Muhammad Qasim | Konkuk University (original) (raw)

Papers by Muhammad Qasim

Nanomaterials

This study demonstrates a scalable fabrication process for producing biodegradable, highly stretc... more This study demonstrates a scalable fabrication process for producing biodegradable, highly stretchable and wearable melt spun thermoplastic polypropylene (PP), poly(lactic) acid (PLA), and composite (PP:PLA = 50:50) conductive yarns through a dip coating process. Polydopamine (PDA) treated and poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) coated conductive PP, PLA, and PP/PLA yarns generated electric conductivity of 0.75 S/cm, 0.36 S/cm and 0.67 S/cm respectively. Fourier Transform Infrared Spectroscopy (FTIR) confirmed the interactions among the functional groups of PP, PLA, PP/PLA, PDA, and PEDOT:PSS. The surface morphology of thermoplastic yarns was characterized by optical microscope and Scanning Electron Microscope (SEM). The mechanical properties of yarns were also assessed, which include tensile strength (TS), Young’s modulus and elongation at break (%). These highly stretchable and flexible conductive PP, PLA, and PP/PLA yarns showed elasticity of 667%,...

Conventional tissue engineering, cell therapy, and current medical approaches were shown to be su... more Conventional tissue engineering, cell therapy, and current medical approaches were
shown to be successful in reducing mortality rate and complications caused by cardiovascular
diseases (CVDs). But still they have many limitations to fully manage CVDs due to complex
composition of native myocardium and microvascularization. Fabrication of fully functional
construct to replace infarcted area or regeneration of progenitor cells is important to address
CVDs burden. Three-dimensional (3D) printed scaffolds and 3D bioprinting technique have
potential to develop fully functional heart construct that can integrate with native tissues rapidly.
In this review, we presented an overview of 3D printed approaches for cardiac tissue engineering,
and advances in 3D bioprinting of cardiac construct and models. We also discussed role
of immune modulation to promote tissue regeneration.

Collagen gene family, comprising 30% of the total protein mass in mammals, is the major part of e... more Collagen gene family, comprising 30% of the total protein mass in mammals, is the major part of extracellular matrix. To
understand the complexity of collagen gene family, detailed sequence, phylogenetic and synteny analyses of 44 collagen genes
were performed. According to sequence analysis results, Fibril-associated collagen with interrupted triple helices (FACITs)
were identified as the most recently evolved vertebrate-specific collagens while Fibril-forming collagens and Collagen VI,
VII, XXVI, and XXVIII were the most ancient collagens, originating at the time of choanoflagellates. Network-forming
collagens were entirely conserved from arthopods to homo sapiens, except one gene loss event. Of note, bird specific gene
dispensability of COL1A1, COL3A1, COL5A3 and COL11A2 genes was observed in Fibril-forming collagens. According to
phylogenetic analysis, gene duplications in collagen family occurred at variable time points during invertebrate to vertebrate
evolution. However, majority of gene duplications in FACITs and network-forming collagens occurred at fish time point,
suggesting large scale duplications at the root of vertebrate lineage. Lastly, synteny analysis identified 12 conserved blocks
containing 27 collagen genes in vertebrate species. Interestingly, dysregulation of seven conserved blocks including block1
(COL11A1), block3 (COL3A1, COL5A2), block5 (COL6A5, COL6A6), block7 (COL1A2), block9 (COL4A1, COL4A2),
block11 (COL6A1, COL6A2, COL18A1) and block12 (COL4A5, COL4A6) were also reported in different diseases including
cancer. The current study revealed many critical insights into sequence, structural and functional diversity of collagen
gene family. In future, by using this information we may be able to establish the clinical and pathological relevance of these
conserved collagen blocks in different diseases.

