IC100, a humanized therapeutic monoclonal anti-ASC antibody alleviates oxygen-induced retinopathy in mice DOI Creative Commons

Huijun Yuan,

Shaoyi Chen,

Matthew R. Duncan

et al.

Angiogenesis, Journal Year: 2024, Volume and Issue: 27(3), P. 423 - 440

Published: May 6, 2024

Abstract Background Retinopathy of prematurity (ROP), which often presents with bronchopulmonary dysplasia (BPD), is among the most common morbidities affecting extremely premature infants and a leading cause severe vision impairment in children worldwide. Activations inflammasome cascade microglia have been implicated playing role development both ROP BPD. Apoptosis-associated speck-like protein containing caspase recruitment domain (ASC) pivotal assembly. Utilizing mouse models oxygen-induced retinopathy (OIR) BPD, this study was designed to test hypothesis that hyperoxia induces ASC speck formation, leads microglial activation retinopathy, inhibition formation by humanized monoclonal antibody, IC100, directed against ASC, will ameliorate abnormal retinal vascular formation. Methods We first tested retina ASC-citrine reporter mice expressing fusion C-terminal citrine (fluorescent GFP isoform) using BPD model causes lung eye injury exposing newborn room air (RA) or 85% O 2 from postnatal day (P) 1 P14. The retinas were dissected on P14 flat mounts used detect endothelium AF-594-conjugated isolectin B4 (IB4) citrine-tagged specks. To assess effects IC100 an OIR model, wildtype (C57BL/6 J) exposed RA P1 P6, then 75% P7 P11, P12 P18. At randomized following groups: placebo PBS (RA-PBS), (O -PBS), + intravitreal injection -IC100-IVT), intraperitoneal -IC100-IP). Retinal vascularization evaluated mount staining IB4. Microglial detected immunofluorescence for allograft inflammatory factor (AIF-1) CD206. structure analyzed H&E-stained sections, function pattern electroretinography (PERG). RNA-sequencing (RNA-seq) performed determine transcriptional treatment OIR. Results specks significantly increased exposure colocalized vasculature models, associated activation. Treatment IC100-IVT IC100-IP reduced vaso-obliteration neovascularization. also activation, restored structure, improved function. RNA-seq showed corrected induction genes angiogenesis, leukocyte migration, VEGF signaling caused . suppression cell junction assembly, neuron projection, recognition Conclusion These data demonstrate crucial pathogenesis efficacy therapeutic anti-ASC antibody treating mice. Thus, may potentially be considered diseases oxygen stresses such as ROP.

Language: Английский

Pyroptosis and degenerative diseases of the elderly DOI Creative Commons
Jiamin Zhou,

Jingjing Qiu,

Yuwan Song

et al.

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(2)

Published: Feb. 9, 2023

Abstract Pyroptosis is a recently described mechanism of programmed cell death mediated by proteins the gasdermin family. Widely recognized signaling cascades include classical, non-classical, caspase-3-dependent E and caspase-8-dependent D pathways. Additional pyroptotic pathways have been subsequently reported. With rising prevalence advanced age, role pyroptosis in degenerative diseases elderly has attracted increased research attention. This article reviews primary mechanisms summarizes progress such as presbycusis, age-related macular degeneration, Alzheimer’s disease, intervertebral disc osteoarthritis.

Language: Английский

Citations

43
Current Approach to the Pathogenesis of Diabetic Cataracts DOI Open Access
Małgorzata Mrugacz,

Magdalena Pony-Uram,

Anna Bryl

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(7), P. 6317 - 6317

Published: March 28, 2023

Cataracts remain the first or second leading cause of blindness in all world regions. In diabetic population, cataracts not only have a 3–5 times higher incidence than healthy population but also affect people at younger age. patients with type 1 diabetes, occur on average 20 years earlier non-diabetic population. addition, risk developing increases duration diabetes and poor metabolic control. A better understanding mechanisms to formation enables more effective treatment holistic approach patient.

Language: Английский

Citations

32
Roles of microglia in adult hippocampal neurogenesis in depression and their therapeutics DOI Creative Commons
Shaoyi Fang,

Zhibin Wu,

Yali Guo

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Oct. 10, 2023

Adult hippocampal neurogenesis generates functional neurons from neural progenitor cells in the dentate gyrus (DG) to complement and repair circuits, thus benefiting treatment of depression. Increasing evidence has shown that aberrant microglial activity can disrupt appropriate formation development properties neurogenesis, which will play a crucial role occurrence However, mechanisms crosstalk between microglia adult depression are not yet fully understood. Therefore, this review, we first introduce recent discoveries regarding roles etiology Then, systematically discuss possible how regulate according studies, involve toll-like receptors, polarization, fractalkine-C-X3-C motif chemokine receptor 1, hypothalamic-pituitary-adrenal axis, cytokines, brain-derived neurotrophic factor, microbiota-gut-brain etc. In addition, summarize promising drugs could improve by regulating microglia. These findings help us understand complicated pathological shed light on new strategies for disease.

Language: Английский

Citations

30
Role of pyroptosis in the pathogenesis and treatment of diseases DOI Creative Commons
Xiangyu Jin, Yinchu Ma, Didi Liu

et al.

