Blocking copper transporter protein-dependent drug efflux with albumin-encapsulated Pt(IV) for synergistically enhanced chemo-immunotherapy DOI Creative Commons

Man Fang,

Lei Cao, Zhao Zhang

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 20, 2024

Abstract Non-small cell lung cancer (NSCLC) represents the most prevalent form of cancer, exerting a substantial impact on global health. Cisplatin-based chemotherapy is standard treatment for NSCLC, but resistance and severe side effects present significant clinical challenges. Recently, novel tetravalent platinum compounds have attracted interest. While numerous studies concentrate their functional modifications targeted delivery, tumor-induced frequently overlooked. Previous compound demonstrated antitumor activity, yet proved ineffective against cells exhibiting to cisplatin. In order enhance efficacy potential applications in glutathione (GSH)-responsive albumin nanoquadrivalent (HSA@Pt) been constructed. light previous research into drug conjugation, this study was develop combined chemo-immunotherapy approach. The HSA@Pt high low toxicity, with tumor accumulation. Furthermore, tetrathiomolybdate (TM) has exert synergistic inhibitory effect Cu2+ Transporting Beta Polypeptide (ATP7B) Programmed Death Ligand 1 (PD-L1), impede efflux, induce cellular stress, activate immunity. findings suggest HSA@Pt's use strategy enhancing utility established drugs through sensitization.

Language: Английский

Lung Immunity to Fungal Infections by Macrophages: Mechanisms and Implications DOI Creative Commons
Jaishree Sharma, Nitish A. Kulkarni, Som G. Nanjappa

et al.

IntechOpen eBooks, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 29, 2024

Pulmonary pathogenic fungi cause severe to fatal disseminated infections, especially in immunocompromised patients. Alveolar macrophages form an essential early innate cellular barrier implicated immunity pulmonary mycoses. The complex interactions of alveolar with lead either effective clearance or disease progression. After sensing through pattern-recognizing receptors, macrophage activation enhances phagocytic and non-phagocytic killing, secretion cytokines/chemokines, other immune cells, including adaptive cells neutrophils. Such orchestrated response involves transcriptomic metabolic adaptations by epigenomic imprinting. Despite their high plasticity the inflammatory cues, recent studies have shed light on longevity functional stability. Nevertheless, some evolved strategies evade subvert function, leading persistent infections. Understanding mechanisms macrophage-fungal interface helps develop a new line therapeutics mitigates challenges limited arsenals antifungals.

Language: Английский

Citations

0
The intersection of inflammation and DNA damage as a novel axis underlying the pathogenesis of autism spectrum disorders DOI Open Access
Megha Jhanji,

Catherine M. Krall,

Ana Guevara

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 11, 2024

ABSTRACT Autism spectrum disorders (ASD) affects 1 in 36 children and is characterized by repetitive behaviors difficulties social interactions communication. The etiology of ASD extremely heterogeneous, with a large number cases that are unknown or complex etiology, which suggests the potential contribution epigenetic risk factors. In particular, epidemiological animal model studies suggest inflammation during pregnancy could lead to an increased offspring. However, molecular mechanisms contribute pathogenesis relation maternal humans underexplored. Several pro-inflammatory cytokines have been associated autistic-like models immune activation, including IL-17A. Using combination patient lymphocytes stem cell-derived human neurons exposed IL-17A we discovered shared signature highlights metabolic translational node altered neuronal excitability. Further, our work on brings forward possibility defects DNA damage response be underlying effect excitatory neurons, linking exacerbated unrepaired pathogenicity connection ASD.

Language: Английский

Citations

0
Blocking copper transporter protein-dependent drug efflux with albumin-encapsulated Pt(IV) for synergistically enhanced chemo-immunotherapy DOI Creative Commons

Man Fang,

Lei Cao, Zhao Zhang

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 20, 2024

Abstract Non-small cell lung cancer (NSCLC) represents the most prevalent form of cancer, exerting a substantial impact on global health. Cisplatin-based chemotherapy is standard treatment for NSCLC, but resistance and severe side effects present significant clinical challenges. Recently, novel tetravalent platinum compounds have attracted interest. While numerous studies concentrate their functional modifications targeted delivery, tumor-induced frequently overlooked. Previous compound demonstrated antitumor activity, yet proved ineffective against cells exhibiting to cisplatin. In order enhance efficacy potential applications in glutathione (GSH)-responsive albumin nanoquadrivalent (HSA@Pt) been constructed. light previous research into drug conjugation, this study was develop combined chemo-immunotherapy approach. The HSA@Pt high low toxicity, with tumor accumulation. Furthermore, tetrathiomolybdate (TM) has exert synergistic inhibitory effect Cu2+ Transporting Beta Polypeptide (ATP7B) Programmed Death Ligand 1 (PD-L1), impede efflux, induce cellular stress, activate immunity. findings suggest HSA@Pt's use strategy enhancing utility established drugs through sensitization.

Language: Английский

Citations

0