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Although the epidemiology of pathogenic Candida species causing invasive human diseases is changing, Candida albicans still remains the most common cause of bloodstream infections worldwide. The propensity of this pathogen to cause infections is undoubtedly the result of its unique genetic plasticity that allow it to adapt and respond quickly to a myriad of changing conditions both in the host and in the environment. For this reason, we decided to investigate the genetic diversity of this important fungal pathogen in a particular category of patients with severe neurological deficits including the hospital environments where they are hospitalized. Genetic diversity of 21 C. albicans isolates recovered from blood, hands of healthcare workers and hospital environments was evaluated by using multilocus sequence typing (MLST) which revealed a high genetic heterogeneity with a set of 18 diploid sequence types (DSTs) recovered among 21 isolates investigated. Interestingly, 13 of these 18 MLST genotypes were completely new and added to the C. albicans MLST central database. Six eBURST clonal complexes (CC-1, CC-2, CC-6, CC-9, CC-27 and CC-42) and three singletons contained all DSTs found in this study. Among all the new DSTs identified, DST3388 was the most intriguing as this genotype was recovered from a typical C. albicans isolate clustering within the MLST-Clade 13, the most divergent evolutionary lineage within C. albicans population containing only isolates with unusual phenotypes originally known as Candida africana. In conclusion, the results of this study expand our understanding of the molecular epidemiology and global population structure of C. albicans suggesting that further studies on different categories of patients and hospital environments are needed to better understand how the population of this species adapts and evolves in heterogeneous hosts and changing environments., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The nuclear factor κB (NF-κB) pathway plays a key role in innate and adaptive immunity, cell proliferation and survival, inflammation and tumors development. MiR-146a is an immune system regulator that has anti-inflammatory function in multiple cell types and conditions. Here we demonstrate activation of canonical NF-κB pathway in monocytic cells upon HSV-1 replication. By constructing and using a recombinant HSV-1\EGFP virus, we monitored the capability of the virus to recruit NF-κB and we report that the phosphorylation of p65 protein correlates with an active virus replication at single-cell level. In addition, we found that upregulation of miR-146a during viral replication is strictly dependent on NF-κB activation and correlates with tight control of the interleukin-1 receptor-associate kinase 1 (IRAK1). Accordingly, THP-1 DN IκBα cells, expressing a dominant negative mIκBα, did not show upregulation of miR-146a upon HSV-1 infection. Our data suggest that the expression of miRNA-146a modulates NF-κB activation through targeting IRAK1 during HSV-1 replication in THP-1 cells.

The transcription factor nuclear factor-kappa B (NF-κB) is a crucial player of the antiviral innate response. Intriguingly, however, NF-κB activation is assumed to favour herpes simplex virus (HSV) infection rather than restrict it. Apoptosis, a form of innate response to viruses, is completely inhibited by HSV in fully permissive cells, but not in cells incapable to fully sustain HSV replication, such as immunocompetent cells. To resolve the intricate interplay among NF-κB signalling, apoptosis and permissiveness to HSV-1 in monocytic cells, we utilized U937 monocytic cells in which NF-κB activation was inhibited by expressing a dominant-negative IκBα. Surprisingly, viral production was increased in monocytic cells in which NF-κB was inhibited. Moreover, inhibition of NF-κB led to increased apoptosis following HSV-1 infection, associated with lysosomal membrane permeabilization. High expression of late viral proteins and induction of apoptosis occurred in distinct cells. Transcriptional analysis of known innate response genes by real-time quantitative reverse transcription-PCR excluded a contribution of the assayed genes to the observed phenomena. Thus, in monocytic cells NF-κB activation simultaneously serves as an innate process to restrict viral replication as well as a mechanism to limit the damage of an excessive apoptotic response to HSV-1 infection. This finding may clarify mechanisms controlling HSV-1 infection in monocytic cells.

