| 1. |
- Tehreem, Syeda, et al.
(författare)
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A UPLC-DAD-Based Bio-Screening Assay for the Evaluation of the Angiotensin Converting Enzyme Inhibitory Potential of Plant Extracts and Compounds : Pyrroquinazoline Alkaloids from Adhatoda vasica as a Case Study
- 2021
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Ingår i: Molecules. - : MDPI. - 1431-5157 .- 1420-3049. ; 26:22
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Tidskriftsartikel (refereegranskat)abstract
- Angiotensin converting enzyme (ACE) plays a crucial role in regulating blood pressure in the human body. Identification of potential ACE inhibitors from medicinal plants supported the idea of repurposing these medicinal plants against hypertension. A method based on ultra-performance liquid chromatography (UPLC) coupled with a diode array detector (DAD) was used for the rapid screening of plant extracts and purified compounds to determine their ACE inhibitory activity. Hippuryl-histidiyl-leucine (HHL) was used as a substrate, which is converted into hippuric acid (HA) by the action of ACE. A calibration curve of the substrate HHL was developed with the linear regression 0.999. The limits of detection and quantification of this method were found to be 0.134 and 0.4061 mM, respectively. Different parameters of ACE inhibitory assay were optimized, including concentration, incubation time and temperature. The ACE inhibition potential of Adhatoda vasica (methanolic-aqueous extract) and its isolated pyrroquinazoline alkaloids, vasicinol (1), vasicine (2) and vasicinone (3) was evaluated. Compounds 1-3 were characterized by various spectroscopic techniques. The IC50 values of vasicinol (1), vasicine (2) and vasicinone (3) were found to be 6.45, 2.60 and 13.49 mM, respectively. Molecular docking studies of compounds 1-3 were also performed. Among these compounds, vasicinol (1) binds as effectively as captopril, a standard drug of ACE inhibition.
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| 2. |
- Bhatti, Muhammad Salman, et al.
(författare)
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Repurposing of pharmaceutical drugs by high-throughput approach for antihypertensive activity as inhibitors of angiotensin-converting enzyme (ACE) using HPLC-ESI-MS/MS method
- 2021
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Ingår i: Arabian Journal of Chemistry. - : Elsevier. - 1878-5352 .- 1878-5379. ; 14:8
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Tidskriftsartikel (refereegranskat)abstract
- Angiotensin-converting enzyme (ACE) plays an important role in regulating blood pressure in the body by converting angiotensin-I into angiotensin-II. It is the basic component of Renin angiotensin aldosterone system (RAAS), imbalance of RAAS may leads to many cardiovascular and renal diseases. There are many marketed available drugs for the inhibition of ACE, but prolonged use of some drugs may cause the progressive side effects. Repurposing of existing drugs can be a way to find new inhibitors of ACE. In this study, a high-throughput and sensitive method of HPLC-ESI-QqQ-MS with good reproducibility (%RSD < 9.98) and linearity (R-2 = 0.999) was used to investigate the 77 commercial drugs for their inhibitory potential as antihypertensive drugs. Among these drugs, 41 drugs were found active and 36 of them showed moderate to good inhibition with lowest IC50 = 272 mu M. This study showed that different pharmaceutical drugs can also be used as ACE inhibitor after necessary clinical trials or validation.
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| 3. |
- Khadim, Adeeba, et al.
(författare)
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Investigation of fragmentation behaviors of steroidal drugs with Li+, Na+, K+ adducts by tandem mass spectrometry aided with computational analysis
- 2022
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Ingår i: Arabian Journal of Chemistry. - : Elsevier BV. - 1878-5352 .- 1878-5379. ; 15:7
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we have investigated the fragmentation of the widely used steroidal pharmaceutical drugs (n = 14), complexed by a singly charged proton or alkali metal ion (Li+, Na+, K+) using Ion trap and quadrupole time-of-flight mass spectrometers. Spectra were collected by LC-MS/MS analysis using system automated collision energy i.e., of 25–60 eV. Theoretical calculations were also calculated using DFT software. The metal complexes showed different fragmentation pathways not commonly observed for protonated compounds. There was a distinct difference observed in the relative intensities of some common fragments for free vs. metallated drugs. Some major fragments from protonated and lithium adducts showed close resemblance, while sodium and potassium adducts showed different fragments. Theoretical calculations showed a distinct difference in the position of attachment of proton and metals. This adducts ion fragmentation information will be helpful for the identification of these compounds in complex samples.
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| 4. |
- Khan, Noman, et al.
