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Article: Editorial: An approach of brain derived extracellular vesicles in diagnosis and prognosis of brain pathologies.

Qadri, Shahnaz / Parray, Aijaz S / Ahmed, Ikhlak

2022 Volume 16, Page(s) 1025277

Language	English
Publishing date	2022-10-13
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2452962-X
ISSN	1662-5145
ISSN	1662-5145
DOI	10.3389/fnint.2022.1025277
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Article ; Online: Biogenesis of Exosomes Laden with Metallic Silver-Copper Nanoparticles Liaised by Wheat Germ Agglutinin for Targeted Delivery of Therapeutics to Breast Cancer.

Ashraf, Sarmadia / Qadri, Shahnaz / Akbar, Shayista / Parray, Aijaz / Haik, Yousef

Advanced biology

2022 Volume 6, Issue 7, Page(s) e2200005

Abstract: The anticancer property of silver-copper metallic nanoparticles (AgCu-NPs) is of greater interest in cancer therapeutics; however, its off-target toxicity limits its therapeutic application. Exosomes emerge as one of the leading idiosyncratic nanocarrier ...

Abstract	The anticancer property of silver-copper metallic nanoparticles (AgCu-NPs) is of greater interest in cancer therapeutics; however, its off-target toxicity limits its therapeutic application. Exosomes emerge as one of the leading idiosyncratic nanocarrier choices for cancer therapeutics due to their size, stability, and phenotypic diversity; however, to encapsulate NPs in extracellular vesicles (EVs) without disrupting their inherited functions is far from the expectations. Here, the loading strategy of AgCu-NP conjugated with wheat germ agglutinin (AgCu-NP-WGA) in exosomes during biogenesis for the targeted delivery of anticancer therapeutics to breast cancer is reported. Based on the intrinsic mechanism of endocytosis of WGA, results show that internalization of WGA or AgCu-NP-WGA bypasses the lysosomal pathway and recycles in EVs. On the contrary, the transport of naked AgCu-NPs to lysosomes; mechanistically, an acidic environment causes oxidation of AgCu-NP. Next, the analysis of EVs harvested by differential centrifugation shows that only AgCu-NPs-WGA (Exo-NP) retain their metallic state. Furthermore, Exo-NP cytotoxicity results manifest that MCF10A-derived Exo-NPs are toxic to its homologous breast cancer cells (MCF-7 and MDA-MB 231) and nontoxic to heterologous cancers NC1-1975 and MCF 10A. In conclusion, this study shows the self-assembly of AgCu-NP in exosomes to target and deliver therapeutics for breast cancer.
MeSH term(s)	Breast Neoplasms/drug therapy ; Copper/pharmacology ; Exosomes/metabolism ; Female ; Humans ; Metal Nanoparticles/therapeutic use ; Silver/pharmacology ; Wheat Germ Agglutinins/metabolism
Chemical Substances	Wheat Germ Agglutinins ; Silver (3M4G523W1G) ; Copper (789U1901C5)
Language	English
Publishing date	2022-04-10
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2701-0198
ISSN (online)	2701-0198
DOI	10.1002/adbi.202200005
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Article ; Online: Central Bank Independence and its Impact on Fiscal Deficit

Ahmad Bhat Aijaz / Iqbal Khan Javaid / Ahmad Bhat Sajad / Ahmad Parray Waseem

Studia Universitatis Vasile Goldis Arad, Seria Stiinte Economice, Vol 33, Iss 2, Pp 71-

Evidence from India

2023 Volume 94

Abstract: The paper explores the relationship between Central bank independence (CBI) and fiscal deficit in India. Moreover, the study tries to assess the impact of CBI on the levels of fiscal deficit. The study incorporates other variables like Gross Domestic ... ...

Abstract	The paper explores the relationship between Central bank independence (CBI) and fiscal deficit in India. Moreover, the study tries to assess the impact of CBI on the levels of fiscal deficit. The study incorporates other variables like Gross Domestic Product, financial development, and trade openness to analyze their impact on the fiscal deficit. The study employed Auto-regressive distributed lag model (ARDL) Bounds test developed by Pesaran, Shin, and Smith (2001) to examine the long-run relationship between CBI and fiscal deficit. The study also employs a legal index for measuring CBI developed by Jasmine et al (2019) as well as an actual measure of independence developed by Cukierman (1992) to measure CBI in India. The study confirms the long-run relationship between the CBI and fiscal deficit as well as among other variables. An increase in the levels of CBI leads to falling in the levels of fiscal deficit. The other explanatory variables used in the study also confirm the long-run relationship and impact fiscal deficit negatively except for trade openness, which positively impacts the fiscal deficit.
Keywords	central bank independence ; indian economy ; fiscal deficit ; turnover rate ; cointegration ; e42 ; e43 ; e58 ; Regional economics. Space in economics ; HT388 ; Economics as a science ; HB71-74
Subject code	337
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	Sciendo
Document type	Article ; Online
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Article ; Online: Human antigen R: Exploring its inflammatory response impact and significance in cardiometabolic disorders.

