Publications by authors named "Muhammad A Shah"

10 Publications

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A Case Report of Giant Ascending Aortic Aneurysm: Role of Multimodality Imaging.

Aorta (Stamford) 2021 Oct 12. Epub 2021 Oct 12.

Department of Adult Cardiac Surgery, King Fahad Medical City, Riyadh, Saudi Arabia.

Giant ascending aortic aneurysm (AscAA >10 cm) is an uncommon entity with a variable presentation. The size of the aneurysm, rapid expansion, and calcification are associated with an increased risk of rupture. Atherosclerosis is the most common etiology of aortic aneurysm in the elderly population. Multimodality imaging can be wisely used for diagnosis, risk stratification, and follow-up. We herein report a case of successfully repaired giant calcified AscAA with a maximum diameter of 10 cm. We also provide a brief discussion on the role of multimodality imaging.
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http://dx.doi.org/10.1055/s-0041-1730005DOI Listing
October 2021

Radioprotective Role of Natural Polyphenols: From Sources to Mechanisms.

Anticancer Agents Med Chem 2021 Apr 18. Epub 2021 Apr 18.

Department of Zoology, Faculty of Life Sciences, Government College University, Faisalabad 38000. Pakistan.

The identification and development of radioprotective agents has emerged as a subject matter of research during recent years due to the growing usage of ionizing radiation in different areas of human life. Previous work on synthetic radioprotectors has achieved limited progress because of the numerous issues associated with toxicity. Compounds extracted from plants have potential to serve as lead candidates for developing ideal radioprotectors due to their low cost, safety and selectivity. Polyphenols are the most abundant and commonly dispersed group of biologically active molecules possessing broad range of pharmacological activities. Polyphenols have displayed efficacy for radioprotection during various investigations and can be administered at high doses with lesser toxicity. Detoxification of free radicals, modulating inflammatory responses, DNA repair, stimulation of hematopoietic recovery, and immune functions are the main mechanisms for radiation protection with polyphenols. Epicatechin, epigallocatechin-3-gallate, apigenin, caffeic acid phenylethylester, and silibinin provide cytoprotection together with the suppression of many pro-inflammatory cytokines owing to their free radical scavenging, anti-oxidant, and anti-inflammatory properties. Curcumin, resveratrol, quercetin, gallic acid, and rutin's radioprotective properties are regulated primarily by direct or indirect decline in cellular stress. Thus, polyphenols may serve as potential candidates for radioprotection in the near future, however, extensive investigations are still required to better understand their protection mechanisms.
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http://dx.doi.org/10.2174/1871520621666210419095829DOI Listing
April 2021

Radioprotective Potential of Nutraceuticals and their Underlying Mechanism of Action.

Anticancer Agents Med Chem 2021 Feb 22. Epub 2021 Feb 22.

Faculty of Pharmacy and Biochemistry, Academic Department of Pharmacology, Bromatology and Toxicology, Centro Latinoamericano de Enseñanza e Investigación en Bacteriología Alimentaria (CLEIBA), Universidad Nacional Mayor de San Marcos, Lima15001. Peru.

Radiations are an efficient treatment modality in cancer therapy. Besides the treatment effects of radiations, the ionizing radiations interact with biological systems and generate reactive oxygen species that interfere with the normal cellular process. Previous investigations of synthetic radioprotectors have shown less effectiveness, mainly owing to some limiting effects. The nutraceuticals act as efficient radioprotectors to protect the tissues from the deleterious effects of radiation. The main radioprotection mechanism of nutraceuticals is the scavenging of free radicals while other strategies are involved modulation of signaling transduction of pathways like MAPK (JNK, ERK1/2, ERK5, and P38), NF-kB, cytokines, and their protein regulatory genes expression. The current review is focused on the radioprotective effects of nutraceuticals including vitamin E, -C, organosulphur compounds, phenylpropanoids, and polysaccharides. These natural entities protect against radiation-induced DNA damage. The review mainly entails the antioxidant perspective and mechanism of action of their radioprotective activities on a molecular level, DNA repair pathway, anti-inflammation, immunomodulatory effects, the effect on cellular signaling pathways, and regeneration of hematopoietic cells.
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http://dx.doi.org/10.2174/1871520621666210223101246DOI Listing
February 2021

Jaceosidin: A Natural Flavone with Versatile Pharmacological and Biological Activities.

Curr Pharm Des 2021 ;27(4):456-466

Department of Medical Biology, Faculty of Medicine, Nigde Ömer Halisdemir University, Campus 51240, Nigde, Turkey.

