AIM OF THE STUDY: This study aimed to evaluate the protective anti-inflammatory potential and better understand the underlying mechanism of action of APEE50 in a clinically-relevant mouse asthma model. Thereafter, develop the ethanolic extract of AP as a supplement for asthma prophylaxis.
MATERIALS AND METHOD: APEE50 was prepared and standardized for AGP, NAG, and DDAG using a high-performance liquid chromatography system. Asthma was induced according to a 14-day house dust mite (HDM) induction protocol. The prophylactic potential of APEE50 (50 mg/kg - 200 mg/kg) was determined by assessing cardinal asthma features, which included BALF leukocyte and differential cell count, BALF cytokine assay, histology, gene expression, and airway hyperreactivity study.
RESULTS: APEE50 significantly inhibited HDM-induced airway eosinophilia and neutrophilia. In addition to decreased levels of IL-4, IL-5, IL-13, and eotaxin in bronchoalveolar fluid, APEE50 abrogated HDM-induced airway mucus over-secretion and airway hyper-responsiveness. Administration of APEE50 downregulated HDM-induced upregulation of the oxidative stress enzyme Duox1 (dual oxidase 1) and marginally induced Nfe2l2 (nuclear factor erythroid 2-related factor 2) gene expressions. Similarly, Th2-related (Serpinb2, Clca3a1, Il4 and Il13) and Muc5ac gene expression were significantly downregulated.
CONCLUSION: Prophylactic administration of APEE50 prevented the progression of HDM-induced asthmatic responses by down-regulating Th2 cytokine gene expression and oxidative stress level.
METHODS: A cohort of 85 consenting MDR-TB patients receiving treatment with second-line antituberculosis drugs had their blood samples amplified for the IL8 (rs4073) gene and genotyped. All patients were clinically screened for evidence of treatment toxicity and categorized accordingly. Crude and adjusted associations were assessed.
RESULTS: The chief complaints fell into the following categories: CNS toxicity; gastrointestinal toxicity; skin toxicity; and eye and ear toxicities. Symptoms of gastrointestinal toxicity were reported by 59% of the patients, and symptoms of CNS toxicity were reported by 42.7%. With regard to the genotypes of IL8 (rs4073), the following were identified: AA, in 64 of the study participants; AT, in 7; and TT, in 11. A significant association was found between the dominant model of inheritance and CNS toxicity for the crude model (p = 0.024; OR = 3.57; 95% CI, 1.18-10.76) and the adjusted model (p = 0.031; OR = 3.92; 95% CI, 1.13-13.58). The AT+TT genotype of IL8 (rs4073) showed a 3.92 times increased risk of CNS toxicity when compared with the AA genotype.
CONCLUSIONS: The AT+TT genotype has a tendency to be associated with an increased risk of adverse clinical features during MDR-TB treatment.
OBJECTIVE: The aim of this review is to examine studies that focused on the different types of samples which may serve as a good and promising biomarker for early diagnosis of CKD or to detect rapidly declining renal function among CKD patient.
METHOD: The review of international literature was made on paper and electronic databases Nature, PubMed, Springer Link and Science Direct. The Scopus index was used to verify the scientific relevance of the papers. Publications were selected based on the inclusion and exclusion criteria.
RESULT: 63 publications were found to be compatible with the study objectives. Several biomarkers of interest with different sample types were taken for comparison.
CONCLUSION: Biomarkers from urine samples yield more significant outcome as compare to biomarkers from blood samples. But, validation and confirmation with a different type of study designed on a larger population is needed. More comparison studies on different types of samples are needed to further illuminate which biomarker is the better tool for the diagnosis and prognosis of CKD.
OBJECTIVE: This study aimed to investigate the effects of HSV-G47Δ oncolytic virus on telomerase and telomere length alterations in U251GBMCSCs (U251-Glioblastoma cancer stem cells) under hypoxia and normoxia conditions.
METHODS: U251-CSCs were exposed to the HSV-G47Δ virus in optimized MOI (Multiplicity of infection= 1/14 hours). An absolute telomere length and gene expression of telomerase subunits were determined using an absolute human telomere length quantification PCR assay. Furthermore, a bioinformatics pathway analysis was carried out to evaluate physical and genetic interactions between dysregulated genes with other potential genes and pathways.
