Limosilactobacillus fermentum CECT5716, a probiotic strain isolated from human milk, has reported beneficial effects on different gastrointestinal disorders. Moreover, it has shown its ability to ...restore altered immune responses, in association with microbiome modulation in different pathological conditions. Therefore, our aim was to assess the effects of a Limosilacbacillus fermentum CECT5716 in a rat experimental model of irritable bowel syndrome (IBS) that resembles human IBS. The experimental IBS was induced by deoxycholic acid (DCA) in rats and then, Limosilactobacillus fermentum CECT5716 (109 CFU/day/rat) was administered. Behavioral studies, hyperalgesia and intestinal hypersensitivity determinations were performed and the impact of the probiotic on the inflammatory and intestinal barrier integrity was evaluated. Additionally, the gut microbiota composition was analyzed. Limosilactobacillus fermentum CECT5716 attenuated the anxiety-like behavior as well as the visceral hypersensitivity and referred pain. Moreover, this probiotic ameliorated the gut inflammatory status, re-establishing the altered intestinal permeability, reducing the mast cell degranulation and re-establishing the gut dysbiosis in experimental IBS. Therefore, our results suggest a potential use of Limosilactobacillus fermentum CECT5716 in clinical practice for the management of IBS patients.
Melatonin has shown beneficial effects on obesity, both in humans and experimental models, via regulating the altered circadian rhythm and thus ameliorating the gut dysbiosis associated with this ...metabolic condition. However, its clinical use is limited, mostly due to its short half-life. Agomelatine is an agonist of the melatonin receptors that could be used to manage obesity and offer a better profile than melatonin.
Male C57BL/6 mice were fed a high fat diet and orally treated for five weeks with agomelatine, or melatonin or metformin, used as control drugs. Metabolic profile, inflammatory status, vascular dysfunction and intestinal microbiota composition were assessed.
Agomelatine lessened body weight gain, enhanced glucose and lipid metabolisms, and improved insulin resistance. It also reduced the obesity-associated inflammatory status and endothelial dysfunction, probably linked to its effect on gut dysbiosis, consisting of the restoration of bacterial populations with key functions, such as short chain fatty acid production.
Agomelatine can be considered as a novel therapeutic tool for the management of human obesity and its associated comorbidities.
Display omitted
•The behavior of arsenosugars on anion exchange-SPE is study for first time.•SPE was assessed as a clean-up method of arsenosugar from algae water extract.•SPE allows to isolate arsenosugars as the ...only arsenic species present in the solution.
Obtaining reliable speciation data for evaluating dietary exposure, and increasing understanding of arsenic biochemistry in algae, are hindered by the availability of suitable standards of arsenosugars, the major species in these types of samples. Moreover, chemical syntheses of such compounds have been reported to be complex and tedious. The aim of this work was to investigate the feasibility of the anionic exchange SPE cartridges (SAX and WAX) as an easy and quick alternative for the isolation and preconcentration of arsenosugars. Two commercial silica-based SPE cartridges strong anion exchange sorbent (DSC-SAX) and weak anion exchange sorbent (DSC-NH2) were compared for the SPE of three arsenosugars (PO4-Sug, SO3-Sug and SO4-Sug). The effect of pH, ionic strength, type of salt and elution solvent on the elution protocols of these arsenosugars are studied. Eluted solutions from SPE were analyzed by ICP-MS for total arsenic content and IC-ICP-MS for the study of arsenic speciation.
The developed SPE procedure allows to obtain a solution containing the three arsenosugars isolated from other arsenic species with recoveries over 75% for SO3-Sug and SO4-Sug, whereas for PO4-Sug were around 45%.
Background: Propyl propane thiosulfonate (PTSO) is an organosulfur compound from Allium spp. that has shown interesting antimicrobial properties and immunomodulatory effects in different experimental ...models. In this sense, our aim was to evaluate its effect on an experimental model of obesity, focusing on inflammatory and metabolic markers and the gut microbiota. Methods and results: Mice were fed a high-fat diet and orally treated with different doses of PTSO (0.1, 0.5 and 1 mg/kg/day) for 5 weeks. PTSO lessened the weight gain and improved the plasma markers associated with glucose and lipid metabolisms. PTSO also attenuated obesity-associated systemic inflammation, reducing the immune cell infiltration and, thus, the expression of pro-inflammatory cytokines in adipose and hepatic tissues (Il-1ẞ, Il-6, Tnf-α, Mcp-1, Jnk-1, Jnk-2, Leptin, Leptin R, Adiponectin, Ampk, Ppar-α, Ppar-γ, Glut-4 and Tlr-4) and improving the expression of different key elements for gut barrier integrity (Muc-2, Muc-3, Occludin, Zo-1 and Tff-3). Additionally, these effects were connected to a regulation of the gut microbiome, which was altered by the high-fat diet. Conclusion: Allium-derived PTSO can be considered a potential new tool for the treatment of metabolic syndrome.
