Frequency and association of Epstein-Barr Virus genotype in rheumatoid arthritis patients of Khyber Pakhtunkhwa, Pakistan.

BACKGROUND: Rheumatoid arthritis (RA) is an immune-mediated, polyarthritis linked with various genetic and environmental causative agents. Among environmental triggers, Epstein-Barr Virus (EBV) is considered the most potent etiological agent. OBJECTIVE: This study aimed to investigate the prevalence of EBV and its genotypes in RA patients and to investigate their association with clinical and laboratory parameters of RA. METHODOLOGY: This study included blood samples of RA and control healthy individuals (100 each). Blood samples along with clinical and laboratory parameters were collected from patients after consent in the Department of Rheumatology, at Lady Reading Hospital, in Peshawar Pakistan. Blood samples were processed for DNA extraction followed by PCR amplification for EBV detection and genotype discrimination. RESULTS: RA patients were 85 females and 15 males with a mean age of 40.13±14.05 years. EBV Type-1 was detected in 45% of RA and 9% of control cases. The mean disease duration of RA patients was 6.61±6.23 years. Out of 100 diseased patients, 43% were seropositive rheumatoid arthritis (SPRA) and showed a significant correlation with a family history of RA in EBV-positive individuals (P = 0.017). The demographic, clinical, and laboratory parameters of RA patients showed a non-significant association with EBV. Moreover, only a family history and Serum creatinine of RA patients showed a significant association with EBV (P = 0.0001 and P = 0.022 respectively). CONCLUSION: It is concluded that EBV-1 is prevalent and associated with RA. Further investigation is required for detailed genetic analysis of EBV to determine its possible role in modulating the immune system in RA.

Structural determinants of phytoremediation capacity in saltmarsh halophyte Diplachne fusca (L.) P. Beauv. ex Roem. & Schult. subsp. fusca.

Micro and macro-morphological features contribute to plants' tolerance to a variety of environmental pollutants. The contribution of such structural modifications in the phytoremediation potential of Diplachne fusca populations collected from five saline habitats were explored when treated with 100 to 400 mM NaCl for 75 days along with control. Structural modifications in the populations from the highest salinity included development of aerenchyma in stem instead of chlorenchyma, absence of excretory hairs in stem, and exceptionally large trichomes on the leaf surface to help excretion of excess salt. Large parenchyma cells provided more space for water and solute storage, while broad metaxylem vessels were linked to better conduction water and nutrients, which ultimately excreted via glandular hairs, microhairs, and vesicular hairs. Broad metaxylem vessels and exceptionally long hairs observed in the populations collected from 52 dS m-1. In conclusion, large stem aerenchyma, exceptionally large trichomes on the leaf surface, and tightly packed outer cortical region in roots with intensive sclerification just inside the epidermis accompanied with salt excretion via glandular hairs, microhairs, and vesicular hairs were the main anatomical modifications involved in the phytoremediation potential of D. fusca in hyper-saline environments.

Morpho-anatomical characteristics of the differently adapted populations of Diplachne fusca has never been reported. In particular, structural variation in their mechanism of adaptation for salinity tolerance was investigated for the first time in current study.

The in silico identification of small molecules for protein-protein interaction inhibition in AKAP-Lbc-RhoA signaling complex.

The rational design of small molecules that mimic key residues at the interface of interacting proteins can be a successful approach to target certain biological signaling cascades causing pathophysiological outcome. The A-Kinase Anchoring Protein, i.e. AKAP-Lbc, catalyses nucleotide exchange on RhoA and is involved in cardiac repolarization. The oncogenic AKAP-Lbc induces the RhoA GTPase hyperactivity and aberrantly amplifies the signaling pathway leading to hypertrophic cardiomyocytes. We took advantage of the AKAP-Lbc-RhoA complex crystal structure to design in silico small molecules predicted to inhibit the associated pathological signaling cascade. We adopted the strategies of pharmacophore building, virtual screening and molecular docking to identify the small molecules capable to target AKAP-Lbc and RhoA interactions. The pharmacophore model based virtual screening unveils two lead compounds from the TIMBAL database of small molecules modulating the targeted protein-protein interactions. The molecular docking analysis revealed the lead compounds' potentialities to establish the essential chemical interactions with the key interactive residues of the complex. These features provided a road map for designing additional potent chemical derivatives and fragments of the original lead compounds to perturb the AKAP-Lbc and RhoA interactions. Experimental validations may elucidate the therapeutic potential of these lead chemical scaffolds to deal with aberrant AKAP-Lbc signaling based cardiac hypertrophy.