Indole-3-acetic acid is the main auxin produced by plants and plays a key role in the plant growth and development. This hormone is also present in humans where it is considered as a uremic toxin deriving from tryptophan metabolism. However, beyond this peculiar aspect, the involvement of auxin in human pathophysiology has not been further investigated. Since it is a growth hormone, we evaluated its proliferative properties in an in vitro model of mammalian renal tubular epithelial cells. We employed an experimental model of renal tubular epithelial cells belonging to the LLC-PK1 cell line that is derived from the kidney of healthy male pig. Growth effects of auxin against LLC-PK1 cell lines were determined by a rapid colorimetric assay. Increasing concentrations of auxin (to give a final concentration from 1 to 1000 ng/mL) were added and microplates were incubated for 72 h. Each auxin concentration was assayed in four wells and repeated four times. Cell proliferation significantly increased, compared to control cells, 72 h after addition of auxin to cultured LLC-PK1 cells. Statistically significant values were observed when 100 ng/mL (p < 0.01) and 1000 ng/mL (p < 0.05) were used. In conclusion, auxin influences cell growth not only in plants, where its role is well documented, but also in mammalian cell lines. This observation opens new scenarios in the field of tissue regeneration and may stimulate a novel line of research aiming at investigating whether this hormone really influences human physiology and pathophysiology and in particular, kidney regeneration.

Vasopressin (AVP) is a hormone with antidiuretic properties that is also involved in cellular proliferation of breast, pulmonary, and pancreatic neoplasias, attributable to the interaction with specific receptors, among which is the V2-R. Using a culture model of CAKI-2 and A498 cancer cells, our study aimed to verify if renal carcinoma cells also express V2-R and whether receptor activation modulates their proliferation. Immunofluorescence and RT-PCR showed that both CAKI-2 and A498 cells effectively synthesize and express the V2-R. Administration of the vasopressin analogue DDAVP induced an evident growth in both CAKI-2 and A498 cell lines. However, this proliferative effect was completely avoided by the preventive addition of the V2-R antagonist SR121463B (satavaptan). Our study shows for the first time that renal cancer may effectively synthesize and express the V2-R. Furthermore, AVP exerts in vitro a proliferative effect by acting on this receptor, as the selective V2-R blockage is able to completely prevent the cellular growth. A validation of these findings with in vivo models is required to ascertain if the eventual presence of V2-R could influence the aggressiveness of human renal neoplasias. From this point of view, a new, interesting therapeutical application of V2-R antagonists in the treatment of renal cancer could also be proposed, similar to that successfully described in the treatment of autosomal polycystic kidney disease (ADPKD)., (Copyright © 2010 Elsevier Inc. All rights reserved.)

In the present paper, we aimed to verify whether the interaction of the glycoprotein D (gD) of herpes simplex 1 (HSV-1) with the HSV-1 receptor HVEM is involved in NF-kappaB-dependent protection against apoptosis by gD. To this purpose, first we utilized MAbs that interfere with gD/HVEM interaction and U937 cells that naturally express human HVEM on their surface. Pre-incubation with these MAbs, but not with a control antibody, partially reverted the protection of infectious HSV-1 towards anti-Fas induced apoptosis in U937 cells. Similarly, pre-incubation of UV-inactivated HSV-1 (UV-HSV-1) or recombinant gD with the same MAbs, significantly reduced the inhibition of Fas-mediated apoptosis by UV-HSV-1 or gD, respectively, in U937 cells. Moreover, coculture with stable transfectants expressing at surface level wild type gD protected U937 cells against Fas-induced apoptosis, while coculture with transfectants expressing a mutated form of gD, incapable to bind HVEM, did not protect. Finally, UV-HSV-1 protected against staurosporine-induced apoptosis in U937 cells as well as in the CHO transfectants expressing human HVEM on their surface, but not in the control CHO transfectants, which did not express HVEM. These results suggest that signaling triggered by binding of gD to HVEM could represent an additional mechanism of evasion from premature apoptotic death exerted by HSV-1-gD in HVEM-expressing cells, disclosing new opportunities of cell death manipulation by using gD preparations.