Severe status of coronavirus disease 2019 (COVID-19) is extremely associated to cytokine release. Moreover, it has been suggested that blood group is also associated with the prevalence and severity ...of this disease. However, the relationship between the cytokine profile and blood group remains unclear in COVID-19 patients. In this sense, we prospectively recruited 108 COVID-19 patients between March and April 2020 and divided according to ABO blood group. For the analysis of 45 cytokines, plasma samples were collected in the time of admission to hospital ward or intensive care unit and at the sixth day after hospital admission. The results show that there was a risk of more than two times lower of mechanical ventilation or death in patients with blood group O (log rank:
= 0.042). At first time, all statistically significant cytokine levels, except from hepatocyte growth factor, were higher in O blood group patients meanwhile the second time showed a significant drop, between 20% and 40%. In contrast, A/B/AB group presented a maintenance of cytokine levels during time. Hepatocyte growth factor showed a significant association with intubation or mortality risk in non-O blood group patients (OR: 4.229, 95% CI (2.064-8.665),
< 0.001) and also was the only one bad prognosis biomarker in O blood group patients (OR: 8.852, 95% CI (1.540-50.878),
= 0.015). Therefore, higher cytokine levels in O blood group are associated with a better outcome than A/B/AB group in COVID-19 patients.
Antiplatelet therapy, the gold standard of care for patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI), is one of the therapeutic approaches most ...associated with the development of adverse drug reactions (ADRs). Although numerous studies have shown that pharmacological intervention based on a limited number of high-evidence variants (primarily CYP2C19*2 and *3) can reduce the incidence of major adverse cardiovascular events (MACEs), ADRs still occur at variable rates (10.1 % in our case) despite personalized therapy.
This study aimed to identify novel genetic variants associated with the endpoint of MACEs 12 months after PCI by designing and analyzing a targeted gene panel. We sequenced 244 ACS-PCI-stent patients (109 with event and 135 without event) and 99 controls without structural cardiovascular disease and performed an association analysis to search for unexpected genetic variants.
No single nucleotide polymorphisms reached genomic significance after correction, but three novel variants, including ABCA1 (rs2472434), KLB (rs17618244), and ZNF335 (rs3827066), may play a role in MACEs in ACS patients. These genetic variants are involved in regulating high-density lipoprotein levels and cholesterol deposition, and as they are regulatory variants, they may affect the expression of nearby lipid metabolism-related genes. Our findings suggest new targets (both at the gene and pathway levels) that may increase susceptibility to MACEs, but further research is needed to clarify the role and impact of the identified variants before these findings can be incorporated into the therapeutic decision-making process.
Abbreviations: ABCA1, ATP binding cassette subfamily a member 1; ACS, acute coronary syndrome; Cv, cardiovascular; DNA, deoxyribonucleic acid; KLB, Klotho Beta; PGx, pharmacogenomics; ZNF335, zinc finger protein 335 Display omitted
•Antiplatelets are drugs frequently implicated in the development of ADRs.•PGx helps select optimal drug and dose to improve ACS-ICP stent patients outcomes.•Certain ADRs cannot be prevented by preemptive genotyping of high-evidence variants.•We analyzed a custom gene panel for new variants for clinical consideration.•MACEs appear to be associated with intronic variants involved in lipid metabolism.
Colorectal cancer is a major health problem, where advances towards computer-aided diagnosis (CAD) systems to assist the endoscopist can be a promising path to improvement. Here, a deep learning ...model for real-time polyp detection based on a pre-trained YOLOv3 (You Only Look Once) architecture and complemented with a post-processing step based on an object-tracking algorithm to reduce false positives is reported. The base YOLOv3 network was fine-tuned using a dataset composed of 28,576 images labelled with locations of 941 polyps that will be made public soon. In a frame-based evaluation using isolated images containing polyps, a general
F
1
score of 0.88 was achieved (recall = 0.87, precision = 0.89), with lower predictive performance in flat polyps, but higher for sessile, and pedunculated morphologies, as well as with the usage of narrow band imaging, whereas polyp size < 5 mm does not seem to have significant impact. In a polyp-based evaluation using polyp and normal mucosa videos, with a positive criterion defined as the presence of at least one 50-frames-length (window size) segment with a ratio of 75% of frames with predicted bounding boxes (frames positivity), 72.61% of sensitivity (95% CI 68.99–75.95) and 83.04% of specificity (95% CI 76.70–87.92) were achieved (Youden = 0.55, diagnostic odds ratio (DOR) = 12.98). When the positive criterion is less stringent (window size = 25, frames positivity = 50%), sensitivity reaches around 90% (sensitivity = 89.91%, 95% CI 87.20–91.94; specificity = 54.97%, 95% CI 47.49–62.24; Youden = 0.45; DOR = 10.76). The object-tracking algorithm has demonstrated a significant improvement in specificity whereas maintaining sensitivity, as well as a marginal impact on computational performance. These results suggest that the model could be effectively integrated into a CAD system.
