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1.
J Coll Physicians Surg Pak ; 30(1): S7-S10, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33650415

RESUMEN

OBJECTIVE: To determine the effects of tocilizumab (TCZ) on inflammatory markers, laboratory indices; and short-term outcome in patients with severe COVID-19. STUDY DESIGN: Cross-sectional analytical study. Place and Duration of the Study: Hayatabad Medical Complex, Peshawar, Pakistan from 10th June till 31st August 2020. METHODOLOGY: Fifty-four patients with severe COVID-19 fulfilled the inclusion criteria and were included. All patients had received TCZ (4 mg/kg) in addition to standard treatment. Serum C-reactive protein (CRP), lactate dehydrogenase (LDH), D-dimer levels, full blood count, and liver function tests (LFTs) were checked before and 24 hours after receiving TCZ. Short-term outcome, defined as survival at day 28, was determined from hospital record/telephonic contact. Paired t-test was employed to assess the statistical significance of mean differences between the pre- and post-TCZ variables, considering a p-value of <0.05 as significant. RESULTS: Overall, the mean pre- and post-TCZ CRP was 18.7 ± 10.7 and 10.2 ± 8.6 mg/dl (p <0.001). It was 18.0 ± 10.3 and 10.3 ± 8.8 mg/dl (p=0.003) in survivors; and 19.4 ± 11.4 and 10.2 ± 8.7 mg/dl (p=0.005) in non-survivors, respectively. Overall, mean D-dimer level decreased from 12.5 ± 23 to 10.3 ± 12.2 µg/ml following TCZ (p=0.643); it decreased from 15.8 ± 29.8 to 11.4 ± 10.6 µg/ml (p=0.612) in survivors; and 9.0 ± 12.8 to 9.2 ± 14.1 µg/ml (p=0.961) in non-survivors, respectively. There were no significant differences in the pre- and post-TCZ LDH levels overall and between the groups. The 28-day mortality was 46.3%. CONCLUSION: Tocilizumab results in a significant reduction in CRP, while mean change in LDH and D-dimers was not substantial. The mean change in inflammatory markers did not predict survival. Key Words: Tocilizumab, COVID-19, Biomarkers, Outcome, Mortality.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Citocinas/metabolismo , Inflamación/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/metabolismo , /metabolismo , Estudios Transversales , Humanos , Persona de Mediana Edad , Pakistán/epidemiología , Pandemias , Estudios Retrospectivos , Sobrevivientes
2.
Front Immunol ; 12: 633297, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33717172

RESUMEN

The C-X-C motif chemokine ligand 17 (CXCL17) is chemotactic for myeloid cells, exhibits bactericidal activity, and exerts anti-viral functions. This chemokine is constitutively expressed in the respiratory tract, suggesting a role in lung defenses. However, little is known about the participation of CXCL17 against relevant respiratory pathogens in humans. Here, we evaluated the serum levels and lung tissue expression pattern of CXCL17 in a cohort of patients with severe pandemic influenza A(H1N1) from Mexico City. Peripheral blood samples obtained on admission and seven days after hospitalization were processed for determinations of serum CXCL17 levels by enzyme-linked immunosorbent assay (ELISA). The expression of CXCL17 was assessed by immunohistochemistry (IHQ) in lung autopsy specimens from patients that succumbed to the disease. Serum CXCL17 levels were also analyzed in two additional comparative cohorts of coronavirus disease 2019 (COVID-19) and pulmonary tuberculosis (TB) patients. Additionally, the expression of CXCL17 was tested in lung autopsy specimens from COVID-19 patients. A total of 122 patients were enrolled in the study, from which 68 had pandemic influenza A(H1N1), 24 had COVID-19, and 30 with PTB. CXCL17 was detected in post-mortem lung specimens from patients that died of pandemic influenza A(H1N1) and COVID-19. Interestingly, serum levels of CXCL17 were increased only in patients with pandemic influenza A(H1N1), but not COVID-19 and PTB. CXCL17 not only differentiated pandemic influenza A(H1N1) from other respiratory infections but showed prognostic value for influenza-associated mortality and renal failure in machine-learning algorithms and regression analyses. Using cell culture assays, we also identified that human alveolar A549 cells and peripheral blood monocyte-derived macrophages increase their CXCL17 production capacity after influenza A(H1N1) pdm09 virus infection. Our results for the first time demonstrate an induction of CXCL17 specifically during pandemic influenza A(H1N1), but not COVID-19 and PTB in humans. These findings could be of great utility to differentiate influenza and COVID-19 and to predict poor prognosis specially at settings of high incidence of pandemic A(H1N1). Future studies on the role of CXCL17 not only in severe pandemic influenza, but also in seasonal influenza, COVID-19, and PTB are required to validate our results.


