BackgroundHuman malaria is still a burden in Dak Nong and Binh Phuoc Provinces in south-central Vietnam that border Cambodia. Several Anopheles species that transmit human malarial Plasmodium may also transmit Wuchereria bancrofti, the nematode that causes Bancroftian lymphatic filariasis. The objective of this study was to investigate the role of Anopheles species in the transmission of these two pathogens in the two highly malaria endemic provinces of Vietnam.MethodsAnopheles mosquitoes were collected in Dak Nong and Binh Phuoc Provinces in November and December of 2010 and 2011. Human landing catches, paired collections on human and buffalo, and resting captures were made with mouth aspirators. Collections were also made with light traps. Morphological and PCR-based methods were used to identify the species. Real-time PCR was used to detect Plasmodium species and W. bancrofti in individual mosquitoes.ResultsTwenty-four Anopheles species were identified among 797 captured mosquitoes. Anopheles dirus was found in both provinces and was the predominant species in Binh Phuoc Province; An. maculatus was the most prevalent species in Dak Nong Province. Anopheles minimus was collected only in Binh Phuoc Province. Some specimens of An. minimus and An. pampanai were misidentified based on morphology. Four specimens of An. scanloni were identified, and this is the first report of this species of the Dirus Complex in Vietnam. Two females, one An. dirus and one An. pampanai, collected in Binh Phuoc Province were infected with P. vivax, for an overall infection rate of 0.41% (2/486): 0.28% for An. dirus (1/361) and 20% for An. pampanai (1/5). No mosquitoes were found to be infected with P. falciparum, P. knowlesi or W. bancrofti in either province.ConclusionA diversity of Anopheles species occurs in Dak Nong and Binh Phuoc Provinces of Vietnam, several of which are considered to be actual and potential vectors of malarial protozoa and microfilariae. It is highly likely that two of the species, An. dirus and An. pampanai, are active in malaria transmission based on the detection of P. vivax in females of these species. This is the first report of An. scanloni in Vietnam.

Inappropriate food intake-related obesity and more importantly, visceral adiposity, are major risk factors for the onset of type 2 diabetes. Evidence is emerging that nutriment-induced β-cell dysfunction could be related to indirect induction of a state of low grade inflammation. Our aim was to study whether hyperphagia associated obesity could promote an inflammatory response in pancreatic islets leading to ß-cell dysfunction. In the hyperphagic obese insulin resistant male Zucker rat, we measured the level of circulating pro-inflammatory cytokines and estimated their production as well as the expression of their receptors in pancreatic tissue and β-cells. Our main findings concern intra-islet pro-inflammatory cytokines from fa/fa rats: IL-1β, IL-6 and TNFα expressions were increased; IL-1R1 was also over-expressed with a cellular redistribution also observed for IL-6R. To get insight into the mechanisms involved in phenotypic alterations, abArrays were used to determine the expression profile of proteins implicated in different membrane receptors signaling, apoptosis and cell cycle pathways. Despite JNK overexpression, cell viability was unaffected probably because of decreases in cleaved caspase3 as well as in SMAC/DIABLO and APP, involved in the induction and amplification of apoptosis. Concerning β-cell proliferation, decreases in important cell cycle regulators (Cyclin D1, p35) and increased expression of SMAD4 probably contribute to counteract and restrain hyperplasia in fa/fa rat islets. Finally and probably as a result of IL-1β and IL-1R1 increased expressions with sub-cellular redistribution of the receptor, islets from fa/fa rats were found more sensitive to both stimulating and inhibitory concentrations of the cytokine; this confers some physiopathological relevance to a possible autocrine regulation of β-cell function by IL-1β. These results support the hypothesis that pancreatic islets from prediabetic fa/fa rats undergo an inflammatory process. That the latter could contribute to β-cell hyperactivity/proliferation and possibly lead to progressive β-cell failure in these animals, deserves further investigations.

