Aim
A remarkable increase in metabolic syndrome (MetS) has occurred in HIV‐infected subjects. Gut dysbiosis is involved in the pathogenesis of metabolic disorders. Therefore, the aim is to explore ...the profile of the gut microbiota in Mexican population with HIV infection and MetS.
Methods and Results
In all, 30 HIV‐infected patients with MetS were compared to a group of 30 patients without MetS, treated with integrase inhibitors and undetectable viral load were included in the study. Stool samples were analysed by 16S rRNA next‐generation sequencing. High‐sensitivity C‐reactive protein >3 mg L−1 and higher scores in cardiometabolic indices were associated with MetS. The group with MetS was characterized by a decrease in α‐diversity, higher abundance of Enterobacteriaceae and Prevotella, as well as a dramatic decrease in bacteria producing short‐chain fatty acids. Prevotella negatively correlated with Akkermansia, Lactobacillus and Anaerostipes. Interestingly, the group without MetS presented higher abundance of Faecalibacterium, Ruminococcus, Anaerofilum, Oscillospira and Anaerostipes. Functional pathways related to energy metabolism and inflammation were increased in the group with MetS.
Conclusions
HIV‐infected patients with MetS present a strong inflammatory microbiota profile; therefore, future strategies to balance intestinal dysbiosis should be implemented.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Light stimulates carotenoid synthesis in plants during photomorphogenesis through the expression of PHYTOENE SYNTHASE (PSY), a key gene in carotenoid biosynthesis. The orange carrot (Daucus carota) ...synthesizes and accumulates high amounts of carotenoids in the taproot that grows underground. Contrary to other organs, light impairs carrot taproot development and represses the expression of carotenogenic genes, such as DcPSY1 and DcPSY2, reducing carotenoid accumulation. By means of RNA-seq, in a previous analysis we observed that carrot PHYTOCHROME RAPIDLY REGULATED1 (DcPAR1) is more highly expressed in the underground grown taproot compared to those grown in light. PAR1 is a transcriptional cofactor with a negative role in shade avoidance syndrome regulation in Arabidopsis (Arabidopsis thaliana) through the dimerization with PHYTOCHROME INTERACTING FACTORs (PIFs), allowing a moderate synthesis of carotenoids. Here, we show that overexpressing AtPAR1 in carrot increases carotenoid production in taproots grown underground as well as DcPSY1 expression. The high expression of AtPAR1 and DcPAR1 led us to hypothesize a functional role of DcPAR1 that was verified through in vivo binding to AtPIF7 and overexpression in Arabidopsis, where AtPSY expression and carotenoid accumulation increased together with a photomorphogenic phenotype. Finally, DcPAR1 antisense carrot lines presented a dramatic decrease in carotenoid levels and in relative expression of key carotenogenic genes as well as impaired taproot development. These results suggest that DcPAR1 is a key factor for secondary root development and carotenoid synthesis in carrot taproot grown underground.
Biological considerations suggest that renin-angiotensin system inhibitors might influence the severity of COVID-19. We aimed to evaluate whether continuing versus discontinuing renin-angiotensin ...system inhibitors (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) affects outcomes in patients admitted to hospital with COVID-19.
The REPLACE COVID trial was a prospective, randomised, open-label trial done at 20 large referral hospitals in seven countries worldwide. Eligible participants were aged 18 years and older who were admitted to hospital with COVID-19 and were receiving a renin-angiotensin system inhibitor before admission. Individuals with contraindications to continuation or discontinuation of renin-angiotensin system inhibitor therapy were excluded. Participants were randomly assigned (1:1) to continuation or discontinuation of their renin-angiotensin system inhibitor using permuted block randomisation, with allocation concealed using a secure web-based randomisation system. The primary outcome was a global rank score in which participants were ranked across four hierarchical tiers incorporating time to death, duration of mechanical ventilation, time on renal replacement or vasopressor therapy, and multiorgan dysfunction during the hospitalisation. Primary analyses were done in the intention-to-treat population. The REPLACE COVID trial is registered with ClinicalTrials.gov, NCT04338009.
Between March 31 and Aug 20, 2020, 152 participants were enrolled and randomly assigned to either continue or discontinue renin-angiotensin system inhibitor therapy (continuation group n=75; discontinuation group n=77). Mean age of participants was 62 years (SD 12), 68 (45%) were female, mean body-mass index was 33 kg/m
(SD 8), and 79 (52%) had diabetes. Compared with discontinuation of renin-angiotensin system inhibitors, continuation had no effect on the global rank score (median rank 73 IQR 40-110 for continuation vs 81 38-117 for discontinuation; β-coefficient 8 95% CI -13 to 29). There were 16 (21%) of 75 participants in the continuation arm versus 14 (18%) of 77 in the discontinuation arm who required intensive care unit admission or invasive mechanical ventilation, and 11 (15%) of 75 participants in the continuation group versus ten (13%) of 77 in the discontinuation group died. 29 (39%) participants in the continuation group and 28 (36%) participants in the discontinuation group had at least one adverse event (χ
test of adverse events between treatment groups p=0·77). There was no difference in blood pressure, serum potassium, or creatinine during follow-up across the two groups.
