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1.
Crit Rev Food Sci Nutr ; : 1-17, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39262156

RESUMEN

Food quality is adversely affected by physical, chemical, enzymatic, and microbiological reactions, leading to it becoming inedible. Thus, finding alternative methods to preserve foods effectively and extend their shelf life is important. While chemical preservatives have been effective in preventing the growth of harmful pathogens in foods and extending their shelf life, they can also adversely affect consumers' health. For example, nitrites commonly used as preservatives in processed meats have been linked to the development of cancer. This is why researchers, and the food industry are exploring various options to find nontoxic and safe biopreservatives that can be used to preserve food. One such promising option is biopreservatives because they are derived from natural sources, such as plants and insects. This review explores the antimicrobial properties of various biopreservatives, including bacteriocins, polymers, bacteriophages, enzymes, and natural oils, and how they work together to create a synergistic effect in food preservation.

2.
Biochem Biophys Res Commun ; 734: 150672, 2024 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-39260206

RESUMEN

AIMS: Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung condition, the cause of which remains unknown and for which no effective therapeutic treatment is currently available. Chlorogenic acid (CGA), a natural polyphenolic compound found in different plants and foods, has emerged as a promising agent due to its anti-inflammatory, antioxidant, and antifibrotic properties. However, the molecular mechanisms underlying the therapeutic effect of CGA in IPF remain unclear. The purpose of this study was to analyze the pharmacological impact and underlying mechanisms of CGA in IPF. MAIN METHODS: Using network pharmacology analysis, genes associated with IPF and potential molecular targets of CGA were identified through specialized databases, and a protein-protein interaction (PPI) network was constructed. Molecular docking was performed to accurately select potential therapeutic targets. To investigate the effects of CGA on lung histology and key gene expression, a murine model of bleomycin-induced lung fibrosis was used. KEY FINDINGS: Network pharmacology analysis identified 384 were overlapped between CGA and IPF. Key targets including AKT1, TP53, JUN, CASP3, BCL2, MMP9, NFKB1, EGFR, HIF1A, and IL1B were identified. Pathway analysis suggested the involvement of cancer, atherosclerosis, and inflammatory processes. Molecular docking confirmed the stable binding between CGA and targets. CGA regulated the expression mRNA of EGFR, MMP9, AKT1, BCL2 and IL1B and attenuated pulmonary fibrosis in the mouse model. SIGNIFICANCE: CGA is a promising multi-target therapeutic agent for IPF, which is supported by its efficacy in reducing fibrosis through the modulation of key pathways. This evidence provides a basis to further investigate CGA as an IPF potential treatment.

3.
EMBO J ; 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39210146

RESUMEN

DNA i-motif structures are formed in the nuclei of human cells and are believed to provide critical genomic regulation. While the existence, abundance, and distribution of i-motif structures in human cells has been demonstrated and studied by immunofluorescent staining, and more recently NMR and CUT&Tag, the abundance and distribution of such structures in human genomic DNA have remained unclear. Here we utilise high-affinity i-motif immunoprecipitation followed by sequencing to map i-motifs in the purified genomic DNA of human MCF7, U2OS and HEK293T cells. Validated by biolayer interferometry and circular dichroism spectroscopy, our approach aimed to identify DNA sequences capable of i-motif formation on a genome-wide scale, revealing that such sequences are widely distributed throughout the human genome and are common in genes upregulated in G0/G1 cell cycle phases. Our findings provide experimental evidence for the widespread formation of i-motif structures in human genomic DNA and a foundational resource for future studies of their genomic, structural, and molecular roles.

4.
Front Chem ; 12: 1423500, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39050374

RESUMEN

Bioactive peptides derived from plant sources have gained significant attention for their potential use in preventing and treating chronic degenerative diseases. However, the efficacy of these peptides depends on their bioaccessibility, bioavailability, and stability. Encapsulation is a promising strategy for improving the therapeutic use of these compounds. It enhances their stability, prolongs their shelf life, protects them from degradation during digestion, and enables better release control by improving their bioaccessibility and bioavailability. This review aims to analyze the impact of various factors related to peptide encapsulation on their stability and release to enhance their biological activity. To achieve this, it is necessary to determine the composition and physicochemical properties of the capsule, which are influenced by the wall materials, encapsulation technique, and operating conditions. Furthermore, for peptide encapsulation, their charge, size, and hydrophobicity must be considered. Recent research has focused on the advancement of novel encapsulation methodologies that permit the formation of uniform capsules in terms of size and shape. In addition, it explores novel wall materials, including polysaccharides derived from unconventional sources, that allow the precise regulation of the rate at which peptides are released into the intestine.