Asunto(s)
Biomarcadores/metabolismo , Quimiocinas CXC/metabolismo , Subtipo H1N1 del Virus de la Influenza A/fisiología , Gripe Humana/diagnóstico , Pulmón/metabolismo , Mycobacterium tuberculosis/fisiología , /fisiología , Adulto , Anciano , /mortalidad , Quimiocinas CXC/genética , Quimiocinas CXC/inmunología , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Humanos , Gripe Humana/mortalidad , Pulmón/patología , Masculino , México , Persona de Mediana Edad , Pandemias , Evaluación del Resultado de la Atención al Paciente , Pronóstico , Análisis de Supervivencia , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/mortalidad , Adulto Joven
4.
Int Heart J ; 62(2): 390-395, 2021 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-33731531

RESUMEN

Perivascular adipose tissue (PVAT) secretes large amounts of inflammatory mediators and plays a certain role in atherosclerosis formation from the exterior of the vessel. In the present study, we examined the expression level of inflammation-related mediators using adipose tissue samples harvested from patients with and without coronary artery disease (CAD). The subjects were 23 patients who underwent elective coronary bypass surgery (CAD group) and 17 patients who underwent elective mitral valve surgery (non-CAD group) between January 2017 and March 2018. The adipose tissue was harvested from three sites: the ascending aorta (AO), subcutaneous fat (SC), and pericoronary artery (CO) for the measurement of the expression levels of interleukin (IL) -1ß, IL-6, IL-10, tumor necrosis factor (TNF) -α, interferon (INF) -γ, and arginase (Arg) -1. In both the non-CAD and CAD groups, the expression levels of all mediators, except Agr-1, which showed a tendency to have higher levels in the SC than in the AO and CO, tended to upregulate in the AO than in the SC and CO. The CAD group had higher values of almost all mediators, except Arg-1. Most importantly, the expression levels of IL-1ß, IL-6, and IL-10 in the coronary artery were significantly higher in the CAD group. The expression levels of inflammatory mediators in the pericoronary adipose tissue were significantly higher in the CAD than in the non-CAD group. The adipose tissue appears to influence atherosclerosis formation from the exterior of the coronary artery.


Asunto(s)
Tejido Adiposo/metabolismo , Aterosclerosis/metabolismo , Enfermedad de la Arteria Coronaria/metabolismo , Mediadores de Inflamación/metabolismo , Anciano , Aterosclerosis/diagnóstico , Biomarcadores/metabolismo , Vasos Coronarios , Femenino , Humanos , Masculino
5.
Anaesthesia ; 76 Suppl 4: 118-130, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33682102

RESUMEN

Cardiovascular disease is the worldwide leading cause of death in women. Biological differences between the sexes, a result of genetic, epigenetic and sex hormone-mediated factors, are complex and incompletely understood. These differences are compounded by socio-cultural factors and together account for the variation in the prevalence, presentation and natural history of cardiovascular disease between men and women. Although there is growing recognition of sex-specific determinants of outcomes, women remain under-represented in clinical trials, and sex-disaggregated diagnostic and management strategies are not currently recommended in clinical guidelines. Women remain more likely to experience delays in diagnosis, to be treated less aggressively and to have worse outcomes. As a consequence, cardiovascular disease in women remains understudied, underdiagnosed and undertreated. This review will focus on female-specific characteristics of cardiovascular disease and how these may impact on anaesthetic and peri-operative risk assessment and care. We highlight significant differences between the sexes in the natural history of cardiovascular disease, including those disease entities that are more common in women, such as sudden coronary artery dissection or microvascular dysfunction. Given the rapidly rising incidence of maternal cardiovascular disease and associated complications, special consideration is given to the risk assessment and management of these conditions during pregnancy. Increased awareness of these issues has the potential to improve the effectiveness of the multidisciplinary heart team and ultimately improve the care provided to women.