MedComm, Journal Year: 2023, Volume and Issue: 4(3)

Published: April 25, 2023

Abstract Programmed cell death (PCD) is regarded as a pathological form of with an intracellular program mediated, which plays pivotal role in maintaining homeostasis and embryonic development. Pyroptosis new paradigm PCD, has received increasing attention due to its close association immunity disease. inflammatory mediated by gasdermin that promotes the release proinflammatory cytokines contents induced inflammasome activation. Recently, evidence studies shows pyroptosis crucial conditions like cardiovascular diseases (CVDs), cancer, neurological (NDs), metabolic (MDs), suggesting targeting potential intervention for treatment these diseases. Based on this, review aims identify molecular mechanisms signaling pathways related activation summarizes current insights into complicated relationship between multiple human (CVDs, NDs, MDs). We also discuss promising novel strategy method treating focus pathway application clinics.

Language: Английский

Citations

28
GSK-3β-dependent Nrf2 antioxidant response modulates ferroptosis of lens epithelial cells in age-related cataract DOI

Dong-yue Ma,

Jinxia Liu, Ludi Wang

et al.

Free Radical Biology and Medicine, Journal Year: 2023, Volume and Issue: 204, P. 161 - 176

Published: May 6, 2023

Language: Английский

Citations

26
Recent advances in melittin-based nanoparticles for antitumor treatment: from mechanisms to targeted delivery strategies DOI Creative Commons
Xiang Yu, Siyu Jia, Yu Shi

et al.

Journal of Nanobiotechnology, Journal Year: 2023, Volume and Issue: 21(1)

Published: Nov. 28, 2023

Abstract As a naturally occurring cytolytic peptide, melittin (MLT) not only exhibits potent direct tumor cell-killing effect but also possesses various immunomodulatory functions. MLT shows minimal chances for developing resistance and has been recognized as promising broad-spectrum antitumor drug because of this unique dual mechanism action. However, still displays obvious toxic side effects during treatment, such nonspecific activity, hemolytic toxicity, coagulation disorders, allergic reactions, seriously hampering its broad clinical applications. With thorough research on mechanisms the rapid development nanotechnology, significant effort devoted to shielding against toxicity achieving tumor-directed delivery improve therapeutic efficacy MLT. Herein, we mainly summarize potential recent progress in targeted strategies therapy, passive targeting, active targeting stimulus-responsive targeting. Additionally, highlight prospects challenges realizing full field therapy. By exploring molecular MLT, comprehensive review may inspire new ideas multimechanism synergistic

Language: Английский

Citations

24
Pyroptosis: Mechanisms and links with diabetic cardiomyopathy DOI
Pan Liu, Zhengdong Zhang,

Huizhen Chen

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 94, P. 102182 - 102182

Published: Jan. 4, 2024

Language: Английский

Citations

12
Targeting inflammasomes and pyroptosis in retinal diseases—molecular mechanisms and future perspectives DOI Creative Commons

Yimeng Sun,

Fan Li,

Yunfei Liu

et al.

Progress in Retinal and Eye Research, Journal Year: 2024, Volume and Issue: 101, P. 101263 - 101263

Published: April 23, 2024

Retinal diseases encompass various conditions associated with sight-threatening immune responses and are leading causes of blindness worldwide. These include age-related macular degeneration, diabetic retinopathy, glaucoma uveitis. Emerging evidence underscores the vital role innate response in retinal diseases, beyond previously emphasized T-cell-driven processes adaptive system. In particular, pyroptosis, a newly discovered programmed cell death process involving inflammasome formation, has been implicated loss membrane integrity release inflammatory cytokines. Several disease-relevant animal models have provided that formation inflammasomes induction pyroptosis cells contribute to inflammation diseases. this review article, we summarize current knowledge about system We also provide insights into translational targeting approaches, including novel drugs countering improve diagnosis treatment

Language: Английский

Citations

9
Oridonin ameliorates ocular surface inflammatory responses by inhibiting the NLRP3/caspase-1/GSDMD pyroptosis pathway in dry eye DOI
Xiaojing Li, Chen Chen, Ying Chen

et al.

Experimental Eye Research, Journal Year: 2024, Volume and Issue: 245, P. 109955 - 109955

Published: June 5, 2024

Language: Английский

Citations

9
The Potential Role of Regulated Cell Death in Dry Eye Diseases and Ocular Surface Dysfunction DOI Open Access
Camilla Scarpellini, Alba Ramos-Llorca, Caroline Lanthier

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(1), P. 731 - 731

Published: Jan. 1, 2023

The research on new treatments for dry eye diseases (DED) has exponentially grown over the past decades. increased prevalence of conditions, particularly in younger population, received much attention. Therefore, it is utmost importance to identify novel therapeutical targets. Regulated cell death (RCD) an essential process control biological homeostasis tissues and organisms. identification different mechanisms RCD stimulated their involvement human pathologies. Whereas apoptosis been widely studied DED included vicious cycle, role still needs be completely elucidated. In this review, we will explore potential roles types ocular surface dysfunction. Starting from evidence oxidative stress inflammation pathology, analyse therapeutic applications following principal mechanisms: ferroptosis, necroptosis, pyroptosis.

Language: Английский

Citations

20