Targeting strategies for bone diseases: signaling pathways and clinical studies

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Май 17, 2023

Abstract Since the proposal of Paul Ehrlich’s magic bullet concept over 100 years ago, tremendous advances have occurred in targeted therapy. From initial selective antibody, antitoxin to drug delivery that emerged past decades, more precise therapeutic efficacy is realized specific pathological sites clinical diseases. As a highly pyknotic mineralized tissue with lessened blood flow, bone characterized by complex remodeling and homeostatic regulation mechanism, which makes therapy for skeletal diseases challenging than other tissues. Bone-targeted has been considered promising approach handling such drawbacks. With deepening understanding biology, improvements some established bone-targeted drugs novel targets deliveries on horizon. In this review, we provide panoramic summary recent strategies based targeting. We highlight targeting structure biology. For agents, addition classic denosumab, romosozumab, PTH1R ligands, potential process key membrane expressions, cellular crosstalk, gene expression, all cells exploited. delivery, different matrix, marrow, are summarized comparison between ligands. Ultimately, review will summarize translation therapies perspective challenges application clinic future trends area.

Язык: Английский

---

Neutrophil extracellular traps in homeostasis and disease

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Сен. 20, 2024

Язык: Английский

---

Potential clinical implications of molecular mimicry‐induced autoimmunity

Immunity Inflammation and Disease, Год журнала: 2024, Номер 12(2)

Опубликована: Фев. 1, 2024

Molecular mimicry is hypothesized to be a mechanism by which autoimmune diseases are triggered. It refers sequence or structural homology between foreign antigens and self-antigens, can activate cross-reactive lymphocytes that attack host tissues. Elucidating the role of molecular in human autoimmunity could have important clinical implications.

Язык: Английский

---

Inhibition of ferroptosis rescues M2 macrophages and alleviates arthritis by suppressing the HMGB1/TLR4/STAT3 axis in M1 macrophages

Redox Biology, Год журнала: 2024, Номер 75, С. 103255 - 103255

Опубликована: Июнь 24, 2024

Язык: Английский

---

Advances in the Regulation of Inflammatory Mediators in Nitric Oxide Synthase: Implications for Disease Modulation and Therapeutic Approaches

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(3), С. 1204 - 1204

Опубликована: Янв. 30, 2025

Nitric oxide synthases (NOS) are crucial enzymes responsible for the production of nitric (NO), a signaling molecule with essential roles in vascular regulation, immune defense, and neurotransmission. The three NOS isoforms, endothelial (eNOS), neuronal (nNOS), inducible (iNOS), tightly regulated by inflammatory mediators cellular pathways. While physiological NO is vital maintaining homeostasis, dysregulated activity contributes to pathogenesis numerous diseases, including cardiovascular disorders, neurodegenerative conditions, cancer. Recent advances understanding molecular mechanisms regulation have unveiled novel therapeutic opportunities, isoform-specific modulators, upstream pathways, nanotechnology-enhanced delivery systems. This review highlights these advancements, offering insights into how targeting its regulatory network can enable precise effective strategies managing inflammation-driven pathologies.

Язык: Английский

---

Triple Cross‐linked Dynamic Responsive Hydrogel Loaded with Selenium Nanoparticles for Modulating the Inflammatory Microenvironment via PI3K/Akt/NF‐κB and MAPK Signaling Pathways

Advanced Science, Год журнала: 2023, Номер 10(31)

Опубликована: Сен. 22, 2023

Modulating the inflammatory microenvironment can inhibit process of diseases (IDs). A tri-cross-linked microenvironment-responsive hydrogel with ideal mechanical properties achieves triggerable and sustained drug delivery regulates microenvironment. Here, this study develops an (OD-PP@SeNPs) composed phenylboronic acid grafted polylysine (PP), oxidized dextran (OD), selenium nanoparticles (SeNPs). The introduction SeNPs as initiators nano-fillers into results in extra cross-linking polymer network through hydrogen bonding. Based on Schiff base bonds, Phenylboronate ester a reactive oxygen species (ROS)/pH dual responsive triple-network is achieved. has injectable, self-healing, adhesion, outstanding flexibility, suitable swelling capacity, optimal biodegradability, excellent stimuli-responsive active substance release performance, prominent biocompatibility. Most importantly, ROS scavenging pH-regulating ability protects cells from oxidative stress induces macrophages M2 polarization to reduce cytokines PI3K/AKT/NF-κB MAPK pathways, exerting anti-inflammatory effects reshaping microenvironment, thereby effectively treating typical IDs, including S. aureus infected wound rheumatoid arthritis rats. In conclusion, dynamically injectable structure provides effective strategy treat holding great promise clinical application.

