Delving into the Latest Updates on Sivelestat Sodium Hydrate with Synapse

PALETTE is a perpetual adaptive platform to efficiently study sepsis interventions within 'treatable traits' in all-ages patients enabling prompt evaluation of pandemic treatments. Treatable traits, therapeutic targets identified by phenotypes or endotypes (defined by biological mechanism or by treatment response) through validated biomarkers (measurable characteristic reflecting normal or pathogenic processes, or treatment responses), may include multi-omics, cellular, immune, metabolic, endocrine features, or intelligent algorithms. PALETTE Bayesian adaptive design enables parallel investigations of multiple interventions for sepsis, and quick inclusion of pandemic pathogens. PALETTE's new conceptual model will respond to the challenges of standard approaches, i.e. series of sepsis trials, each investigating one or two interventions, expensive, time consuming, and inappropriate in pandemic context.

Start Date01 Apr 2026

Sponsor / Collaborator

Assistance Publique des Hôpitaux de Paris SA

ChiCTR2400086632 / SuspendedPhase 2IIT

The feaSibility and safety of sIvelestat soDIum hydrate adjunct to fentaNyl for analGesia in patients under mechanical ventilation : a multi-center, randomized, controlled trial (The SIDING trial)

Start Date15 Jul 2024

Sponsor / Collaborator

Huai'an First People's Hospital

NCT06387823 / RecruitingNot ApplicableIIT

Efficacy and Safety of Sivelestat Sodium and Dexamethasone in the Treatment of ARDS: a Pilot Study of a Prospective, Multicenter, Double-blind, Double-mock Randomized Controlled Clinical Study

The goal of this clinical trial is to evaluate the efficacy and safety of Sivelestat sodium and dexamethasone in the treatment of patients with moderate to severe ARDS. The main questions it aims to answer are:
Is Sivelestat sodium more effective in the treatment of patients with moderate to severe ARDS compared with placebo?
Is dexamethasone more effective in the treatment of patients with moderate to severe ARDS compared with placebo? Participants will receive Sivelestat sodium, dexamethasone or placebo. Researchers will compare the efficacy and safety of Sivelestat sodium, dexamethasone and placebo.

Start Date15 Apr 2024

Sponsor / Collaborator

Peking Union Medical College Hospital

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100 Clinical Results associated with Sivelestat Sodium Hydrate

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100 Translational Medicine associated with Sivelestat Sodium Hydrate

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100 Patents (Medical) associated with Sivelestat Sodium Hydrate

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469

Literatures (Medical) associated with Sivelestat Sodium Hydrate

01 Dec 2024·Annals of the Rheumatic Diseases

SerpinA3N limits cartilage destruction in osteoarthritis by inhibiting macrophage-derived leucocyte elastase

Article

Author: Latourte, Augustin ; Richette, Pascal ; Grange, Thierry ; Daligault, Julien ; Cherifi, Chahrazad ; Cohen-Solal, Martine ; Combier, Alice ; Hay, Eric ; Jaulerry, Sarah ; Ea, Hang-Korng ; Jouan, Yohan

ObjectivesInflammatory mediators such as interleukin 6 (IL-6) are known to activate catabolic responses in chondrocytes during osteoarthritis (OA). This study aimed to investigate the role of a downstream target gene of IL-6, the serine protease inhibitor SerpinA3N, in the development of cartilage damage in OA.MethodsRNA sequencing was performed in murine primary chondrocytes treated with IL-6, and identified target genes were confirmed in human and murine OA cartilage samples. Male cartilage-specificSerpina3n-deficient mice and control mice underwent meniscectomy (MNX) or sham surgery at 10 weeks of age. Intra-articular injections of SerpinA3N or sivelestat (an inhibitor of leucocyte elastase (LE), a substrate for SerpinA3N) were performed in wild-type mice after MNX. Joint damage was assessed 3–9 weeks after surgery by histology and micro-CT. The effect of sivelestat was assessed in cartilage explants exposed to macrophage-derived conditioned media.ResultsRNA sequencing revealed that SerpinA3N is a major target gene of IL-6 in chondrocytes. The expression of SerpinA3N is increased in OA cartilage. Conditional loss of SerpinA3N in chondrocytes aggravated OA in mice, while intra-articular injection of SerpinA3N limited joint damage. Chondrocytes did not produce serine proteases targeted by SerpinA3N. By contrast, macrophages produced LE on IL-6 stimulation. Sivelestat limited the cartilage catabolism induced by conditioned media derived from IL-6-stimulated macrophages. Additionally, an intra-articular injection of sivelestat is protected against OA in the MNX model.ConclusionsSerpinA3N protects cartilage against catabolic factors produced by macrophages, including LE. SerpinA3N and LE represent new therapeutic targets to dampen cartilage damage in OA.