Abdelsam, Shahenda Salah / Ghanem, Sarah Khalaf / Zahid, Muhammad Ammar / Abunada, Hanan H / Bader, Loulia / Raïq, Hicham / Khan, Abbas / Parray, Aijaz / Djouhri, Laiche / Agouni, Abdelali

Journal of cellular physiology

2024

Abstract: RNA-binding proteins (RBPs) play a crucial role in the regulation of posttranscriptional RNA networks, which can undergo dysregulation in many pathological conditions. Human antigen R (HuR) is a highly researched RBP that plays a crucial role as a ... ...

Abstract	RNA-binding proteins (RBPs) play a crucial role in the regulation of posttranscriptional RNA networks, which can undergo dysregulation in many pathological conditions. Human antigen R (HuR) is a highly researched RBP that plays a crucial role as a posttranscriptional regulator. HuR plays a crucial role in the amplification of inflammatory signals by stabilizing the messenger RNA of diverse inflammatory mediators and key molecular players. The noteworthy correlations between HuR and its target molecules, coupled with the remarkable impacts reported on the pathogenesis and advancement of multiple diseases, position HuR as a promising candidate for therapeutic intervention in diverse inflammatory conditions. This review article examines the significance of HuR as a member of the RBP family, its regulatory mechanisms, and its implications in the pathophysiology of inflammation and cardiometabolic illnesses. Our objective is to illuminate potential directions for future research and drug development by conducting a comprehensive analysis of the existing body of research on HuR.
Language	English
Publishing date	2024-03-01
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	3116-1
ISSN	1097-4652 ; 0021-9541
ISSN (online)	1097-4652
ISSN	0021-9541
DOI	10.1002/jcp.31229
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Article ; Online: Sestrin2 as a Protective Shield against Cardiovascular Disease.

Zahid, Muhammad Ammar / Abdelsalam, Shahenda Salaheldin / Raïq, Hicham / Parray, Aijaz / Korashy, Hesham Mohamed / Zeidan, Asad / Elrayess, Mohamed A / Agouni, Abdelali

International journal of molecular sciences

2023 Volume 24, Issue 5

Abstract: A timely and adequate response to stress is inherently present in each cell and is important for maintaining the proper functioning of the cell in changing intracellular and extracellular environments. Disruptions in the functioning or coordination of ... ...

Abstract	A timely and adequate response to stress is inherently present in each cell and is important for maintaining the proper functioning of the cell in changing intracellular and extracellular environments. Disruptions in the functioning or coordination of defense mechanisms against cellular stress can reduce the tolerance of cells to stress and lead to the development of various pathologies. Aging also reduces the effectiveness of these defense mechanisms and results in the accumulation of cellular lesions leading to senescence or death of the cells. Endothelial cells and cardiomyocytes are particularly exposed to changing environments. Pathologies related to metabolism and dynamics of caloric intake, hemodynamics, and oxygenation, such as diabetes, hypertension, and atherosclerosis, can overwhelm endothelial cells and cardiomyocytes with cellular stress to produce cardiovascular disease. The ability to cope with stress depends on the expression of endogenous stress-inducible molecules. Sestrin2 (SESN2) is an evolutionary conserved stress-inducible cytoprotective protein whose expression is increased in response to and defend against different types of cellular stress. SESN2 fights back the stress by increasing the supply of antioxidants, temporarily holding the stressful anabolic reactions, and increasing autophagy while maintaining the growth factor and insulin signaling. If the stress and the damage are beyond repair, SESN2 can serve as a safety valve to signal apoptosis. The expression of SESN2 decreases with age and its levels are associated with cardiovascular disease and many age-related pathologies. Maintaining sufficient levels or activity of SESN2 can in principle prevent the cardiovascular system from aging and disease.
MeSH term(s)	Humans ; Cardiovascular Diseases ; Endothelial Cells ; Signal Transduction ; Aging ; Apoptosis ; Sestrins
Chemical Substances	SESN2 protein, human ; Sestrins
Language	English
Publishing date	2023-03-02
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24054880
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Article ; Online: Sestrin2 as a Protective Shield against Cardiovascular Disease

