Pharmacological Activities of Fingerroot Extract and Its Phytoconstituents Against SARS-CoV-2 Infection in Golden Syrian Hamsters.

Background: The outbreak of COVID-19 has led to the suffering of people around the world, with an inaccessibility of specific and effective medication. Fingerroot extract, which showed in vitro anti-SARS-CoV-2 activity, could alleviate the deficiency of antivirals and reduce the burden of health systems. Aim of Study: In this study, we conducted an experiment in SARS-CoV-2-infected hamsters to determine the efficacy of fingerroot extract in vivo. Materials and Methods: The infected hamsters were orally administered with vehicle control, fingerroot extract 300 or 1000 mg/kg, or favipiravir 1000 mg/kg at 48 h post-infection for 7 consecutive days. The hamsters (n = 12 each group) were sacrificed at day 2, 4 and 8 post-infection to collect the plasma and lung tissues for analyses of viral output, lung histology and lung concentration of panduratin A. Results: All animals in treatment groups reported no death, while one hamster in the control group died on day 3 post-infection. All treatments significantly reduced lung pathophysiology and inflammatory mediators, PGE2 and IL-6, compared to the control group. High levels of panduratin A were found in both the plasma and lung of infected animals. Conclusion: Fingerroot extract was shown to be a potential of reducing lung inflammation and cytokines in hamsters. Further studies of the full pharmacokinetics and toxicity are required before entering into clinical development.

Immunogenicity and efficacy of recombinant subunit SARS-CoV-2 vaccine candidate in the Syrian hamster model.

SARS-CoV-2 causes devastating impact on the human population and has become a major public health concern. The frequent emergence of SARS-CoV-2 variants of concern urges the development of safe and efficacious vaccine against SARS-CoV-2 variants. We developed a candidate vaccine Baiya SARS-CoV-2 Vax 1, based on SARS-CoV-2 receptor-binding domain (RBD) by fusing with the Fc region of human IgG. The RBD-Fc fusion was produced in Nicotiana benthamiana. Previously, we reported that this plant-produced vaccine is effective in inducing immune response in both mice and non-human primates. Here, the efficacy of our vaccine candidate was tested in Syrian hamster challenge model. Hamsters immunized with two intramuscular doses of Baiya SARS-CoV-2 Vax 1 induced neutralizing antibodies against SARS-CoV-2 and protected from SARS-CoV-2 challenge with reduced viral load in the lungs. These preliminary results demonstrate the ability of plant-produced subunit vaccine Baiya SARS-CoV-2 Vax 1 to provide protection against SARS-CoV-2 infection in hamsters.

Development of polyurethane foam dressing containing silver and asiaticoside for healing of dermal wound.

Polyurethane foam dressings for dermal wounds were formulated with natural polyols in order to improve the foam characteristics and the release of 2 active agents, silver and asiaticoside (AS) as an antimicrobial agent and an herbal wound healing agent, respectively. The foam was instantly formed by interaction of polyols and diisocyanate. Hydroxypropyl methylcellulose, chitosan and sodium alginate were individually mixed with the main polyols, polypropylene glycol, in the formulation while the active components were impregnated into the obtained foam dressing sheets. Although the type and amount of the natural polyols slightly affected the pore size, water sorption-desorption profile and compression strength of the obtained foam sheets, a prominent effect was found in the release of both active components. Among natural polyols formulations, foam sheets with alginate showed the highest silver and AS release. Non-cytotoxicity of these foam sheets to human fibroblast cells was confirmed. Antimicrobial testing on four bacteria strains showed that 1 mg/cm2 silver in formulations with 6% of natural polyols and without natural polyols had sufficient content of the silver release with comparable inhibition zone and significantly larger zone than other formulations. In pig study, the foam dressing with 6% alginate, 1 mg/cm2 silver and 5% AS could improve wound healing in both the percentage of the wound closure and histological parameters of the dermal wound without any dermatologic reactions. In conclusion, this innovative foam dressing had potential to be a good candidate for wound treatment.

