| 1. |
- Adil, Nurmeen, et al.
(författare)
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Evaluation of cytotoxicity of areca nut and its commercial products on normal human gingival fibroblast and oral squamous cell carcinoma cell lines
- 2021
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Ingår i: Journal of Hazardous Materials. - : Elsevier. - 0304-3894 .- 1873-3336. ; 403
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Tidskriftsartikel (refereegranskat)abstract
- Consumption of areca nut products is the most common cause of oral cancers, particularly in South Asian countries. This study evaluates the cytotoxic and necrotizing effects of areca nut and its formulations on normal human gingival fibroblasts (HGF-1) and oral squamous cell carcinoma (OSCC, CAL-27) cell lines. Identification of various carcinogens and adulterants using LC-HR-ESI-MS/MS analysis was performed in the extracts of areca nut and its products. Apart from alkaloids and flavonoids, a major adulterant, saccharin was found in all the samples of chalia (one of the most common chewing products of areca nut) in the ranges between 1.697-7.170 mg/g of the sample. Cytotoxic studies showed that most of the areca nut products were found cytotoxic to HGF-1 cells while being relatively non-cytotoxic against CAL-27 cells, rather they promote the growth of cancer cells. Our findings revealed that the components of areca nut and its products were injurious to HGF-1 cells and caused necrosis, which may attenuate HGF-1 protection toward oral epithelial cells. Moreover, the non-cytotoxic effect of these products on cancer cell lines suggests further predisposal of the habitual chewers for developing oral carcinomas. This study will give a better understanding of the hazardous effects of areca nut products.
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| 2. |
- Kanwal, Nayab, et al.
(författare)
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Two-stage mass spectrometry approach for the analysis of triterpenoid glycosides in Fagonia indica
- 2018
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Ingår i: RSC Advances. - : ROYAL SOC CHEMISTRY. - 2046-2069. ; 8:71, s. 41023-41031
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Tidskriftsartikel (refereegranskat)abstract
- Triterpenoid glycosides are molecules widely distributed in plants and have shown a wide range of biological activities against various diseases. This paper describes the qualitative and quantitative analysis of triterpenoid glycoside (saponins) using a two-stage mass spectrometry approach in five samples of Fagonia indica collected from various parts of the country. In the first stage, triterpenoid glycosides were identified using liquid chromatography high-resolution mass spectrometry using UHPLC-QTOF-MS system. In the second stage, compounds were quantified using a multiple reaction monitoring (MRM) approach using an UHPLC-QQQ-MS system. Fagonia indica has shown a wide range of biological activities and found to be rich in saponin or triterpenoid glycoside constituents. A total of thirteen triterpenoid saponins were identified based on high-resolution analysis, MS/MS and database comparison, while six of them were simultaneously quantified using the multiple reaction monitoring (MRM) approach. The results indicate that the samples share a similar UHPLC pattern, however, the amount of these saponins in samples varies greatly. Compound 4i.e. nayabin D was the major constituent (1.4-3.8 g g(-1)) among the six analyzed compounds. The results demonstrated that the developed multi-compound determination in combination with a fingerprint analysis method is rapid, accurate, precise and sensitive and can be utilized for quality control and high-throughput quantification of various saponins in Fagonia indica may be extended to other plant species.
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| 3. |
- 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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| 4. |
- Khan, Noman, et al.
