Abstract: DNAzymes are still fairly recent man-made additions to the growing spectrum of synthetic molecules dramatically advancing the field of biomolecular science. These catalytically active nucleic acids have great potential in personalized medicine and as internal biosensors owing to their low immunogenicity, as well as in bio-computing, because of their robust nature and large data storage capacity. Their future potential is evident in areas that range from the development of biofuel cells to power implanted electronics, like pacemakers, where they could exceed capabilities and circumvent obstacles of existing protein-based catalysis.
Abstract: Drug users constitute a leading risk group associated with hepatitis C infection. In Pakistan, a large number of drug users retain hepatitis C virus (HCV). In the current study, occurrence of HCV was assessed in drug users of Swat, Pakistan. A total of 128 study subjects were enrolled and anti-HCV screening was carried out clinically. Seropositive samples were analyzed for the presence of viremia. Results indicated seroprevalence in 37.5% and active infection in 24.21% of the included drug users. HCV occurrence was found higher in males (93.54%) as compared to females (P= 0.7822). Age wise, age group 31-45 was found to have the highest (70.96%) HCV occurrence (P= 0.0022). Based on the type of drug users, injection drug users (IDUs) category was found highly affected (58.06%) with HCV infection (P= 0.1346). Awareness programs should be initiated and preventive strategies must be strictly implemented by government and administrative units to curtail the spread of HCV in drug users.
Abstract: We evaluated the impact of pre-operative biopsy types on interpreting frozen resection margins. We included 301 patients who underwent breast conserving therapy (BCT). During operation, we evaluated the frozen biopsy for resection margin status, and if a positive resection margin was found, re-excision was performed. The following factors were evaluated for correlation with initial frozen margins, re-excision rate, and final operation method: mean age, histologic grade, histology, lymphovascular invasion (LVI), estrogen receptor (ER) status and biopsy type: excisional, vacuum-assisted breast biopsy (VABB) or needle biopsy. A total of 265 patients (88.0%) had negative frozen resection margins, and 36 patients (12%) had positive frozen margins. For patients who underwent needle biopsy, 10.5% (23/219) had positive frozen margins compared with 14.0% (8/57) for excisional biopsy and 20.0% (5/25) for VABB. HG (
Abstract: Dengue is a rapidlyemerging vector-borne viral disease of humans transmitted by mosquitoes of the genus Aedes. Dengue viruses are divided into five antigenically distinct serotypes, DENV-1 to -5. The disease is endemic in over 130 countries, placing almost half of the world’s population at risk. Clinical disease presents as either a mild self-limiting infection or severe complications. Recovery from primary infection by one serotype provides life-long immunity against reinfection by that particular serotype whereas with subsequent infections by other serotypes the risk of developing severe dengue is increased. In contrast to previous understanding that immature dengue virus particles are non-infective it was shown recently that they become highly infectious in the presence of antibodies raised to the pre-membrane protein, prM, of the virion. While no licensed dengue treatment is currently available, several prototype vaccines are being evaluated in clinical studies. Most of these vaccine candidates contain native dengue prM, the presence of which can have the opposite effect to that desired by making immature dengue particles infective. This occurs through a mechanism of prM-specific antibody-dependent enhancement of infection. Hence, in order to safeguard patient welfare when designing future dengue vaccine constructs, provision of another anti-idiotype antibody that binds to and blocks the pathogen-activating region of anti-prM antibody, thus rendering it inactive, should be considered as an adjunct therapy. This strategy would have a potentially significant benefit by reducing cases of secondary infection, which is the major cause of dengue morbidity and mortality.
Epigenetic changes such as promoter specific DNA hypermethylation and histone deacetylation cause tumor suppressor genes to become transcriptionally silent and contribute to malignant transformation. DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibitors can reactivate silenced genes, block cell cycle and induce cell apoptosis which provides rationale for their use in cancer treatment. DNMT and HDAC inhibitors have therefore emerged as an effective strategy against cancer. Epigenetic modifications have a key role in the pathophysiology of many cancers such as myelodysplastic syndrome (MDS), lymphoma, and leukemia and the use of drugs targeting epigenetic changes has become a topic of intense interest in cancer research. The role of transcriptional repression through epigenetic modulation in carcinogenesis has clinically validated the use of inhibitors of DNMT and HDAC. Epigenetic changes can be pharmacologically reversed resulting in gene re-expression.
DNMT inhibitors 5-azacytocine (azacytidine/ AZA) and 2’-deoxy-5-azacytidine (decitabine/ DAC) are cytosine analogues and are currently the most advanced drugs for epigenetic cancer therapy. AZA and DAC have been approved by FDA for the treatment of MDS. HDAC inhibitors-Vorinostat (SAHA), Romidepsin (depsipeptide FK 219), Belinostat (PXD 101) and LAQ 824/LBH 589 have demonstrated therapeutic benefit in Cutaneous T-cell Lymphoma (CTCL). Both romidepsin and vorinostat are approved by FDA for the treatment of CTCL. In this review, we describe the current status of DNMT inhibitors and HDAC inhibitors usage in cancer treatment and discuss the challenges involved in successful establishment of these novel drugs either alone or in combination therapy for the treatment of various cancers.