The rapid development of nanotechnology has led to the use of silver nanoparticles (AgNPs) in bio... more The rapid development of nanotechnology has led to the use of silver nanoparticles (AgNPs)
in biomedical applications, including antibacterial, antiviral, anti-inflammatory, and anticancer
therapies. The molecular mechanism of AgNPs-induced cytotoxicity has not been studied thoroughly
using a combination of cellular assays and RNA sequencing (RNA-Seq) analysis. In this study,
we prepared AgNPs using myricetin, an anti-oxidant polyphenol, and studied their effects
on NIH3T3 mouse embryonic fibroblasts as an in vitro model system to explore the potential
biomedical applications of AgNPs. AgNPs induced loss of cell viability and cell proliferation
in a dose-dependent manner, as evident by increased leakage of lactate dehydrogenase (LDH)
from cells. Reactive oxygen species (ROS) were a potential source of cytotoxicity. AgNPs also
incrementally increased oxidative stress and the level of malondialdehyde, depleted glutathione
and superoxide dismutase, reduced mitochondrial membrane potential and adenosine triphosphate
(ATP), and caused DNA damage by increasing the level of 8-hydroxy-20-deoxyguanosine and the
expressions of the p53 and p21 genes in NIH3T3 cells. Thus, activation of oxidative stress may be
crucial for NIH3T3 cytotoxicity. Interestingly, gene ontology (GO) term analysis revealed alterations
in epigenetics-related biological processes including nucleosome assembly and DNA methylation
due to AgNPs exposure. This study is the first demonstration that AgNPs can alter bulk histone gene
expression. Therefore, our genome-scale study suggests that the apoptosis observed in NIH3T3 cells
treated with AgNPs is mediated by the repression of genes required for cell survival and the aberrant
enhancement of nucleosome assembly components to induce apoptosis.

Objectives: : We aimed to determine the characteristics, treatment outcomes and risk factors for ... more Objectives: : We aimed to determine the characteristics, treatment outcomes and risk factors for poor treatment outcomes among multidrug-resistant (MDR) tuberculosis (TB) patients in Khyber Pak-htunkhwa province, Pakistan. Methods: A retrospective cohort study including all patients with MDR-TB who sought care at the MDR-TB unit in Peshawar was conducted between January 2012 and April 2014. Patients were followed until an outcome of TB treatment was recorded as successful (cured or completed) or unsuccessful. Binary logistic regression was used to identify predictors of poor outcome, i.e. unsuccessful treatment outcomes. Results: Overall, 535 patients were included. The proportion of female subjects was relatively higher (n ¼ 300, 56.1%) than male subjects. The mean (standard deviation) age of patients was 30.37 (14.09) years. Of 535 patients for whom treatment outcomes were available, 402 (75.1%) were cured, 4 (0.7%) completed therapy, 34 (6.4%) had disease that failed to respond to therapy, 93 (17.4%) died and two (0.4%) defaulted; in total, 129 (24.1%) had an unsuccessful outcome. We found three significant predictors of unsuccessful treatment during multivariate logistic regression: being married (odds ratio (OR) ¼ 2.17, 95% confidence interval (CI) 1.01, 4.66), resistance to second-line drugs (OR ¼ 2.61, 95% CI 1.61, 4.21) and presence of extensively drug-resistant TB (OR ¼ 7.82, 95% CI 2.90, 21.07). Conclusions: Approximately 75% of the treatment success rate set by the Global Plan to Stop TB was achieved. Resistance to second-line drugs and presence of extensively drug-resistant TB are the main risk factors for poor treatment outcomes. A. Javaid, Clin Microbiol Infect 2017;▪:1

Cancer represents a group of heterogeneous diseases characterized by uncontrolled growth and spre... more Cancer represents a group of heterogeneous diseases characterized by uncontrolled growth and spread of abnormal cells, ultimately leading to death. Nanomedicine plays a significant role in the development of nanodrugs, nanodevices, drug delivery systems and nanocarriers. Some of the major issues in the treatment of cancer are multidrug resistance (MDR), narrow therapeutic window and undesired side effects of available anticancer drugs and the limitations of anticancer drugs. Several nanosystems being utilized for detection, diagnosis and treatment such as theranostic carriers, liposomes, carbon nanotubes, quantum dots, polymeric micelles, dendrimers and metallic nanoparticles. However, nonbiodegradable nanoparticles causes high tissue accumulation and leads to toxicity. MDR is considered a major impediment to cancer treatment due to metastatic tumors that develop resistance to chemotherapy. MDR contributes to the failure of chemotherapies in various cancers, including breast, ovarian, lung, gastrointestinal and hematological malignancies. Moreover, the therapeutic efficiency of anticancer drugs or nanoparticles (NPs) used alone is less than that of the combination of NPs and anticancer drugs. Combination therapy has long been adopted as the standard first-line treatment of several malignancies to improve the clinical outcome. Combination therapy with anticancer drugs has been shown to generally induce synergistic drug actions and deter the onset of drug resistance. Therefore, this review is designed to report and analyze the recent progress made to address combination therapy using NPs and anticancer drugs. We first provide a comprehensive overview of the angiogenesis and of the different types of NPs currently used in treatments of cancer; those emphasized in this review are liposomes, polymeric NPs, polymeric micelles (PMs), dendrimers, carbon NPs, nanodiamond (ND), fullerenes, carbon nanotubes (CNTs), graphene oxide (GO), GO nanocomposites and metallic NPs used for combination therapy with various anticancer agents. Nanotechnology has provided the convenient tools for combination therapy. However, for clinical translation, we need continued improvements in the field of nanotechnology.