(författare)
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Understanding of metals dysregulation in patients with systolic and diastolic dysfunction in ischemic heart disease
- 2020
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Ingår i: Scientific Reports. - : NATURE RESEARCH. - 2045-2322. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Ischemic heart disease (IHD) is the leading cause of death and chronic disability in the world. IHD affects both the systolic and diastolic function of the heart which progressively leads to heart failure; a structural and functional impairment of filling or ejection of blood from the heart. In this study, the progression of systolic and diastolic dysfunction characterized according to their echocardiographic parameters including left ventricular ejection fraction (EF), grades of diastolic dysfunction and ratio between early mitral inflow velocity and mitral annular early diastolic velocity (E/e'), were correlated with differential regulation of various metals in patients sera samples (n = 62) using inductive coupled plasma-mass spectrometry (ICP-MS). Chromium, nickel and selenium were found significant (p < 0.05) in patients having EF < 45% compared with EF > 45%. In patients with systolic dysfunction (EF < 45%), the level of selenium was decreased while the level of chromium and nickel was increased compared to patients with EF > 45%. Selenium level was also decreased significantly (p < 0.05) in grade 1A and 2 patients that are considered as higher grades of diastole dysfunction in comparison to grade 0-1. Overall, selenium deficiency was identified in both systolic and diastolic dysfunctions of IHD patients corresponding to the progression of disease that could be related to many metabolic and translational pathways specifically which involve selenoproteins.
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| 5. |
- Kumari, Sindhia, et al.
(författare)
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Metabolomics approach to understand the hepatitis C virus induced hepatocellular carcinoma using LC-ESI-MS/MS
- 2021
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Ingår i: Arabian Journal of Chemistry. - : Elsevier. - 1878-5352 .- 1878-5379. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Hepatocellular carcinoma (HCC) is a typical cancer that has region specified analysis with the incidence of hepatitis C virus (HCV) infection. This study was conducted to improve the understanding of metabolic alterations associated with HCV induced HCC which can open up new strategies to monitor the high risk of HCC. Samples of the subjects with HCV, HCV induced chronic liver disease (CLD), HCV induced HCC, and healthy controls (HS) were collected after complete blood count (CBC), hepatitis viral load, st-fetoprotein (AFP), liver function tests, and albumin. A total of 147 serum samples including HCC (n = 11), CLD (n = 24), HCV (n = 71), and HS (n = 41) were analyzed by LC-ESI-MS/MS. The 21 compounds were found to be responsible for group discrimination after the application of chemometric tools. Nfructosyl tyrosine and hydroxyindoleacetic acid showed an increase in level whereas L-aspartylL-phenylalanine and thyroxine showed a consistent decrease in the progression of HCV to HCC in comparison with HS indicating their importance for early detection. The biological pathways such as glycerophospholipid metabolism, phenylalanine, tyrosine, and tryptophan biosynthesis, phenylalanine metabolism and tryptophan metabolism showed alteration in some metabolites. The method was internally validated by ROC plot showing AUC value for HS, HCV, CLD, and HCC as 0.99, 1, 1, and 0.89, respectively; while 16 blind samples were also validated with 93% specificity. The untargeted metabolomics investigation of HCV, CLD, and HCC can help to understand the progression of HCV-induced HCC. It reveals significant differences in metabolites to predict prognostic and diagnostic markers. (C) 2020 The Author(s). Published by Elsevier B.V. on behalf of King Saud University.
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| 6. |
- Nisa, Zaib Un, et al.
(författare)
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A comparative metabolomic study on desi and kabuli chickpea (Cicer arietinum L.) genotypes under rainfed and irrigated field conditions
- 2020
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Ingår i: Scientific Reports. - BERLIN GERMANY : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Chickpea is considered among the most important leguminous crops in the world. However, in recent years drought conditions and/or limited availability of water have significantly reduced the production of chickpea. The current study was aimed to understand the legume stress response at the metabolic level for the determination of chickpea genotypes which can resist yield losses and could be cultivated with limited water availability. Here, we have analyzed two genotypes of chickpea, desi and kabuli under rainfed condition using a GC-MS based untargeted metabolomics approach. Results revealed significant differences in several metabolite features including oxalic acid, threonic acid, inositol, maltose and L-proline between studied groups. Accumulation of plant osmoprotectants such as L-proline, sugars and sugar alcohols was higher in desi genotype than kabuli genotype of chickpea when grown under the rainfed condition. Metabolic pathway analysis suggests that the inositol phosphate metabolism was involved in plant defense mechanisms against the limited water availability.
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| 7. |
- 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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| 8. |
- 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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