Qaisar Mansoor

Angiotensin-converting enzyme (ACE) gene II genotype protects against the development of diabetic peripheral neuropathy in type 2 diabetes mellitus

Background:  Diabetic peripheral neuropathy (DPN) is one of the complications of type 2 diabetes mellitus (T2DM) that decreases the quality of life of T2DM patients. Very few studies have found an association between the development and progression of DPN in T2DM and angiotensin‐converting enzyme (ACE) gene insertion/deletion (I/D) polymorphisms.

Genetic variants of ACE (Insertion/Deletion) and AGT (M268T) genes in patients with diabetes and nephropathy

Introduction: Diabetes mellitus (DM) has been a growing epidemic worldwide and poses a major socio-economic challenge. The leading cause of DM death is nephropathy due to end-stage renal disease (ESRD). This study aims to identify the possible association of I/D variants of the ACE gene and M268T (rs699) of the AGT gene of renin–angiotensin–aldosterone system (RAAS). Materials and methods: Study subjects include 115 patients with DM, 110 with diabetic nephropathy (DN) and 110 controls. Fasting blood samples were collected for biochemical analyses and PCR amplification of specific regions of the ACE and AGT genes using primers. Results: The distribution of ACE (I/D) II 28.8%, ID 35.6% and DD 35.6% while in DN II 24.5%, ID 41% and DD 34.5%. The AGT (M268T) genotypes were distributed in DM as TT 30.4%, MT 66.9% and MM 2.6% while in DN subjects TT 56.4%, MT 42.7% and MM 0.9%. Conclusion: Significant differences were observed in the DD genotype and D allele of the ACE gene and the TT genotype and T allele of AGT genes between diabetic patients with and without nephropathy. The study may conclude that the D allele polymorphism in the ACE gene and the T allele polymorphism in AGT gene may be considered as genetic risk factors for the development of nephropathy in diabetes.

Graphene nanoplatelets induced tailoring in photocatalytic activity and antibacterial characteristics of MgO/graphene nanoplatelets nanocomposites

The synthesis, physical, photocatalytic, and antibacterial properties of MgO and graphene nanoplatelets (GNPs) nanocomposites are reported. The crystallinity, phase, morphology, chemical bonding, and vibrational modes of prepared nanomaterials are studied. The conductive nature of GNPs is tailored via photocatalysis and enhanced antibacterial activity. It is interestingly observed that the MgO/GNPs nanocomposites with optimized GNPs content show a significant photocatalytic activity (97.23% degradation) as compared to bare MgO (43%) which makes it the potential photocatalyst for purification of industrial waste water. In addition, the effect of increased amount of GNPs on antibacterial performance of nanocomposites against pathogenic micro-organisms is researched, suggesting them toxic. MgO/GNPs 25% nanocomposite may have potential applications in waste water treatment and nanomedicine due its multifunctionality.

Graphene/SiO2 nanocomposites: The enhancement of photocatalytic and biomedical activity of SiO2 nanoparticles by graphene

The exceptional conducting nature of graphene makes it a viable candidate for enhancing the effectiveness of photocatalytic and biomedical nanomaterials. Herein, the immobilization of monodispersed silicon dioxide (SiO2) nanoparticles on multiple graphene layers is demonstrated for intercalation of graphene nanoplatelets. Interestingly, the addition of graphene nanoplatelets with SiO2 nanoparticles enhances the photocatalytic efficiency from 46% to 99%. For biomedical applications, it is found that 75% of Gram positive and 50% of Gram negative bacteria have been killed; hence, bacterial proliferation is significantly restricted. Further, the cytotoxicity study reveals that the synthesised nanocomposites are non-toxic for both normal (human corneal epithelial cells) and cancerous (MCF-7, HEp-2) cell lines which signify their potential as carriers for drug delivery. The prepared nanocomposites with a controlled amount of carbon in the form of graphene can be employed for photocatalysis based waste water rem...