Muhammad Ammar Zahid / Shahenda Salaheldin Abdelsalam / Hicham Raïq / Aijaz Parray / Hesham Mohamed Korashy / Asad Zeidan / Mohamed A. Elrayess / Abdelali Agouni

International Journal of Molecular Sciences, Vol 24, Iss 4880, p

2023 Volume 4880

Abstract	A timely and adequate response to stress is inherently present in each cell and is important for maintaining the proper functioning of the cell in changing intracellular and extracellular environments. Disruptions in the functioning or coordination of defense mechanisms against cellular stress can reduce the tolerance of cells to stress and lead to the development of various pathologies. Aging also reduces the effectiveness of these defense mechanisms and results in the accumulation of cellular lesions leading to senescence or death of the cells. Endothelial cells and cardiomyocytes are particularly exposed to changing environments. Pathologies related to metabolism and dynamics of caloric intake, hemodynamics, and oxygenation, such as diabetes, hypertension, and atherosclerosis, can overwhelm endothelial cells and cardiomyocytes with cellular stress to produce cardiovascular disease. The ability to cope with stress depends on the expression of endogenous stress-inducible molecules. Sestrin2 (SESN2) is an evolutionary conserved stress-inducible cytoprotective protein whose expression is increased in response to and defend against different types of cellular stress. SESN2 fights back the stress by increasing the supply of antioxidants, temporarily holding the stressful anabolic reactions, and increasing autophagy while maintaining the growth factor and insulin signaling. If the stress and the damage are beyond repair, SESN2 can serve as a safety valve to signal apoptosis. The expression of SESN2 decreases with age and its levels are associated with cardiovascular disease and many age-related pathologies. Maintaining sufficient levels or activity of SESN2 can in principle prevent the cardiovascular system from aging and disease.
Keywords	Sestrin2 ; cardiovascular disease ; cellular stress ; cardioprotective ; oxidative stress ; antioxidant ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Exosomes Derived Neuronal Markers: Immunoaffinity Isolation and Characterization.

Yousif, Ghada / Qadri, Shahnaz / Parray, Aijaz / Akhthar, Naveed / Shuaib, Ashfaq / Haik, Yousef

Neuromolecular medicine

2021 Volume 24, Issue 3, Page(s) 339–351

Abstract: Neuronal exosomes play a crucial role in intercellular communication in the brain and represent a promising biomarker for neurological diseases, including stroke. However, limited techniques are available for isolating neuronal exosomes due to their ... ...

Abstract	Neuronal exosomes play a crucial role in intercellular communication in the brain and represent a promising biomarker for neurological diseases, including stroke. However, limited techniques are available for isolating neuronal exosomes due to their small number in the serum exosomes. Thus, the development of efficient tools with brain-specific markers is needed. Here, we show the optimization of an immunoaffinity assay-based isolation protocol for specific exosomes or neuronally derived exosomes (NDE). Our results demonstrated that one-micron functionalized magnetic beads successfully separated CD63+ and L1CAM+ exosomes from serum. The size and shape of exosomes or exosomes pulled by beads were confirmed by Dynamic light scattering and Transmission electron microscopy; also, beads were well resolved in conventional flow cytometry analysis, which revealed that CD63-pulled serum exosomes had 5% expression of L1CAM. Furthermore, transmission electron microscopy showed that exosomes eluted from magnetic beads retained their original size, shape, and form without any damage. Furthermore, we showed isolation of NDE using GluR2/3-capturing antibody (α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor) using an optimized immunoaffinity bead assay utilizing 100 µl serum of stroke patients or age-matched healthy group. GluR2/3-captured exosomes were confirmed by western blot analysis. The western blot analysis showed a significant increase in the 35KDa subunit of GluR2/3 receptor protein in the exosomes of stroke patients compared to the healthy group. In addition, the multimeric GluR2/3 receptor protein in exosomes was further validated by the presence of the GluR2 subunit. Thus, our study shows GluR3/2 may be an effective candidate to isolate neuronal exosomes.
MeSH term(s)	Biomarkers ; Exosomes/metabolism ; Humans ; Neural Cell Adhesion Molecule L1/metabolism ; Neurons/metabolism ; Proteins/metabolism ; Stroke/metabolism
Chemical Substances	Biomarkers ; Neural Cell Adhesion Molecule L1 ; Proteins
Language	English
Publishing date	2021-11-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	2077809-0
ISSN	1559-1174 ; 1535-1084
ISSN (online)	1559-1174
ISSN	1535-1084
DOI	10.1007/s12017-021-08696-6
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Article ; Online: Circulating Exosomes of Neuronal Origin as Potential Early Biomarkers for Development of Stroke.

