Asma Gul

Isolation and molecular characterization of potentially pathogenic Acanthamoeba genotypes from diverse water resources including household drinking water from Khyber Pakhtunkhwa, Pakistan.

Acanthamoeba, an opportunistic protozoan pathogen, is ubiquitous in nature, and therefore plays a predatory role and helps control microbial communities in the ecosystem. These Acanthamoeba species are recognized as opportunistic human pathogens that may cause blinding keratitis and rare but fatal granulomatous encephalitis. To date, there is not a single report demonstrating Acanthamoeba isolation and identification from environmental sources in Pakistan, and that is the aim of this study. Acanthamoeba were identified by morphological characteristics of their cysts on non-nutrient agar plates seeded with Escherichia coli. Additionally, the polymerase chain reaction (PCR) was performed with genus-specific primers followed by direct sequencing of the PCR product for molecular identification. Furthermore, our PCR and sequencing results confirmed seven different pathogenic and nonpathogenic genotypes, including T2–T10, T4, T5, T7, T15, T16, and T17. To the best of our knowledge, we have identified and isolated Acanthamoeba sp., for the first time, from water resources of Khyber Pakhtunkhwa, Pakistan. There is an urgent need to address (1) the pathogenic potential of the identified genotypes and (2) explore other environmental sources from the country to examine the water quality and the current status of Acanthamoeba species in Pakistan, which may be a potential threat for public health across the country.

Quick survey for detection, identification and characterization of Acanthamoeba genotypes from some selected soil and water samples across Pakistan.

Acanthamoeba is an opportunistic protozoan pathogen which is widely distributed in nature and plays a pivotal role in ecosystem. Acanthamoeba species may cause blinding keratitis and fatal granulomatous encephalitis involving central nervous system. In this study, we investigated the presence of Acanthamoeba in soil and water resources of Pakistan. Here, Acanthamoeba were recovered on non-nutrient agar plate lawn with E. coli and identified by morphological characteristics of the cyst. Furthermore PCR was performed with genus-specific primers followed by direct sequencing of the PCR product for molecular identification. Overall our PCR and sequencing results confirmed pathogenic genotypes including T4 and T15 from both soil and water samples. This is our first report of Acanthamoeba isolation from both soil and water resources of Pakistan which may serve as a potential treat to human health across the country.

Updated strategies for the management, pathogenesis and molecular genetics of different forms of ichthyosis syndromes with prominent hair abnormalities

Syndromic ichthyosis is rare inherited disorders of cornification with varied disease complications. This disorder appears in seventeen subtypes associated with severe systematic manifestations along with medical, cosmetic and social problems. Syndromic ichthyosis with prominent hair abnormalities covers five major subtypes: Netherton syndrome, trichothiodystrophy, ichthyosis hypotrichosis syndrome, ichthyosis hypotrichosis sclerosing cholangitis and ichthyosis follicularis atrichia photophobia syndrome. These syndromes mostly prevail in high consanguinity states, with distinctive clinical features. The known pathogenic molecules involved in ichthyosis syndromes with prominent hair abnormalities include SPINK5, ERCC2, ERCC3, GTF2H5, MPLKIP, ST14, CLDN1 and MBTPS2. Despite underlying genetic origin, most of the health professionals solely rely on phenotypic expression of these disorders that leads to improper management of patients, hence making these patients living an orphanage life. After dermal features, association of other systems such as nervous system, skeletal system, hair abnormalities or liver problems may sometimes give clues for diagnosis but still leaving place for molecular screening for efficient diagnosis. In this paper, we have presented a review of ichthyosis syndrome with prominent hair abnormalities, with special emphasis on their updated genetic consequences and disease management. Additionally, we aim to update health professionals about the practice of molecular screening in ichthyosis syndromes for appropriate diagnosis and treatment.

Parkinson disease and use of stem cells for therapeutic approaches of Parkinson disease

Parkinsons disease involves a progressive loss of midbrain dopaminergic neurons in the substantia nigra, which causes motor symptoms such as dysfunctional bradykinesia, rigidity and tremor. Genetic mutations in Parkinson disease are infrequent and important because they represent potential therapeutic targets. Unfortunately, there is currently no treatment to stop the progression of the disease but only few improvements in symptoms are accessible by current treatments based on levodopa and dopaminergic therapy. Embryonic stem cells, Neural stem cells, Mesenchymal stem cell and induce pluripotent stem cell are a good source for dopaminergic neurons and can be used for cellular therapeutic approaches. Mesenchymal stem cells are thought to be among the easiest to harvest stem cells from individual sources. Embryonic stem cells and induced pluripotent stem cells have more advantages than other two. Embryonic stem cells remain highly proliferative after in vivo expansion. They can generate dopaminergic neurons and survive after transplantation. Along with it, induced pluripotent stem cells generate unlimited Parkinsons disease patient specific cells. They show some degree of functional recovery after transplantation. Hence, these two have potential to enhance the success rate of clinical trial in Parkinson disease and to tolerate adverse effects of transplantation. This review will provide an insight into therapeutic approaches of Parkinson disease by the help of different types of stem cells.

Role of epigenetic modifications in stem cell regulatory regions (Oct4, Sox2 and Nanog) and cancer

Epigenetics is the study which involves the modifications in gene expression without changes in DNA nucleotide sequences. Methylation of DNA and chromatin remodeling through histone proteins are believed to be the most crucial epigenetic changes. Micro RNAs (miRNAs) are also shown to mediate the epigenetic gene regulation in mammals.DNA methylation can activate or inhibit the differentiation of stem cells by affecting the regulatory regions of its developmental genes like Oct4, Nanog and Sox2. In cancer, mutations in genetic as well as epigenetic elements play a vital role. The epigenetic changes in cancer are distinct in that they can be therapeutically reversed more easily. Aberrant DNA methylation (hypomethylation, hypermethylation) has its role at the molecular level in a number of cancers. This review will provide an insight into the epigenetic mechanisms involved in the regulation of stem cell specific genes Oct4, Sox2 and Nanog, alongwith the epigenetic modifications leading to cancer. Keywords: Cancer epigenetics, DNA methylation, Epigenetics, Histone modifications, Oct4, Sox2 and Nanog, Stem cells.