Silver nanoparticles (AgNPs) have gained attention for use in cancer therapy. In this study, AgNP... more Silver nanoparticles (AgNPs) have gained attention for use in cancer therapy. In this study, AgNPs were biosynthesized using naringenin. We investigated the anti-colon cancer activities of biogenic AgNPs through transcriptome analysis using RNA sequencing, and the mechanisms of AgNPs in regulating colon cancer cell growth. The synthesized AgNPs were characterized using UV–visible spectroscopy (UV–vis), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), and transmission electron microscopy (TEM). The AgNPs were spherical with sizes of 2–10 nm. Cytotoxicity assays indicated that the AgNPs in HCT116 colorectal cancer cells were very effective at low concentrations. The viability and proliferation of colon cancer cells treated with 5 µg/mL biogenic AgNPs were reduced by 50%. Increased lactate dehydrogenase leakage (LDH), reactive oxygen species (ROS) generation, malondialdehyde (MDA), and decreased dead-cell protease activity and ATP generation were observed. This impaired mitochondrial function and DNA damage led to cell death. The AgNPs upregulated and downregulated the most highly ranked biological processes of oxidation–reduction and cell-cycle regulation, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that AgNPs upregulated GADD45G in the p53 pathway. Thus, the AgNP tumor suppressive effects were mediated by cell apoptosis following DNA damage, as well as by mitochondrial dysfunction and cell-cycle arrest following aberrant regulation of p53 effector proteins. It is of interest to mention that, to the best of our knowledge, this study is the first report demonstrating cellular responses and molecular pathways analysis of AgNPs in HCT116 colorectal cancer cells.

Purpose The MammaPrint™ gene signature, currently used in clinical practice, provides prognostic ... more Purpose
The MammaPrint™ gene signature, currently used in clinical practice, provides prognostic information regarding the recurrence and potential metastasis in breast cancer patients. However, the prognostic information of the 70 genes included can only be estimated at the RNA expression level. In this study, we investigated whether copy number information of MammaPrint™ genes at the DNA level can be used as a prognostic tool for breast cancer, as copy number variations (CNVs) are major contributors to cancer progression.

Methods
We performed CNV profiling of MammaPrint™ genes in 59 breast cancer cell lines and 650 breast cancer patients, using publicly available data in The Cancer Genome Atlas (TCGA) database. Statistical analyses including Fisher exact test, chi-square test, and Kaplan-Meier survival analyses were performed.

Results
All MammaPrint™ genes showed recurrent CNVs, particularly in TCGA cohort. CNVs of 32 and 36 genes showed significant associations with progesterone receptor and estrogen rector, respectively. No genes showed a significant association with human epidermal growth factor receptor 2 status and lymph node status. In addition, only six genes were associated with tumor stages. RFC4, HRASLS, NMU, GPR126, SCUBE2, C20orf46, and EBF4 were associated with reduced survival and RASSF7 and ESM1 were associated with reduced disease-free survival.

Conclusion
Based on these findings, a concordance of CNV-based genomic rearrangement with expression profiling of these genes and their putative roles in disease tumorigenesis was established. The results suggested that the CNV profiles of the MammaPrint™ genes can be used to predict the prognosis of breast cancer patients. In addition, this approach may lead to the development of new cancer biomarkers at the DNA level.