5.
Molecules ; 29(14)2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-39064822

RESUMEN

Chysobalanus icaco L. (C. icaco) is a plant that is native to tropical America and Africa. It is also found in the southeast region of Mexico, where it is used as food and to treat certain diseases. This study aimed to carry out a phytochemical analysis of an aqueous extract of C. icaco seed (AECS), including its total phenol content (TPC), total flavonoid content (TFC), and condensed tannins (CT). It also aimed to examine the antioxidant and metal-ion-reducing potential of the AECS in vitro, as well as its toxicity and anti-inflammatory effect in mice. Antioxidant and metal-ion-reducing potential was examined by inhibiting DPPH, ABTS, and FRAP. The acute toxicity test involved a single administration of different doses of the AECS (0.5, 1, and 2 g/kg body weight). Finally, a single administration at doses of 150, 300, and 600 mg/kg of the AECS was used in the carrageenan-induced model of subplantar acute edema. The results showed that the AECS contained 124.14 ± 0.32 mg GAE, 1.65 ± 0.02 mg EQ, and 0.910 ± 0.01 mg of catechin equivalents/g dried extract (mg EC/g de extract) for TPC, TFC and CT, respectively. In the antioxidant potential assays, the values of the median inhibition concentration (IC50) of the AECS were determined with DPPH (0.050 mg/mL), ABTS (0.074 mg/mL), and FRAP (0.49 mg/mL). Acute toxicity testing of the AECS revealed no lethality, with a median lethal dose (LD50) value of >2 g/kg by the intragastric route. Finally, for inhibition of acute edema, the AECS decreased inflammation by 55%, similar to indomethacin (59%, p > 0.05). These results demonstrated that C. icaco seed could be considered a source of bioactive molecules for therapeutic purposes due to its antioxidant potential and anti-inflammatory activity derived from TPC, with no lethal effect from a single intragastric administration in mice.


Asunto(s)
Antiinflamatorios , Antioxidantes , Edema , Extractos Vegetales , Semillas , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/química , Ratones , Antioxidantes/farmacología , Antioxidantes/química , Semillas/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Edema/tratamiento farmacológico , Edema/inducido químicamente , Carragenina/toxicidad , Flavonoides/farmacología , Flavonoides/química , Modelos Animales de Enfermedad , Pruebas de Toxicidad Aguda , Fitoquímicos/farmacología , Fitoquímicos/química , Masculino , Fenoles/química , Fenoles/farmacología
6.
Molecules ; 29(12)2024 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-38930808

RESUMEN

In this study, a beverage made from a combination of Agave sap (AS) and prickly pear juice (PPJ) was analyzed for its nutrients and bioactive and potentially health-promoting compounds. The beverage was evaluated for its ability to act as an antioxidant, regulate glycemic properties, and undergo gut bacterial fermentation in vitro. The major mono- and oligosaccharides present in the beverage were galacturonic acid (217.74 ± 13.46 mg/100 mL), rhamnose (227.00 ± 1.58 mg/100 mL), and fructose (158.16 ± 8.86 mg/mL). The main phenolic compounds identified were protocatechuic acid (440.31 ± 3.06 mg/100 mL) and catechin (359.72 ± 7.56 mg/100 mL). It was observed that the beverage had a low glycemic index (<40) and could inhibit digestive carbohydrases. The combination of ingredients also helped to reduce gas production during AS fermentation from 56.77 cm3 to 15.67 cm3. The major SCFAs produced during fermentation were butyrate, acetate, and propionate, with valerate being produced only during the late fermentation of the AS. This beverage is rich in bioactive compounds, such as polyphenols and dietary fiber, which will bring health benefits when consumed.