Gelatinolytic matrix metalloproteinases (MMP-2, -9) play a critical role not only in mammals physiology but also during inflammation and healing processes. The natural stilbenoid, resveratrol (RES), exhibits potent antioxidant effects, in a hormetic mode of action, and is known to inhibit MMP-9. However, RES administration exhibits major issues, including poor bioavailability and water solubility, hampering its potential therapeutic effect in vivo. In the present study, we synthesized and evaluated five novel RES–lipid conjugates to increase their cell membrane penetration and improve their bioavailability. The best in vitro MMP-9 inhibitory activity of RES–lipids conjugates was observed with RES-linoleic acid (LA) (5 µM), when dissolved in a natural deep eutectic solvent (NADES), composed of an equimolar content of 1,2-propanediol:choline chloride (ChCl):water. The inhibition of MMP-9 expression by RES-LA in activated THP-1 monocytes, was, at least due to the deactivation of ERK1/2 and JNK1/2 MAP kinase signaling pathways. Moreover, RES-LA exhibited a strong effect protecting the TNF-α-induced exacerbated permeability in an HUVEC in vitro monolayer (by 81%) via the integrity protection of intercellular junction proteins from the MMP-9 activity. This effect was confirmed by using several complementary approaches including, the real-time monitoring of trans-endothelial electric resistance (TEER), the Transwell HUVEC permeability level, the microscopic examination of the platelet endothelial cell adhesion molecule-1 (CD31/PECAM-1) integrity as well as the fluorescence in intercellular spaces. Consequently, following this strong in vitro proof-of-concept, there is a need to test this promising RES–lipid derivative compound to control the pathological endothelial permeability in vivo.

Despite the promising anti-oxidant and anti-inflammatory effects of resveratrol (RES) on human health, pre-clinical and clinical studies are frequently disappointing, probably due to its low water-solubility and poor bioavailability. Even though a hormetic mode of action was clearly established for RES, the high doses commonly used to mitigate these issues, lead to adverse effects. Common hallmarks of multiple pathologies results from pathological-enhanced endothelial permeability due to both enhanced inflammation and matrix metalloprotease-9 (aMMP-9) activities. The main aim of this work was to optimize the RES capacity to inhibit aMMP-9 by using a new class of solvents, natural deep eutectic solvents (NADES) for a new RES formulation as compared with dimethyl-sulfoxide (DMSO). To obtain the appropriate NADES, 18 compounds combinations were prepared to select those exhibiting the optimized capacity to dissolve RES. The RES-NADES 1,2-propanediol:choline-chloride:water (PCW, 1:1:1 molar ratio) and compared with RES-DMSO for their aMMP-9-inhibitory capacities. Low concentrations of RES-NADES/PCW formulation exhibited both a biocompatible solubility and a strong increased aMMP-9-inhibitory activity, at least 10-fold, higher than RES-DMSO, reaching its hormetic mode of action. Following in vivo validations, some particular NADES could potentially be considered as the new generation of formulation for druggable compounds. Practical applications: Formulation of resveratrol in Natural Deep Eutectic solvents (NADES) optimizes its capacity to inhibit active matrix metalloprotease-9. The Resveratrol-NADES 1,2-propanediol:choline-was the most efficient and low concentrations exhibited both a biocompatible solubility and an increased aMMP-9-inhibitory activity, at least 10-fold, higher than RES-DMSO. Consequently, the NADES/PCW formulation allowed resveratrol to reach its hormetic mode of action. Following in vivo validations, some particular NADES could potentially be considered as the new generation of formulation for druggable compounds. The effect of resveratrol (RES) dissolved in either NADES/PCW or DMSO was assessed on the TNFa-activated human monocytes (THP-1). NADES/PCW was able to confer a significant increase of the MMP-9 inhibitory activity of RES, at low doses (at least 10-fold higher) than DMSO, Thus, these data on RES-NADES/PCW formulation support the hormetic effect of resveratrol in preserving the endothelial monolayer integrity by decreasing the exacerbated vascular permeability induced by the overproduction of active MMP-9, during inflammation resulting from infections, cancer, or other pathologies. (Résumé d'auteur