Background: Human Papillomavirus (HPV) is well known pathogen that can cause benign and malignant... more Background: Human Papillomavirus (HPV) is well known pathogen that can cause benign and malignant tumors in humans, yet there is very little information regarding HPV types prevalent in Pakistan. Methods: A total of 92 cervical secretions were collected from suspected married female patients and used for DNA isolation using a novel isolation method. The samples were tested through Polymerase Chain Reaction (PCR) using already reported primers MY09/MY11, GP5/GP6, GP5+/GP6+, CP65/CP70, CP66/CP69 and SPF1/SPF2 and with those developed in this study including HRT1 and HRT2 primer sets for typing HPV types and HACTB primer set for human beta actin gene as internal positive control. Sequencing and phylogenetic analyses were performed for two isolates to determine circulating HPV types. Results: PCR with HRT1 and HRT2 indicated 2 (2.17 %) patients were positive for HPV type-16 while 1 (1.08 %) with HPV type 18. Sequencing and phylogenetic analysis of isolates confirmed HPV type-16 in genus alpha 9 which have 99 % homology with already reported HPV from Japan and Costa Rica. Conclusion: This is the first report of HPV type-16 genus alpha 9 in Pakistan and the reported assay and sequence data will serve as valuable tools in further epidemiological studies for HPV surveillance to improve public health, especially of females in Pakistan.

Background: Human Papillomavirus (HPV) is well known pathogen that can cause benign and malignant... more Background: Human Papillomavirus (HPV) is well known pathogen that can cause benign and malignant tumors in
humans, yet there is very little information regarding HPV types prevalent in Pakistan.
Methods: A total of 92 cervical secretions were collected from suspected married female patients and used for
DNA isolation using a novel isolation method. The samples were tested through Polymerase Chain Reaction (PCR)
using already reported primers MY09/MY11, GP5/GP6, GP5+/GP6+, CP65/CP70, CP66/CP69 and SPF1/SPF2 and with
those developed in this study including HRT1 and HRT2 primer sets for typing HPV types and HACTB primer set for
human beta actin gene as internal positive control. Sequencing and phylogenetic analyses were performed for two
isolates to determine circulating HPV types.
Results: PCR with HRT1 and HRT2 indicated 2 (2.17 %) patients were positive for HPV type- 16 while 1 (1.08 %) with
HPV type 18. Sequencing and phylogenetic analysis of isolates confirmed HPV type-16 in genus alpha 9 which have
99 % homology with already reported HPV from Japan and Costa Rica.
Conclusion: This is the first report of HPV type-16 genus alpha 9 in Pakistan and the reported assay and sequence
data will serve as valuable tools in further epidemiological studies for HPV surveillance to improve public health,
especially of females in Pakistan.
Keywords: Cervical carcinoma, Sexually Transmitted Diseases, Papillomavirus, Phylogenetic, Molecular epidemiology

Background: For physicians, nurses and laboratory technologists, blood plays a vital role in our ... more Background: For physicians, nurses and laboratory technologists, blood plays a vital role in our work.
And of the different blood components, glucose is one of those commonly measured. This may be because of its central role in metabolism and the dominance of diseases of glucose homeostasis. A problem seen in the accurate measurement of glucose is the loss of glucose because of glycolysis, during collection, transport and processing of the specimen.
Method: Specimens were taken from laboratory staff volunteers of PSMMC. Considered variables in
the study were type of specimen tubes used, temperature and time elapsed before the specimen was analyzed.
Result: Results obtained showed the difference in glucose values obtained. Serum glucose measurement was higher than whole blood glucose. Whole blood glucose remained stable in
refrigerated samples compared to those left at room emperature.
Conclusion: Fluoride oxalate effectively preserves glucose concentration in whole blood specimens. After the initial hour when the fluoride starts its inhibitory action, and with the specimens kept at refrigerated temperature, whole blood glucose remained stable. Temperature plays an important role in prolonging the enzymatic activity of the anticoagulant in the glycolytic pathway. Serum glucose levels can be even more reliable than whole blood specimens if the specimens are immediately spun and the serum separated from the red cells.

