Augmenting Immunotherapy via Bioinspired MOF‐Based ROS Homeostasis Disruptor with Nanozyme‐Cascade Reaction

Advanced Materials, Journal Year: 2023, Volume and Issue: 35(49)

Published: Sept. 10, 2023

Despite its remarkable clinical breakthroughs, immune checkpoint blockade (ICB) therapy remains limited by the insufficient response in "cold" tumor. Nanozyme-based antitumor catalysis is associated with precise activation tumor microenvironment (TME). In this study, a cascade-augmented nanoimmunomodulator (CMZM) multienzyme-like activities, which includes superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and glutathione oxidase (GSHOx), that dissociates under an acidic abundant GSH TME, proposed for multimodal imaging-guided chemodynamic (CDT)/photodynamic (PDT) enhanced immunotherapy. Vigorous activities can not only produce O2 to alleviate hypoxia promote polarization of M2 M1 macrophages, but also generate ROS (•OH 1 ) deplete TME expose necrotic cell fragments reverse immunosuppressive eliciting maturation dendritic cells infiltration cytotoxic T lymphocytes (CTLs) tumors. Therefore, inhibitory effects on both primary distant tumors are achieved through synergy α-PD-L1 blocking antibody. This cascade multienzyme-based nanoplatform provides smart strategy highly efficient ICB immunotherapy against revising TME.

Language: Английский

---

The role of the immune system in osteoarthritis: mechanisms, challenges and future directions

Nature Reviews Rheumatology, Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

Language: Английский

---

The role of chronic low-grade inflammation in the development of sarcopenia: Advances in molecular mechanisms

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 147, P. 114056 - 114056

Published: Jan. 11, 2025

Language: Английский

---

Bone and muscle crosstalk in ageing and disease

Nature Reviews Endocrinology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 26, 2025

Language: Английский

---

Neuroinflammatory Biomarkers for Traumatic Brain Injury Diagnosis and Prognosis: A TRACK-TBI Pilot Study

Neurotrauma Reports, Journal Year: 2023, Volume and Issue: 4(1), P. 171 - 183

Published: March 1, 2023

The relationship between systemic inflammation and secondary injury in traumatic brain (TBI) is complex. We investigated associations inflammatory markers clinical confirmation of TBI diagnosis prognosis. prospective TRACK-TBI Pilot (Transforming Research Clinical Knowledge Traumatic Brain Injury Pilot) study enrolled patients triaged to head computed tomography (CT) received blood draw within 24 h injury. Healthy controls (HCs) orthopedic (OCs) were included. Thirty-one analyzed from plasma. Area under the receiver operating characteristic curve (AUC) was used evaluate discriminatory ability. AUC >0.7 considered acceptable. Criteria included: (vs. OC/HC); moderate/severe vs. mild (Glasgow Coma Scale; GCS); radiographic (CT positive CT negative); 3- 6-month Glasgow Outcome Scale-Extended (GOSE) dichotomized death/greater relative disability versus less (GOSE 1-4/5-8); incomplete full recovery <8/ = 8). One-hundred sixty subjects, 28 OCs, 18 HCs Markers discriminating TBI/OC: HMGB-1 (AUC 0.835), IL-1b (0.795), IL-16 (0.784), IL-7 (0.742), TARC (0.731). GCS 3-12/13-15: IL-6 0.747), CRP (0.726), IL-15 (0.720), SAA (0.716). positive/CT negative: 0.767), (0.757), (0.733), (0.724). At 3 months, 0.738) IL-2 (0.705) discriminated GOSE 5-8/1-4. 6 1-4/5-8 0.704) 8 (0.711); (0.704). identified a profile acute circulating proteins with potential relevance for diagnosis, severity differentiation, serum amyloid A are priority acceptable discrimination across multiple diagnostic outcome categories. Validation larger cohorts needed. ClinicalTrials.gov Registration: NCT01565551.

Language: Английский

---

Biomarkers of aging in frailty and age-associated disorders: State of the art and future perspective

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 91, P. 102044 - 102044

Published: Aug. 28, 2023

According to the Geroscience concept that organismal aging and age-associated diseases share same basic molecular mechanisms, identification of biomarkers age can efficiently classify people as biologically older (or younger) than their chronological (i.e. calendar) is becoming paramount importance. These will be in fact at higher lower) risk for many different diseases, including cardiovascular neurodegeneration, cancer, etc. In turn, patients suffering from these are healthy age-matched individuals. Many correlate with have been described so far. The aim present review discuss usefulness some (especially soluble, circulating ones) order identify frail patients, possibly before appearance clinical symptoms, well diseases. An overview selected discussed this regard, particular we focus on related metabolic stress response, inflammation, cell death (in neurodegeneration), all phenomena connected inflammaging (chronic, low-grade, inflammation). second part review, next-generation markers such extracellular vesicles cargos, epigenetic gut microbiota composition, discussed. Since recent progresses omics techniques allowed an exponential increase production laboratory data also field age, making it difficult extract biological meaning huge mass available data, Artificial Intelligence (AI) approaches increasingly important strategy extracting knowledge raw providing practitioners actionable information treat patients.

