Background In people with SLE and in the MRL-Fas lpr lupus mouse model, macrophages and autoantibodies are central to lupus nephritis. IL-34 mediates macrophage survival and proliferation, is expressed by tubular epithelial cells (TECs), and binds to the cFMS receptor on macrophages and to a newly identified second receptor, PTPRZ. Methods To investigate whether IL-34-dependent intrarenal and systemic mechanisms promote lupus nephritis, we compared lupus nephritis and systemic illness in MRL-Fas lpr mice expressing IL-34 and IL-34 knockout (KO) MRL-Fas lpr mice. We also assessed expression of IL-34 and the cFMS and PTPRZ receptors in patients with lupus nephritis. Results Intrarenal IL-34 and its two receptors increase during lupus nephritis in MRL-Fas lpr mice. In knockout mice lacking IL-34, nephritis and systemic illness are suppressed. IL-34 fosters intrarenal macrophage accumulation via monocyte proliferation in bone marrow (which increases circulating monocytes that are recruited by chemokines into the kidney) and via intrarenal macrophage proliferation. This accumulation leads to macrophage-mediated TEC apoptosis. We also found suppression of circulating autoantibodies and glomerular antibody deposits in the knockout mice. This is consistent with fewer activated and proliferating intrarenal and splenic B cells in mice lacking IL-34, and with our novel discovery that PTPRZ is expressed by macrophages, B and T cells. These findings appear translatable to human patients with lupus nephritis, whose expression of IL-34, cFMS, and PTPRZ is similar to that seen in the MRL-Fas lpr lupus mouse model. Moreover, expression of IL-34 in TECs correlates with disease activity. Conclusions IL-34 is a promising novel therapeutic target for patients with lupus nephritis.
Cytomegalovirus (CMV) is the most common cause of congenital infection in developed countries and a major cause of neurological disability in children. Although CMV can affect multiple organs, the most important sequelae of intrauterine infection are related to lesions of the central nervous system. However, little is known about the pathogenesis and the cellular events responsible for neuronal damage in infants with congenital infection. Some studies have demonstrated that neural precursor cells (NPCs) show the greatest susceptibility to CMV infection in the developing brain. We sought to establish an in vitro model of CMV infection of the developing brain in order to analyze the cellular events associated with invasion by this virus. To this end, we employed two cell lines as a permanent source of NPC, avoiding the continuous use of human fetal tissue, the human SK-N-MC neuroblastoma cell line, and an immortalized cell line of human fetal neural origin, hNS-1. We also investigated the effect of the differentiation stage in relation to the susceptibility of these cell lines by comparing the neuroblastoma cell line with the multipotent cell line hNS-1. We found that the effects of the virus were more severe in the neuroblastoma cell line. Additionally, we induced hNS-1 to differentiate and evaluated the effect of CMV in these differentiated cells. Like SK-N-MC cells, hNS-1-differentiated cells were also susceptible to infection. Viability of differentiated hNS-1 cells decreased after CMV infection in contrast to undifferentiated cells. In addition, differentiated hNS-1 cells showed an extensive cytopathic effect whereas the effect was scarce in undifferentiated cells. We describe some of the effects of CMV in neural stem cells, and our observations suggest that the degree of differentiation is important in the acquisition of susceptibility.
Objective: Cytomegalovirus (CMV) is widely distributed and constitutes the main cause of congenital infections worldwide. CMV transmission during pregnancy represents one of the major impacts of this virus on public health. This study aimed at assessing glycoprotein B (gB) CMV genotypes in Mexican children and pregnant women, since there is limited information regarding CMV genomic diversity in Mexico. Methods: We analyzed CMV strains detected in Mexican children (n = 38) and women (n = 38) between 2001 and 2012. A fragment of the gB gene was amplified and sequenced, and genotypes were defined based on prototype sequences. Results: The gB1 genotype was detected more frequently in children (68.4%) compared to women (31.6%; p = 0.0028), while genotype 2 was more common in women (65.8%) compared to children (26.3%, p = 0.0012). Genotype 3 was uncommon in both groups (5.3 and 2.6%). Nucleotide sequences exhibited a high degree of similarity to prototype strains. However, we identified 17 distinct sequences that resulted in changes in the encoded amino acid sequence in four strains. Conclusions: gB1 and gB2 are the most common strains associated with CMV infection in Mexican children and women. In addition, we found that the frequency for each genotype differed amongst them, possibly due to variability in transmission or reactivation dynamics.