Asunto(s)
Agave , Antioxidantes , Jugos de Frutas y Vegetales , Agave/química , Jugos de Frutas y Vegetales/análisis , Antioxidantes/química , Antioxidantes/farmacología , Antioxidantes/análisis , Fermentación , Hidroxibenzoatos/análisis , Polifenoles/análisis , Polifenoles/química , Pyrus/química , Fenoles/análisis , Fenoles/química , Ramnosa/análisis , Ramnosa/química , Catequina/análisis , Catequina/química , Catequina/análogos & derivados , Ácidos Hexurónicos
7.
Methods Protoc ; 7(3)2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38804337

RESUMEN

Intestinal macrophages have been poorly studied in fish, mainly due to the lack of specific molecular markers for their identification and isolation. To address this gap, using the zebrafish Tg(mpeg1:EGFP) transgenic line, we developed a fluorescence-activated cell sorting strategy (FACS) that allows us to isolate different intestinal macrophage subpopulations, based on GFP expression and morphological differences. Also, we achieved the purification of high-quality total RNA from each population to perform transcriptomic analysis. The complete strategy comprises three steps, including intestine dissection and tissue dissociation, the isolation of each intestinal macrophage population via FACS, and the extraction of total RNA. To be able to characterize molecularly different macrophage subpopulations and link them to their functional properties will allow us to unravel intestinal macrophage biology.

8.
Am J Ophthalmol Case Rep ; 34: 102039, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38680527

RESUMEN

Purpose: To describe the use of FLACS (Femtosecond-Laser-Assisted Cataract Surgery) and pupiloplasty technique employed in a cataract surgery associated with iris-lens-zonule coloboma, as well as to report the advantages that FLACS can provide in this type of complicated surgery. Observations: During FLACS (Victus® - TECHNOLAS, Bausch and Lomb Incorporated, USA), after the docking procedure, the parameters of capsulotomy, fragmentation and incisions were manually adjusted. Iris retractors were anchored to the edge of the anterior lens capsule to provide stability to the bag during phacoemulsification maneuvers, and a capsular tension ring and intraocular lens (IOL) were implanted. Iris repair was approached using a modification of the slip-knot technique. For this purpose, a 10.0 Prolene on a straight needle was used and knotted extraocularly, over the conjunctiva. Finally, an anterior vitrectomy was performed as a precaution. Conclusions and importance: In spite of the existing controversy regarding FLACS technology compared to conventional surgery, it seems to be beneficial in complicated cases such as cataracts associated with iris and lens coloboma, since it allows the modification of different parameters that facilitate and ensure surgery safety. On the other hand, the iris repair technique described facilitates manipulation of the iris sutures. In addition, complementary techniques such as the use of a capsular tension ring and pupiloplasty help to center and stabilize the IOL, and to reduce the symptoms derived from iris coloboma, obtaining a better visual quality.

9.
Int J Rheum Dis ; 27(3): e15122, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38487975

RESUMEN

Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes inflammation and pain, which can lead to the loss of normal joint function. Although the exact cause of the disease is not yet fully understood, both environmental factors and genetics may play a role in its development. Moreover, research suggests microbiota contributes to the onset and progression of RA. People with RA show higher quantities of bacteria such as Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Prevotella copri, Proteus mirabilis, and Lactobacillus salivarius compared to healthy individuals. Conversely, studies propose that Lactobacillus casei, a probiotic bacterium with immunomodulatory properties, has beneficial effects for RA in murine and human models. Therefore, this work reviews the potential role of the gut microbiota in the development of RA and explores the feasibility of using probiotic bacteria as a supplementary treatment for this disease.


Asunto(s)
Artritis Reumatoide , Microbioma Gastrointestinal , Microbiota , Probióticos , Humanos , Ratones , Animales , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/terapia , Inflamación , Probióticos/uso terapéutico
10.
Chemistry ; 30(27): e202400295, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38462477

RESUMEN

We demonstrate the formation of supramolecular nanotubes from molecular triangles in a single crystal by balancing the hydrogen bonds and halogen interactions between individual macrocycles. Thereby, we template the supramolecular nanotube growth by intermolecular interactions encoded directly in the macrocycles instead of those provided by the crystallization solvent. Ultimately, we show that replacing bromines for iodines in the macrocycle is necessary to achieve this supramolecular organization by enhancing the strength of the halogen interactions and concomitant reduction of the detrimental hydrogen bonds. We investigated the nature and the interplay of the individual intermolecular interactions by analysis of the experimental single crystal data and quantum chemical calculations. This work enriches the available toolbox of supramolecular interactions and will aid and abet the development of rationally-designed materials with a long-range 1D tubular organization.