Nature always remains an inexhaustible source of treasures for mankind. It remains a mystery for every challenge until the completion of the challenge. While we talk about the complicated health issues, nature offers us a great variety of chemical scaffolds and their various moieties packed in the form of natural products e.g., plants, microorganisms (fungi, algae, protozoa), and terrestrial vertebrates and invertebrates. This review article is an update about jaceosidin, a bioactive flavone, from genus Artemisia. This potentially active compound exhibits a variety of pharmacological activities including anti-inflammatory, anti-oxidant, anti-bacterial, antiallergic and anti-cancer activities. The bioactivities and the therapeutic action of jaceosidin, especially the modulation of different cell signaling pathways (ERK1/2, NF-κB, PI3K/Akt and ATM-Chk1/2) which become deregulated in various pathological disorders, have been focused here. The reported data suggest that the bioavailability of this anti-cancer compound should be enhanced by utilizing various chemical, biological and computational techniques. Moreover, it is recommended that researchers and scientists should work on exploring the mode of action of this particular flavone to precede it further as a potent anti-cancer compound.
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http://dx.doi.org/10.2174/1381612826666200429095101DOI Listing
April 2021

Palynological investigation of lactiferous flora (Apocynaceae) of District Rawalpindi, Pakistan, using light and scanning electron microscopy.

Microsc Res Tech 2019 Sep 20;82(9):1410-1418. Epub 2019 May 20.

Department of Pharmacognosy, GC University Faisalabad, Punjab, Pakistan.

This was the first comprehensive pollen micromorphological investigation of lactiferous flora (Apocynaceae) of District Rawalpindi, Pakistan. The pollen morphology of 10 species of the family Apocynaceae was observed and documented using light microscopy and scanning electron microscopy. Pollen was found subspheroidal in shape in most of the species, however peroblate shape was noted in Vinca major. Exine sculpturing patterns (psilate, rugulate, scabrate, and microreticulate) were observed. The result indicated that exine ornamentation of Apocynaceae taxa is systematically informative at generic and species levels. Most of the species have tricolporate type pollen but tetraporate pollen was also observed in Trachelospermum jasminoides and tetracolpate in V. major. Minimum equatorial diameter was noted in Carissa edulis (27.13 μm) and maximum in V. major (108.25 μm). Similarly, maximum exine thickness was found in Cascabela thevetia (9.5 μm). In the present findings, the pollen morphological data are compared with available other pollen studies to evaluate the taxonomic value of pollen traits in Apocynaceae taxa by using multiple microscopic techniques. Furthermore, molecular and phylogenetic studies were recommended to strengthen the systematics of Apocynaceae taxa.
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http://dx.doi.org/10.1002/jemt.23293DOI Listing
September 2019

netDx: interpretable patient classification using integrated patient similarity networks.

Mol Syst Biol 2019 03 14;15(3):e8497. Epub 2019 Mar 14.

The Donnelly Centre, University of Toronto, Toronto, ON, Canada

Patient classification has widespread biomedical and clinical applications, including diagnosis, prognosis, and treatment response prediction. A clinically useful prediction algorithm should be accurate, generalizable, be able to integrate diverse data types, and handle sparse data. A clinical predictor based on genomic data needs to be interpretable to drive hypothesis-driven research into new treatments. We describe netDx, a novel supervised patient classification framework based on patient similarity networks, which meets these criteria. In a cancer survival benchmark dataset integrating up to six data types in four cancer types, netDx significantly outperforms most other machine-learning approaches across most cancer types. Compared to traditional machine-learning-based patient classifiers, netDx results are more interpretable, visualizing the decision boundary in the context of patient similarity space. When patient similarity is defined by pathway-level gene expression, netDx identifies biological pathways important for outcome prediction, as demonstrated in breast cancer and asthma. netDx can serve as a patient classifier and as a tool for discovery of biological features characteristic of disease. We provide a free software implementation of netDx with automation workflows.
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http://dx.doi.org/10.15252/msb.20188497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6423721PMC
March 2019

Reviving Phage Therapy for the Treatment of Cholera.

J Infect Dis 2019 02;219(5):786-794

School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, Leicestershire.

