The chorioallantoic membrane: A novel approach to extrapolate data from a well‐established method

A Novel Approach for Quantitative Characterization of Hydrolytic Action of Glycosidases to Glycoconjugates in Leather Manufacturing by Fengxiang Luo,1,2 Zhong Xiang,1,2 Zhang Chunxiao,1,2 Biyu Peng,1,2* and Zh

Journal of the American Leather Chemists Association ◽

10.34314/jalca.v115i7.3836 ◽

2020 ◽

Vol 115 (7) ◽

pp. 263-269

Author(s):

Fengxiang Luo ◽

Zhong Xiang ◽

Zhang Chunxiao ◽

Biyu Peng ◽

Zhongzhen Long

Keyword(s):

Enzyme Concentration ◽

Quantitative Characterization ◽

Established Method ◽

Protein Conjugates ◽

Leather Processing ◽

Novel Approach ◽

Novel Method ◽

Main Components ◽

Opening Up

Glycoconjugates, herein glyco-protein conjugates, composed of protein and saccharide chains are the main components of the interfibrillar matrix in skin which need to be fully removed in the leather making process. The application of glycosidases can assist unhairing and skin fiber opening-up, resulting in the improvement of leather quality, by breaking the glycoconjugates safely and efficiently in mild conditions. The biotechnology assisted by glycosidases, a big family of over 200 kinds of enzymes, has a great potential but the related mechanisms and the efficiency of different glycosidases are still not clear, which interferes with its wide application. To screen the proper glycosidases, a novel method of evaluating the catalytic hydrolysis properties of glycosidases towards skin glycoconjugates based a special hide powder substrate, simulating the actual leather processing, was established through detecting the produced amount of the total sugar in the solution. The special substrate was prepared, the determination conditions were optimized, then the performances of several typical glycosidases were evaluated and their application effects in soaking process of leather making were also investigated. The results show that the optimum testing conditions are lower than 4 h of the reacting time, optimally 2 h, and lower than 40 U/mL of the enzyme concentration, optimally 0-25 U/mL based on 2 g of the substrate; the results to evaluate the properties of some glycosidases based on the established method are positively related to their applying effects in soaking. The new method with better repeatability can be used as an available tool to correctly select glycosidases and optimize process parameters for correct use.

Download Full-text

New 3-Aryl-2-(2-thienyl)acrylonitriles with High Activity Against Hepatoma Cells

International Journal of Molecular Sciences ◽

10.3390/ijms22052243 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2243

Author(s):

Eva Schaller ◽

Andi Ma ◽

Lisa Chiara Gosch ◽

Adrian Klefenz ◽

David Schaller ◽

...

Keyword(s):

Mode Of Action ◽

Kinase Inhibitors ◽

Hepatoma Cell ◽

Chorioallantoic Membrane ◽

Bioinformatic Analysis ◽

Binding Modes ◽

Multikinase Inhibitor ◽

Novel Approach ◽

Ic50 Values

New 2-(thien-2-yl)-acrylonitriles with putative kinase inhibitory activity were prepared and tested for their antineoplastic efficacy in hepatoma models. Four out of the 14 derivatives were shown to inhibit hepatoma cell proliferation at (sub-)micromolar concentrations with IC50 values below that of the clinically relevant multikinase inhibitor sorafenib, which served as a reference. Colony formation assays as well as primary in vivo examinations of hepatoma tumors grown on the chorioallantoic membrane of fertilized chicken eggs (CAM assay) confirmed the excellent antineoplastic efficacy of the new derivatives. Their mode of action included an induction of apoptotic capsase-3 activity, while no contribution of unspecific cytotoxic effects was observed in LDH-release measurements. Kinase profiling of cancer relevant protein kinases identified the two 3-aryl-2-(thien-2-yl)acrylonitrile derivatives 1b and 1c as (multi-)kinase inhibitors with a preferential activity against the VEGFR-2 tyrosine kinase. Additional bioinformatic analysis of the VEGFR-2 binding modes by docking and molecular dynamics calculations supported the experimental findings and indicated that the hydroxy group of 1c might be crucial for its distinct inhibitory potency against VEGFR-2. Forthcoming studies will further unveil the underlying mode of action of the promising new derivatives as well as their suitability as an urgently needed novel approach in HCC treatment.