11.
Rural Remote Health ; 23(4): 8227, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37988704

RESUMEN

INTRODUCTION: Sexual and gender minority people who live in rural areas are less likely to have had a HIV test in the previous 12 months compared with those who live in non-rural areas. We assessed the independent contribution of distance and time required to travel to receive a HIV test on recent uptake of HIV testing. METHODS: We conducted a cross-sectional survey of sexual and gender minority populations in the southern US. We used Poisson regression with robust standard errors to estimate prevalence ratios to compare uptake of HIV testing in the previous 12 months among those who traveled more than 20 miles (~32 km) and more than 30 minutes to their most recent HIV test compared with those who traveled less distance and time to their most recent test, respectively. RESULTS: A total of 508 (n=155 rural, n=348 non-rural) participants completed the survey. Of these, 398 (78.5%) had received a HIV test in the previous 12 months. Those who traveled more than 20 miles (~32 km) to their most recent test were more likely to have not received a HIV test in the previous 12 months compared with those who traveled 20 miles (~32 km) or less (adjusted prevalence ratio 2.25; 95% confidence interval 1.22-4.17). There were no differences based on travel time to the most recent test. CONCLUSION: Distance, but not time, to travel to receive a HIV test is independently associated with reduced HIV testing. More geographically proximal options or access to home-based testing might reduce this barrier.


Asunto(s)
Infecciones por VIH , Minorías Sexuales y de Género , Humanos , Estudios Transversales , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Conducta Sexual , Prueba de VIH
12.
Foods ; 12(22)2023 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-38002201

RESUMEN

Cocoa is rich in polyphenols and alkaloids that act as antioxidants, anticarcinogens, and anti-inflammatories. Analytical methods commonly used to determine the proximal chemical composition of cocoa, total phenols, and antioxidant capacity are laborious, costly, and destructive. It is important to develop fast, simple, and inexpensive methods to facilitate their evaluation. Chemometric models were developed to identify the variety and predict the chemical composition (moisture, protein, fat, ash, pH, acidity, and phenolic compounds) and antioxidant capacity (ABTS and DPPH) of three cocoa varieties. SIMCA model showed 99% reliability. Quantitative models were developed using the PLS algorithm and favorable statistical results were obtained for all models: 0.93 < R2c < 0.98 (R2c: calibration determination coefficient); 0.03 < SEC < 4.34 (SEC: standard error of calibration). Independent validation of the quantitative models confirmed their good predictive ability: 0.93 < R2v < 0.97 (R2v: validation determination coefficient); 0.04 < SEP < 3.59 (SEP: standard error of prediction); 0.08 < % error < 10.35). SIMCA model and quantitative models were applied to five external cocoa samples, obtaining their chemical composition using only 100 mg of sample in less than 15 min. FT-MIR spectroscopy coupled with chemometrics is a viable alternative to conventional methods for quality control of cocoa beans without using reagents, and with the minimum sample preparation and quantity.

13.
Microbiol Spectr ; 11(6): e0042923, 2023 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-37800972

RESUMEN

IMPORTANCE: Nowadays, the routine herd diagnosis is usually performed exclusively on bulls, as they remain permanently infected, and prevention and control of Tritrichomonas foetus transmission are based on identifying infected animals and culling practices. The existence of other forms of transmission and the possible role of pseudocysts or cyst-like structures as resistant forms requires rethinking the current management and control of this parasitic disease in the future in some livestock regions of the world.


Asunto(s)
Enfermedades de los Bovinos , Parásitos , Infecciones Protozoarias en Animales , Tritrichomonas foetus , Animales , Bovinos , Masculino , Infecciones Protozoarias en Animales/parasitología , Agua , Enfermedades de los Bovinos/prevención & control , Tracto Gastrointestinal
14.
Plant Foods Hum Nutr ; 78(3): 493-505, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37578677

RESUMEN

Hypertension is a condition induced by oxidative stress causing an alteration in the endothelium, which increases the risk of suffering from other degenerative diseases. This review compiles the findings on peptides from food proteins with antioxidant and antihypertensive activities. Antihypertensive peptides are mainly focused on renin inhibition. Peptides containing hydrophobic amino acids have antioxidant and renin inhibitory activities, as reported by studies on the biological activity of peptides from various food sources evaluated separately and simultaneously. Peptides from food sources can present multiple biological activities. Moreover, antioxidant peptides have the potential to be evaluated against renin, offering an alternative for hypertension therapy without causing adverse side effects.


