9 results on '"Syed, Aun Muhammad"'
Search Results
2. Advances in immunomodulatory therapy for severe acute pancreatitis
- Author
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Syed Aun Muhammad, Fahad Munir, Numan Shahid, QiYu Zhang, Abdullah Al Mamun, Hajar Mansoor Hussain, and Muhammad Babar Jamshed
- Subjects
0301 basic medicine ,Combination therapy ,T-Lymphocytes ,Inflammatory response ,Immunology ,Bioinformatics ,Immunomodulation ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Animals ,Humans ,Immunology and Allergy ,Medicine ,Inflammation ,business.industry ,Mesenchymal stem cell ,Mesenchymal Stem Cells ,Dendritic Cells ,medicine.disease ,Killer Cells, Natural ,030104 developmental biology ,Pancreatitis ,Apoptosis ,Cytokines ,Acute pancreatitis ,Immunomodulation Therapy ,business ,030215 immunology - Abstract
Severe acute pancreatitis (SAP) has a complex course and a worse prognosis. Immune response imbalance is an important cause of severe pancreatitis or even death in patients. Immunomodulation therapy can regulate the imbalance of inflammatory response, alleviate SAP-related organ damage and improve the prognosis of patients. There are some problems in early immune regulation measures, such as single target and simple way. In recent years, new treatment methods, such as regulating the maturation and apoptosis of immune cells, the application of mesenchymal stem cells (MSCs) and multifactor combination therapy, have provided new ideas and hope for the future treatment of SAP. This article reviews the development of SAP immunoregulation and its recent progress.
- Published
- 2020
3. Reprofiling analysis of FDA approved drugs with upregulated differential expression genes found in hypertension
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Fawad Ali, He Liu Fang, Fawad Ali Shah, Syed Aun Muhammad, Arifullah Khan, and Shupeng Li
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Health Informatics - Published
- 2022
4. Studying association of GTF2H4 , SULF1 , OAS3 , and IFNG genes polymorphism and risk of head and neck cancer in Southern Punjab, Pakistan
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Mehreen Ismail, Nighat Fatima, Juweria Khawar, and Syed Aun Muhammad
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0301 basic medicine ,education.field_of_study ,biology ,Population ,Head and neck cancer ,Cancer ,Single-nucleotide polymorphism ,Odds ratio ,medicine.disease ,Betel ,biology.organism_classification ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Genetics ,medicine ,Naswar ,education ,Genetics (clinical) ,Gutka ,Demography - Abstract
Genetic variations develop inherited tendency to progress cancer. The incidence rate of head and neck cancer (HNC) is 15–40% of all cancer types worldwide but this ratio is worse in South Asian region of Pakistan. We collected 185 samples and observed variations in IFNG, GTF2H4, OAS3 and SULF1 genes of HNC samples associated with tobacco, betel leaf and nuts, naswar and gutka. We performed the tetra-arm PCR and found significant allelic associations of IFNG rs11177074 (P = 0.001135), GTF2H4 rs2894054 (P = 0.0001), OAS3 rs12302655 (P = 0.000001) and SULF1 rs4737999 (P = 0.00001) with HNC. The cancer and control samples were in Hardy–Weinberg equilibrium and the pooled odds ratios was 95% of confidence. Tobacco and naswar was progressive factor of HNC compare to betel leaves and nuts. The irrational habits of population of the Southern Punjab is bringing a substantial change in SNPs and therefore these variants could be used as genetic biomarkers to diagnose HNC.