01 Nov 2024·Journal of Controlled Release

Elastase-targeting biomimic nanoplatform for neurovascular remodeling by inhibiting NETosis mediated AlM2 inflammasome activation in ischemic stroke

Article

Author: Lu, Xiaowei ; Jia, Feng ; Ding, Yan ; Chen, Xufeng ; Xu, Huae ; Tang, Chunming ; Chen, Weilin ; Wu, Min ; Han, Feng ; Li, Jinyu ; Wang, Yanling

Neutrophil elastase (NE) is a protease released by activated neutrophils in the brain parenchyma after cerebral ischemia, which plays a pivotal role in the regulation of neutrophil extracellular traps (NETs) formation. The excess NETs could lead to blood-brain barrier (BBB) breakdown, overwhelming neuroinflammation, and neuronal injury. While the potential of targeting neutrophils and inhibiting NE activity to mitigate ischemic stroke (IS) pathology has been recognized, effective strategies that inhibit NETs formation remain under-explored. Herein, a biomimic multifunctional nanoplatform (HM@ST/TeTeLipos) was developed for active NE targeting and IS treatment. The core of the HM@ST/TeTeLipos consisted of sivelestat-loaded ditelluride-containing liposomes with ROS-responsive and NE-inhibiting properties. The outer shell was composed of platelet-neutrophil hybrid membrane vesicles (HMVs), which acted to hijack neutrophils and neutralize proinflammatory cytokines. Our studies revealed that HM@ST/TeTeLipos could effectively inhibit NE activity, thereby suppressing the release of NETs, impeding the activation of the AIM2 inflammasome, and consequently redirecting the immune response away from a pro-inflammatory M1 microglia phenotype. This resulted in enhanced neurovascular remodeling, reduced BBB disruption, and diminished neuroinflammation, ultimately promoting neuron survival. We believe that this innovative approach holds significant potential for improving the treatment of IS and various NE-mediated inflammatory diseases.

01 Oct 2024·International Journal of Cosmetic Science

Cosmetic application of the stem‐bark extract of Bertholletia excelsa H.B.K

Article

Author: Silva, Márcia J. A. ; Acho, Leonard D. R. ; Lima, Emerson S. ; Guimarães, Anderson C. ; Carneiro, Simone B.

AbstractObjectiveThe Amazon has a rich biodiversity where many different plant species can be found. This diversity is an important source of bioactive substances, mainly due to the different structural components of their phytometabolites. Research for natural products is a strategy for the development of new agents in therapeutic applications, especially cosmetic applications, that have better pharmacological potential. Within this perspective, the objective of the study was to investigate the cosmetic application (anti‐aging potential) of the stem‐bark extract of Bertholletia excelsa H.B.K – (SBEBE), popularly known as the Brazil nut tree, here called SBEBE, a noble plant species of the Amazon that is rich in selenium.MethodsEnzymatic, glycation, proliferation, cell‐healing, collagen quantification, toxicity and genotoxicity assays were used.ResultsAmong the enzymes involved in the extracellular matrix of the skin, SBEBE was able to inhibit only elastase (62.67 ± 3.75) when compared to the standard sivelestat (89.04 ± 0.53), and the extract was also able to inhibit both the oxidative and the non‐oxidative pathway. When cell toxicity in fibroblasts (MRC‐5) and keratinocytes (HACAT) was evaluated, SBEBE did not present toxicity in 24 h of incubation. After this period, the extract showed average cytotoxicity in 48 and 72 h, but not enough to reach the concentration of 50% of MRC‐5 fibroblasts. In the trypan blue assay, the extract promoted fibroblast proliferation in 24, 48 and 72 h of incubation, which was evaluated through exponential cell growth, with emphasis mainly on the lowest concentration with results higher than the standard. When the cell healing capacity was evaluated, in 48 h of exposure to fibroblast, SBEBE was able to induce a cell carpet (cell film) in the cell monolayer scratch assay.ConclusionsSBEBE stimulated collagen production at all concentrations tested. In the alkaline comet assay, at the lowest concentration, the extract did not induce DNA damage when compared to the reference drug doxorubicin. This study proved that SBEBE extract can be considered an ally in the treatment of skin anti‐ageing as a possible biotechnological, phytocosmetic product.

100 Deals associated with Sivelestat Sodium Hydrate

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KEGG	Wiki	ATC	Drug Bank
-	Sivelestat Sodium Hydrate	R03	DB12863

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Acute Lung Injury	JP	Ono Pharmaceutical Co., Ltd.	11 Apr 2002
Acute Lung Injury	JP	Maruishi Pharmaceutical Co., Ltd.	11 Apr 2002
Systemic Inflammatory Response Syndrome	JP	Ono Pharmaceutical Co., Ltd.	11 Apr 2002

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Acute Lung Injury	Phase 3	AU	Eli Lilly & Co.	01 Aug 2001
Acute Lung Injury	Phase 3	ES	Eli Lilly & Co.	01 Aug 2001
Acute Lung Injury	Phase 3	CA	Eli Lilly & Co.	01 Aug 2001
Acute Lung Injury	Phase 3	US	Eli Lilly & Co.	01 Aug 2001
Acute Lung Injury	Phase 3	NZ	Eli Lilly & Co.	01 Aug 2001
Acute Lung Injury	Phase 3	BE	Eli Lilly & Co.	01 Aug 2001
Respiratory Distress Syndrome, Adult	Phase 3	NZ	Eli Lilly & Co.	01 Aug 2001
Respiratory Distress Syndrome, Adult	Phase 3	BE	Eli Lilly & Co.	01 Aug 2001
Respiratory Distress Syndrome, Adult	Phase 3	US	Eli Lilly & Co.	01 Aug 2001
Respiratory Distress Syndrome, Adult	Phase 3	AU	Eli Lilly & Co.	01 Aug 2001