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Metabolic Myopathy
Published in Maher Kurdi, Neuromuscular Pathology Made Easy, 2021
Pompe disease is the most common glycogen storage disease in clinical practice that is characterized clinically by spinal muscular atrophy-like disease, floppy baby syndrome, and facial dysmorphism. Patients can also present in late adulthood with variable weakness distribution ranging from proximal weakness to limb-girdle muscular weakness. The disease may progress to involve organs such as liver, spleen, lungs, and, rarely, heart. The disease is inherited as autosomal recessive and associated with GAA gene mutation, which causes deficiency of acid maltase or α-1, 4-glycosidase enzyme.
Ameliorating Insulin Signalling Pathway by Phytotherapy
Published in Mahendra Rai, Shandesh Bhattarai, Chistiane M. Feitosa, Ethnopharmacology of Wild Plants, 2021
To be proven potential anti-hyperglycemic agents of T. cordifolia leaves against alpha amylase enzyme. Shareef et al. (2014) had extracted leaves in petroleum ether, chloroform, ethyl acetate and methanol solvents. The percentage inhibition of α-amylase by the extracts was studied in a concentration range of 10–640 μg/mL. Of the four extracts, ethyl acetate and methanol were comparatively effective than in petroleum ether and chloroform in inhibiting α-amylase. The IC50of petroleum ether and chloroform extract was 100 and 120 μg/mL, respectively, and methanol extracts were 20 μg/mL. The ethylacetate and methanol exhibited a maximum inhibition of 98% at 50 μg/mL concentration. Dinesh Kumar et al. (2010) had performed in vitro assay by taking ethanolic extract against α-amylase at concentrations 10–100 μg/mL, which exhibited minimum alpha-amylase inhibitory effects from 12.32 ± 0.79 to 36.41 ± 0.39 μg/mL with an IC50 value 138.80 ± 0.16 μg/mL. Dichloromethane (DCM) extract demonstrated 100% inhibition of the α-glucosidase (Chougale et al. 2009), but in the case of, salivary amylase and pancreatic amylase were 75% and 83%, respectively. Introducing maltose load of 2 mg/g along with 0.3 mg/g b. w. of the DCM stem extract to the normal and diabetic rats, the hypoglycemic activity was raised by 50 and 58%, respectively, as compared to the controls. The extract happened to inhibit α-glycosidase in a non-competitive way.
Engineered Nanoparticles for Drug Delivery in Cancer Therapy *
Published in Valerio Voliani, Nanomaterials and Neoplasms, 2021
Tianmeng Sun, Yu Shrike Zhang, Pang Bo, Dong Choon Hyun, Miaoxin Yang, Younan Xia
An enzyme-sensitive release system includes either a structure scaffold that is susceptible to the degradation by a specific enzyme or a linker between the drug and the carrier as the product of an enzymatic reaction [69d]. Hydrolases are the most widely used enzymes for such an application, which can break covalent bonds or modify certain chemical groups by altering the balance between electrostatic, hydrophobic, and van der Waals forces, p–p interactions, or hydrogen bonding [104b, 105]. For example, proteases can induce the release of a drug linked to a carrier through a peptide bond; glycosidases can trigger the release from a polysaccharide-based carrier; lipases can facilitate the drug release by hydrolyzing the phospholipid building blocks in a liposome; and hydrolases can be used to maneuver the assembly and disassembly of inorganic nanoparticles, as well as the degradation of a gatekeeping material that blocks the pores of a carrier [104b, 106]. In addition, kinases and phosphatases have been used to reversibly break/form covalent bonds, achieving the release of a drug in an “on-off” manner [107].
Molecular docking studies, anti-Alzheimer’s disease, antidiabetic, and anti-acute myeloid leukemia potentials of narcissoside
Published in Archives of Physiology and Biochemistry, 2023
Tingting Liu, Lixia Cao, Tingting Zhang, Huan Fu
Narcissoside was effective inhibiting AChE as metabolic enzyme. Ki values for AChE were obtained to be 6.64 ± 1.54 nM (Table 3). Also, the Tacrine (TAC) molecule was used as AChE enzyme control molecule; it had Ki values of 122.21 ± 14.04 nM. Narcissoside and TAC values IC50 were: Narcissoside (11.54 nM, r2: 0.9889) < TAC (148.98 nM, r2: 0.9108) for AChE. AChE inhibitor compound is a neurotoxic molecule capable of causing central, peripheral, or both peripheral and central cholinergic crises. The molecule investigated in the present study can record application as medicinal products developed to treat myasthenia gravis and AD (Van De Laar et al.2005). On the other hand, narcissoside shown as IC50 and Ki values are 65.58 nM, r2:0.9097 and 78.21 ± 6.65 (Table 3). For the α-glycosidase present on cells lining, and the intestine, hydrolysing monosaccharides are absorbed through the intestine. The results of the α-glycosidase assay showed that narcissoside has an effective α-glycosidase inhibition profile compared to that of acarbose (IC50: 8.81 nM, Ki: 11.53 ± 2.73) as a standard α-glycosidase inhibitor (Lineweaver and Burk 1934). The inhibition of α-glycosidase digestive enzyme was of great importance for the treatment and prevention of diabetes, postprandial glucose levels and hyperglycaemia (Aktas et al.2020, Artunc et al.2020, Bursal et al.2020, Lolak et al.2020).
Unambiguous identification of α-Gal epitopes in intact monoclonal antibodies by NMR spectroscopy
Published in mAbs, 2022
Arthur Hinterholzer, Jennifer Moises, Christof Regl, Sebastian Schwap, Erdmann Rapp, Christian G. Huber, Mario Schubert
Confirming the absence or presence of α-Gal epitopes in therapeutic proteins by the classical proteomics approach of mass spectrometry (MS) coupled to high-performance liquid chromatography (HPLC) is analytically challenging because the difference between an N-glycan containing Galα1,3Gal and one lacking it lies in the mass difference of one or several hexose moieties (n × 162 Da), which may be galactose, mannose or glucose. More importantly, the key characteristic for immunogenicity is the α1,3 linkage between the terminal galactose and the underlying galactose.9 One possibility to confirm this is the analysis by porous graphitized carbon-liquid chromatography coupled to tandem MS (PGC-MS2).10 However, the sample preparation and data analysis are very elaborate. Treatment with α1,3Gal-specific glycosidases followed by MS is another possibility, but this method is indirect.
Enhanced anti-cancer effect using MMP-responsive L-asparaginase fused with cell-penetrating 30Kc19 protein
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2022
Jina Ryu, Sung Jae Yang, Boram Son, Haein Lee, Jongmin Lee, Jinmyoung Joo, Hee Ho Park, Tai Hyun Park
Structural perturbation is the major concerns for fusion protein design. The lack of structural space could interfere with protein function [42]. A cleavable linker can be applied to a wide range of cancer types due to their ability to separate and release functional cargo proteins from the fusion protein [43]. Cleavable linkers can be categorized as chemical-cleavable or enzyme-cleavable, and exploitation of specific conditions can lead to release of the therapeutic protein at the target cell [44]. For the chemically cleavable linkers, acid cleavable linkers, reducible disulphide linkers, and cleavable by exogenous stimuli linkers are available. As for enzyme cleavable linkers, they can be used to be selectively cleaved intracellularly, and dipeptide-containing linkers, glycosidase-cleavable linkers, phosphatase-cleavable linkers are available for selective cargo release at the tumour site.