Dengue Fever: A Continuous Threat

Dengue fever is a vector borne disease and is caused by DEN Virus. This virus has four different serotypes. The vectors are two mosquitoes known as Aedesaegypti (the yellow fever mosquito) and Aedesalbopictus(the Asian tiger mosquito).  First case of dengue fever was reported back in 1994 in Karachi. A complete outbreak of this epidemic shook the whole nation in 2012. Uptill now, Lahore a city full of culture, witnessed about 16,580 confirmed cases and 257 deaths. About 5000 confirmed cases with 60 deaths were reported from the rest of the provinces. Under guidelines of WHO, Government has made efforts to combat this epidemic. Although the overall efforts have minimized the outbreak on controllable levels but dengue fever is a continuous threat. Since no permanent cure is available, the transmission of DEN virus is controlled indirectly. So the prime focus is to control mosquito population and decrease the possible hot spots i.e. Mosquito breeding sites in human habitations. Every year, the country witnesses monsoon season which brings vast areas full of clear standing waters providing breeding sites for mosquitoes which ultimately leads to increased number of patients suffering from dengue fever. Efforts have been made to fight against dengue including formation of dengue wards in hospitals, vector surveillance, community education, reactive vector control etc. A study has shown prevalence of four mosquito genera in Pakistan including Aedes, Culex, Armigeresand Anopheles. All of the above mentioned genera are associated with disease transmissions as they are the vectors of different viruses and parasites. It is the need of hour to do a collaborative effort stressing the community mobilization and management in war against dengue.

Identification and Modeling of Regulatory Networks and Development of Anti-Cancer Drug-Conjugated Nanoparticles for Breast Cancer Therapy

Breast cancer is the second leading cause of cancer-related mortalities among females worldwide. It is genetically heterogeneous disease caused by various environmental and genetic factors. Abnormal expression of various genes/proteins such as chemokine C-X-C motif (receptor 4), insulin like growth factor-1 receptor and estrogen growth factor receptor and their associated biological regulatory networks are linked with breast cancer. In this study, the crosstalk interaction between these genes/proteins and their associated signaling networks involved in breast cancer metastasis were studied by using both in-silico (qualitative modeling, hybrid PetriNet modeling, pharmacophore modeling and virtual screening) and in-vitro approaches (genotyping, cell viability assay, quantitative real time polymerase chain reaction and western blotting). The association of rs1801157 single nucleotide polymorphism, located within the C-X-C motif ligand 12 (CXCL12) gene, with the development of breast cancer was assessed. The results of genotyping showed the significant prevalence of genotype GG (p<0.05) with a number of variables including patient’s age, weight, lymph nodes status, hormonal imbalances (ER and PR) and family history using multivariable logistic regression among Pakistani breast cancer patients as compared to AA genotype. Our in-silico results suggested that rs1801157 single nucleotide polymorphism identified in CXCL12 gene has crosstalk link with insulin like growth factor-1 receptor (IGF-1R) and epidermal growth factor receptor (EGFR) signaling and is an important factor in predicting the outcomes of breast cancer therapy, which can also result in multidrug resistance due to induction of insulin like growth factor-1. Furthermore, to address the problem of multidrug resistance in breast cancer cells, an effective and non-toxic biologically synthesized silver nanoparticles (drug delivery vehicles) were conjugated with anti-cancer inhibitors such as fulvestrant and gefitinib to inhibit the activity of multiple genes and proteins such as estrogen growth factor receptor, C-X-C motif (ligand 12), phosphoinositide 3 kinase, insulin receptor substrate-1, insulin like growth factor-1 receptor, PDZ domain containing 1 and estrogen receptor-α to treat breast cancer cells. In conclusion, for a multifactorial disease like breast cancer, more than one therapeutic targets should be inhibited with an effective drug delivery vehicle to induce apoptosis in cancer cells.