Asunto(s)
Enfermedades Cardiovasculares/patología , Anestésicos/administración & dosificación , Biomarcadores/metabolismo , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/cirugía , Femenino , Humanos , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/patología , Hipertensión Pulmonar/cirugía , Infarto del Miocardio/patología , Infarto del Miocardio/cirugía , Embarazo , Factores de Riesgo , Factores Sexuales
6.
Braz J Biol ; 82: e230147, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33729329

RESUMEN

Metals and agrochemicals are among the main aquatic contaminants, being able to trigger oxidative stress in exposed organisms. The objective of this work was to evaluate the correlation between the level of oxidative stress biomarkers in Aegla crabs (Crustacea, Anomura) with (i) the set of metals present in the streams sediment and (ii) with land uses of three hydrographic basins. The study was carried out in streams (≤ 2nd order) of hydrographic basins in southern Brazil (Basins of Rio Suzana, Rio Ligeirinho-Leãozinho and Rio Dourado). In these streams were quantified the land uses and Cu, Cr, Cd, Fe, Mn and Zn concentrations in the sediment. The enzymes Catalase (CAT) and Glutathione Reductase (GR), as well as the level of membrane lipid peroxidation (TBARS), were analyzed in adult females. The PCA analysis showed that the distribution of metals was different between the basins. Cd, Cr and Fe were correlated positively with CAT and negatively with TBARS and GR. The Dourado basin had the lowest concentrations of these three metals and the highest levels of TBARS. However, in Dourado basin there is predominance of agriculture land use, and TBARS was positively correlated with agricultural land use. Besides in Dourado basin, GR activity was higher than in the others basins, indicating a compensatory response in relation to CAT inhibition. The basins of Suzana and Ligeirinho-Leãozinho rivers had lower TBARS values, which may be due to the induction of CAT in response to metals accumulated in sediment. In summary, this work indicates that in the basins with a higher concentration of toxic metals there is an adaptive response of CAT induction, which reduces TBARS in Aegla. On the other hand, in the basin with lower metallic contamination, TBARS occurrence was primarily influenced by agricultural land use.


Asunto(s)
Anomuros , Metales Pesados , Contaminantes Químicos del Agua , Agricultura , Animales , Biomarcadores/metabolismo , Brasil , Monitoreo del Ambiente , Femenino , Metales Pesados/análisis , Estrés Oxidativo , Ríos , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/toxicidad
8.
Environ Health Prev Med ; 26(1): 35, 2021 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-33743595

RESUMEN

BACKGROUND: Body mass-independent parameters might be more appropriate for assessing cardiometabolic abnormalities than weight-dependent indices in Asians who have relatively high visceral adiposity but low body fat. Dual-energy X-ray absorptiometry (DXA)-measured trunk-to-peripheral fat ratio is one such body mass-independent index. However, there are no reports on relationships between DXA-measured regional fat ratio and cardiometabolic risk factors targeting elderly Asian men. METHODS: We analyzed cross-sectional data of 597 elderly men who participated in the baseline survey of the Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) study, a community-based single-center prospective cohort study conducted in Japan. Whole-body fat and regional fat were measured with a DXA scanner. Trunk-to-appendicular fat ratio (TAR) was calculated as trunk fat divided by appendicular fat (sum of arm and leg fat), and trunk-to-leg fat ratio (TLR) as trunk fat divided by leg fat. RESULTS: Both TAR and TLR in the group of men who used ≥ 1 medication for hypertension, dyslipidemia, or diabetes ("user group"; N = 347) were significantly larger than those who did not use such medication ("non-user group"; N = 250) (P < 0.05). After adjusting for potential confounding factors including whole-body fat, both TAR and TLR were significantly associated with low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, fasting serum insulin, and the insulin resistance index in the non-user group and non-overweight men in the non-user group (N = 199). CONCLUSION: The trunk-to-peripheral fat ratio was associated with cardiometabolic risk factors independently of whole-body fat mass. Parameters of the fat ratio may be useful for assessing cardiometabolic risk factors, particularly in underweight to normal-weight populations.