RESULTS: Data revealed that U251CSCs had longer telomeres when exposed to HSV-G47Δ in normoxic conditions but had significantly shorter telomeres in hypoxic conditions. Furthermore, hTERC, DKC1, and TEP1 genes were significantly dysregulated in hypoxic and normoxic microenvironments. The analysis revealed that the expression of TERF2 was significantly reduced in both microenvironments, and two critical genes from the MRN complex, MER11 and RAD50, were significantly upregulated in normoxic conditions. RAD50 showed a significant downregulation pattern in the hypoxic niche. Our results suggested that repair complex in the telomeric structure could be targeted by HSV-G47Δ in both microenvironments.
CONCLUSION: In the glioblastoma treatment strategy, telomerase and telomere complex could be potential targets for HSV-G47Δ in both microenvironments.
AIM OF THE STUDY: To determine the inhibitory properties of FD aqueous extract on pro-inflammatory mediators involved in lipopolysaccharide (LPS)-induced microglial cells.
METHODS: Vitexin and isovitexin in the extract were quantified via high performance liquid chromatography (HPLC). The extract was evaluated for its cytotoxicity activity via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Pre-treatment with the extract on LPS-induced microglial cells was done to determine its antioxidant and anti-neuroinflammatory properties by measuring the level of reactive oxygen species (ROS), nitric oxide (NO), tumour necrosis factor alpha (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) via 2'-7'-dichlorofluorescin diacetate (DCFDA) assay, Griess assay and Western blot respectively.
RESULTS: The extract at all tested concentrations (0.1 μg/mL, 1 μg/mL, 10 μg/mL, 100 μg/mL) were not cytotoxic as the percentage viability of microglial cells were all above ~80%. At the highest concentration (100 μg/mL), the extract significantly reduced the formation of ROS, NO, TNF-α, IL-1β and IL-6 in microglial cells induced by LPS.
CONCLUSION: The extract showed neuroprotective effects by attenuating the levels of pro-inflammatory and cytotoxic factors in LPS-induced microglial cells, possibly by mediating the nuclear factor-kappa B (NF-κB) signalling pathway.
RESULTS: The present study reveals that both vitexin and donepezil are able to bind at the close proximity of LPS binding site located at the TLR4/MD-2 complex with the binding energy of - 4.35 and - 9.14 kcal/mol, respectively. During molecular dynamic simulations, both vitexin and donepezil formed stable complex with TLR4/MD-2 throughout the 100 ns time length with the root mean square deviation (RMSD) values of 2.5 Å and 4.0 Å, respectively. The root mean square fluctuation (RMSF) reveals that both compounds are stable. Interestingly, the radius of gyration (rGyr) for donepezil shows notable fluctuations when compare with vitexin. The MM-GBSA results showed that vitexin has higher binding energy in comparison with donepezil.
CONCLUSIONS: Taken together, the findings suggest that vitexin is able to bind at the binding site of TLR4/MD-2 complex with more stability than donepezil throughout the course of 100 ns simulation. Hence, vitexin has the potential to be an antagonist candidate for LPS.
METHODS: The correlation of these variants to the plasma BDNF level among Malaysian MDD patients was assessed. A total of 300 cases and 300 matched controls recruited from four public hospitals within the Klang Valley of Selangor State, Malaysia and matched for age, sex and ethnicity were screened for BDNF rs6265, rs1048218 and rs1048220 using high resolution melting (HRM).
FINDINGS: BDNF rs1048218 and BDNF rs1048220 were monomorphic and were excluded from further analysis. The distribution of the alleles and genotypes for BDNF rs6265 was in Hardy-Weinberg equilibrium for the controls (p = 0.13) but was in Hardy Weinberg disequilibrium for the cases (p = 0.011). Findings from this study indicated that having BDNF rs6265 in the Malaysian population increase the odds of developing MDD by 2.05 folds (95% CI = 1.48-3.65). Plasma from 206 cases and 206 controls were randomly selected to measure the BDNF level using enzyme-linked immunosorbent assay (ELISA). A significant decrease in the plasma BDNF level of the cases as compared to controls (p<0.0001) was observed. However, there was no evidence of the effect of the rs6265 genotypes on the BDNF level indicating a possible role of other factors in modulating the BDNF level that warrants further investigation.
CONCLUSION: The study indicated that having the BDNF rs6265 allele (A) increase the risk of developing MDD in the Malaysian population suggesting a possible role of BDNF in the etiology of the disorder.