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Dive into the research topics where Jalaluddin M. Ashraf is active.

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Featured researches published by Jalaluddin M. Ashraf.


Glycobiology | 2014

Glycoxidation of biological macromolecules: A critical approach to halt the menace of glycation

Saheem Ahmad; M. Salman Khan; Firoz Akhter; Mohd Sajid Khan; Amir Khan; Jalaluddin M. Ashraf; R. P. Pandey; Uzma Shahab

Glycation is the result of covalent bonding of a free amino group of biological macromolecules with a reducing sugar, which results in the formation of a Schiff base that undergoes rearrangement, dehydration and cyclization to form a more stable Amadori product. The final products of nonenzymatic glycation of biomacromolecules like DNA, proteins and lipids are known as advanced glycation end products (AGEs). AGEs may be generated rapidly or over long times stimulated by distinct triggering mechanisms, thereby accounting for their roles in multiple settings and disease states. Both Schiff base and Amadori glycation products generate free radicals resulting in decline of antioxidant defense mechanisms and can damage cellular organelles and enzymes. This critical review primarily focuses on the mechanistic insight of glycation and the most probable route for the formation of glycation products and their therapeutic interventions. Furthermore, the prevention of glycation reaction using therapeutic drugs such as metformin, pyridoxamine and aminoguanidine (AG) are discussed with special emphasis on the novel concept of the bioconjugation of these drugs like, AG with gold nanoparticles (GNPs). At or above 10 mM concentration, AG is found to be toxic and therefore has serious health concerns, and the study warrants doing this novel bioconjugation of AG with GNPs. This approach might increase the efficacy of the AG at a reduced concentration with low or no toxicity. Using the concept of synthesis of GNPs with abovementioned drugs, it is assumed that toxicity of various drugs which are used at high doses can be minimized more effectively.


Archives of Biochemistry and Biophysics | 2012

Structural and immunological characterization of Amadori-rich human serum albumin: role in diabetes mellitus.

Binish Arif; Jalaluddin M. Ashraf; Jamal Ahmad; Zarina Arif; Khursheed Alam

Proteins modifications in diabetes may lead to early glycation products (EGPs) as well as advanced glycation end products (AGEs). Whereas no extensive studies have been carried out to assess the role of EGPs in secondary complications of diabetes, numerous investigators have demonstrated the role of AGEs. Early glycation involves attachment of glucose on ε-NH2 of lysine residues of proteins leading to generation of the Amadori product (an early glycation species). This study reports the structural and immunological characterization of EGPs of HSA because we believe that during persistent hyperglycemia the HSA, one of the major blood proteins, can undergo fast glycation. Glucose mediated generation of EGPs of HSA was quantitated as Amadori products by NBT assay and authenticated by boronate affinity chromatography and LC/MS. Compared to native HSA changes in glycated-HSA were characterized by hyperchromicity, loss in fluorescence intensity and a new peak in the FTIR profile. Immunogenicity of native- and glycated-HSA was evaluated by inducing antibodies in rabbits. Results suggest generation of neo-epitopes on glycated-HSA rendering it highly immunogenic compared to native HSA. Quantization of EGPs of HSA by authentic antibodies against HSA-EGPs can be used as marker for early detection of the initiation/progression of secondary complications of diabetes.


Current Pharmaceutical Design | 2016

Computer Aided Drug Design: Success and Limitations.

Mohammad Hassan Baig; Khurshid Ahmad; Sudeep Roy; Jalaluddin M. Ashraf; Mohd Adil; Mohammad Haris Siddiqui; Saif Khan; Mohammad A. Kamal; Ivo Provaznik; Inho Choi

Over the last few decades, computer-aided drug design has emerged as a powerful technique playing a crucial role in the development of new drug molecules. Structure-based drug design and ligand-based drug design are two methods commonly used in computer-aided drug design. In this article, we discuss the theory behind both methods, as well as their successful applications and limitations. To accomplish this, we reviewed structure based and ligand based virtual screening processes. Molecular dynamics simulation, which has become one of the most influential tool for prediction of the conformation of small molecules and changes in their conformation within the biological target, has also been taken into account. Finally, we discuss the principles and concepts of molecular docking, pharmacophores and other methods used in computer-aided drug design.


Scientific Reports | 2016

Green synthesis of silver nanoparticles and characterization of their inhibitory effects on AGEs formation using biophysical techniques.