Cholera remains a major risk in developing countries, particularly after natural or man-made disasters. Vibrio cholerae El Tor is the most important cause of these outbreaks, and is becoming increasingly resistant to antibiotics, so alternative therapies are urgently needed. In this study, a single bacteriophage, Phi_1, was used to control cholera prophylactically and therapeutically in an infant rabbit model. In both cases, phage-treated animals showed no clinical signs of disease, compared with 69% of untreated control animals. Bacterial counts in the intestines of phage-treated animals were reduced by up to 4 log10 colony-forming units/g. There was evidence of phage multiplication only in animals that received a V. cholerae challenge. No phage-resistant bacterial mutants were isolated from the animals, despite extensive searching. This is the first evidence that a single phage could be effective in the treatment of cholera, without detectable levels of resistance. Clinical trials in human patients should be considered.
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http://dx.doi.org/10.1093/infdis/jiy563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610978PMC
February 2019

A global assessment of cancer genomic alterations in epigenetic mechanisms.

Epigenetics Chromatin 2014 4;7(1):29. Epub 2014 Dec 4.

Structural Genomics Consortium, University of Toronto, MaRS Centre, South Tower, 101 College Street, Toronto, M5G 1L7 ON Canada ; Department of Pharmacology and Toxicology, University of Toronto, 1 King's College Circle, Toronto, M5S 1A8 ON Canada.

Background: The notion that epigenetic mechanisms may be central to cancer initiation and progression is supported by recent next-generation sequencing efforts revealing that genes involved in chromatin-mediated signaling are recurrently mutated in cancer patients.

Results: Here, we analyze mutational and transcriptional profiles from TCGA and the ICGC across a collection 441 chromatin factors and histones. Chromatin factors essential for rapid replication are frequently overexpressed, and those that maintain genome stability frequently mutated. We identify novel mutation hotspots such as K36M in histone H3.1, and uncover a general trend in which transcriptional profiles and somatic mutations in tumor samples favor increased transcriptionally repressive histone methylation, and defective chromatin remodeling.

Conclusions: This unbiased approach confirms previously published data, uncovers novel cancer-associated aberrations targeting epigenetic mechanisms, and justifies continued monitoring of chromatin-related alterations as a class, as more cancer types and distinct cancer stages are represented in cancer genomics data repositories.
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http://dx.doi.org/10.1186/1756-8935-7-29DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4258301PMC
December 2014

ChromoHub V2: cancer genomics.

Bioinformatics 2014 Feb 6;30(4):590-2. Epub 2013 Dec 6.

Structural Genomics Consortium, and Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON M5G 1L7, Canada.

Summary: Cancer genomics data produced by next-generation sequencing support the notion that epigenetic mechanisms play a central role in cancer. We have previously developed Chromohub, an open access online interface where users can map chemical, structural and biological data from public repositories on phylogenetic trees of protein families involved in chromatin mediated-signaling. Here, we describe a cancer genomics interface that was recently added to Chromohub; the frequency of mutation, amplification and change in expression of chromatin factors across large cohorts of cancer patients is regularly extracted from The Cancer Genome Atlas and the International Cancer Genome Consortium and can now be mapped on phylogenetic trees of epigenetic protein families. Explorators of chromatin signaling can now easily navigate the cancer genomics landscape of writers, readers and erasers of histone marks, chromatin remodeling complexes, histones and their chaperones.

Availability And Implementation: http://www.thesgc.org/chromohub/.
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http://dx.doi.org/10.1093/bioinformatics/btt710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3928521PMC
February 2014

Fear of death.

Oncologist 2005 Feb;10(2):160-9

Department of Medicine, Division of Hematology-Oncology, Palliative Care Service, Massachusetts General Hospital, Boston, Massachusetts, USA.

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH) founded The Kenneth B. Schwartz Center at MGH. The Schwartz Center is a nonprofit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient and support to caregivers and encourages the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. For many, cancer is synonymous with death. Fearing death is a rational response. For too long, medicine has ignored this primeval fear. Increasingly, clinicians recognize and address end-of-life issues, facing patients' and our own emotional vulnerabilities in order to connect and explore problems and fears. Listening and learning from the patient guides us as we acknowledge much of the mystery that still surrounds the dying process. Rarely is there a simple or right answer. An empathetic response to suffering patients is the best support. Support is vital in fostering the adjustment of patients. A silent presence may prove more helpful than well-meant counsel for many patients. Through an examination of eight caregiver narratives of their patients' experiences, the role of the health care provider in the dying process, particularly in regard to challenging fear, is reviewed.
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http://dx.doi.org/10.1634/theoncologist.10-2-160DOI Listing
February 2005
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