- Published
- 2018
5. Cisplatin's potential for type 2 diabetes repositioning by inhibiting CDKN1A, FAS, and SESN1
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QiYu Zhang, Fahad Munir, Syed Aun Muhammad, Muhammad Babar Jamshed, Xiaogang Wu, Thanh Nguyen, and Syeda Tahira Qousain Naqvi
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Cyclin-Dependent Kinase Inhibitor p21 ,MAPK/ERK pathway ,endocrine system diseases ,medicine.medical_treatment ,Antineoplastic Agents ,Health Informatics ,Insulin resistance ,medicine ,Humans ,Insulin ,Protein kinase B ,Heat-Shock Proteins ,PI3K/AKT/mTOR pathway ,Cisplatin ,biology ,medicine.disease ,Computer Science Applications ,Insulin receptor ,Diabetes Mellitus, Type 2 ,Cancer research ,biology.protein ,Signal transduction ,Signal Transduction ,medicine.drug - Abstract
Cisplatin is a DNA-damaging chemotherapeutic agent used for treating cancer. Based on cDNA dataset analysis, we investigated how cisplatin modified gene expression and observed cisplatin-induced dysregulation and system-level variations relating to insulin resistance and type 2 diabetes mellitus (T2DM). T2DM is a multifactorial disease affecting 462 million people in the world, and drug-induced T2DM is a serious issue. To understand this etiology, we designed an integrative, system-level study to identify associations between cisplatin-induced differentially expressed genes (DEGs) and T2DM. From a list of differential expressed genes, cisplatin downregulated the cyclin-dependent kinase inhibitor 1 (CDKN1A), tumor necrosis factor (FAS), and sestrin-1 (SESN1) genes responsible for modifying signaling pathways, including the p53, JAK-STAT, FOXO, MAPK, mTOR, P13-AKT, Toll-like receptor (TLR), adipocytokine, and insulin signaling pathways. These enriched pathways were expressively associated with the disease. We observed significant gene signatures, including SMAD3, IRS, PDK1, PRKAA1, AKT, SOS, RAS, GRB2, MEK1/2, and ERK, interacting with source genes. This study revealed the value of system genetics for identifying the cisplatin-induced genetic variants responsible for the progression of T2DM. Also, by cross-validating gene expression data for T2DM islets, we found that downregulating IRS and PRK families is critical in insulin and T2DM signaling pathways. Cisplatin, by inhibiting CDKN1A, FAS, and SESN1, promotes IRS and PRK activity in a similar way to rosiglitazone (a popular drug used for T2DM treatment). Our integrative, network-based approach can help in understanding the drug-induced pathophysiological mechanisms of diabetes.
- Published
- 2021
6. Polymorphic evaluation of NFKBIA and SRR with type 2 diabetes mellitus in population of southern Punjab
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Syed Aun Muhammad, Waseem Raza, Syeda Zahra Abbas, and Saba Ghafoor
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0301 basic medicine ,medicine.medical_specialty ,education.field_of_study ,Population ,Type 2 Diabetes Mellitus ,Single-nucleotide polymorphism ,Biology ,medicine.disease ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Insulin resistance ,Endocrinology ,030220 oncology & carcinogenesis ,Internal medicine ,Genotype ,Genetics ,medicine ,SNP ,Allele ,education ,Genotyping ,Genetics (clinical) - Abstract
Insulin resistance and β-cell dysfunction are two major metabolic disorders in diabetic patients. Many genes are linked with insulin secretions and contribute to the pathogenesis of Type 2 diabetes mellitus (T2DM). This study is designed to investigate the single nucleotide polymorphism (SNP) of NFKB1A (rs7152376, rs1951276) and SRR k(rs1490763013) association with T2DM in the population of Southern Punjab Pakistan. We found a significant association of T2DM and our genetic variants among different associated genetic and environmental risk factors. The total study subjects in this investigation included 136 controls and 122 cases. The polymorphic genotyping was studied by Tetra ARMS-PCR. We found a significant association of the disease with genotypes of NFKB1A and SRR. We observed that NFKB1A (rs7152376) showed the ratio of mutant homozygous allele T is 0.7% in cases as compared to 0.5% in controls presenting increased disease-risk in our population. Similarly, the other SNP rs1951276 of NFKB1A revealed homozygous wild type G-allele higher in cases (0.91%). Similarly, the SRR (rs1490763013) showed that homozygous wild T-allele is 0.47% as compared to homozygous mutant C-allele 0.52% in control sample population. The stratification of our genetic variants with T2DM also revealed a significant association with smoking, cholesterol, and depression having P = 0.00001, at significance odd ratio level and 95% Confidence interval. Therefore, these polymorphic variants of NFKB1A and SRR are likely to be used in prognostics of T2DM.