Язык: Английский

---

Cardiovascular Brain Circuits

Circulation Research, Год журнала: 2023, Номер 132(11), С. 1546 - 1565

Опубликована: Май 25, 2023

The cardiovascular system is hardwired to the brain via multilayered afferent and efferent polysynaptic axonal connections. Two major anatomically functionally distinct though closely interacting subcircuits within have recently been defined: artery-brain circuit heart-brain circuit. However, how nervous impacts disease progression remains poorly understood. Here, we review recent findings on anatomy, structures, inner workings of lesser-known better-established We explore evidence that signals from arteries or heart form a systemic finely tuned circuit: inputs originating in arterial tree are conveyed sensory neurons brain. There, primary integration centers act as hubs receive integrate circuit–derived process them together with connections humoral cues distant regions. To conclude circuit, transmit constantly modified which transfer back system. Importantly, wired information secondary control wide variety traits encoded engrams including immune memory, stress-regulating hormone release, pain, reward, emotions, even motivated types behavior. Finally, important possibility effector network connect other peripheral organs system, gut, liver, adipose tissue. enormous progress vis-à-vis allows us propose novel neurobiology-centered hypothesis term neuroimmune hypothesis.

Язык: Английский

---

“Smart” stimuli-responsive biomaterials revolutionizing the theranostic landscape of inflammatory arthritis

Materials Today Chemistry, Год журнала: 2024, Номер 39, С. 102178 - 102178

Опубликована: Июль 1, 2024

Inflammatory arthritis is a growing worldwide concern, afflicting millions of individuals and leading to depreciating quality life, significant morbidity, subsequent healthcare burden. Conventional therapies for inflammatory often hold limitations, including systemic cross-reactivities, side effects, inadequate management inflammation. Therefore, "Smart" stimuli-responsive biomaterials are materialized as promising theranostic approaches management. These designed specific external internal stimulation, enabling the sustained release bioactive therapeutic agents during local or administration. Stimuli-responsive allow precise spatiotemporal control over drug release, minimizing exposure, reducing off-target real-time monitoring pathological conditions, driving potential breakthrough in managing arthritis. Owing this prominence, review article expounds on emerging prospects targeting molecular signatures associated with intricately elicit minimal no contradictory effects. In addition, application these disease progression multi-stimuli-responsive comprehended show progress diagnosis treatment. This "single-platted" comprehensive acquaintance clinical-based outcomes navigates microenvironment, proposing an optimistic avenue personalized effective minimized

Язык: Английский

---

Microenvironment‐Activatable Probe for Precise NIR‐II Monitoring and Synergistic Immunotherapy in Rheumatoid Arthritis

Advanced Materials, Год журнала: 2024, Номер 36(48)

Опубликована: Окт. 6, 2024

Rheumatoid arthritis (RA) represents an insidious autoimmune inflammatory disorder that severely lowers the life quality by progressively destructing joint functions and eventually causing permanent disability, posing a serious public health problem. Here, advanced theranostic probe is introduced integrates activatable second near-infrared (NIR-II) fluorescence imaging for precise RA diagnosis with multi-pronged treatments. A novel molecular comprising long-wavelength aggregation-induced emission unit manganese carbonyl cage motif synthesized, which enables NIR-II activation concurrently releasing therapeutic carbon monoxide (CO) gas in inflamed microenvironment. This self-assembles into biocompatible nanoprobe, subsequently conjugated anti-IL-6R antibody to afford active-targeting ability of RA. The nanoprobe exhibits significant turn-on signal at lesion, enabling highly sensitive real-time monitoring. combination ROS scavenging, on-demand CO release, IL-6 signaling blockade results potent effect synergistic immunomodulation impact, significantly alleviating symptoms preventing destruction. research introduces paradigm development high-performance, strategies facilitate detection enhanced treatment RA-related diseases.

Язык: Английский

---

Evolving understanding of autoimmune mechanisms and new therapeutic strategies of autoimmune disorders

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Окт. 4, 2024

Autoimmune disorders are characterized by aberrant T cell and B reactivity to the body's own components, resulting in tissue destruction organ dysfunction. diseases affect a wide range of people many parts world have become one major concerns public health. In recent years, there been substantial progress our understanding epidemiology, risk factors, pathogenesis mechanisms autoimmune diseases. Current approved therapeutic interventions for mainly non-specific immunomodulators may cause broad immunosuppression that leads serious adverse effects. To overcome limitations immunosuppressive drugs treating diseases, precise target-specific strategies urgently needed. date, significant advances made immune tolerance, offering new avenue developing antigen-specific immunotherapies These approaches shown great potential various preclinical animal models recently evaluated clinical trials. This review describes common manifestation with focus on typical including multiple sclerosis, type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus, sjögren's syndrome. We discuss current therapeutics developed this field, highlight use nanomaterials mRNA vaccine techniques induce tolerance.

Язык: Английский

---