Yousif, Ghada / Qadri, Shahnaz / Haik, Mahmoud / Haik, Yousef / Parray, Aijaz Sultan / Shuaib, Ashfaq

Molecular diagnosis & therapy

2021 Volume 25, Issue 2, Page(s) 163–180

Abstract: Stroke is one of the major causes of morbidity and mortality globally, with devastating effects. It is diagnosed mainly by clinical assessment and brain imaging; however, it is challenging to discriminate stroke from similar conditions with parallel ... ...

Abstract	Stroke is one of the major causes of morbidity and mortality globally, with devastating effects. It is diagnosed mainly by clinical assessment and brain imaging; however, it is challenging to discriminate stroke from similar conditions with parallel presentations. While brain imaging provides detection of stroke infarcts, it does not provide useful information on the biology and prognosis of the underlying disease process. The complex pathophysiology of stroke infarcts is a barrier in developing sensitive diagnostic tools, which consequently has a detrimental effect on development of treatment regimens. Early diagnosis of stroke is vital for better management, but currently there is no diagnostic blood-based biomarker. The cargo of exosomes can give an insight into the physiological or pathophysiological status of the cell. Exosomes have gained great interest as a means of intercellular communication and recently have been explored as a potential biomarker tool. Circulating exosomes in the blood result from of a contribution from all tissues. The sub-population of exosomes released from brain cells circulating in body fluids are known as neuronal exosomes. This overview presents the vital diagnostic function that could be performed by circulating exosomes of neuronal origin in identifying the subtype of stroke, its severity, and the recovery stages. A number of potential biomarkers that are obtained from circulating exosomes have showed promising potential to function as stroke biomarkers; however, further work is needed to characterize the neuronal exosomes and its payload and to determine the pathways it uses in the complex pathophysiology of stroke. The identification is a subset of exosomal biomarkers that are specific to stroke will enhance the early detection and prognosis of the disease.
MeSH term(s)	Biomarkers/blood ; Early Diagnosis ; Exosomes/genetics ; Humans ; MicroRNAs/blood ; Neurons/metabolism ; Neurons/pathology ; Prognosis ; Stroke/blood ; Stroke/genetics ; Stroke/pathology
Chemical Substances	Biomarkers ; MicroRNAs
Language	English
Publishing date	2021-01-16
Publishing country	New Zealand
Document type	Journal Article ; Review
ZDB-ID	2232796-4
ISSN	1179-2000 ; 1177-1062
ISSN (online)	1179-2000
ISSN	1177-1062
DOI	10.1007/s40291-020-00508-0
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Article ; Online: Untargeted Metabolomic Profiling Reveals Differentially Expressed Serum Metabolites and Pathways in Type 2 Diabetes Patients with and without Cognitive Decline: A Cross-Sectional Study.

Al-Akl, Neyla S / Khalifa, Olfa / Ponirakis, Georgios / Parray, Aijaz / Ramadan, Marwan / Khan, Shafi / Chandran, Mani / Ayadathil, Raheem / Elsotouhy, Ahmed / Own, Ahmed / Al Hamad, Hanadi / Decock, Julie / Alajez, Nehad M / Albagha, Omar / Malik, Rayaz A / El-Agnaf, Omar M A / Arredouani, Abdelilah

International journal of molecular sciences

2024 Volume 25, Issue 4

Abstract: Diabetes is recognized as a risk factor for cognitive decline, but the underlying mechanisms remain elusive. We aimed to identify the metabolic pathways altered in diabetes-associated cognitive decline (DACD) using untargeted metabolomics. We conducted ... ...

