conclusion A high concordance between observed. No unique identified other than those indicating mutant variants blood.

Language: Английский

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Integration of long-acting antiretroviral therapies and latency-reversing agents for reservoir reduction and viral suppression: a comprehensive review

InterConf, Journal Year: 2025, Volume and Issue: 53(232), P. 258 - 270

Published: Jan. 20, 2025

Despite significant advancements in antiretroviral therapy (ART), the persistent latent HIV reservoir remains a major barrier to achieving complete cure. Current ART regimens effectively suppress viral replication but necessitate lifelong adherence due their inability eradicate HIV. Long-acting therapies (LA-ARTs) have emerged as an innovation improve and reduce burden of daily dosing. Additionally, latency-reversing agents (LRAs) aim reactivate virus, making it susceptible immune clearance. The combination LA-ART LRAs offers promising therapeutic approach address both challenges eradication. Objective: This review explores potential synergy between LRAs, focusing on individual combined roles reducing reservoirs sustaining suppression. Methodology: A systematic search peer-reviewed articles clinical studies was conducted following SANRA guidelines. Inclusion criteria included involving PLWH, and/or evaluating outcomes such reduction Studies without applicability or reporting relevant were excluded. Discussion: enhances quality life by dosing frequency, while utilize “shock kill” strategy virus. potential, suboptimal LRA efficacy, clearance limitations, accessibility barriers persist. Combining these may create robust treatment framework, further research is needed optimize overcome implementation challenges. highlights need for collaborative efforts policy refine integrate therapies, moving closer functional cure

Language: Английский

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Yoda1, a Piezo1 agonist, induced latent HIV reactivation associated with upregulation of CD3/TCR complex and HLA genes

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: April 10, 2025

There is currently no cure for HIV because of the presence latent viral reservoirs in people with (PWH) on antiretroviral therapy (ART). Latency-reversing agents (LRAs) that can effectively reactivate and destroy are being developed as a possible HIV. Here, we identify Yoda1, Piezo1 agonist, novel LRA. Yoda1 reactivated vitro ACH2 cells ex vivo PBMCs from an patient ART. induced infectious virus production gene expression via activation calcium signaling. Transcriptomic proteomic analyses revealed unique reactivation pathway involving T cell activation, upregulation TCR/CD3 HLA genes, well modulation host transcription translation favors expression. These findings suggest further testing development effective LRA to

Language: Английский

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Diverse potential of chimeric antigen receptor‐engineered cell therapy: Beyond cancer

Clinical and Translational Medicine, Journal Year: 2025, Volume and Issue: 15(4)

Published: April 1, 2025

Language: Английский

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