Structural, morphological, Raman, optical, magnetic, and antibacterial characteristics of CeO2 nanostructures

In this study, CeO2 nanostructures were synthesized by a soft chemical method. A hydrothermal treatment was observed to lead to an interesting morphological transformation of the nanoparticles into homogeneous microspheres composed of nanosheets with an average thickness of 40 nm. Structural analysis revealed the formation of a single-phase cubic fluorite structure of CeO2 for both samples. A Raman spectroscopic study confirmed the XRD results and furthermore indicated the presence of a large number of oxygen vacancies in the nanosheets. These oxygen vacancies led to room-temperature ferromagnetism (RTFM) of the CeO2 nanosheets with enhanced magnetic characteristics. Amazingly, the nanosheets exhibited substantially greater antibacterial activity than the nanoparticles. This greater antibacterial activity was attributed to greater exposure of high-surface-energy polar surfaces and to the presence of oxygen vacancies.

Epigenetic mechanisms in cancer: push and pull between kneaded erasers and fate writers

Research concerning the epigenome over the years has systematically and sequentially shown substantial development and we have moved from global inhibition of modifications of the epigenome toward identification and targeted therapy against tumor-specific epigenetic mechanisms. In accordance with this approach, several drugs with epigenetically modulating activity have received considerable attention and appreciation, and recently emerging scientific evidence is uncovering details of their mode of action. High-throughput technologies have considerably improved our existing understanding of tumor suppressors, oncogenes, and signaling pathways that are key drivers of cancer. In this review, we summarize the general epigenetic mechanisms in cancer, including: the post-translational modification of DNA methyltransferase and its mediated inactivation of Ras association domain family 1 isoform A, Sonic hedgehog signaling, Wnt signaling, Notch signaling, transforming growth factor signaling, and natural products with epigenetic modification ability. Moreover, we introduce the importance of nanomedicine for delivery of natural products with modulating ability to epigenetic machinery in cancer cells. Such in-depth and comprehensive knowledge regarding epigenetic dysregulation will be helpful in the upcoming era of molecular genomic pathology for both detection and treatment of cancer. Epigenetic information will also be helpful when nanotherapy is used for epigenetic modification.

Facile synthesis of Zn doped CuO hierarchical nanostructures: Structural, optical and antibacterial properties

ZnxCu1−xO (where x= 0, 0.01, 0.03, 0.05, 0.07 and 0.1 mol%) hierarchical nanostructures have been prepared via soft chemical route. X-ray diffraction(XRD) results of the synthesized samples reveal the monoclinic structure of CuO without any impurity related phases. The micro-structural parameters such as crystallite size and microstrain have been strongly influenced by Zndoping.Scanning electron microscope(SEM) analyses depict the formation of hierarchical nanostructures having average particle size in the range of 26-43 nm. The surface area of CuO nanostructures has been reduced systematically with the increase in Zn content which is linked with the variations in particle size. An obvious decrease in the optical band gap energy of the synthesized CuO hierarchical nanostructures has been observed with Zndoping which is assigned to the formation of shallow levels in the band gap of CuO and combined transition from oxygen 2p states to d sates of Cu and Zn ions. The bactericidal potency of the CuO hierarchical nanostructures have been found to be enhanced remarkably with Zndoping.

Distribution of ACE I/D Polymorphism in the Patients of Diabetes and Nephropathy in Pakistan