Abstract	Diabetes is recognized as a risk factor for cognitive decline, but the underlying mechanisms remain elusive. We aimed to identify the metabolic pathways altered in diabetes-associated cognitive decline (DACD) using untargeted metabolomics. We conducted liquid chromatography-mass spectrometry-based untargeted metabolomics to profile serum metabolite levels in 100 patients with type 2 diabetes (T2D) (54 without and 46 with DACD). Multivariate statistical tools were used to identify the differentially expressed metabolites (DEMs), and enrichment and pathways analyses were used to identify the signaling pathways associated with the DEMs. The receiver operating characteristic (ROC) analysis was employed to assess the diagnostic accuracy of a set of metabolites. We identified twenty DEMs, seven up- and thirteen downregulated in the DACD vs. DM group. Chemometric analysis revealed distinct clustering between the two groups. Metabolite set enrichment analysis found significant enrichment in various metabolite sets, including galactose metabolism, arginine and unsaturated fatty acid biosynthesis, citrate cycle, fructose and mannose, alanine, aspartate, and glutamate metabolism. Pathway analysis identified six significantly altered pathways, including arginine and unsaturated fatty acid biosynthesis, and the metabolism of the citrate cycle, alanine, aspartate, glutamate, a-linolenic acid, and glycerophospholipids. Classifier models with AUC-ROC > 90% were developed using individual metabolites or a combination of individual metabolites and metabolite ratios. Our study provides evidence of perturbations in multiple metabolic pathways in patients with DACD. The distinct DEMs identified in this study hold promise as diagnostic biomarkers for DACD patients.
MeSH term(s)	Humans ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/metabolism ; Cross-Sectional Studies ; Metabolome ; Aspartic Acid/metabolism ; Metabolomics ; Cognitive Dysfunction ; Alanine/metabolism ; Arginine/metabolism ; Citrates ; Glutamates/metabolism ; Fatty Acids, Unsaturated
Chemical Substances	Aspartic Acid (30KYC7MIAI) ; Alanine (OF5P57N2ZX) ; Arginine (94ZLA3W45F) ; Citrates ; Glutamates ; Fatty Acids, Unsaturated
Language	English
Publishing date	2024-02-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25042247
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Article ; Online: Increase in repulsive guidance molecule-a (RGMa) in lacunar and cortical stroke patients is related to the severity of the insult.

Parray, Aijaz / Akhtar, Naveed / Pir, Ghulam Jeelani / Pananchikkal, Sajitha V / Ayadathil, Raheem / Mir, Fayaz Ahmad / Francis, Reny / Own, Ahmed / Shuaib, Ashfaq

Scientific reports

2022 Volume 12, Issue 1, Page(s) 20788

Abstract: Repulsive guidance molecule-a (RGMa) inhibits angiogenesis and increases inflammation. Animal models of cerebral ischemia have shown that an increased expression of RGMa leads to larger infarction and its inhibition attenuates effects of ischemia. We ... ...

Abstract	Repulsive guidance molecule-a (RGMa) inhibits angiogenesis and increases inflammation. Animal models of cerebral ischemia have shown that an increased expression of RGMa leads to larger infarction and its inhibition attenuates effects of ischemia. We report on the relationship of RGMa to stroke types and severity. This is a prospective study in patients admitted to the stroke service in Qatar. We collected the clinical determinants, including NIHSS at admission, imaging and outcome at discharge and 90-days. RGMa levels were determined by measuring mRNA levels extracted from peripheral blood mononuclear cells (PBMCs) within 24 h of onset and at 5 days. There were 90 patients (lacunar: 64, cortical: 26) and 35 age-matched controls. RGMa mRNA levels were significantly higher in the stroke patients: day 1: 1.007 ± 0.13 versus 2.152 ± 0.19 [p < 0.001] and day-5: 3.939 ± 0.36 [p < 0.0001]) and significantly higher in patients with severe stroke (NIHSS ≥ 8) compared to milder symptoms (NIHSS < 8) at day 1 (NIHSS ≥ 8: 2.563 ± 0.36; NIHSS < 8: 1.947 ± 0.2) and day 5 (NIHSS ≥ 8: 5.25 ± 0.62; NIHSS < 8: 3.259 ± 0.419). Cortical stroke patients had marginally higher RGMa mRNA levels compared to lacunar stroke at day 1 (cortical stroke: 2.621 ± 0.46 vs lacunar stroke: 1.961 ± 0.19) and day 5 (cortical stroke: 4.295 ± 0.76 vs lacunar stroke: 3.774 ± 0.39). In conclusion, there is an increase in the level of RGMa mRNA in patients with acute stroke and seen in patients with lacunar and cortical stroke. The increase in RGMa mRNA levels is related to the severity of the stroke and increases over the initial 5 days. Further studies are required to determine the effects of the increase in RGMa on stroke recovery.
MeSH term(s)	Animals ; Humans ; Stroke, Lacunar ; Leukocytes, Mononuclear ; Prospective Studies ; Stroke/genetics ; Cerebral Infarction ; Gastropoda
Language	English
Publishing date	2022-12-01
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-24481-2
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