| 1. |
- Khan, Ammad Aslam, et al.
(författare)
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Evolutionary History of Alzheimer Disease-Causing Protein Family Presenilins with Pathological Implications
- 2020
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Ingår i: Journal of Molecular Evolution. - : SPRINGER. - 0022-2844 .- 1432-1432. ; 88:8-9, s. 674-688
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Tidskriftsartikel (refereegranskat)abstract
- Presenilin proteins make the catalytic component of gamma-secretase, a multiprotein transmembrane protease, and are type II transmembrane proteins. Amyloid protein, Notch, and beta catenin are among more than 90 substrates of Presenilins. Mutations in Presenilins lead to defects in proteolytic cleavage of its substrate resulting in some of the most devastating pathological conditions including Alzheimer disease (AD), developmental disorders, and cancer. In addition to catalytic roles, Presenilin protein is also shown to be involved in many non-catalytic roles, i.e., calcium homeostasis, regulation of autophagy, and protein trafficking, etc. These proteolytic proteins are highly conserved and are present in almost all the major eukaryotic groups. Studies, performed on a wide variety of organisms ranging from human to unicellular dictyostelium, have shown the important catalytic and non-catalytic roles of Presenilins. In this study, we infer the evolutionary patterns and history of Presenilins as well as of other gamma-secretase proteins. We show that Presenilins are the most ancient of the gamma-secretase proteins and that Presenilins may have their origin in the last common ancestor (LCA) of Eukaryotes. We also demonstrate that Presenilin proteins generally lack diversifying selection during the course of their evolution. Through evolutionary trace analysis, we show that Presenilin protein sites that undergo mutations in Familial Alzheimer disease, are highly conserved in metazoans. Finally, we discuss the evolutionary, physiological, and pathological implications of our findings and propose that the evolutionary profile of Presenilins supports the loss of function hypothesis of AD pathogenesis.
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| 2. |
- Mahmood, Rashid, et al.
(författare)
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Assessment of antidiabetic potential and phytochemical profiling of Rhazya stricta root extracts
- 2020
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Ingår i: BMC Complementary Medicine and Therapies. - : Springer Nature. - 2662-7671. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Diabetes mellitus is a chronic disease characterized by hyperglycemia that may occur due to genetic, environmental or lifestyle factors. Natural remedies have been used to treat diabetes since long and many antidiabetic compounds of varied efficacies have been isolated from medicinal plants. Rhazya stricta has been used for decades for the treatment of diabetes mellitus and associated ailments. Considering the folkloric use of R. stricta against diabetes, it was aimed to investigate the effectiveness of its root extracts against diabetes through in vitro assays and in vivo studies using animal model along with phytochemical profiling through GCMS. Methods: Various fractions of Rhazya stricta obtained through column chromatography were evaluated for a variety of assays including a-glucosidase, Dipeptidyl peptidase-IV (DPP-IV), beta-secretase and Glucagon-like peptide-1 (GLP-1) secretion studies. For the in vivo studies the alloxan-induced diabetic mice were treated with root extracts and blood glucose levels, HbA1C, and other biochemical markers along with the histological study of the liver were done. The phytochemical identification was performed using an Agilent 7890B GC coupled to a 7010 Triple Quadrupole (MS/MS) system. GraphPad Prism software version 5.01 was used for statistical analysis. Results: Majority of the extract fractions showed excellent results against diabetes by inhibiting enzymes DPP-IV (Up to 61%) and beta-secretase (Up to 83%) with IC50s 979 pg/ml and 169 mu g/ml respectively with increase in the GLP1 secretion. The results of in vivo studies indicated a marked reduction in blood glucose and HbA1c levels along with positive effects on other parameters like lipid profile, liver functions and renal functions of extract-treated mice as compared to control. The histological examination of the liver demonstrated hepatoprotective effects against diabetes led changes and various classes of phytochemicals were also identified through GCMS in different fractions. Conclusion: The results revealed strong antidiabetic activity of R. stricta root with the potential to protect body organs against diabetic changes. Moreover, a variety of phytochemicals has also been identified through GCMS that might be responsible for the antidiabetic potential of Rhazya stricta root.
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| 3. |
- Mushtaq, Irrum, et al.
(författare)
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Engineering electroactive and biocompatible tetra(aniline)-based terpolymers with tunable intrinsic antioxidant properties in vivo
- 2020
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Ingår i: Materials science & engineering. C, biomimetic materials, sensors and systems. - : Elsevier. - 0928-4931 .- 1873-0191. ; 108
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Tidskriftsartikel (refereegranskat)abstract
- Under different pathological conditions, high levels of reactive oxygen species (ROS) cause substantial damage to multiple organs. To counter these ROS levels in multiple organs, we have engineered highly potent novel terpolymers. We found that combination of FDA-approved polyethylene glycol, fumaric acid moieties and electroactive tetra(aniline) by varying the content of tetra(aniline) results into a novel drug composition with biologically active tunable intrinsic antioxidant properties. To test tunable intrinsic antioxidative properties of these engineered novel terpolymers, we used alloxan to induce diabetes in rats where ROS generation is known to be higher. The systemic administration of terpolymers to the diabetic rats showed strong electroactive antioxidant behavior which normalized ROS levels, enzymatic antioxidants including superoxide dismutase, catalase, but also reduced glutathione. As a proof-of-principle, we here show TANI based novel drug composition of terpolymers with tunable intrinsic antioxidant effects confirmed in multiple organs.
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| 4. |
- Shah, Faiz Ullah, et al.
(författare)
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Influence of Ferrocene and Transition Metals on the Biological Activities of Schiff Bases
- 2016
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Ingår i: Journal of the Chemical Society of Pakistan. - 0253-5106. ; 38:6, s. 1112-1120
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Tidskriftsartikel (refereegranskat)abstract
- A series of organic and organometallic Schiff bases bearing phenylferrocene and their six transition metal complexes have been prepared and tested for their potential biological applications by using antifungal, antibacterial, antitumor activities, toxicity testing against the brine shrimp and DNA damage analysis. The copper and cobalt complexes of organic Schiff base showed significant antibacterial activity. The antifungal activities tested against six fungal strains revealed that N-(4-hydroxybenzylidene) aniline (A5) had the highest antifungal activity. Most of these compounds showed cytotoxic activity against the brine shrimp. The results of showed that these compounds had significant antitumor activity, up to 97% in the case of N-(4-chlorobenzylidene) aniline (A3). Only two compounds N-(2-hydroxy benzylidene) 4-ferrocenylaniline (F2) and Nickel (II) complex of organic Schiff base (CO2) had DNA damaging activity at 20mg/ml concentration.
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