Jalaluddin M. Ashraf; Mohammad Azam Ansari; Haris M. Khan; Mohammad A. Alzohairy; Inho Choi

Advanced glycation end-products (AGEs) resulting from non-enzymatic glycation are one of the major factors implicated in secondary complications of diabetes. Scientists are focusing on discovering new compounds that may be used as potential AGEs inhibitors without affecting the normal structure and function of biomolecules. A number of natural and synthetic compounds have been proposed as AGE inhibitors. In this study, we investigated the inhibitory effects of AgNPs (silver nanoparticles) in AGEs formation. AgNPs (~30.5 nm) synthesized from Aloe Vera leaf extract were characterized using UV-Vis spectroscopy, energy-dispersive X-ray spectroscopy (EDX), high resolution-transmission electron microscopy, X-ray diffraction and dynamic light scattering (DLS) techniques. The inhibitory effects of AgNPs on AGEs formation were evaluated by investigating the degree of reactivity of free amino groups (lysine and arginine residues), protein-bound carbonyl and carboxymethyl lysine (CML) content, and the effects on protein structure using various physicochemical techniques. The results showed that AgNPs significantly inhibit AGEs formation in a concentration dependent manner and that AgNPs have a positive effect on protein structure. These findings strongly suggest that AgNPs may play a therapeutic role in diabetes-related complications.


PLOS ONE | 2015

3-Deoxyglucosone: A Potential Glycating Agent Accountable for Structural Alteration in H3 Histone Protein through Generation of Different AGEs

Jalaluddin M. Ashraf; Saheem Ahmad; Gulam Rabbani; Qambar Hasan; Arif Tasleem Jan; Eun Ju Lee; Rizwan Hasan Khan; Khursheed Alam; Inho Choi

Advanced glycation end-products (AGEs) are heterogeneous group of compounds, known to be implicated in diabetic complications. One of the consequences of the Maillard reaction is attributed to the production of reactive intermediate products such as α-oxoaldehydes. 3-deoxyglucosone (3-DG), an α-oxoaldehyde has been found to be involved in accelerating vascular damage during diabetes. In the present study, calf thymus histone H3 was treated with 3-deoxyglucosone to investigate the generation of AGEs (Nε-carboxymethyllysine, pentosidine), by examining the degree of side chain modifications and formation of different intermediates and employing various physicochemical techniques. The results clearly indicate the formation of AGEs and structural changes upon glycation of H3 by 3-deoxyglucosone, which may hamper the normal functioning of H3 histone, that may compromise the veracity of chromatin structures and function in secondary complications of diabetes.


Iubmb Life | 2014

Physicochemical Analysis of Structural Alteration and Advanced Glycation End Products Generation During Glycation of H2A Histone by 3-Deoxyglucosone

Jalaluddin M. Ashraf; Saheem Ahmad; Gulam Rabbani; Arif Tasleem Jan; Eun Ju Lee; Rizwan Hasan Khan; Inho Choi

Advanced glycation end‐products comprise a complex and heterogeneous group of compounds that have been implicated in diabetes‐related complications. The importance of the Maillard reaction is depicted by the formation of reactive intermediate products known as α‐oxoaldehydes, such as 3‐deoxyglucosone (3‐DG). This product has been found to be involved in accelerated vascular damage in diabetes. In the present study, calf thymus histone H2A was reacted with 3‐DG, and the generation of advanced glycation end products was investigated by determining the degree of side chain modifications (lysine and arginine residues), Amadori products, carbonyl content, Nε‐carboxymethyl lysine, and pentosidine using various physicochemical techniques. Moreover, fluorescence, absorbance as well as structural characteristics of glycated‐H2A were comprehensively investigated. Overall, this study demonstrates structural perturbation, formation of different intermediates, and AGEs that are believed to hamper the normal functioning of H2A histone, compromising the integrity of chromatin structures and function in secondary complications of diabetes.


PLOS ONE | 2015

Glycation of H1 Histone by 3-Deoxyglucosone: Effects on Protein Structure and Generation of Different Advanced Glycation End Products.

Jalaluddin M. Ashraf; Gulam Rabbani; Saheem Ahmad; Qambar Hasan; Rizwan Hasan Khan; Khursheed Alam; Inho Choi

Advanced glycation end products (AGEs) culminate from the non-enzymatic reaction between a free carbonyl group of a reducing sugar and free amino group of proteins. 3-deoxyglucosone (3-DG) is one of the dicarbonyl species that rapidly forms several protein-AGE complexes that are believed to be involved in the pathogenesis of several diseases, particularly diabetic complications. In this study, the generation of AGEs (Nε-carboxymethyl lysine and pentosidine) by 3-DG in H1 histone protein was characterized by evaluating extent of side chain modification (lysine and arginine) and formation of Amadori products as well as carbonyl contents using several physicochemical techniques. Results strongly suggested that 3-DG is a potent glycating agent that forms various intermediates and AGEs during glycation reactions and affects the secondary structure of the H1 protein. Structural changes and AGE formation may influence the function of H1 histone and compromise chromatin structures in cases of secondary diabetic complications.