Asunto(s)
Adiposidad/fisiología , Grasa Intraabdominal , Absorciometría de Fotón , Anciano , Anciano de 80 o más Años , Biomarcadores/metabolismo , Estudios Transversales , Humanos , Grasa Intraabdominal/anatomía & histología , Grasa Intraabdominal/diagnóstico por imagen , Japón , Masculino , Osteoporosis/etiología , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Tórax/anatomía & histología , Tórax/diagnóstico por imagen
9.
Medicine (Baltimore) ; 100(9): e24887, 2021 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-33655949

RESUMEN

RATIONALE: Membranous glomerulonephritis (MN) is the leading cause of nephrotic syndrome in adults and is classified as primary or secondary. Secondary MN accounts for 20% to 30% of all MN cases and can arise from a number of conditions, including autoimmune diseases. Recently exostosin 1/exostosin 2 (EXT1/EXT2) have been identified as the common antigens in secondary autoimmune MN and are present in cases of pure membranous lupus nephritis (LN). The treatment of EXT1/EXT2-associated MN remains elusive. PATIENT CONCERNS: We present the case of a 15-year-old female who presented with nephrotic syndrome, positive ANA and dsDNA, and low serum complements. A renal biopsy revealed pure membranous nephritis with IgG and C3 deposition. EXT1 was found along the glomerular capillary walls and stained positive, while phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain-containing 7A (THSD7A) were negative. DIAGNOSIS: The patient was diagnosed with ETX1-associated membranous LN. INTERVENTIONS: She was treated with prednisone and multiple low-dose rituximab (4 200 mg doses, approximately every 2 months, based on CD19+ cells counts). OUTCOMES: The patient had complete remission within 8 months later, and she remained in remission for the 16-month period of follow-up. LESSONS: To our knowledge, this is the first case of EXT1-associated MN that has been successfully treated by multiple low-dose rituximab. Further studies can investigate the optimal dosage and treatment protocol.


Asunto(s)
Autoanticuerpos/inmunología , Nefritis Lúpica/tratamiento farmacológico , N-Acetilglucosaminiltransferasas/inmunología , Rituximab/administración & dosificación , Adolescente , Autoanticuerpos/metabolismo , Biomarcadores/metabolismo , Biopsia , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Factores Inmunológicos/administración & dosificación , Glomérulos Renales/patología , Nefritis Lúpica/inmunología , Nefritis Lúpica/metabolismo , N-Acetilglucosaminiltransferasas/metabolismo
10.
Orv Hetil ; 162(14): 523-529, 2021 03 30.
Artículo en Húngaro | MEDLINE | ID: mdl-33784245

