Lertyot Treeratanapiboon

Neutrophils cross the BBB primarily on transcellular pathways: An in vitro study

The cerebral microcapillary endothelium forms a highly important barrier between the blood and the interstitial fluid of the brain (blood-brain barrier) that controls the passage of molecules and cells in and out of the CNS. Several CNS diseases include leukocyte extravasation through the endothelium via two mechanistically distinct routes, the paracellular and the transcellular pathway. We established a new in vitro model of the inflamed blood-brain barrier consisting of primary cultured porcine brain capillary endothelial cells which express a tight endothelial barrier even under inflammatory conditions. By means of this specialized blood-brain barrier model we extensively studied the transmigration of neutrophils. Electron and scanning force microscopy as well as immunofluorescence imaging captured the penetrating neutrophil on the endothelial cellular body in between the junctions clearly suggesting a transcellular migration pathway. Electric cell-substrate impedance sensing and transendothelial electrical resistance measurements in combination with expression analysis of tight junction proteins demonstrate that the neutrophil-endothelial interaction does not disrupt the barrier. In conclusion, this study, based on an in vitro model of the blood-brain barrier under inflammatory conditions, evidently implicates that neutrophils preferentially migrate across the BBB via the transcellular route without impairing endothelial barrier function whereas paracellular transmigration plays only a minor role if the barrier is strongly expressed.

Bioactive 4-hydroxycinnamide and bioactivities of Polyalthia cerasoides

Constituents from Polyalthia cerasoides, stem bark methanol extract, were previously documented. This study reports the first isolation of bioactive N-(4-hydroxy-β-phenethyl)-4-hydroxycinnamide (1) from ethyl acetate extract of the plant species including stigmasterol and a mixture of triterpenes from hexane and dichloromethane extracts. Trace essential elements were found in the hexane extract in ppm level. The plant extracts were evaluated for their antimicrobial and antioxidative activities. The dichloromethane extract displayed the highest activity against Corynebacterium diphtheriae NCTC 10356 with MIC of 32 µg/mL, as well as, the highest SOD activity with an IC50 of 4.51 µg/mL.

Novel activities of 1-adamantylthiopyridines as antibacterials, antimalarials and anticancers

To discover new bioactive lead compounds for medicinal purposes, herein, 2(1adamantylthio)pyridine and derivatives (1-10) were prepared and tested for antibacterial (agar dilution method against 27 strains of microorganisms), antimalarial (against Plasmodium falciparum) and anticancer (MOLT-3, HepG2, HuCCA-1 and A549) activities. Results showed that all the tested derivatives selectively exerted antigrowth activity against Streptococci at 15-30 µg/mL. 3-Substituted (R) thiopyridines; 3 (R = NAc2), 5 (R = OH) and 6 (R = Br) exhibited antibacterials, antimalarials and anticancers. Significantly, 6-(1-adamantylthio) nicotinonitrile (10) is a promising antibacterial which selectively displays antigrowth activity against Vibrio cholerae, Vibrio parahaemolyticus, Edwardsiella tarda and β-hemolytic Streptococcus group A with minimum inhibitory concentration of 30 µg/mL. The findings reveal that these 1-adamantylthiopyridines represent a novel class of antibacterial, antimalarial and anticancer agents with potential medicinal values.

Antimalarial and antimicrobial activities of 8-Aminoquinoline-Uracils metal complexes

8-Aminoquinoline (8AQ) derivatives have been reported to have antimalarial, anticancer, and antioxidant activities. This study investigated the potency of 8AQ-5-substituted (iodo and nitro) uracils metal (Mn, Cu, Ni) complexes (1-6) as antimalarial and antimicrobial agents. Interestingly, all of these metal complexes (1-6) showed fair antimalarial activities. Moreover, Cu complexes 2 (8AQ-Cu-5Iu) and 5 (8AQ-Cu-5Nu) exerted antimicrobial activities against Gram-negative bacteria including P. shigelloides and S. dysenteriae. The results reveal application of 8AQ and its metal complexes as potential compounds to be further developed as novel antimalarial and antibacterial agents.

Cervical Cancer Markers: Epigenetics and microRNAs

Gynecologic malignant neoplasms are a severe health problem among female patients, of which cervical cancer (CC), in particular, is a common disease leading to high mortality rates. Despite extensive attempts by researchers to solve the molecular mystery of CC, the mechanisms of its pathogenesis remain unclear. Tumor markers used in the clinical laboratory, such as squamous cell carcinoma (SCC), cancer antigen (CA)-125, and CA19-9, provide some help in diagnosing patients with CC. However, finding new molecular markers with high sensitivity and specificity is necessary. This review focuses on the role of epigenetic changes, particularly microRNAs (miRNAs), to CC. Several miRNAs that associated with CC potentially have the advantage of being early biomarkers. Moreover, altered serum miRNAs or single nucleotide polymorphisms in miRNA patterns may predict disease progression.

In vitro study of parasite elimination and endothelial protection by curcumin

Plasmodium falciparum infection can abruptly progress to severe malaria and cerebral malaria. Despite the current efficiency of antimalarial drugs in killing parasites, no specific effective treatment has been found for cerebral malaria. Thus, a new strategy targeting both parasite elimination and endothelial cell protection is urgently needed in this field. In this study, we determined whether curcumin, which has blood-brain permeability, antioxidative activity and/or immunomodulation property, provided a potential effect on both parasite elimination and endothelial protection. Murine brain microvascular endothelial cells (bEnd.3; ATCC) were cocultured with Plasmodium falciparum-infected red blood cells (Pf-IRBC), peripheral blood mononuclear cell (PBMC) and platelets. Apoptosis of endothelial cells was demonstrated by annexin V staining. Interestingly, curcumin exhibited high efficiency of antimalarial activity (IC50 ~10 µM) and decreased bEnd.3 apoptosis down to 60.0 % and 79.6 % upon pre-treatment and co-treatment, respectively, with Pf-IRBC, platelets and PBMC. Our findings open up a high feasibility of applying curcumin as a potential adjunctive compound for cerebral malaria treatment in the future.