- Published
- 2020
7. Therapeutic potential of Taraxacum officinale against HCV NS5B polymerase: In-vitro and In silico study
- Author
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Bushra Ijaz, Sidra Rehman, Nighat Fatima, Sheikh Riazuddin, and Syed Aun Muhammad
- Subjects
0301 basic medicine ,Taraxacum ,Sofosbuvir ,Cell Survival ,Hepatitis C virus ,Phytochemicals ,CHO Cells ,Hepacivirus ,Viral Nonstructural Proteins ,Biology ,Ligands ,medicine.disease_cause ,Antiviral Agents ,Gene Expression Regulation, Enzymologic ,03 medical and health sciences ,chemistry.chemical_compound ,Cricetulus ,Taraxacum officinale ,Cell Line, Tumor ,Cricetinae ,Gene expression ,medicine ,Animals ,Humans ,Computer Simulation ,NS5B ,Gene ,Cell Proliferation ,Pharmacology ,Binding Sites ,Plant Extracts ,virus diseases ,General Medicine ,Molecular biology ,digestive system diseases ,Molecular Docking Simulation ,030104 developmental biology ,Viral replication ,chemistry ,Viral genome replication ,medicine.drug - Abstract
Discovery of alternative and complementary regimens for HCV infection treatment is a need of time from clinical as well as economical point of views. Low cost of bioactive natural compounds production, high biochemical diversity and inexistent/milder side effects contribute to new therapies. Aim of this study is to clarify anti-HCV role of Taraxacum officinale, a natural habitat plant rich of flavonoids. In this study, methanol extract of T. officinale leaves was initially analyzed for its cytotoxic activity in human hepatoma (Huh-7) and CHO cell lines. Hepatoma cells were transfected with pCR3.1/Flagtag/HCV NS5B gene cloned vector (genotype 1a) along with T. officinale extract. Considering NS5B polymerase as potential therapeutic drug target, twelve phytochemicals of T. officinale were selected as ligands for molecular interaction with NS5B protein using Molecular Operating Environment (MOE) software. Sofosbuvir (Sovaldi: brand name) currently approved as new anti-HCV drug, was used as standard in current study for comparative analysis in computational docking screening. HCV NS5B polymerase as name indicates plays key role in viral genome replication. On the basis of which NS5B gene is targeted for determining antiviral role of T. officinale extract and 65% inhibition of NS5B expression was documented at nontoxic dose concentration (200μg/ml) using Real-time PCR. In addition, 57% inhibition of HCV replication was recorded when incubating Huh-7 cells with high titer serum of HCV infected patients along with leaves extract. Phytochemicals for instance d-glucopyranoside (-31.212 Kcal/mol), Quercetin (-29.222 Kcal/mol), Luteolin (-26.941 Kcal/mol) and some others displayed least binding energies as compared to standard drug Sofosbuvir (-21.0746 Kcal/mol). Results of our study strongly revealed that T. officinale leaves extract potentially blocked the viral replication and NS5B gene expression without posing any toxic effect on normal fibroblast cells of body.
- Published
- 2016
8. Anti-proliferative and computational studies of two new pregnane glycosides from Desmidorchis flava
- Author
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Ahmed Al-Rawahi, Ivan R. Green, Ali Elyassi, Ghulam Abbas, Talat Mahmood, René Csuk, Najeeb Ur Rehman, Ahmed Al-Harrasi, Mohammed Al-Broumi, Muhammad Adil Raees, Husain Yar Khan, Hidayat Hussain, and Syed Aun Muhammad
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Cell Survival ,Stereochemistry ,01 natural sciences ,Biochemistry ,Structure-Activity Relationship ,chemistry.chemical_compound ,Cell Line, Tumor ,Drug Discovery ,Humans ,Structure–activity relationship ,Glycosides ,Molecular Biology ,Cell Proliferation ,chemistry.chemical_classification ,Dose-Response Relationship, Drug ,Molecular Structure ,010405 organic chemistry ,Organic Chemistry ,Pregnane ,Glycoside ,Pregnanes ,Ligand (biochemistry) ,Antineoplastic Agents, Phytogenic ,Small molecule ,0104 chemical sciences ,Apocynaceae ,Molecular Docking Simulation ,010404 medicinal & biomolecular chemistry ,chemistry ,Docking (molecular) ,Cancer cell ,Drug Screening Assays, Antitumor ,Growth inhibition - Abstract