Consistent with international society recommendations, renin-angiotensin system inhibitors can be safely continued in patients admitted to hospital with COVID-19.
REPLACE COVID Investigators, REPLACE COVID Trial Social Fundraising Campaign, and FastGrants.
HIV infection results in marked alterations in the gut microbiota (GM), such as the loss of microbial diversity and different taxonomic and metabolic profiles. Despite antiretroviral therapy (ART) ...partially ablating gastrointestinal alterations, the taxonomic profile after successful new ART has shown wide variations. Our objective was to determine the GM composition and functions in people living with HIV (PLWHIV) under ART in comparison to seronegative controls (SC). Fecal samples from 21 subjects (treated with integrase strand-transfer inhibitors, INSTIs) and 18 SC were included. We employed 16S rRNA amplicon sequencing, coupled with PICRUSt2 and fecal short-chain fatty acid (SCFA) quantification by gas chromatography. The INSTI group showed a decreased α-diversity (
< 0.001) compared to the SC group, at the expense of increased amounts of
(
),
,
, and Gram-negative bacteria. Concurrently, we observed an enrichment in
and
, both SCFA-producing bacteria, and significant elevations in fecal butyrate in this group (
< 0.001). Interestingly, gut dysbiosis in PLWHIV was characterized by a proinflammatory environment orchestrated by
and elevated levels of butyrate associated with bacterial metabolic pathways, as well as the evident presence of butyrogenic bacteria. The role of this unique GM in PLWHIV should be evaluated, as well as the use of butyrate-based supplements and ART regimens that contain succinate, such as tenofovir disoproxil succinate. This mixed profile is described for the first time in PLWHIV from Mexico.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
HIV infection is characterized by CD4
T-cells depletion related to gut damage, microbial translocation, immune activation and intestinal and systemic low-grade inflammation. With the use of ...antiretroviral treatment, these alterations in HIV+ patients reach similar levels to HIV- controls. However, almost 20% patients have deficient immune reconstitution of CD4
T-cells, which make them more susceptible to develop non-AIDS and AIDS comorbidities.
HIV+ patients on ART, with sustained virologic control were grouped according to their immune reconstitution as: immunological responders (
= 18) and immunological non-responders (
= 18); also, HIV- controls were enrolled (
= 14). CD4
and CD8
T-cell activation (HLA-DR
and CD38
single and co-expression) were measured by flow cytometry. Serum levels of sCD14, sCD163, lipopolysaccharide, I-FABP, sST2, as well as fecal levels of calprotectin, lactoferrin and secretory IgA were evaluated by ELISA. Levels of C-reactive protein were determined by a high sensibility singleplex bead-based immunoassay. Serum and fecal concentrations of proinflammatory cytokines were quantified by multiplex bead-based immunoassay.
HLA-DR
and CD38
co-expression, as well as median fluorescence intensity in CD4
and CD8
T-cells subpopulations was greater in immunological non-responders group, after normalization and fold change calculation. Similarly, this group presented higher levels of sCD14, C-reactive protein, as well as fecal calprotectin and lactoferrin. Furthermore, both HIV+ groups showed elevated levels of proinflammatory cytokines in stool.
Our data suggests that despite the virologic control, HIV+ patients under treatment with deficient immune reconstitution showed elevation of both innate and T-cells immune activation, as well as intestinal and systemic inflammation. However, some patients with CD4
T-cells count above 350 cells/μL also presented these alterations. Future studies are necessary to evaluate the dynamics of multiple systemic and intestinal biomarkers in diverse types of HIV+ patients, as such as their clinical impact.
The study of stool microbiota has taken great relevance in the last years, given its role in the maintenance of the intestinal metabolic, physiological, and immunological homeostasis, as well as, its ...effect over HIV biomarkers levels such as CD4/CD8 ratio, high sensitivity C-Reactive Protein (hs-CRP), related to poor outcomes (rapid progression to AIDS). Several efforts have been made to characterize the gut microbiome. In HIV infection, most of the studies report the presence of a dysbiotic pattern; however, few of them have made an approach in elderly HIV-positive subjects despite the fact that nowadays this subgroup is rising. In this study, we compared the composition of faecal microbiota, Short Chain Fatty Acids (SCFAs), and systemic biomarkers between elderly HIV-positive and HIV-negative subjects.
A cross-sectional study with 18 HIV-negative controls and 20 HIV-positive patients. The quantification of Bacteroidetes, Firmicutes, Proteobacteria, Actinobacteria, Lactobacillus, Enterobacteriaceae, Bifidobacterium, Escherichia coli, Clostridium leptum, Clostridium coccoides was performed in faecal samples by qPCR. The analysis was performed by calculating the ΔCq of each microorganism using 16S rDNA as a reference gene. Faecal SCFAs were measured by HPLC. The hs-CRP and sCD14 were performed by ELISA.