International Journal of Biological Macromolecules | 2015

Quercetin as a finer substitute to aminoguanidine in the inhibition of glycation products

Jalaluddin M. Ashraf; Uzma Shahab; Shams Tabrez; Eun Ju Lee; Inho Choi; Saheem Ahmad

Non-enzymatic glycation is the addition of a free carbonyl group of a reducing sugar to the free amino groups of proteins, which results in the formation of early and advanced glycation end-products (AGEs). Glycation reaction is profoundly associated with diabetes and its secondary complications, such as nephropathy and neuropathy. Glyoxal is a carbonyl species that reacts rapidly with the free amino groups of proteins to form AGEs. While the formation of AGEs with various glycating agents has previously been demonstrated, no extensive studies have been conducted to assess the role of quercetin in all three stages of glycation (early, intermediate and late). In this study, we report the glycation of HSA (human serum albumin) and its characterization by several spectroscopic techniques. Furthermore, inhibition of products at all stages of glycation was studied by various assays. Spectroscopic analysis suggests structural perturbations in the HSA macromolecule as a result of modification, which might be due to the generation of free radicals and the formation of AGEs. Inhibition in the formation of glycation has established that quercetin is a better and a more potent antiglycating agent than aminoguanidine at all stages of glycation.


Cell Biochemistry and Biophysics | 2016

DNA Glycation from 3-Deoxyglucosone Leads to the Formation of AGEs: Potential Role in Cancer Auto-antibodies

Jalaluddin M. Ashraf; Uzma Shahab; Shams Tabrez; Eun Ju Lee; Inho Choi; Mohd Aslam Yusuf; Saheem Ahmad

The non-enzymatic glycation reaction results in the generation of free radicals which play an important role in the pathophysiology of aging, diabetes, and cancer. 3-Deoxyglucosone (3-DG) is a dicarbonyl species which may lead to the formation of advanced glycation end products (AGEs). 3-DG also reacts with free amino group of nucleic acids resulting in the formation of DNA-AGEs. While the establishment of nucleoside AGEs has been revealed before, no extensive studies have been done to probe the role of 3-DG in the generation of immunogenicity and induction of cancer auto-antibodies. In this study, we report the immunogenicity of AGEs formed by 3-DG-Arg-Fe3+ system. Spectroscopic analysis and melting temperature studies suggest structural perturbations in the DNA as a result of modification. Immunogenicity of native and 3-DG-Arg-Fe3+ DNA was probed in female rabbits. The modified DNA was highly immunogenic eliciting high-titer immunogen-specific antibodies, while the unmodified form was almost non-immunogenic. We also report the presence of auto-antibodies against 3-DG-Arg-Fe3+-modified DNA in the sera of patients with different types of cancers. The glycoxidative lesions were also detected in the lymphocyte DNA isolated from selected cancer patients. The results show structural perturbations in 3-DG-Arg-Fe3+–DNA generating new epitopes that render the molecule immunogenic.


The FASEB Journal | 2016

Fibromodulin: a master regulator of myostatin controlling progression of satellite cells through a myogenic program

Eun Ju Lee; Arif Tasleem Jan; Mohammad Hassan Baig; Jalaluddin M. Ashraf; Sang-Soep Nahm; Yong-Woon Kim; So-Young Park; Inho Choi

Differentiation of muscle satellite cells (MSCs) involves interaction of the proteins present in the extracellular matrix (ECM) with MSCs to regulate their activity, and therefore phenotype. Herein, we report fibromodulin (FMOD), a member of the proteoglycan family participating in the assembly of ECM, as a novel regulator of myostatin (MSTN) during myoblast differentiation. In addition to having a pronounced effect on the expression of myogenic marker genes [myogenin (MYOG) and myosin light chain 2 (MYL2)], FMOD was found to maintain the transcriptional activity of MSTN. Moreover, coimmunoprecipitation and in silico studies performed to investigate the interaction of FMOD helped confirm that it antagonizes MSTN function by distorting its folding and preventing its binding to activin receptor type IIB. Furthermore, in vivo studies revealed that FMOD plays an active role in healing by increasing satellite cell recruitment to sites of injury. Together, these findings disclose a hitherto unrecognized regulatory role for FMOD in MSCs and highlight new mechanisms whereby FMOD circumvents the inhibitory effects of MSTN and triggers myoblast differentiation. These findings offer a basis for the design of novel MSTN inhibitors that promote muscle regeneration after injury or for the development of pharmaceutical agents for the treatment of different muscle atrophies.—Lee, E. J., Jan, A. T., Baig M. H., Ashraf, J. M., Nahm, S.‐S., Kim, Y.‐W., Park, S.‐Y., Choi, I. Fibromodulin: a master regulator of myostatin controlling progression of satellite cells through a myogenic program. FASEB J. 30, 2708‐2719 (2016). www.fasebj.org

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Khursheed Alam

Aligarh Muslim University

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Uzma Shahab

King George's Medical University

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Sana Fatma

Banaras Hindu University

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