Candidiasis is a disease with skin rashes caused by the infectious fungus, Candida albicans, and ... more Candidiasis is a disease with skin rashes caused by the infectious fungus, Candida albicans, and can be potentially life-threatening, especially in immunodeficient patients. Amphotericin B (AmB) is a potent antifungal agent with a broad spectrum to treat Candidiasis, but its inherent low solubility and limited skin bioavailability have prevented its wider clinical use. In this study, we developed poly(N-isopropylacrylamide) (pNIPAM)-based nanogels as a versatile carrier to enhance AmB solubility and its efficacy. pNIPAM nanogels enhanced the solubility of AmB by 1.6-fold versus AmB alone. Accordingly, pNIPAM markedly improved the minimal fungicidal concentration (MFC) of AmB by 8 folds from 3.91 to 0.49 μg/mL. We also attached NH2 group to the pNIPAM nanogel to increase surface charges and investigated its effect on AmB antifungal activity. pNIPAM-NH2 has comparable activity in solid culture to pNIPAM, but 2-fold higher antifungal activity in liquid culture. Our pNIPAM and pNIPAM-NH2 nanogels may be useful
as drug delivery agents for the treatment of local antifungal infections by AmB in solid and liquid environments, such as on skin and in blood, with high efficacy and sustainability.

The emergence of co-infections and the evolution of drug-resistant pathogens limit the utility of... more The emergence of co-infections and the evolution of drug-resistant pathogens limit the utility of current therapies against infections, and developing countries in particular are facing a great challenge in combating infectious disease. Moreover, any failure to control the spread of infectious diseases would also represent a threat to developed countries. Recent developments in nanotechnology allow us to address this issue at two levels: diagnostics and treatment. Prevention of the
spread of infectious pathogens requires rapid and accurate identification of the infectious agents for proper treatment. Recently developed fluorescent nanoparticles are so sensitive that even a single nanoparticle is capable of emitting a strong enough signal to be captured, thus enabling early identification of infections. Proper and effective treatment not only saves the patient, but also prevents the spread of the pathogens. Specific nanoparticle vehicles developed to encapsulate therapeutic
agents and deliver them to a target site represent a promising strategy to boost immune responses for vaccination and boost the efficacy of drugs for treatment. Here, we describe a variety
of nanotechnologies for use in applications such as immune response modulation, drug delivery, diagnostics, and treatment, which are especially needed in developing countries.

Books by Muhammad Qasim

Landau Network-Centro Volta is a non-profit and non-governmental organization operating as a glob... more Landau Network-Centro Volta is a non-profit and non-governmental organization operating as a global network of international experts supporting global science cooperation, security, and disarmament. Its programmes include research on scientific and technologic cooperation for global peace support, international security, and policy issues; worldwide disarmament of Weapons of Mass Destruction; and water and energy security. LNCV is also the seat of the Executive Secretariat of the International Working Group (IWG), an informal think-tank of experts and officials sharing their personal capacities. www.centrovolta.it/landau

Bone tissue engineering (BTE) using scaffolds with growth factors/ stem cells has received some s... more Bone tissue engineering (BTE) using scaffolds with growth factors/ stem cells has received some success in clinical trials. Recently, osteogenic scaffolds using absorbable or nonabsorbable biomaterials have being investigated to repair bone defects. Scaffolds can provide the osteoconduction effect as well as a media to trap cells and allow them to proliferate and differentiate. Bioreactors provide a means to

Nanomaterials

Background: Human Papillomavirus (HPV) is well known pathogen that can cause benign and malignant... more Background: Human Papillomavirus (HPV) is well known pathogen that can cause benign and malignant tumors in
humans, yet there is very little information regarding HPV types prevalent in Pakistan.
Methods: A total of 92 cervical secretions were collected from suspected married female patients and used for
DNA isolation using a novel isolation method. The samples were tested through Polymerase Chain Reaction (PCR)
using already reported primers MY09/MY11, GP5/GP6, GP5+/GP6+, CP65/CP70, CP66/CP69 and SPF1/SPF2 and with
those developed in this study including HRT1 and HRT2 primer sets for typing HPV types and HACTB primer set for
human beta actin gene as internal positive control. Sequencing and phylogenetic analyses were performed for two
isolates to determine circulating HPV types.
Results: PCR with HRT1 and HRT2 indicated 2 (2.17 %) patients were positive for HPV type- 16 while 1 (1.08 %) with
HPV type 18. Sequencing and phylogenetic analysis of isolates confirmed HPV type-16 in genus alpha 9 which have
99 % homology with already reported HPV from Japan and Costa Rica.
Conclusion: This is the first report of HPV type-16 genus alpha 9 in Pakistan and the reported assay and sequence
data will serve as valuable tools in further epidemiological studies for HPV surveillance to improve public health,
especially of females in Pakistan.
Keywords: Cervical carcinoma, Sexually Transmitted Diseases, Papillomavirus, Phylogenetic, Molecular epidemiology