(författare)
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Dysregulation of metalloproteins in ischemic heart disease patients with systolic dysfunction
- 2023
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Ingår i: International Journal of Biological Macromolecules. - : Elsevier. - 0141-8130 .- 1879-0003. ; 232
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Tidskriftsartikel (refereegranskat)abstract
- Ischemic heart disease (IHD) is the leading cause of mortality worldwide. Metalloproteins have been linked to human health and diseases. The molecular functions of metalloproteins in IHD is not well understood and require further exploration. The objective of this study was to find out the role of metalloproteins in the pericardial fluid of IHD patients having normal (EF > 45) and impaired (EF < 45) left ventricular ejection fraction (LVEF). IHD patients were grouped into two categories: LVEF<45 (n = 12) and LVEF >45 (n = 33). Pooled samples of pericardial fluid were fractionated by using ZOOM-isoelectric focusing (IEF) followed by further processing using one-dimensional gel electrophoresis (1D SDS-PAGE) and filter-aided sample preparation (FASP). Tryptic peptides of each fraction and differential bands were then analyzed by nano-LC-ESI-MS/MS. Protein identification was performed through a Mascot search engine using NCBI-Prot and SwissProt databases. A total of 1082 proteins including 154 metalloproteins were identified. In the differential bands, 60 metalloproteins were identified, while 115 metalloproteins were identified in all ZOOM-IEF fractions. Twelve differentially expressed metalloproteins were selected in the intense bands according to their molecular weight (MW) and isoelectric point (pI). The 12 differentially expressed metalloprotein includes ceruloplasmin, Prothrombin, Vitamin K-dependent protein, Fibulin-1, Ribosomal protein S6 kinase alpha-6, nidogen, partial, Serum albumin, Hemopexin, C-reactive protein, Serum amyloid P-component, and Intelectin-1 protein which were all up-regulated while serotransferrin is the only metalloprotein that was down-regulated in impaired (LVEF<45) group. Among the metalloproteins, Zn-binding proteins are 36.5 % followed by Ca-binging 32.2 %, and Fe-binging 12.2 %. KEGG, pathway analysis revealed the association of ceruloplasmin and serotransferrin with the ferroptosis pathway. In conclusion, 154 metalloproteins were identified of them the Zn-binding protein followed by Ca-binding and Fe-binding proteins were the most abundant metalloproteins. The two metalloproteins, the Cu-binding protein ceruloplasmin, and Fe-binding protein serotransferrin are involved in the ferroptosis pathway, an iron-dependent form of regulated cell death that has been linked to cardiac pathology, especially in IHD patients having impaired systolic (LVEF<45) dysfunction. However, further research is required to validate these findings.
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| 5. |
- Siddiqui, Amna Jabbar, et al.
(författare)
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Serum metallomics reveals insights into the associations of elements with the progression of preleukemic diseases toward acute leukemia
- 2024
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Ingår i: Biology Methods and Protocols. - : Oxford University Press. - 2396-8923. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Acute leukemia (AL) is a critical neoplasm of white blood cells with two main subtypes: acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). This study is focused on understanding the association of the preleukemic disease aplastic anemia (APA) with ALL and AML at metallomic level, using healthy subjects as a control. In this study, a validated and efficient inductively coupled plasma-mass spectrometry/MS-based workflow was employed to profile a total of 13 metallomic features. The study encompassed 41 patients with AML, 62 patients with ALL, 46 patients with APA, and 55 age-matched healthy controls. The metallomic features consisted of eight essential elements (Ca, Co, Cu, Fe, Mg, Mn, Se, and Zn) and five non-essential/toxic elements (Ag, Cd, Cr, Ni, and Pb). Six out of the 13 elements were found to be substantially different (P < .05) using absolute concentrations between serum samples of AL (ALL and AML) and preleukemia (APA) patients in comparison with healthy subjects. Elements including magnesium, calcium, iron, copper, and zinc were upregulated and only one element (chromium) was downregulated in serum samples of disease when compared with healthy subjects. Through the utilization of both univariate tests and multivariate classification modeling, it was determined that chromium exhibited a progressive behavior among the studied elements. Specifically, chromium displayed a sequential upregulation from healthy individuals to preleukemic disease (APA), and ultimately in patients diagnosed with ALL. Overall, metallomic-based biomarkers may have the utility to predict the association of APA with ALL.
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| 6. |
- Uddin, Mohammad Jalal, et al.
(författare)
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Loss and Thermal Analysis of a 100 kW Converter Module Mounted on a Cold-Plate for Fast Charging Applications
- 2019
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Ingår i: 2019 21st European Conference on Power Electronics and Applications, EPE 2019 ECCE Europe. ; September 2019
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Konferensbidrag (refereegranskat)abstract
- For a 100 kW power converter module for fast charging application, the loss and thermal analysis are performed where the results are presented in this paper. The two-stage power conversion of the converter has an efficiency value of 95%. A liquid cooling system is designed, and thermal performance analysis is performed. The results show that the junction temperature is maintained below 110°C for 8 liters per minute of liquid flow rate by the cooling system.
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| 7. |
- Usman, Muhammad, et al.
(författare)
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Evaluation of the chronic intoxication of fluoride on human serum metabolome using untargeted metabolomics
- 2022
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Ingår i: Arabian Journal of Chemistry. - : Elsevier BV. - 1878-5352 .- 1878-5379. ; 15:7
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Tidskriftsartikel (refereegranskat)abstract
- Drinking water is the main source of fluoride intake for the human body and its regulated consumption helps in decreasing dental caries. However, excessive fluoride consumption over a prolonged time period causes fluorosis disease which adversely affects many tissues and organs of the body. This paper describes the evaluation of chronic intoxication of fluoride on human serum metabolome. The untargeted metabolomics approach using UPLC-QTOF-MS/MS is applied for metabolomic profiling, whereas the estimation of fluoride in serum samples was carried out using the ion-selective electrode (ISE). Fluoride concentration was found to be 0.16–1.25 mg/L in serum samples of 39 fluorosis patients and 0.008–0.045 mg/L in 20 healthy samples. A total of 47 metabolites were identified based on the high-resolution mass spectrometry analysis. A volcano plot was generated to discriminate features that are significantly different between the fluorosis and healthy groups at the probability of 0.05 and fold change ≥ 2. Among all identified metabolites, intensities of ten differential identified metabolites including inosine, α-linolenic acid, guanosine, octanoyl-L-carnitine, His-Trp, phytosphingosine, lauroyl-L-carnitine, hydrocortisone, deoxyinosine and dodecanedioic acid have been found altered in disease samples compared to healthy controls. Major pathways identified based on these metabolites include energy metabolism, fatty acid oxidation, purine degradation pathway, elevated protein degradation, and increased ω-6 fatty acid linoleate signatures were observed.
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