Acute and long-term effects of endovascular debanding of pulmonary arteries in a swine model.

OBJECTIVES: The primary objective of this study was to demonstrate that pulmonary artery (PA) debanding via cardiac catheterization using balloon angioplasty is feasible and safe in swine. The secondary objectives were to determine the acute and long-term effects of this therapy. DESIGN: This is a chronic survival experimental study in newborn swine. BACKGROUND: PA bands are used in infants for transient palliation of congenital heart defects with excessive pulmonary blood flow. Although rare, if these defects should close spontaneously or become hemodynamically insignificant, a sternotomy and occasionally cardiopulmonary bypass may still be required for band removal. Alternatively, debanding could be accomplished through less invasive methods. INTERVENTIONS: The main pulmonary artery was banded in three piglets, and the left pulmonary artery in five piglets via mini-thoracotomy at a mean weight of 2.5 kg. Following a threefold increase in weight, the piglets underwent PA debanding via balloon angioplasty. Four piglets were sacrificed to evaluate the acute effects. The remainder were followed to evaluate long-term effects. Histopathology was performed on all piglets. OUTCOME MEASURES: Reintervention rates. Histopathologic consequences of high pressure balloon angioplasty used for PA debanding acutely and after reinterventions. RESULTS: Debanding was performed at a mean weight of 8.1 ± 2.23 kg. The median preintervention gradient across the band was 18 mm Hg. Debanding was successful in all piglets. The median postintervention gradient was 3.5 mm Hg. All piglets in the long-term model required re-interventions for recurrent stenosis at mean weights of 26 ± 1.6 and 61 ± 3.2 kg. Histopathology demonstrated vessel wall injury in only one piglet. CONCLUSIONS: Endovascular PA debanding can be safely achieved in a swine model. Angioplasty following debanding may be necessary for recurrent stenosis. This catheter-based therapy may provide a less-invasive alternative to surgery.

Maternal alcohol exposure during mid-pregnancy dilates fetal cerebral arteries via endocannabinoid receptors.

Prenatal alcohol exposure often results in fetal alcohol syndrome and fetal alcohol spectrum disorders. Mechanisms of fetal brain damage by alcohol remain unclear. We used baboons (Papio spp.) to study alcohol-driven changes in the fetal cerebral artery endocannabinoid system. Pregnant baboons were subjected to binge alcohol exposure via gastric infusion three times during a period equivalent to the second trimester of human pregnancy. A control group was infused with orange-flavored drink that was isocaloric to the alcohol-containing solution. Cesarean sections were performed at a time equivalent to the end of the second trimester of human pregnancy. Fetal cerebral arteries were harvested and subjected to in vitro pressurization followed by pharmacological profiling. During each alcohol-infusion episode, maternal blood alcohol concentrations (BAC) reached 80 mg/dL, that is, equivalent to the BAC considered legal intoxication in humans. Circulating anandamide (AEA) and 2-arachidonoylglycerol (2-AG) remained unchanged. Ultrasound studies on pregnant mothers revealed that fetal alcohol exposure decreased peak systolic blood velocity in middle cerebral arteries when compared to pre-alcohol levels. Moreover, ethanol-induced dilation was observed in fetal cerebral arteries pressurized in vitro. This dilation was abolished by the mixture of AM251 and AM630, which block cannabinoid receptors 1 and 2, respectively. In the presence of AM251, the cannabinoid receptor agonist AEA evoked a higher, concentration-dependent dilation of cerebral arteries from alcohol-exposed fetuses. The difference in AEA-induced cerebral artery dilation vanished in the presence of AM630. CB1 and CB2 receptor mRNA and protein levels were similar in cerebral arteries from alcohol-exposed and control-exposed fetuses. In summary, alcohol exposure dilates fetal cerebral arteries via endocannabinoid receptors and results in an increased function of CB2.