In vitro and in vivo studies reveal α-Mangostin, a xanthonoid from Garcinia mangostana, as a promising natural antiviral compound against chikungunya virus.

BACKGROUND: Chikungunya virus (CHIKV), a serious health problem in several tropical countries, is the causative agent of chikungunya fever. Approved antiviral therapies or vaccines for the treatment or prevention of CHIKV infections are not available. As diverse natural phenolic compounds have been shown to possess antiviral activities, we explored the antiviral activity of α-Mangostin, a xanthanoid, against CHIKV infection. METHODS: The in vitro prophylactic and therapeutic effects of α-Mangostin on CHIKV replication in Vero E6 cells were investigated by administering it under pre, post and cotreatment conditions. The antiviral activity was determined by foci forming unit assay, quantitative RT-PCR and cell-based immune-fluorescence assay. The molecular mechanism of inhibitory action was further proposed using in silico molecular docking studies. RESULTS: In vitro studies revealed that 8 µM α-Mangostin completely inhibited CHIKV infectivity under the cotreatment condition. CHIKV replication was also inhibited in virus-infected mice. This is the first in vivo study which clearly showed that α-Mangostin is effective in vivo by significantly reducing virus replication in serum and muscles. Molecular docking indicated that α-Mangostin can efficiently interact with the E2-E1 heterodimeric glycoprotein and the ADP-ribose binding cavity of the nsP3 macrodomain. CONCLUSIONS: The findings suggest that α-Mangostin can inhibit CHIKV infection and replication through possible interaction with multiple CHIKV target proteins and might act as a prophylactic/therapeutic agent against CHIKV.

In Vitro Antiviral Activity of α-Mangostin against Dengue Virus Serotype-2 (DENV-2).

Dengue virus (DENV), a member of the family Flaviviridae, is a threat for global health as it infects more than 100 million people yearly. Approved antiviral therapies or vaccines for the treatment or prevention of DENV infections are not available. In the present study, natural compounds were screened for their antiviral activity against DENV by in vitro cell line-based assay. α-Mangostin, a xanthanoid, was observed to exert antiviral activity against DENV-2 under pre-, co- and post-treatment testing conditions. The antiviral activity was determined by foci forming unit (FFU) assay, quantitative RT-PCR and cell-based immunofluorescence assay (IFA). A complete inhibition of DENV-2 was observed at 8 µM under the co-treatment condition. The possible inhibitory mechanism of α-Mangostin was also determined by docking studies. The molecular docking experiments indicate that α-Mangostin can interact with multiple DENV protein targets such as the NS5 methyltransferase, NS2B-NS3 protease and the glycoprotein E. The in vitro and in silico findings suggest that α-Mangostin possesses the ability to suppress DENV-2 production at different stages of its replication cycle and might act as a prophylactic/therapeutic agent against DENV-2.

Dietary intake and glutamine-serine metabolism control pathologic vascular stiffness.

Perivascular collagen deposition by activated fibroblasts promotes vascular stiffening and drives cardiovascular diseases such as pulmonary hypertension (PH). Whether and how vascular fibroblasts rewire their metabolism to sustain collagen biosynthesis remains unknown. Here, we found that inflammation, hypoxia, and mechanical stress converge on activating the transcriptional coactivators YAP and TAZ (WWTR1) in pulmonary arterial adventitial fibroblasts (PAAFs). Consequently, YAP and TAZ drive glutamine and serine catabolism to sustain proline and glycine anabolism and promote collagen biosynthesis. Pharmacologic or dietary intervention on proline and glycine anabolic demand decreases vascular stiffening and improves cardiovascular function in PH rodent models. By identifying the limiting metabolic pathways for vascular collagen biosynthesis, our findings provide guidance for incorporating metabolic and dietary interventions for treating cardiopulmonary vascular disease.

16S rRNA sequencing as a diagnostic tool in the identification of culture-negative endocarditis in surgically treated patients.

BACKGROUND AND AIM OF THE STUDY: Infective endocarditis (IE) is a worldwide problem, and at least one-third of cases are culture-negative despite the use of appropriate laboratory techniques. METHODS: A broad-range polymerase chain reaction (PCR) amplification was performed of the 16S rRNA gene, followed by single-strand sequencing for 26 surgically removed heart valves from patients with culture-negative endocarditis who had undergone valve repair or replacement. RESULTS: Two of the 26 patients were PCR-positive, and sequencing of the amplicon identified the etiological agent. Gram-stained smears of the heart valves were positive in both cases. Three of the remaining 24 cases which were negative by PCR also showed the presence of micro-organisms in Gram-stained smears. CONCLUSION: The study results emphasize that, in suspected IE cases when there is no growth in culture, a combination of microscopy and 16S rRNA sequencing can be used to identify the pathogen in excised valvular tissue.

Superstition and post-tonsillectomy hemorrhage.

OBJECTIVES/HYPOTHESIS: The objective was to determine whether post-tonsillectomy hemorrhages occur more frequently in redheaded children, in patterns of threes, on Friday-the-13th days, or with the full moon. STUDY DESIGN: Case-control analysis. METHODS: The authors performed multiple statistical analyses of all children undergoing tonsillectomy at Temple University Children's Medical Center (Philadelphia, PA) during a 29-month period. Children readmitted to the hospital with or without surgical control of bleeding were compared with children who did not bleed. Relation of post-tonsillectomy hemorrhages to the phase of the moon was evaluated using a standard normal deviate. The frequency of surgery performed on Friday-the-13th days was compared with a differently dated Friday chosen at random. Clusters of three hemorrhages in a 7-day period were recorded. Families of children were contacted and asked whether their child had red hair. A chi analysis compared redheaded and non-redheaded tonsillectomy patients. RESULTS: Twenty-eight of 589 tonsillectomy cases performed required readmission for bleeding events. Twenty tonsillectomies occurred on a full-moon day, resulting in one bleeding event. One cluster of three post-tonsillectomy hemorrhages occurred in a 7-day period. Four of the children who bled had red hair. Two tonsillectomies occurred on Friday the 13th, with no associated hemorrhage. Statistical analysis revealed a random pattern to post-tonsillectomy hemorrhage. CONCLUSION: Post-tonsillectomy hemorrhages do not occur in clusters of three and are not more frequent with the full moon or on Friday the 13th. The bleeding rate among children with red hair is similar to that of non-redheaded children.