An increase in the Firmicutes/Bacteroidetes ratio, coupled with a significant increase in the proteobacteria phylum was detected in HIV-positive subjects. In contrast, a decrease in the Clostridium leptum group was observed. Nevertheless, these elderly HIV-positive patients showed higher levels of total SCFAs mainly by an augmented propionic acid values, compared to HIV-negative subjects. Whereas high levels of hs-CRP were positively correlated with sCD14 in the HIV-positive group.
Alterations in bacterial communities reveals a dysbiotic state related to an unbalance of faecal SCFAs. Therefore, these intestinal conditions might drive an increase of poor prognostic biomarkers in elderly HIV-positive subjects.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
HIV-infection results in damage and dysfunction of the gastrointestinal system. HIV enteropathy includes pronounced CD4+ T-cell loss, increased intestinal permeability, and microbial translocation ...that promotes systemic immune activation, which is implicated in disease progression. A synbiotic is the combination of probiotics and prebiotics that could improve gut barrier function. Our study goal was to determine whether the use of a synbiotic, probiotics or a prebiotic can recover immunological parameters in HIV-infected subjects through of a reduction of microbial translocation and pro-inflammatory cytokine production.
A randomized, double-blind controlled study was performed; twenty Antiretroviral treatment-naïve HIV-infected subjects were subgrouped and assigned to receive a synbiotic, probiotics, a prebiotic, or a placebo throughout 16 weeks.
We had no reports of serious adverse-events. From baseline to week 16, the synbiotic group showed a reduction in bacterial DNA concentrations in plasma (p = 0.048). Moreover, the probiotic and synbiotic groups demonstrated a decrease in total bacterial load in feces (p = 0.05). The probiotic group exhibited a significant increment of beneficial bacteria load (such as Bifidobacterium; p = 0.05) and a decrease in harmful bacteria load (such as Clostridium; p = 0.063). In the synbiotic group, the CD4+ T-cells count increased (median: +102 cells/μL; p = 0.05) and the level of Interleukin 6 cytokine decreased significantly (p = 0.016).
Our study showed a significant increase in CD4+ T lymphocyte levels in the synbiotic group, which could delay the initiation of antiretroviral therapy and decrease costs in countries with limited resources.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Facial emotion recognition is one of the psychological processes of social cognition that begins during the first year of life, though the accuracy and speed of emotion recognition improves ...throughout childhood. The objective of this study was to carry out a preliminary study for the adaptation and validation of the CAM-C FACE test in Argentine children from 9 to 14 years old, by measuring hit rates and reaction times. The results of this study show that the unidimensional model is more appropriate when assessing the speed of performance (reaction times), with a satisfactory reliability (ρ = .950). Results also indicated that girls presented more correct answers compared to boys, while boys had longer reaction times. In addition, the group of children from 12 to 14 years old presented more correct answers compared to the group from 9 to 11 years old, while no differences were observed between groups in terms of reaction times.
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IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, UL, UM, UPUK
Agricultural activity demands the use of pesticides for plague control and extermination. In that matter, diazinon is one of the most widely used organophosphorus pesticides (OPs). Despite its ...benefits, the use of OPs in agricultural activities can also have negative effects since the excessive use of these substances can represent a major contamination problem for water bodies and organisms that inhabit them. The aim of this paper was to evaluate oxidative damage in lipids and proteins of Nile tilapia (Oreochromis niloticus) exposed acutely to diazinon (0.97, 1.95 and 3.95ppm) for 12 or 24h. The evaluation of oxidative damage was determined by quantifying lipid hydroperoxides (Fox method) and oxidized proteins (DNPH method). The data from this study suggest that diazinon induces a concentration-dependent oxidative damage in proteins, but not lipids, of the liver and gills of Nile tilapia. Furthermore, the treatment leads to a decrease in the concentration of total proteins, which can have serious consequences in cell physiology and fish development.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK, ZRSKP
Plants synthesize an astonishing diversity of isoprenoids, some of which play essential roles in photosynthesis, respiration, and the regulation of growth and development. Two independent pathways ...for the biosynthesis of isoprenoid precursors coexist within the plant cell: the cytosolic mevalonic acid (MVA) pathway and the plastidial methylerythritol phosphate (MEP) pathway. In at least some plants (including Arabidopsis), common precursors are exchanged between the cytosol and the plastid. However, little is known about the signals that coordinate their biosynthesis and exchange. To identify such signals, we arrested seedling development by specifically blocking the MVA pathway with mevinolin (MEV) or the MEP pathway with fosmidomycin (FSM) and searched for MEV-resistant Arabidopsis mutants that also could survive in the presence of FSM. Here, we show that one such mutant, rim1, is a new phyB allele (phyB-m1). Although the MEV-resistant phenotype of mutant seedlings is caused by the upregulation of MVA synthesis, its resistance to FSM most likely is the result of an enhanced intake of MVA-derived isoprenoid precursors by the plastid. The analysis of other light-hyposensitive mutants showed that distinct light perception and signal transduction pathways regulate these two differential mechanisms for resistance, providing evidence for a coordinated regulation of the activity of the MVA pathway and the crosstalk between cell compartments for isoprenoid biosynthesis during the first stages of seedling development.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
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