CRITICAL ISSUES: While HbE by itself presents as a mild anemia and a single gene for β-thalassemia is not serious, it remains unexplained why HbE/β-thalassemia (HbE/β-thal) is a grave disease with high morbidity and mortality. Patients often exhibit defective physical development, severe chronic anemia, and often die of cardiovascular disease and severe infections. Recent Advances: This article presents an overview of HbE/β-thal disease with an emphasis on new findings pointing to pathophysiological mechanisms derived from and initiated by the dysfunctional property of HbE as a reduced nitrite reductase concomitant with excess α-chains exacerbating unstable HbE, leading to a combination of nitric oxide imbalance, oxidative stress, and proinflammatory events.
FUTURE DIRECTIONS: Additionally, we present new therapeutic strategies that are based on the emerging molecular-level understanding of the pathophysiology of this and other hemoglobinopathies. These strategies are designed to short-circuit the inflammatory cascade leading to devastating chronic morbidity and fatal consequences. Antioxid. Redox Signal. 26, 794-813.
METHODS: Postbiotic metabolites (PM) produced by six strains of L. plantarum were determined for their antiproliferative and cytotoxic effects on normal human primary cells, breast, colorectal, cervical, liver and leukemia cancer cell lines via MTT assay, trypan blue exclusion method and BrdU assay. The toxicity of PM was determined for human and various animal red blood cells via haemolytic assay. The cytotoxicity mode was subsequently determined for selected UL4 PM on MCF-7 cells due to its pronounced cytotoxic effect by fluorescent microscopic observation using AO/PI dye reagents and flow cytometric analyses.
RESULTS: UL4 PM exhibited the lowest IC50 value on MCF-7, RG14 PM on HT29 and RG11 and RI11 PM on HL60 cell lines, respectively from MTT assay. Moreover, all tested PM did not cause haemolysis of human, dog, rabbit and chicken red blood cells and demonstrated no cytotoxicity on normal breast MCF-10A cells and primary cultured cells including human peripheral blood mononuclear cells, mice splenocytes and thymocytes. Antiproliferation of MCF-7 and HT-29 cells was potently induced by UL4 and RG 14 PM respectively after 72 h of incubation at the concentration of 30% (v/v). Fluorescent microscopic observation and flow cytometric analyses showed that the pronounced cytotoxic effect of UL4 PM on MCF-7 cells was mediated through apoptosis.
CONCLUSION: In conclusion, PM produced by the six strains of L. plantarum exhibited selective cytotoxic via antiproliferative effect and induction of apoptosis against malignant cancer cells in a strain-specific and cancer cell type-specific manner whilst sparing the normal cells. This reveals the vast potentials of PM from L. plantarum as functional supplement and as an adjunctive treatment for cancer.
RESULTS: In this study, the alignment analysis based on structural similarity allows the prediction of 48 potential interactions between 27 human RPs and the EBV proteins EBNA1, LMP1, LMP2A, and LMP2B. Gene ontology analysis of the putative protein-protein interactions (PPIs) reveals their probable involvement in RNA binding, ribosome biogenesis, metabolic and biosynthetic processes, and gene regulation. Pathway analysis shows their possible participation in viral infection strategies (viral translation), as well as oncogenesis (Wnt and EGFR signalling pathways). Finally, our molecular docking assay predicts the functional interactions of EBNA1 with four RPs individually: EBNA1-eS10, EBNA1-eS25, EBNA1-uL10 and EBNA1-uL11.
CONCLUSION: These interactions have never been revealed previously via either experimental or in silico approach. We envisage that the calculated interactions between the ribosomal and EBV proteins herein would provide a hypothetical model for future experimental studies on the functional relationship between ribosomal proteins and EBV infection.
DESIGN: A comparative cross sectional study.
PARTICIPANTS: Patients were divided into Group 1 (allergic rhinitis without conjunctivitis), Group 2 (allergic rhinoconjunctivitis), and Group 3 (normal population).
METHODS: A comparative cross-sectional study was conducted. Patients were divided into; Group 1 (allergic rhinitis without conjunctivitis), Group 2 (allergic rhinoconjunctivitis), and Group 3 (normal controls). Tears were collected using Schirmer strips and cytokine analysis performed using enzyme linked immunosorbent assay.
RESULTS: There were a total of 68 subjects. Median values of cytokines in the allergic rhinitis group were as follows; TNFa (45.34 pg/ml), IL-4 (61.91 pg/ml), IL-5 (8.92 pg/ml), IL-6 (538.37 pg/ml) and IL-8 (1438.72 pg/ml). Cytokine levels in the group with allergic rhinoconjunctivitis were approximately two-fold higher than in the group with allergic rhinitis only. The median cytokine level in the control group was lowest. A significant inter-group difference was observed for TNF-alpha, IL-4, IL-6 and IL-8 levels, with allergic rhinoconjunctivitis patients demonstrating significantly elevated cytokines compared to those with allergic rhinitis only (p<0.001). These four cytokines were also significantly higher in those with allergic rhinitis than in controls (p<0.005). Although the group with allergic rhinoconjunctivitis had the highest levels of IL-5, no statistically significant inter-group difference was noted (p=0.479).
CONCLUSION: This study demonstrated the presence of raised tear film inflammatory cytokines even in allergic rhinitis patients without ocular symptoms. These patients may be at increased risk of developing allergic conjunctivitis. These findings not only substantiate the immunological theory of the naso-ocular reflex, but have clinical and therapeutic implications for the holistic management of allergic rhinitis and conjunctivitis.