RESUMEN

Összefoglaló. A szerzok ismertetik vizsgálataik eredményeit, melyeket a közelmúltban az in vitro fertilizációs kezelésben részesülo betegeikben a tüszofolyadék biomarkereinek analízisével értek el. A vizsgálatok célja annak feltárása volt, hogy az in vitro fertilizációs eljárás során a petesejtek aspirációjakor nyert tüszofolyadék-biomarkerek lokális/ovarialis vagy szisztémás eredetuek, és milyen összefüggést mutatnak az in vitro fertilizáció eredményességét jelzo paraméterekkel. Megerosítettük, hogy az autokrin/parakrin szerotoninrendszer már a fejlodés legkorábbi idoszakában is muködoképes, és mind az anyai szérum, mind a tüszofolyadék szerotoninszintje szignifikáns pozitív összefüggést mutatott az érett petesejtek számával és a klinikai terhességgel (ß = 0,447, p = 0,015, illetve ß = 0,443, p = 0,016). Az agyi eredetu neurotrofikus faktor (BDNF) esetében ilyen kapcsolat nem volt igazolható, de a tüszofolyadék BDNF- és szerotoninszintjei közötti pozitív korreláció (r = 0,377, p = 0,040) azt mutatja, hogy a két neurohormon 'feed-forward' (elorecsatoló ) szabályozása ovarialis szinten is muködik. A hypothalamicus kisspeptin esetében csupán a posztstimulációs anyai szérumhormonszint befolyásolta az érett petesejtek számát (ß = 0,398, p = 0,029). A triptofán-kinurenin-szerotonin rendszer elemzése azt mutatta, hogy kedvezobb in vitro fertilizációs kimenetel várható, ha a szerotonin-kinurenin egyensúly a szerotonin javára tolódik el. Az oxidatívstressz-markerek közül vizsgálták a DNS-károsodás biomarkerét, a 8-hidroxi-2'-deoxiguanozin és a totális antioxidáns-kapacitás szérum- és tüszofolyadékszintjeit, és megállapították, hogy mindkét marker kedvezotlenül befolyásolja az életképes embriók számát (r = 0,302, p = 0,027 és r = 0,268, p = 0,039). A protektív hatású szirtuinok - nikotinamid-adenin-dinukleotid-függo hiszton-deacetiláz fehérjék - közül a vizsgált szirtuin-1 és szirtuin-6 a szérumszintektol függetlenül kimutatható a tüszofolyadékban. Szignifikáns pozitív korreláció van a tüszofolyadék-szirtuin-6 és az érettpetesejt-szám (F = 6,609, p = 0,016), valamint a szérum-szirtuin-1 (F = 10,008, p = 0,005) és a szérum-szirtuin-6 (F = 5,268, p = 0,031) és a klinikai terhesség gyakorisága között. Eredményeink alapján megállapítható, hogy a tüszofolyadék biomarkereinek vizsgálata javíthatja az in vitro fertilizáció kimenetelének megítélését. Orv Hetil. 2021; 162(14): 523-529. Summary. This article outlines the result of recent studies on several follicular fluid biomarkers in patients undergoing in vitro fertilization. The aim of these studies was to investigate whether 1) the follicular fluid biomarkers in question are produced locally by the ovaries or they originate from the circulating plasma, 2) and to establish their association with parameters of in vitro fertilization outcome. It was confirmed that the autocrine/paracrine serotonin system is functional already at the earliest stage of development and both maternal serum and follicular fluid serotonin levels were positively related to the number of mature oocytes (ß = 0.447, p = 0.015 and ß = 0.443, p = 0.016, respectively) and clinical pregnancy (ß = 1.028, p = 0.047). Such associations for brain-derived neurotrophic factor (BDNF) could not be found, but BDNF and serotonin in the follicular fluid were closely related (r = 0.377, p<0.040) suggesting that the feed-forward regulation of these neurohormones is activated at ovarian level. The hypothalamic kisspeptin in the post-stimulation maternal serum also increased the number of mature oocytes (ß = 0.398, p = 0.029). Analysis of the tryptophan-kynurenine-serotonin system showed a more favourable in vitro fertilization outcome when the serotonin-kynurenine balance was shifted and serotonin predominated over kynurenine. The oxidative stress markers, 8-hydroxy-2'-deoxyguanosine, an indicator of DNA damage and the total antioxidant capacity in follicular fluid and maternal serum had negative impact on the number of viable embryos (r = 0.302, p = 0.027 and r = 0.268, p = 0.039), respectively. The protective sirtuins - the nicotinamide adenine dinucleotide-dependent histone deacetylase proteins - could be detected in follicular fluid irrespective of their maternal serum levels. Significant positive relationship was demonstrated between follicular fluid sirtuin 6 and mature oocytes (F = 6.609, p = 0.016) as well as between serum sirtuin 1 (F = 10.008, p = 0.005) and serum sirtuin 6 (F = 5.268, p = 0.031) and the rate of clinical pregnancy, respectively. On the basis of these results, it can be concluded that measuring several follicular fluid biomarkers may improve the prediction of the outcome of in vitro fertilization. Orv Hetil. 2021; 162(14): 523-529.