Objective. To determine the prevalence of SARS-CoV-2 antibodies among healthcare workers (HCW) and to identify factors associated with infection. Materials and methods. A cross-sectional study was conducted in a Covid-19 hospital in Morelos, Mexico. Antibodies against SARS-CoV-2 spike and nucleocapsid proteins were detected by ELISA. A bivariate and multivariable Poisson regression model were performed to identify factors associated with infection. Results. Among all participants, 31% had anti-SARS-CoV-2 antibodies, while only 13.1% had reported a history of positive RT-PCR. Individuals who reported cohabiting with someone with Covid-19, and those who had a previous RT-PCR test, were more likely to be seropositive. Laboratory personnel had the lowest seroprevalence (12.0%), while social workers had the highest (35.7%). Conclusions. The results of this study show the seroprevalence of SARS-CoV-2 antibodies among HCW in a hospital in Mexico, and underline the importance of serological tests for a better estimate of prevalence in health systems where only symptomatic cases are recorded.
class III/IV LN. Using RNA-in-situ hybridization methods, we document infiltration of class III/IV nephrtis biopsy tissue with PDCs with IFN-signature positive cells surrounding them, supporting local production of type I IFNs. Conclusions Our data support an association between type I IFN and class III/IV nephritis that is independent of overall SLEDAI and anti-dsDNA antibodies, suggesting that IFN is involved in renal pathogenesis. These data also suggest that IFN could predict renal disease activity or the future risk of developing LN, especially class III/IV LN in EA SLE patients.
Conjugated linoleic acid (CLA) is a mixture of positional and geometric isomers of linoleic acid (LA), which is reported as anti‐proliferative against glioblastoma (GBM). However, its toxicity on primary astrocytes remains unclear. The aim of this study is to evaluate the selectivity of bioactive isomers (CLA1) toward GBM and elucidate the possible mechanism of cytotoxicity. The findings show that CLA1 (a 50:50 mixture of cis‐9,trans‐11 CLA and trans‐10,cis‐12 CLA) decreases the viability of GBM but not the viability of normal astrocytes. In contrast, linoleic acid (LA) and CLA2 (a 25:25:50 mixture of cis‐9,trans‐11 CLA, trans‐10,cis‐12 CLA, and trans,trans‐CLA) does not modify the GBM viability, indicating that positional and geometric isomerism is relevant for CLA toxicity. Mitochondrial dysfunction and reactive oxygen species are involved in the toxic effects induced by CLA1 on transformed cells but not in astrocytes, while cell membrane integrity is not altered. In conclusion, these data suggest that CLA represents a possible adjuvant in the GBM therapy since it does not induce adverse side effects on primary astrocytes. Practical Applications: The practical applications of the present work are related to the potential and selective applications of CLA1 as adjuvant in the anti‐glioma therapy, studying firstly the effect of chemical structures derived from LA conversion to CLA, and the consequent mechanism of action induced by synthetic bioactive CLA isomers. The implication of this research is providing evidences that support the potential use of antitumoral drugs in combination with CLA1: 1) as an efficient vehicle for antitumoral drugs crossing the blood brain barrier in order to increase their bioavailability and destroy the tumor cells and 2) CLA1 per se promotes the low survival of glioma as is shown in the research. Bioactive Conjugated linoleic acid (CLA) isomers mixture (CLA1) decreases the viability of glioma C6 cells in comparison to its healthy counterpart, the astrocytes, which survive in presence of increasing concentrations of CLA1. That difference conducts to explore how CLA1 can act upon glioma C6 cells, showing that CLA1 increases the ROS concentration, decreases the MMP which affect the mitochondrion function and promoting apoptosis. In this study, the activation of the PPARγ receptor is not observed, suggesting that these actions are PPARγ receptor independent mechanism.
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