Acute kidney injury (AKI) often triggers physiological processes aimed at restoring renal function and architecture. However, this response can become maladaptive, leading to nephron loss and ...fibrosis. Although the therapeutic effects of resveratrol (RSV) are well established, its impact after AKI and for subsequent chronic kidney disease (CKD) remains unclear. This study assessed whether transient administration of RSV following ischaemia–reperfusion injury (IRI) could prevent the progression to CKD. Forty‐one male Wistar rats were assigned randomly to sham surgery, bilateral renal ischaemia for 30 min (IR) or IR+RSV. The RSV treatment commenced 24 h after IRI and continued for 10 days. The rats were studied for either 10 days or 5 months, after which kidney function and structure were evaluated. Mitochondrial homeostasis, oxidant defence and renal inflammation state were also evaluated. Despite having the same severity of AKI, rats receiving RSV for 10 days after IRI exhibited significant improvement in kidney histological injury and reduced inflammation, although renal haemodynamic recovery was less pronounced. Resveratrol effectively prevented the elevation of tubular injury‐related molecules and profibrotic signalling with reduced myofibroblast proliferation. Furthermore, RSV substantially improved the antioxidant response and mitochondrial homeostasis. After 5 months, RSV prevented the transition to CKD, as evidenced by the prevention of progressive proteinuria, renal dysfunction and tubulointerstitial fibrosis. This study demonstrates that a brief treatment with RSV following IRI is enough to prevent maladaptive repair and the development of CKD. Our findings highlight the importance of the early days of reperfusion, indicating that maladaptive responses can be reduced effectively following severe AKI.
Key points
Physiological processes activated after acute kidney injury (AKI) can lead to maladaptive responses, causing nephron loss and fibrosis. Prophylactic renoprotection with resveratrol (RSV) has been described in experimental AKI, but its impact after AKI and for subsequent chronic kidney disease (CKD) remains unclear.
In this study, we found that histological tubular injury persists 10 days after ischaemia–reperfusion injury and contributes to a failed repair phenotype in proximal tubular cells.
Short‐term RSV intervention influenced the post‐ischaemic repair response and accelerated tubular recovery by reducing oxidative stress and mitochondrial damage. Furthermore, RSV targeted inflammation and profibrotic signalling during the maladaptive response, normalizing both processes.
Resveratrol effectively prevented AKI‐to‐CKD transition even 5 months after the intervention.
The study serves as a proof of concept, proposing RSV as a valuable candidate for further translational clinical studies to mitigate AKI‐to‐CKD transition.
figure legend In rodents experiencing ischaemic (I/R) acute kidney injury, a 10 day regimen of resveratrol (RSV) post‐injury ameliorated multiple aspects of maladaptive repair, including tubular injury, cellular death, mitochondrial dysfunction, disrupted antioxidant response, inflammatory processes and the initiation of fibrotic pathways. These beneficial effects led to a reduction in the progression towards chronic kidney disease (CKD), evident even 5 months post‐injury. Created with Biorender.com.
Mental load and fatigue are important causes of performance decreases and accidents in different activities. However, a robust systematic review, detailing the instruments used to quantify them, is ...currently lacking. The purpose of this study was to summarize and classify by derivations the validated instruments used to quantify mental load and fatigue. The most representative electronic databases in the scope of this review, PubMed, WOS, Scopus, SPORTDiscus, and PsycINFO (until September 2020) were searched for studies that included instruments to analyze mental load and fatigue. The quality of the selected studies was scored using a quality assessment checklist. A total of 40 papers were included. Most of the papers used subjective scales (75%) to quantify mental load and fatigue, with a small presence of behavioral (
= 5) and objective techniques (
= 5). Less is known about the analysis of mental load and fatigue using a combination of derivations. Despite the high cost and complexity of objective techniques, research that applies these measures is important for further analysis of brain processes in mental load and fatigue. The design of a battery of tests that include the three types of derivations also seems necessary.
This study describes, to some extent, the VCC contribution as an early stimulation of the macrophage lineage. Regarding the onset of the innate immune response caused by infection, the β form of IL-1 ...is the most important interleukin involved in the onset of the inflammatory innate response. Activated macrophages treated in vitro with VCC induced the activation of the MAPK signaling pathway in a one-hour period, with the activation of transcriptional regulators for a surviving and pro-inflammatory response, suggesting an explanation inspired and supported by the inflammasome physiology. The mechanism of IL-1β production induced by VCC has been gracefully outlined in murine models, using bacterial knockdown mutants and purified molecules; nevertheless, the knowledge of this mechanism in the human immune system is still under study. This work shows the soluble form of 65 kDa of the
cytotoxin (also known as hemolysin), as it is secreted by the bacteria, inducing the production of IL-1β in the human macrophage cell line THP-1. The mechanism involves triggering the early activation of the signaling pathway MAPKs pERK and p38, with the subsequent activation of (p50) NF-κB and AP-1 (cJun and cFos), determined by real-time quantitation. The evidence shown here supports that the monomeric soluble form of the VCC in the macrophage acts as a modulator of the innate immune response, which is consistent with the assembly of the NLRP3 inflammasome actively releasing IL-1β.