Asunto(s)
Biomarcadores , Fertilización In Vitro , Líquido Folicular , Biomarcadores/metabolismo , Femenino , Líquido Folicular/metabolismo , Humanos , Resultado del Tratamiento
11.
J Vis Exp ; (168)2021 02 12.
Artículo en Inglés | MEDLINE | ID: mdl-33645584

RESUMEN

Human skin equivalents (HSEs) are tissue engineered constructs that model epidermal and dermal components of human skin. These models have been used to study skin development, wound healing, and grafting techniques. Many HSEs continue to lack vasculature and are additionally analyzed through post-culture histological sectioning which limits volumetric assessment of the structure. Presented here is a straightforward protocol utilizing accessible materials to generate vascularized human skin equivalents (VHSE); further described are volumetric imaging and quantification techniques of these constructs. Briefly, VHSEs are constructed in 12 well culture inserts in which dermal and epidermal cells are seeded into rat tail collagen type I gel. The dermal compartment is made up of fibroblast and endothelial cells dispersed throughout collagen gel. The epidermal compartment is made up of keratinocytes (skin epithelial cells) that differentiate at the air-liquid interface. Importantly, these methods are customizable based on needs of the researcher, with results demonstrating VHSE generation with two different fibroblast cell types: human dermal fibroblasts (hDF) and human lung fibroblasts (IMR90s). VHSEs were developed, imaged through confocal microscopy, and volumetrically analyzed using computational software at 4- and 8-week timepoints. An optimized process to fix, stain, image, and clear VHSEs for volumetric examination is described. This comprehensive model, imaging, and analysis techniques are readily customizable to the specific research needs of individual labs with or without prior HSE experience.


Asunto(s)
Neovascularización Fisiológica , Piel Artificial , Piel/irrigación sanguínea , Ingeniería de Tejidos/métodos , Animales , Biomarcadores/metabolismo , Células Cultivadas , Colágeno/metabolismo , Dermis/metabolismo , Epidermis/metabolismo , Técnica del Anticuerpo Fluorescente , Humanos , Imagenología Tridimensional , Imagen Óptica , Permeabilidad , Ratas , Coloración y Etiquetado , Suspensiones
12.
Nat Commun ; 12(1): 1816, 2021 03 22.
Artículo en Inglés | MEDLINE | ID: mdl-33753741

RESUMEN

X-linked adrenoleukodystrophy (X-ALD), the most frequent monogenetic disorder of brain white matter, is highly variable, ranging from slowly progressive adrenomyeloneuropathy (AMN) to life-threatening inflammatory brain demyelination (CALD). In this study involving 94 X-ALD patients and 55 controls, we tested whether plasma/serum neurofilament light chain protein (NfL) constitutes an early distinguishing biomarker. In AMN, we found moderately elevated NfL with increased levels reflecting higher grading of myelopathy-related disability. Intriguingly, NfL was a significant predictor to discriminate non-converting AMN from cohorts later developing CALD. In CALD, markedly amplified NfL levels reflected brain lesion severity. In rare cases, atypically low NfL revealed a previously unrecognized smoldering CALD disease course with slowly progressive myelin destruction. Upon halt of brain demyelination by hematopoietic stem cell transplantation, NfL gradually normalized. Together, our study reveals that blood NfL reflects inflammatory activity and progression in CALD patients, thus constituting a potential surrogate biomarker that may facilitate clinical decisions and therapeutic development.


Asunto(s)
Adrenoleucodistrofia/metabolismo , Biomarcadores/metabolismo , Degeneración Nerviosa/metabolismo , Proteínas de Neurofilamentos/metabolismo , Adolescente , Adrenoleucodistrofia/diagnóstico , Adulto , Biomarcadores/sangre , Niño , Estudios de Cohortes , Progresión de la Enfermedad , Humanos , Filamentos Intermedios/metabolismo , Persona de Mediana Edad , Degeneración Nerviosa/diagnóstico , Proteínas de Neurofilamentos/sangre
13.
Nat Med ; 27(2): 333-343, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33574608