We evaluated the clinical features, disease severity, laboratory findings and outcome of serologically confirmed cases of Dengue fever in Patients during the recent outbreak in two districts (Buner & Shangla) in 2013, Khyber Pkhtunkhwa, Pakistan. We encountered 320 cases of Dengue fever during 5 months period (July to November, 2013). The dengue infection rate in females (180: 56%.2) was higher as compared to males (140: 43.8%). The dengue infections were more frequently seen in the post-monsoon season than in the monsoon period. The death ratio in the overall weighted prevalence was 0%. All the patients suffered from fever but no specific pattern could be identified, degree was variable ranging from low to high grade. Abdominal pain was the next most common symptom followed by vomiting and diarrhea. Only (45%) patients complained of body aches and pains, (30%) patients had hemorrhagic manifestations in the form of gum bleed, and (05%) patients had melena while (15%) patient’s complained of skin rashes. The most common clinical sign was the Enlarged liver that was present in (75%) patients. There is critical need for molecular and entomological surveillance of dengue among the dengue epidemics-prone areas to eliminate the disease.
Abstract: The root of the Plumbago species were examined phytochemically and their potentials are well studied. The spectrometric and chromatographic screening methods could provide the needed preliminary observations to select crude plant extracts with potentially useful properties for further chemical and pharmacological investigations. Objective: The present study was aimed to reveal the inter-specific similarity and variation among the selected Plumbago species viz., Plumbago zeylanica Linn, Plumbago auriculata Lam, Plumbago rosea Linn. using UV-VIS and FTIR profiles.Methods: To know the various phytoconstituents and functional groups and similarity and variation present in the Plumbago species aerial parts, the UV-VIS spectroscopic analysis and FTIR analysis was carriedout using Shimazdu and Perkin Elmer spectrophotometer respectively. Result: The UV-VIS spectroscopic analysis revealed the presence of various functional compounds and groups and similarity and variation in the aerial parts of studied Plumbago species. The FTIR analysis identified various functional groups like alcohols, phenols, alkanes, alkynes, alkyl halides, aldehydes, carboxylic acids, aromatics, nitro compounds and amines presence in the crude powder of Plumbago species aerial parts. Conclusion: The results of the present study paved a way to predict and compare the phytoconstituents presence in all the three selected Plumbago species which can be used for further characterization. In addition it provides the pharmacognostical marker to distinguish the medicinally important Plumbago species using relatively simple, cost-effective spectroscopic profile.
Abstract: With the advent of whole genome screens, promoter-proximal pausing of RNA polymerase II (RNAPII) has been shown to play a much more significant role in eukaryotic systems than previously thought. This type of transcription inhibition is dependent on the binding of the Negative Elongation Factor (NELF) complex which is composed of four sub-units, presenting unique domains and consequently fulfilling different functions. Numerous questions still surround the mechanism by which NELF is recruited, stabilised and dissociated from the RNAPII complex. Furthermore, not much is known about which other transcription stages the NELF complex is involved in and through which sub-units it carries out such functions. Based on the current knowledge of the role of NELF in transcription pausing, it is hypothesised that different interaction partners are required to direct context-specific functions of the NELF complex. This review covers some of the known roles and contexts in which NELF acts in an attempt to identify key questions for future NELF-dependent transcriptional research.
Abstract: Cancer cells generally exhibit re-programming of their pathways. The expression of certain genes that directly control the rate of key metabolic pathways are drastically altered. Indeed, cancer cells show high rates of aerobic glycolysis (known as the Warburg effect) and an increase in pentose phosphate pathway activity due to the up-regulation of glucose-6-phosphate dehydrogenase (G6PD) in comparison to their non-transformed counterparts. These alterations are usually considered as an adaptation of tumor cells; however, they also contribute to the progression of tumor cells towards more aggressive phenotypes. Here we will discuss the critical role of G6PD in neoplastic transformation focusing on its potential utility as diagnostic marker as well as a novel potential therapeutic target.
Abstract: Dengue is a mosquito-borne viral disease of humans that is a major public health concern in tropical and sub-tropical regions of the world. The increasing mortality and morbidity rates caused by infection in recent years are attributable partly to a lack of availability of effective antiviral therapies and vaccines. In a concerted attempt to arrest this global expansion, several dengue vaccine candidates have progressed from pre-clinical testing into clinical trials. However, the advancement of vaccine development has manifest challenges to be overcome. A principal tenet underpinning dengue vaccine design is balanced immunity to all five recognised virus serotypes, but difficulties in achieving optimal attenuation of each virus and interference between individual attenuated viruses are significant hurdles to successful implementation. Currently, the most advanced vaccine candidate, the recombinant, live-attenuated ChimeriVax-DEN1-4 preparation developed by Sanofi Pasteur, is likely to achieve licensure at the completion of phase III trials and undergo population safety surveillance. Subunit and DNA vaccines are also in various stages of clinical evaluation. The intrinsic rationale is to produce a safe, efficacious and cost-effective vaccine. While this remains an achievable goal, progress is limited by an incomplete understanding of dengue viral pathogenesis, together with a lack of suitable animal models for fundamental pre-clinical development. This editorial highlights current approaches and future directions for vaccine strategies to combat the global expansion of this infectious disease.