Background
We have focused on the alteration of the PD-1/PD-L1 pathway in celiac disease and discussed the roles of the PD1 pathway in regulating the immune response. We explored the idea that the ...altered mRNA splicing process in key regulatory proteins could represent a novel source to identify diagnostic, prognostic, and therapeutic targets in celiac disease.
Methods
We characterized the PD1 mRNA variants’ profile in CD patients and in response to gluten peptides’ incubation after
in vitro
experiments. Total RNA from whole blood was isolated, and the coding region of the human
PD-1
mRNA was amplified by cDNA PCR.
Results
PCR amplification of the human PD-1 coding sequence revealed an association between the over-expression of the sPD-1 protein and the PD-1Δex3 transcript in celiac disease. Thus, we have found three novel alternative spliced isoforms, two of which result in a truncated protein and the other isoform with a loss of 14 aa of exon 2 and complete exon 3 (Δ3) which could encode a new soluble form of PD1 (sPD-1).
Conclusions
Our study provides evidence that dietary gluten can modulate processes required for cell homeostasis through the splicing of pre-mRNAs encoding key regulatory proteins, which represents an adaptive mechanism in response to different nutritional conditions.
•We present a probability-based DTW for gesture segmentation.•We present the BoVDW framework for gesture classification.•New VFHCRH descriptor for depth images.
We present a methodology to address ...the problem of human gesture segmentation and recognition in video and depth image sequences. A Bag-of-Visual-and-Depth-Words (BoVDW) model is introduced as an extension of the Bag-of-Visual-Words (BoVW) model. State-of-the-art RGB and depth features, including a newly proposed depth descriptor, are analysed and combined in a late fusion form. The method is integrated in a Human Gesture Recognition pipeline, together with a novel probability-based Dynamic Time Warping (PDTW) algorithm which is used to perform prior segmentation of idle gestures. The proposed DTW variant uses samples of the same gesture category to build a Gaussian Mixture Model driven probabilistic model of that gesture class. Results of the whole Human Gesture Recognition pipeline in a public data set show better performance in comparison to both standard BoVW model and DTW approach.
Celiac Disease Autoimmunity López Casado, Miguel Ángel; Lorite, Pedro; Ponce de León, Candelaria ...
Archivum Immunologiae et Therapiae Experimentalis,
12/2018, Letnik:
66, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Celiac disease is an autoimmune condition triggered by the ingestion of gluten, the protein fraction of wheat, barley and rye. It is not simply an intestinal disease; it is multifactorial caused by ...many different genetic factors acting together with non-genetic causes. Similar to other autoimmune diseases, celiac disease is a polygenic disorder for which the major histocompatibility complex locus is the most important genetic factor, and is the result of an immune response to self-antigens leading to tissue destruction and the autoantibodies production. Celiac disease exemplifies how an illness can have autoimmune-like features having to be driven by exogenous antigen and how can be reasonably considered as a model of organ-specific autoimmunity.
Highly diverse bacterial populations inhabit the gastrointestinal tract and modulate host inflammation and promote immune tolerance. In allogeneic hematopoietic stem cell transplantation (allo-HSCT), ...the gastrointestinal mucosa is damaged, and colonizing bacteria are impacted, leading to an impaired intestinal microbiota with reduced diversity. We examined the impact of intestinal diversity on subsequent mortality outcomes following transplantation. Fecal specimens were collected from 80 recipients of allo-HSCT at the time of stem cell engraftment. Bacterial 16S rRNA gene sequences were characterized, and microbial diversity was estimated using the inverse Simpson index. Subjects were classified into high, intermediate, and low diversity groups and assessed for differences in outcomes. Mortality outcomes were significantly worse in patients with lower intestinal diversity; overall survival at 3 years was 36%, 60%, and 67% for low, intermediate, and high diversity groups, respectively (P = .019, log-rank test). Low diversity showed a strong effect on mortality after multivariate adjustment for other clinical predictors (transplant related mortality: adjusted hazard ratio, 5.25; P = .014). In conclusion, the diversity of the intestinal microbiota at engraftment is an independent predictor of mortality in allo-HSCT recipients. These results indicate that the intestinal microbiota may be an important factor in the success or failure in allo-HSCT.
•Intestinal diversity is predictive of mortality in allo-HSCT.
PDF