RESUMEN

To address how the microbiome might modify the interaction between diet and cardiometabolic health, we analyzed longitudinal microbiome data from 307 male participants in the Health Professionals Follow-Up Study, together with long-term dietary information and measurements of biomarkers of glucose homeostasis, lipid metabolism and inflammation from blood samples. Here, we demonstrate that a healthy Mediterranean-style dietary pattern is associated with specific functional and taxonomic components of the gut microbiome, and that its protective associations with cardiometabolic health vary depending on microbial composition. In particular, the protective association between adherence to the Mediterranean diet and cardiometabolic disease risk was significantly stronger among participants with decreased abundance of Prevotella copri. Our findings advance the concept of precision nutrition and have the potential to inform more effective and precise dietary approaches for the prevention of cardiometabolic disease mediated through alterations in the gut microbiome.


Asunto(s)
Enfermedades Cardiovasculares/microbiología , Microbioma Gastrointestinal/genética , Microbiota/genética , Biomarcadores/metabolismo , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/patología , Dieta , Dieta Mediterránea/efectos adversos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Prevotella/genética , Prevotella/aislamiento & purificación
14.
Neurology ; 96(11): e1491-e1500, 2021 03 16.
Artículo en Inglés | MEDLINE | ID: mdl-33568538

RESUMEN

OBJECTIVE: To examine whether amyloid PET in cognitively normal (CN) individuals screened for the Anti-Amyloid in Asymptomatic Alzheimer's Disease (A4) study differed across self-identified non-Hispanic White and Black (NHW and NHB) groups. METHODS: We examined 3,689 NHW and 144 NHB participants who passed initial screening for the A4 study and underwent amyloid PET. The effect of race on amyloid PET was examined using logistic (dichotomous groups) and linear (continuous values) regression controlling for age, sex, and number of APOE ε4 and APOE ε2 alleles. Associations between amyloid and genetically determined ancestry (reflecting African, South Asian, East Asian, American, and European populations) were tested within the NHB group. Potential interactions with APOE were assessed. RESULTS: NHB participants had lower rates of amyloid positivity and lower continuous amyloid levels compared to NHW participants. This race effect on amyloid was strongest in the APOE ε4 group. Within NHB participants, those with a lower percentage of African ancestry had higher amyloid. A greater proportion of NHB participants did not pass initial screening compared to NHW participants, suggesting potential sources of bias related to race in the A4 PET data. CONCLUSION: Reduced amyloid was observed in self-identified NHB participants who passed initial eligibility criteria for the A4 study. This work stresses the importance of investigating AD biomarkers in ancestrally diverse samples as well as the need for careful consideration regarding study eligibility criteria in AD prevention trials.


Asunto(s)
Enfermedad de Alzheimer/etnología , Enfermedad de Alzheimer/patología , Proteínas Amiloidogénicas/metabolismo , Encéfalo/patología , Afroamericanos , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/diagnóstico por imagen , Proteínas Amiloidogénicas/análisis , Apolipoproteínas E/genética , Biomarcadores/análisis , Biomarcadores/metabolismo , Encéfalo/diagnóstico por imagen , Femenino , Humanos , Masculino , Tomografía de Emisión de Positrones , Estados Unidos
15.
Sci Total Environ ; 772: 145034, 2021 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-33571776

RESUMEN

Fish can be highly vulnerable to environmental pressures because they are exposed to oxidative stressors in the aquatic environment. Such stressors can affect the levels of antioxidant biomarkers against reactive oxygen species (ROS). With this study we investigated the oxidative stress ecology in Danube barbel (Barbus balcanicus) from the Barbucina creek (northeast Italy), a watercourse in the Collio winegrowing district. To do this, superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST) activity was measured in gills, liver, and muscle, while metallothioneins (MT) and trace and rare earth elements (REEs) levels were determined in muscle. The effect of environmental factors (physicochemical parameters of water, trace elements and REEs) on oxidative stress biomarkers was thus assessed. High concentrations were determined for cerium (Ce), scandium (Sc), neodymium (Nd), lanthanum (La), yttrium (Y), and praseodymium (Pr) among the REEs. Among the trace elements, arsenic (As), copper (Cu), and mercury (Hg) levels were higher compared to published data, suggesting their role as stressors. The multiple linear regression (MLR) model showed a statistically significant association (R2 = 0.858; F = 10.07; p = 0.015) between As, Cu, Hg, and Pr and SOD activity in the gills, indicating a functional relationship between them. Differently, CAT activity was significantly higher in the liver, probably in response to long-term Cu contamination of the watercourse. This was confirmed by the MLR model that showed a significant association (R2 = 0.638; F = 8.152; p = 0.02) between the concentration of MT and of Cu. Our data show a biochemical defensive response by Danube barbel to the disturbances in the aquatic ecosystem of the Barbucina creek. These insights advance our understanding of the role and the effects of environmental factors as trace elements and REEs on oxidative stress in fish.