Two new pregnane glycosides named desmiflavasides C (1) and D (2) were isolated from the sap of Desmidorchis flava (N.E.Br.) Meve & Liede and have had their structures confirmed from 1D and 2D NMR spectroscopic techniques and mass spectrometry (ESIMS). Further, the effects of desmiflavasides C (1) and D (2) on the proliferation of breast and ovarian cancer cells as well as normal breast epithelial cells in culture were examined. Interestingly, desmiflavasides C (1) and D (2) were able to cause a substantial decline in the viability of cancer cells in a concentration-dependent manner. Moreover, treatment of normal cells with compound 2 resulted in no significant growth inhibition, indicating that its cytotoxicity was selective towards cancer cells. Furthermore, the activity of compound 2 against cancer as well as normal epithelial cells was found to be similar to that of a previously reported pregnane glycoside, nizwaside (3). Molecular docking studies of desmiflavasides C (1) and D (2) and nizwaside (3) were carried out to ascertain if it was possible to predict any important binding orientations required of small molecule drug candidates with suggested protein target molecules for the purposes of being able to predict the affinity and activity to an acceptable degree by such compounds. Desmiflavaside D (2) showed a relatively good binding affinity (-22.4449kcal/mol) as compared to the other two compounds viz., nizwaside (3) (-20.0319kcal/mol), and desmiflavaside C (1) (-19.4042kcal/mol). Docking results of the three pregnane glycosides viz., 1-3 revealed that these ligand molecules can accurately interact with the target protein.
- Published
- 2016
9. Design and synthesis of new flavonols as dual ɑ-amylase and ɑ-glucosidase inhibitors: Structure-activity relationship, drug-likeness, in vitro and in silico studies
- Author
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Amina Sadiq, Nafeesa Naeem, Jamshaid Ashraf, Bilal Ahmad Khan, Muhammad Anees, Ehsan Ullah Mughal, Tahira Qousain, Syed Aun Muhammad, and Muhammad Naveed Zafar
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chemistry.chemical_classification ,biology ,010405 organic chemistry ,Chemistry ,Stereochemistry ,In silico ,Organic Chemistry ,Active site ,Carbon-13 NMR ,010402 general chemistry ,01 natural sciences ,0104 chemical sciences ,Analytical Chemistry ,Inorganic Chemistry ,Enzyme ,biology.protein ,Lipinski's rule of five ,medicine ,Proton NMR ,Structure–activity relationship ,Spectroscopy ,Acarbose ,medicine.drug - Abstract
In this study, a library of new intriguing flavonol derivatives (1–17) was designed and synthesized through a facile route involving Algar-Flynn-Oyamada reaction in a one-pot synthesis. The molecular structures of all newly synthesized compounds were unequivocally corroborated by different spectroscopic techniques such as FTIR, UV–Vis, 1H NMR and 13C NMR and mass spectrometry (EI-MS). All the synthesized analogs (1-17) were evaluated in vitro for their inhibitory potential against ɑ-amylase and ɑ-glucosidase enzymes. Interestingly, all the synthetic compounds displayed good to moderate inhibition potential with IC50 values ranging from 4.86 ± 1.39 to 265.61 ± 5.85 μM for a-amylase, and 70.57 ± 1.13 to 322.98 ± 4.43 μM for a-glucosidase in comparison to the standard acarbose (IC50 = 5.03 ± 9.44 μM for a-amylase and IC50 = 75.26 ± 0.15 μM for α-glucosidase). It is worth mentioning that amongst the series, the compounds 9 (IC50 = 4.86 ± 1.39 μM for a-amylase and IC50 = 70.57 ± 1.13 μM for α-glucosidase) and 14 (IC50 = 5.02 ± 1.35 for a-amylase and IC50 = 71.69 ± 5.85 μM for α-glucosidase) were found the most potent dual inhibitors, even more active than standard. Furthermore, the target compounds (1-17) exhibited moderate to good antioxidant activities. Molecular simulations studies were conducted to correlate the in vitro results and to identify the possible mode of binding interaction of ligands with the active site of enzymes. Moreover, molecular description was performed with the drug-likeness and bioactivity scores. The results showed that some compounds are in a linear correlation with Lipinski’s rule of five demonstrating good drug-likeness and bioactivity score for drug targets. Structure-activity relationships delivered useful insights towards this class of compounds, and thus paved the way to design novel analogs with improved potency.
- Published
- 2020
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