AbstractThe need for the restoration of buildings that have been suddenly damaged either by natural or human factors affects the tenants of the buildings and can generate posttraumatic stress. Few ...studies have been conducted on how to repair buildings under such circumstances, and no tools are available that facilitate either the decision-making or the management of social factors under a strategy that simultaneously considers social, technical, and planning aspects. In these cases, an intervention can be considered successful when it is technically and socially satisfactory for the tenants throughout the whole process of rehabilitation work. The emergency work that took place in a building of 40 dwellings is analyzed, which, following damage to an adjacent building, involved the evacuation of all residents and the immediate implementation of psychological first aid and building damage containment. The work was completed successfully in all aspects: economic, temporal, and social. The technical solutions and their implementation are discussed. Finally, an innovative model of action for the restoration of buildings under emergency conditions is proposed.
Ethnopharmacological relevance:
Serpylli herba
extract (SHE), composed of the aerial parts of wild thyme (
Thymus serpyllum
L.) (
Lamiaceae
family), is traditionally used in Europe and North Africa ...to treat diarrhea, gastric ulcers, intestinal parasites and upper respiratory tract infections. Recently, SHE has generated a great interest for irritable bowel syndrome (IBS) management, probably due to its intestinal anti-inflammatory properties shown in experimental colitis and the fact that its active components could preserve the intestinal barrier integrity, which is altered in patients with IBS.
Aim of study:
We aimed to test the effects of a SHE in a rat experimental model resembling human IBS.
Materials and methods:
IBS was provoked by deoxycholic acid (DCA). Rats were then treated with SHE (100 mg/kg) or gabapentin (70 mg/kg) and different inflammatory and gut barrier integrity markers were evaluated. Moreover, several gut hypersensitivity and hyperalgesia determinations were performed.
Results:
SHE improved referred pain and visceral hypersensitivity. Additionally, SHE enhanced immune status by downregulating of the expression of the pro-inflammatory mediators Il-1β, Il-6, Ifn-γ, Tlr-4, and the inducible enzyme
Cox-2
, thus inducing visceral analgesia, and promoting the restore of the gut barrier function by upregulating the mucins
Muc-2
and
Muc-3
. These anti-inflammatory effects could be related to its action on mast cells since it significantly inhibited the
β
-Hexosaminidase production in RBL-2H3 cells. Lastly, SHE also seems to modulate the serotonin pathway by restoring the altered expression of the 5-HT receptors
Htr-3
and
Htr-4
.
Conclusion:
SHE could be considered a potential new treatment for IBS, since it ameliorates hypersensitivity, visceral hyperalgesia, and inflammation. These beneficial effects may be due to the inhibition of mast cells degranulation and serotonin pathway.
Most consensus recommendations for the genetic diagnosis of neurodevelopmental disorders (NDDs) do not include the use of next generation sequencing (NGS) and are still based on chromosomal ...microarrays, such as comparative genomic hybridization array (aCGH). This study compares the diagnostic yield obtained by aCGH and clinical exome sequencing in NDD globally and its spectrum of disorders. To that end, 1412 patients clinically diagnosed with NDDs and studied with aCGH were classified into phenotype categories: global developmental delay/intellectual disability (GDD/ID); autism spectrum disorder (ASD); and other NDDs. These categories were further subclassified based on the most frequent accompanying signs and symptoms into isolated forms, forms with epilepsy; forms with micro/macrocephaly and syndromic forms. Two hundred and forty-five patients of the 1412 were subjected to clinical exome sequencing. Diagnostic yield of aCGH and clinical exome sequencing, expressed as the number of solved cases, was compared for each phenotype category and subcategory. Clinical exome sequencing was superior than aCGH for all cases except for isolated ASD, with no additional cases solved by NGS. Globally, clinical exome sequencing solved 20% of cases (versus 5.7% by aCGH) and the diagnostic yield was highest for all forms of GDD/ID and lowest for Other NDDs (7.1% versus 1.4% by aCGH) and ASD (6.1% versus 3% by aCGH). In the majority of cases, diagnostic yield was higher in the phenotype subcategories than in the mother category. These results suggest that NGS could be used as a first-tier test in the diagnostic algorithm of all NDDs followed by aCGH when necessary.
PDF
