Contribution of Nucleotide-Binding Oligomerization Domain-like (NOD) Receptors to the Immune and Metabolic Health.

Nucleotide-binding oligomerization domain-like (NOD) receptors rely on the interface between immunity and metabolism. Dietary factors constitute critical players in the activation of innate immunity and modulation of the gut microbiota. The latter have been involved in worsening or improving the control and promotion of diseases such as obesity, type 2 diabetes, metabolic syndrome, diseases known as non-communicable metabolic diseases (NCDs), and the risk of developing cancer. Intracellular NODs play key coordinated actions with innate immune 'Toll-like' receptors leading to a diverse array of gene expressions that initiate inflammatory and immune responses. There has been an improvement in the understanding of the molecular and genetic implications of these receptors in, among others, such aspects as resting energy expenditure, insulin resistance, and cell proliferation. Genetic factors and polymorphisms of the receptors are determinants of the risk and severity of NCDs and cancer, and it is conceivable that dietary factors may have significant differential consequences depending on them. Host factors are difficult to influence, while environmental factors are predominant and approachable with a preventive and/or therapeutic intention in obesity, T2D, and cancer. However, beyond the recognition of the activation of NODs by peptidoglycan as its prototypical agonist, the underlying molecular response(s) and its consequences on these diseases remain ill-defined. Metabolic (re)programming is a hallmark of NCDs and cancer in which nutritional strategies might play a key role in preventing the unprecedented expansion of these diseases. A better understanding of the participation and effects of immunonutritional dietary ingredients can boost integrative knowledge fostering interdisciplinary science between nutritional precision and personalized medicine against cancer. This review summarizes the current evidence concerning the relationship(s) and consequences of NODs on immune and metabolic health.

Vulvovaginal candidiasis and asymptomatic vaginal colonization in Portugal: Epidemiology, risk factors and antifungal pattern.

Vulvovaginal candidiasis (VVC) has been identified as a global issue of concern due to its clinical, social and economic implications. The emerging relevance of VVC makes it crucial to increase the knowledge on its epidemiological and etiological features in order to improve its prevention and treatment. Thus, this study aimed to reveal the incidence, microbiology, antifungal pattern and risk factors of VVC in Portugal. For that, high vaginal samples were collected from 470 symptomatic and asymptomatic participants; Candida spp. were identified with molecular techniques and their antifungal susceptibility was analyzed with E-tests. The results revealed an incidence of VVC among women with vulvovaginitis of 74.4%. Furthermore, 63.7% of asymptomatic women were colonized with Candida spp. Importantly, women with history of recurrent vaginal infections, those who use over-the-counter antifungals, oral contraceptive pills and non-cotton underwear were found to be at significantly higher risk of developing VVC. Candida albicans was the most common species (59%), followed by Candida glabrata (27%), in a total of eight distinct species, with similar distribution among colonized and infected participants. Of note, various isolates, especially of the most common species, showed low susceptibility towards fluconazole. In contrast, only few isolates showed low susceptibility towards caspofungin. Overall, this study suggests that the identification of species causing VVC and their antifungal susceptibility are urgently needed in clinical practice in order to improve the decision for the most adequate treatment. It also suggests that avoiding certain risk behaviors may prevent the development of VVC. LAY SUMMARY: Vaginal candidiasis (VVC) is a relevant infection worldwide. In this study, we identified several risk behaviors that may promote VVC and concluded that vaginal microbiologic analyses are urgently required in clinical practice in order to improve the prevention and treatment of this disease.

Development and Characterization of Monoolein-Based Liposomes of Carvacrol, Cinnamaldehyde, Citral, or Thymol with Anti-Candida Activities.

There is an increasing need for novel drugs and new strategies for the therapy of invasive candidiasis. This study aimed to develop and characterize liposome-based nanoparticles of carvacrol, cinnamaldehyde, citral, and thymol with anti-Candida activities. Dioctadecyldimethylammonium bromide- and monoolein-based liposomes in a 1:2 molar ratio were prepared using a lipid-film hydration method. Liposomes were assembled with equal volumes of liposomal stock dispersion and stock solutions of carvacrol, cinnamaldehyde, citral, or thymol in dimethyl sulfoxide. Cytotoxicity was tested on RAW 264.7 macrophages. In vitro antifungal activity of liposomes with phytocompounds was evaluated according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) methodology using clinical isolates of Candida albicans, Candida auris, Candida dubliniensis, and Candida tropicalis Finally, the ability of macrophage cells to kill Candida isolates after addition of phytocompounds and their nanoparticles was determined. Nanoparticles with 64 µg/ml of cinnamaldehyde, 256 µg/ml of citral, and 128 µg/ml of thymol had the best characteristics among the formulations tested. The highest encapsulation efficiencies were achieved with citral (78% to 83%) and carvacrol (66% to 71%) liposomes. Carvacrol and thymol in liposome-based nanoparticles were nontoxic regardless of the concentration. Moreover, carvacrol and thymol maintained their antifungal activity after encapsulation, and there was a significant reduction (∼41%) of yeast survival when macrophages were incubated with carvacrol or thymol liposomes. In conclusion, carvacrol and thymol liposomes possess high stability, low cytotoxicity, and antifungal activity that act synergistically with macrophages.