12 research outputs found
Molecular identification and anticancer activity of alkylphenol from cashew nut shell oil (Anacardium occidentale) grown In Timor Island
Isolation of anacardic acid and cardanol from cashew nut shell liquid and their cytotoxic activity to on ward HeLa cancer cell line has been done. The objective of this research is to isolate and identify anacardic acid and cardanol from CNSL along with their cytototoxic activity towards HeLa cancer cell lines. Anacardic acid was isolated as calcium anacardate. Hydrolisis of this acid with acid chloride yields anacardic acid . Liquor ammonia was added to the acid-free CNSL and extracted with hexane/ethyl acetate (98:2) to isolate cardanol and with ethyl acetate/hexane (80:20) to separate cardol. Cardanol was obtained as the main chemical component of CNSL derived from Kupang district. Anacardic acid and cardanol was analyzed using IR and GC-MS. Anticancer activity of chemical components of CNSL against HeLa cancer cell lines were studied using MTT. Cytotoxic activity test showed that CNSL, anacardic acid and cardanol can be developed as anticancer agent.Key words : CNSL, anacardic acid, cardanol, anticancer
The disruption of proteostasis in neurodegenerative diseases
Cells count on surveillance systems to monitor and protect the cellular proteome which, besides being highly heterogeneous, is constantly being challenged by intrinsic and environmental factors. In this context, the proteostasis network (PN) is essential to achieve a stable and functional proteome. Disruption of the PN is associated with aging and can lead to and/or potentiate the occurrence of many neurodegenerative diseases (ND). This not only emphasizes the importance of the PN in health span and aging but also how its modulation can be a potential target for intervention and treatment of human diseases.info:eu-repo/semantics/publishedVersio
Chaperone-assisted selective autophagy is essential for muscle maintenance
How are biological structures maintained in a cellular environment that constantly threatens protein integrity? Here we elucidate proteostasis mechanisms affecting the Z disk, a protein assembly essential for actin anchoring in striated muscles, which is subjected to mechanical, thermal, and oxidative stress during contraction [1]. Based on the characterization of the Drosophila melanogaster cochaperone Starvin (Stv), we define a conserved chaperone machinery required for Z disk maintenance. Instead of keeping Z disk proteins in a folded conformation, this machinery facilitates the degradation of damaged components, such as filamin, through chaperone-assisted selective autophagy (CASA). Stv and its mammalian ortholog BAG-3 coordinate the activity of Hsc70 and the small heat shock protein HspB8 during disposal that is initiated by the chaperone-associated ubiquitin ligase CHIP and the autophagic ubiquitin adaptor p62. CASA is thus distinct from chaperone-mediated autophagy, previously shown to facilitate the ubiquitin-independent, direct translocation of a client across the lysosomal membrane [2]. Impaired CASA results in Z disk disintegration and progressive muscle weakness in flies, mice, and men. Our findings reveal the importance of chaperone-assisted degradation for the preservation of cellular structures and identify muscle as a tissue that highly relies on an intact proteostasis network, thereby shedding light on diverse myopathies and aging.Verena Arndt, Nikolaus Dick, Riga Tawo, Michael Dreiseidler, Daniela Wenzel, Michael Hesse, Dieter O. FĂŒrst, Paul Saftig, Robert Saint, Bernd K. Fleischmann, Michael Hoch, and Jörg Höhfel
Long-Term Safety of Dupilumab in Patients With Moderate-to-Severe Asthma : TRAVERSE Continuation Study
Altres ajuts: Sanofi and Regeneron Pharmaceuticals, Inc (NCT02134028 and NCT03620747)Background: Previous clinical trials have demonstrated dupilumab efficacy and safety in adults and adolescents with moderate to severe asthma for up to 3 years. Objective: The TRAVERSE continuation study (NCT03620747), a single-arm, open-label study, assessed safety and tolerability of dupilumab 300 mg every 2 weeks up to an additional 144 weeks (âŒ3 years) in patients with moderate to severe asthma who previously completed TRAVERSE (NCT02134028). Methods: Primary end points were incidence and event rates per 100 patient-years of treatment-emergent adverse events (TEAEs). Secondary end points included adverse events (AEs) of special interest, serious AEs, and AEs leading to study discontinuation. Results: A total of 393 patients participated in the TRAVERSE continuation study (cumulative dupilumab exposure, 431.7 patient-years; median treatment duration, 309 days). A total of 29 patients (7.4%) received more than 958 days of treatment. A total of 214 (54.5%) patients reported at least 1 TEAE (event rate: 171.4); 37 (9.4%) experienced at least 1 treatment-related TEAE, none of which were considered severe; 2 patients reported 6 TEAEs of moderate intensity. A total of 22 (5.6%) patients reported serious AEs (event rate: 6.9). AEs of special interest were reported in 24 patients (6.1%; event rate: 6.0). Five (1.3%) deaths occurred (event rate: 1.2) following serious AEs of coronavirus disease 2019 (COVID-19)-related pneumonia (3 patients), pancreatitis (1 patient), and pulmonary embolism (1 patient). None of the TEAEs leading to death were considered treatment-related. Conclusions: Dupilumab treatment was well tolerated for up to an additional 3 years. Safety findings were consistent with the known safety profile of dupilumab. These findings further support the long-term use of dupilumab in patients with moderate to severe asthma
Assessment of the long-term safety and efficacy of dupilumab in children with asthma: LIBERTY ASTHMA EXCURSION
Hamelmann E, Bacharier L, Maspero J, et al. Assessment of the long-term safety and efficacy of dupilumab in children with asthma: LIBERTY ASTHMA EXCURSION. Pneumologie. 2023;77(S 01):S90-S91