Download Full-text

Copper-dependent ATP7B up-regulation drives the resistance of TMEM16A-overexpressing head-and-neck cancer models to platinum toxicity

Biochemical Journal ◽

10.1042/bcj20190591 ◽

2019 ◽

Vol 476 (24) ◽

pp. 3705-3719 ◽

Cited By ~ 2

Author(s):

Avani Vyas ◽

Umamaheswar Duvvuri ◽

Kirill Kiselyov

Keyword(s):

Oxidative Stress ◽

Head And Neck ◽

Transcriptional Activation ◽

Platinum Resistance ◽

Mrna Levels ◽

Strong Positive Correlation ◽

Platinum Compounds ◽

Copper Chelation ◽

Novel Approach ◽

Cancer Models

Platinum-containing drugs such as cisplatin and carboplatin are routinely used for the treatment of many solid tumors including squamous cell carcinoma of the head and neck (SCCHN). However, SCCHN resistance to platinum compounds is well documented. The resistance to platinum has been linked to the activity of divalent transporter ATP7B, which pumps platinum from the cytoplasm into lysosomes, decreasing its concentration in the cytoplasm. Several cancer models show increased expression of ATP7B; however, the reason for such an increase is not known. Here we show a strong positive correlation between mRNA levels of TMEM16A and ATP7B in human SCCHN tumors. TMEM16A overexpression and depletion in SCCHN cell lines caused parallel changes in the ATP7B mRNA levels. The ATP7B increase in TMEM16A-overexpressing cells was reversed by suppression of NADPH oxidase 2 (NOX2), by the antioxidant N-Acetyl-Cysteine (NAC) and by copper chelation using cuprizone and bathocuproine sulphonate (BCS). Pretreatment with either chelator significantly increased cisplatin's sensitivity, particularly in the context of TMEM16A overexpression. We propose that increased oxidative stress in TMEM16A-overexpressing cells liberates the chelated copper in the cytoplasm, leading to the transcriptional activation of ATP7B expression. This, in turn, decreases the efficacy of platinum compounds by promoting their vesicular sequestration. We think that such a new explanation of the mechanism of SCCHN tumors’ platinum resistance identifies novel approach to treating these tumors.

Download Full-text

Collecting Words: A Clinical Example of a Morphology-Focused Orthographic Intervention

Language Speech and Hearing Services in Schools ◽

10.1044/2020_lshss-19-00050 ◽

2020 ◽

Vol 51 (3) ◽

pp. 544-560 ◽

Cited By ~ 3

Author(s):

Kimberly A. Murphy ◽

Emily A. Diehm

Keyword(s):

Written Language ◽

Morphological Knowledge ◽

English Orthography ◽

Word Level ◽

Novel Approach ◽

Language Pathology ◽

The One ◽

Critical Intervention ◽

Reading And Spelling ◽

Reading And Spelling Difficulties

Purpose Morphological interventions promote gains in morphological knowledge and in other oral and written language skills (e.g., phonological awareness, vocabulary, reading, and spelling), yet we have a limited understanding of critical intervention features. In this clinical focus article, we describe a relatively novel approach to teaching morphology that considers its role as the key organizing principle of English orthography. We also present a clinical example of such an intervention delivered during a summer camp at a university speech and hearing clinic. Method Graduate speech-language pathology students provided a 6-week morphology-focused orthographic intervention to children in first through fourth grade ( n = 10) who demonstrated word-level reading and spelling difficulties. The intervention focused children's attention on morphological families, teaching how morphology is interrelated with phonology and etymology in English orthography. Results Comparing pre- and posttest scores, children demonstrated improvement in reading and/or spelling abilities, with the largest gains observed in spelling affixes within polymorphemic words. Children and their caregivers reacted positively to the intervention. Therefore, data from the camp offer preliminary support for teaching morphology within the context of written words, and the intervention appears to be a feasible approach for simultaneously increasing morphological knowledge, reading, and spelling. Conclusion Children with word-level reading and spelling difficulties may benefit from a morphology-focused orthographic intervention, such as the one described here. Research on the approach is warranted, and clinicians are encouraged to explore its possible effectiveness in their practice. Supplemental Material https://doi.org/10.23641/asha.12290687

Download Full-text