Asunto(s)
Antihipertensivos , Hipertensión , Antihipertensivos/farmacología , Renina , Antioxidantes/farmacología , Péptidos/farmacología , Hipertensión/tratamiento farmacológico
15.
Nucleic Acids Res ; 51(15): 7736-7748, 2023 08 25.
Artículo en Inglés | MEDLINE | ID: mdl-37439359

RESUMEN

Nucleic acids not only form the basis of heredity, but are increasingly a source of novel nano-structures, -devices and drugs. This has spurred the development of chemically modified alternatives (xeno nucleic acids (XNAs)) comprising chemical configurations not found in nature to extend their chemical and functional scope. XNAs can be evolved into ligands (XNA aptamers) that bind their targets with high affinity and specificity. However, detailed investigations into structural and functional aspects of XNA aptamers have been limited. Here we describe a detailed structure-function analysis of LYS-S8-19, a 1',5'-anhydrohexitol nucleic acid (HNA) aptamer to hen egg-white lysozyme (HEL). Mapping of the aptamer interaction interface with its cognate HEL target antigen revealed interaction epitopes, affinities, kinetics and hot-spots of binding energy similar to protein ligands such as anti-HEL-nanobodies. Truncation analysis and molecular dynamics (MD) simulations suggest that the HNA aptamer core motif folds into a novel and not previously observed HNA tertiary structure, comprising non-canonical hT-hA-hT/hT-hT-hT triplet and hG4-quadruplex structures, consistent with its recognition by two different G4-specific antibodies.


Asunto(s)
Aptámeros de Nucleótidos , G-Cuádruplex , Ácidos Nucleicos , Ligandos , Aptámeros de Nucleótidos/química , Ácidos Nucleicos/química , Simulación de Dinámica Molecular , Técnica SELEX de Producción de Aptámeros
16.
Plants (Basel) ; 12(12)2023 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-37375942

RESUMEN

Chickpeas are one of the most widely consumed legumes worldwide and they might prevent diseases such as cancer. Therefore, this study evaluates the chemopreventive effect of chickpea (Cicer arietinum L.) on the evolution of colon carcinogenesis induced with azoxymethane (AOM) and dextran sodium sulfate (DSS) in a mice model at 1, 7, and 14 weeks after induction. Accordingly, the expression of biomarkers-such as argyrophilic nucleolar organizing regions (AgNOR), cell proliferation nuclear antigen (PCNA), ß-catenin, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2)-was assessed in the colon of BALB/c mice fed diets supplemented with 10 and 20% cooked chickpea (CC). The results showed that a 20% CC diet significantly reduced tumors and biomarkers of proliferation and inflammation in AOM/DSS-induced colon cancer mice. Moreover, body weight loss decreased and the disease activity index (DAI) was lower than the positive control. Lastly, tumor reduction was more evident at week 7 in the groups fed a 20% CC diet. In conclusion, both diets (10% and 20% CC) exert a chemopreventive effect.

17.
Artículo en Inglés | MEDLINE | ID: mdl-37174177

RESUMEN

There is no definitive evidence on the extent of SARS-CoV-2's effect on the retina. This study aims to determine if the natural history of SARS-CoV-2 infection affects tomographic findings in the retina of patients with COVID-19 pneumonia. This is a prospective cohort study of patients hospitalized with COVID-19 pneumonia. The patients underwent ophthalmological explorations and optical coherence tomography during the acute phase of the infection and at a follow-up 12 weeks later. The primary outcomes were the central retinal thickness and central choroidal thickness, which were compared longitudinally and with non-COVID-19 historical controls. No statistically relevant differences were observed in the longitudinal analysis of the thickness of the central retina (p = 0.056), central choroid (p = 0.99), retinal nerve fiber layer (p = 0.21), or ganglion cell layer (p = 0.32). Patients with acute COVID-19 pneumonia showed significantly greater central retinal thickness than non-COVID controls (p = 0.006). In conclusion, tomographic measures of the retina and choroid are not influenced by the phase of COVID-19 infection and remain stable during 12 weeks. The central retinal thickness may increase in the acute phase of COVID-19 pneumonia, but more epidemiological studies using optical coherence tomography in the early stages of the disease are needed.