Abstract Diabetes mellitus (DM) is a chronic metabolic syndrome that can lead to serious vascular complications. Diabetic nephropathy (DN) has been established as the leading cause of deaths in diabetes due to ESRF. The association between ACE gene polymorphism and onset of DN has not been explored in Pakistani diabetic patients. This study investigates the possible association of insertion (I) and deletion (D) polymorphism of ACE gene in patients of diabetes with and without nephropathy. Total 296 diabetic patients without nephropathy (DM), 168 with nephropathy (DN) and 150 normal healthy individuals were selected followed by informed consent. Fasting blood samples were collected for biochemical analyses and PCR amplification was done to genotype the DNA, for ACE I/D using specific primers. In DM group, the ACE genotypes were distributed as II, 41.55%, DD, 8.45% and ID, 50%. In DN patients, II, 10.71%, DD, 30.95% and ID, 58.33%. The II and DD genotype, and I and D allele distributions were significantly different in DN vs. DM patients (χ2 = 9.879, P=0.00167). The I/D genotypes and allele distributions were significantly different in DM patients vs. controls (χ2 = 22.252, P=0.00000239). The DN patients have significantly higher prevalence of D allele and DD genotype in comparison to DM. Results indicated a clear association of D allele polymorphism in ACE gene with nephropathy in patients of diabetes. It is suggested that D allele polymorphism may be considered as genetic risk factor and disease marker for nephropathy in diabetes.

MicroRNA Regulation of Telomerase Reverse Transcriptase (TERT): Micro Machines Pull Strings of Papier-Mâché Puppets

Substantial fraction of high-quality information is continuously being added into the existing pool of knowledge related to the biology of telomeres. Based on the insights gleaned from decades of research, it is clear that chromosomal stability needs a highly controlled and dynamic balance of DNA gain and loss in each terminal tract of telomeric repeats. Telomeres are formed by tandem repeats of TTAGGG sequences, which are gradually lost with each round of division of the cells. Targeted inhibition of telomerase to effectively induce apoptosis in cancer cells has attracted tremendous attention and overwhelmingly increasingly list of telomerase inhibitors truthfully advocates pharmacological significance of telomerase. Telomerase reverse transcriptase (TERT) is a multi-talented and catalytically active component of the telomerase-associated protein machinery. Different proteins of telomerase-associated machinery work in a synchronized and orchestrated manner to ensure proper maintenance of telomeric length of chromosomes. Rapidly emerging scientific findings about regulation of TERT by microRNAs has revolutionized our understanding related to the biology of telomeres and telomerase. In this review, we have comprehensively discussed how different miRNAs regulate TERT in different cancers. Use of miRNA-based therapeutics against TERT in different cancers needs detailed research in preclinical models for effective translation of laboratory findings to clinically effective therapeutics.

Homozygous frame shift mutation in ECM1 gene in two siblings with lipoid proteinosis

BACKGROUND The extracellular matrix protein 1 (ECM1) is a glycoprotein, expressed in skin and other tissues. Loss-of-function mutation in ECM1 causes a rare autosomal recessive disorder called lipoid proteinosis. Lipoid proteinosis is presented by varying degrees of skin scars, beaded papules along the eyelid margins, variable signs of hoarseness of voice and respiratory disorders. More than 250 cases of this disorder have been described in the literature, but occurrence of lipoid proteinosis in siblings is very rare. This study was designed to investigate the possible mutation causing lipoid proteinosis in a Pakistani family and to elaborate the scope of possible genetic changes, causing the genodermatosis in Pakistan. MAIN OBSERVATIONS In this study, two siblings (12 and 9-years sisters) were presented with scaly itchy lesions on whole body, hoarse voice and macroglossia. Their deceased father had similar clinical manifestations but mother and younger brother were unaffected. Blood samples from clinically affected and unaffected family members were collected with informed consent. The coding region of ECM1 gene containing 10 exons were amplified and sequenced. Both the affected siblings were shown to have homozygous frame shift mutation by deletion of the nucleotide T at 507, codon 169, exon 6. This resulted in a frame shift from codon 169 and appearance of a premature stop codon at 177, causing formation of a mutated protein (176 amino acids) instead of normal ECM1 protein (540 amino acids). CONCLUSION A case of homozygous 62-bp insertion in ECM1 gene causing lipoid proteinosis has been reported in another Pakistani family. The current study presents a homozygous frame shift mutation supporting an unusual function of ECM1 protein and broadens the spectrum of disease-linked mutations in this rare case of genodermatosis in this region.