Among infectious diseases, tuberculosis is the biggest cause of death worldwide. Thus, controlling TB, a global epidemic, is a major public health concern on a worldwide scale. According to epidemiological modelling, a new vaccination that can prevent TB, especially in adults and adolescents, is necessary to control the disease’s spread, even while medication therapies for the disease are still improving. The development of novel vaccines with broader applicability and improved, long-lasting effectiveness becomes increasingly crucial as strains resistant to various drugs emerge. This work designed a multi-epitope subunit vaccine (MESV) candidateusing immunoinformatic approaches that targets five virulence-associated proteins, Rv0227c, Rv0584, Lipoprotein LprA, Phospholipase C, and Antigen 85 C. Antigenicity, non-allergenicity, and non-toxicity were the criteria used to identify and filter potential CTL, HTL, and B-cell epitopes. High-affinity epitopes connected with suitable spacers and an adjuvant for improved immunogenicity were included in the carried-out vaccine formulation. Validation and structural modelling verified the MESV’s quality and stability. TLR2 and TLR4 receptors have strong interactions, which were further demonstrated through molecular docking, and molecular dynamics simulations showed low fluctuations and good structural stability. Further, the MMPBSA analysis was introduced to determine the binding affinity of the vaccine construct, and a more pronounced binding affinity was established by the designed vaccine with TLR4. Increased cytokine release, memory cell development, and the developed MESV candidateare viable options warranting further experimental validation, as it may elicit potent humoral and cellular immune responses against M. tuberculosis.
Swagat Ranjan Maharana, S. Khan, Kiran Mahapatra et al.· Scientific Reports· 0 citations
BACKGROUND
The Cytochrome 4F2 (CYP4F2) rs2108622 genetic variant influences the production of 20-Hydroxyeicosatetraenoic acid (20-HETE), which affects the blood pressure. Previous findings from our group indicate that CYP4F2 rs2108622 genotype is associated with essential hypertension.
AIMS
This study aims to find out the association of CYP4F2 rs2108622 genotype with the response of valsartan and amlodipine among hypertensive patients.
METHODS
56 hypertensive patients on 80mg valsartan and 34 on 5mg amlodipine were genotyped for CYP4F2 rs2108622 genetic variant using PCR-RFLP method. The systolic (SBP) and diastolic (DBP) blood pressures data before and after one month antihypertensive treatment were collected from the computer record of the hospital. The patients were unrelated Arabs attending the University of Jordan Hospital.
RESULTS
We found that carriers of CYP4F2 rs2108622 CC genotype have greater reduction in SBP (mean difference -28.5±15.2 for valsartan and vs. -32.3±5.5mmHg for amlodipine) in comparison with CT and TT genotypes, this difference did not reach the statistical significance (P value> 0.05). Furthermore, the CYP4F2 rs2108622 genotype was not associated significantly (P value> 0.05) with valsartan and amlodipine responses after adjustment the responses with sex, BMI, age, and smoking status of the patients.
DISCUSSION
While there is a trend suggesting CYP4F2 rs2108622 CC genotype may respond better to valsartan and amlodipine responses, the absence of statistical significance supports the need for larger pharmacogenetic studies.
CONCLUSIONS
It can be concluded from the findings of this study that there is a lack of association between the CYP4F2 rs2108622 genotype and valsartan and amlodipine responses among a sample of Jordanians with essential hypertension.
Y. Jarrar, Enas Yousef Alkasasbeh, Dalia Abdelrazaq et al.· Prostaglandins & other lipid...· 0 citations