Asunto(s)
COVID-19 , Neumonía , Humanos , Estudios Prospectivos , Estudios Longitudinales , COVID-19/diagnóstico por imagen , SARS-CoV-2 , Retina/diagnóstico por imagen , Tomografía de Coherencia Óptica/métodos
19.
Antioxidants (Basel) ; 12(3)2023 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-36978791

RESUMEN

Sepsis syndrome is a highly lethal uncontrolled response to an infection, which is characterized by sepsis-induced coagulopathy (SIC). High-density lipoprotein (HDL) exhibits antithrombotic activity, regulating coagulation in vascular endothelial cells. Sepsis induces the release of several proinflammatory molecules, including reactive oxygen species, which lead to an increase in oxidative stress in blood vessels. Thus, circulating lipoproteins, such as HDL, are oxidized to oxHDL, which promotes hemostatic dysfunction, acquiring prothrombotic properties linked to the severity of organ failure in septic-shock patients (SSP). However, a rigorous and comprehensive investigation demonstrating that oxHDL is associated with a coagulopathy-associated deleterious outcome of SSP, has not been reported. Thus, we investigated the participation of plasma oxHDL in coagulopathy-associated sepsis pathogenesis and elucidated the underlying molecular mechanism. A prospective study was conducted on 42 patients admitted to intensive care units, (26 SSP and 16 non-SSP) and 39 healthy volunteers. We found that an increased plasma oxHDL level in SSP was associated with a prothrombotic phenotype, increased mortality and elevated risk of death, which predicts mortality in SSP. The underlying mechanism indicates that oxHDL triggers an endothelial protein expression reprogramming of coagulation factors and procoagulant adhesion proteins, to produce a prothrombotic environment, mainly mediated by the endothelial LOX-1 receptor. Our study demonstrates that an increased plasma oxHDL level is associated with coagulopathy in SSP through a mechanism involving the endothelial LOX-1 receptor and endothelial protein expression regulation. Therefore, the plasma oxHDL level plays a role in the molecular mechanism associated with increased mortality in SSP.

20.
Biol Res ; 56(1): 8, 2023 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-36869357

RESUMEN

BACKGROUND: Sepsis is an uncontrolled inflammatory response against a systemic infection that results in elevated mortality, mainly induced by bacterial products known as endotoxins, producing endotoxemia. Disseminated intravascular coagulation (DIC) is frequently observed in septic patients and is associated with organ failure and death. Sepsis activates endothelial cells (ECs), promoting a prothrombotic phenotype contributing to DIC. Ion channel-mediated calcium permeability participates in coagulation. The transient reception potential melastatin 7 (TRPM7) non-selective divalent cation channel that also contains an α-kinase domain, which is permeable to divalent cations including Ca2+, regulates endotoxin-stimulated calcium permeability in ECs and is associated with increased mortality in septic patients. However, whether endothelial TRPM7 mediates endotoxemia-induced coagulation is not known. Therefore, our aim was to examine if TRPM7 mediates coagulation during endotoxemia. RESULTS: The results showed that TRPM7 regulated endotoxin-induced platelet and neutrophil adhesion to ECs, dependent on the TRPM7 ion channel activity and by the α-kinase function. Endotoxic animals showed that TRPM7 mediated neutrophil rolling on blood vessels and intravascular coagulation. TRPM7 mediated the increased expression of the adhesion proteins, von Willebrand factor (vWF), intercellular adhesion molecule 1 (ICAM-1), and P-selectin, which were also mediated by the TRPM7 α-kinase function. Notably, endotoxin-induced expression of vWF, ICAM-1 and P-selectin were required for endotoxin-induced platelet and neutrophil adhesion to ECs. Endotoxemic rats showed increased endothelial TRPM7 expression associated with a procoagulant phenotype, liver and kidney dysfunction, increased death events and an increased relative risk of death. Interestingly, circulating ECs (CECs) from septic shock patients (SSPs) showed increased TRPM7 expression associated with increased DIC scores and decreased survival times. Additionally, SSPs with a high expression of TRPM7 in CECs showed increased mortality and relative risk of death. Notably, CECs from SSPs showed significant results from the AUROC analyses for predicting mortality in SSPs that were better than the Acute Physiology and Chronic Health Evaluation II (APACHE II) and the Sequential Organ Failure Assessment (SOFA) scores. CONCLUSIONS: Our study demonstrates that sepsis-induced DIC is mediated by TRPM7 in ECs. TRPM7 ion channel activity and α-kinase function are required by DIC-mediated sepsis-induced organ dysfunction and its expression are associated with increased mortality during sepsis. TRPM7 appears as a new prognostic biomarker to predict mortality associated to DIC in SSPs, and as a novel target for drug development against DIC during infectious inflammatory diseases.


Asunto(s)
Coagulación Intravascular Diseminada , Endotoxemia , Sepsis , Canales Catiónicos TRPM , Animales , Ratas , Molécula 1 de Adhesión Intercelular , Selectina-P , Células Endoteliales , Calcio , Factor de von Willebrand , Endotoxinas
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