Language: Английский

---

The double-edged effects of IL-6 in liver regeneration, aging, inflammation, and diseases

Experimental Hematology and Oncology, Journal Year: 2024, Volume and Issue: 13(1)

Published: June 18, 2024

Abstract Interleukin-6 (IL-6) is a pleiotropic cytokine and exerts its complex biological functions mainly through three different signal modes, called cis- , trans- cluster signaling. When IL-6 binds to membrane or soluble receptors, the co-receptor gp130 activated initiate downstream signaling induce expression of target genes. In liver, can perform anti-inflammatory activities promote hepatocyte reprogramming liver regeneration. On contrary, also pro-inflammatory aging, fibrosis, steatosis, carcinogenesis. However, understanding roles underlying mechanisms in physiological pathological processes still an ongoing process. So far, therapeutic agents against IL‑6, IL‑6 receptor (IL‑6R), IL-6-sIL-6R complex, transducers have been developed, determined be effective intervention inflammatory diseases cancers. this review, we summarized highlighted double-edged effects homeostasis, inflammation, chronic diseases, for better shifting “negative” “beneficial” actions, further discussed potential targeting clinics.

Language: Английский

---

Development and Validation of a Diagnostic Model for Stanford Type B Aortic Dissection Based on Proteomic Profiling

Journal of Inflammation Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 533 - 547

Published: Jan. 1, 2025

Purpose: Stanford Type B Aortic Dissection (TBAD), a critical aortic disease, has exhibited stable mortality rates over the past decade. However, diagnostic approaches for TBAD during routine health check-ups are currently lacking. This study focused on developing model to improve diagnosis in population. Patients and Methods: Serum biomarkers were investigated 88 participants using proteomic profiling combined with machine learning. The findings validated ELISA other 80 participants. Subsequently, integrating clinical indicators was developed assessed Results: Six differentially expressed proteins (DEPs) identified through learning discovery derivation cohorts. Five of these (GDF-15, IL6, CD58, LY9, Siglec-7) further verified validation within cohort. In addition, ten blood-related selected as indicators. Combining indicators, learning-based models performed well (AUC biomarker = 0.865, AUC 0.904, 0.909) relative quantitation. performance three 0.866, 0.868, 0.886) absolute Crucially, outperformed individual models, demonstrating superior efficacy. Conclusion: Using profiling, we serum IL-6, GDF-15, Siglec-7 biomarkers. machine-learning-based significant potential only blood samples Keywords: type dissection, proteomics, learning, biomarkers,

Language: Английский

---

Cytokine Storm in COVID-19: Exploring IL-6 Signaling and Cytokine-Microbiome Interactions as Emerging Therapeutic Approaches

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(21), P. 11411 - 11411

Published: Oct. 24, 2024

IL-6 remains a key molecule of the cytokine storms characterizing COVID-19, exerting both proinflammatory and anti-inflammatory effects. Emerging research underscores significance trans-signaling over classical signaling pathways, which has shifted focus therapeutic strategies. Additionally, synergistic action TNF-α IFN-γ been found to induce inflammatory cell death through PANoptosis, further amplifying severity storms. Long COVID-19 patients, as well those with triggered by other conditions, exhibit distinct laboratory profiles, indicating need for targeted approaches diagnosis management. Growing evidence also highlights gut microbiota's crucial role in modulating immune response during affecting production, adding complexity disease's immunological landscape. Targeted intervention strategies should on specific cutoffs, though accurate quantification clinical challenge. Current treatment are increasingly focused inhibiting trans-signaling, offers promise more precise manage hyperinflammatory responses COVID-19. In light recent discoveries, this review summarizes findings storms, particularly their conditions. It explores emerging targeting cytokines like IL-6, TNF-α, IFN-γ, while addressing open questions, such better biomarkers detect ongoing challenges developing treatments that mitigate hyperinflammation without compromising function, emphasizing importance continued field.

Language: Английский

---

Causal associations between circulating inflammatory cytokines and blinding eye diseases: a bidirectional Mendelian randomization analysis

Frontiers in Aging Neuroscience, Journal Year: 2024, Volume and Issue: 16

Published: Jan. 23, 2024

Background Previous studies have explored the associations between circulating inflammatory cytokines and blinding eye diseases, including glaucoma, cataract macular degeneration. However, causality of these remains controversial. This study employs a bidirectional Mendelian randomization (MR) to investigate causal relationships 41 diseases. Methods Summary data for cataract, degeneration were publicly available. The inverse variance weighted (IVW) method was employed as main analysis method. Additionally, various sensitivity tests, MR–Egger regression, median, weight mode, Cochran’s Q test, MR pleiotropy Residual Sum Outlier leave-one-out conducted evaluate stability results. Results IVW identified six causally associated with risk diseases: Monokine induced by interferon-gamma (MIG) interleukin-1 receptor antagonist (IL-1ra), IL-6, IL-10, platelet derived growth factor BB (PDGFbb) MIG hepatocyte (HGF) it is noteworthy that none remained significant after Bonferroni correction ( p &lt; 0.0004). Reverse analyses indicated may lead decrease in vascular endothelial (VEGF) levels (OR: 3.326 × 10 −04 , 95% CI: 5.198 −07 − 2.129 −01 = 0.0151). Conclusion highlights potential roles specific development Moreover, suggests VEGF likely be involved downstream. These findings offer insights early prevention novel therapeutic strategies

Language: Английский

---