Asunto(s)
Cyprinidae , Contaminantes Químicos del Agua , Animales , Biomarcadores/metabolismo , Catalasa/metabolismo , Cyprinidae/metabolismo , Ecosistema , Branquias/metabolismo , Glutatión Transferasa/metabolismo , Italia , Estrés Oxidativo , Superóxido Dismutasa/metabolismo , Agua , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/toxicidad
16.
Chem Biol Interact ; 338: 109402, 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33587916

RESUMEN

Cisplatin is an important antineoplastic drug used in multiple chemotherapeutic regimens but unfortunately causes serious toxic effects as ovarian and uterine toxicity. This study aimed to investigate the potential protective effect of resveratrol (RSV) against cisplatin-induced ovarian and uterine toxicity in female rats. Thirty-two female Wistar rats were divided randomly into four groups (n = 8 in each). Control group received oral normal saline for 28 days; RSV group received RSV (10 mg/kg; daily) via oral gavage; CIS group received a single dose of CIS (7 mg/kg; i.p.) on the 21st day; (CIS + RSV) group received both RSV and CIS by the same schedules and doses of RSV and CIS groups, respectively. Results demonstrated a significant decrease in MDA level and a significant increase in both glutathione content and activity of the antioxidant enzymes GPx, SOD, and CAT in the tissues of the ovary and uterus of CIS + RSV group in comparison to that of CIS group (P<0.05), also there are significantly decreased tissue levels of the proinflammatory cytokines and enzymes (NF-κB, IL-1ß, IL-6, TNF-α, COX-2, and iNOS), increased estradiol, progesterone, prolactin and decreased FSH serum levels in CIS + RSV group compared to CIS group (P < 0.05). Moreover, there is downregulation of tissues Cleaved Caspase-3, NF-κB and Cox-2 proteins as shown in Western blot analysis, also apoptosis was significantly inhibited, evidenced by downregulation of Bax and upregulation of Bcl-2 proteins, and the ovarian and uterine histological architecture and integrity were maintained in CIS + RSV group compared to CIS group. In conclusion, these findings indicate that RSV has beneficial effects in ameliorating cisplatin-induced oxidative stress, inflammation, and apoptosis in the ovarian and uterine tissues of female rats.


Asunto(s)
Apoptosis/efectos de los fármacos , Cisplatino/efectos adversos , Inflamación/patología , Ovario/patología , Estrés Oxidativo/efectos de los fármacos , Sustancias Protectoras/farmacología , Resveratrol/farmacología , Útero/patología , Animales , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Catalasa/metabolismo , Ciclooxigenasa 2/metabolismo , Citocinas/metabolismo , Estradiol/sangre , Femenino , Hormona Folículo Estimulante/sangre , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Malondialdehído/metabolismo , Modelos Biológicos , FN-kappa B/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Ovario/efectos de los fármacos , Progesterona/sangre , Prolactina/sangre , Carbonilación Proteica/efectos de los fármacos , Ratas Wistar , Superóxido Dismutasa/metabolismo , Proteína X Asociada a bcl-2/metabolismo
17.
J Vis Exp ; (167)2021 01 30.
Artículo en Inglés | MEDLINE | ID: mdl-33586700

RESUMEN

Epithelial dysregulation is a node for a variety of human conditions and ailments, including chronic wounding, inflammation, and over 80% of all human cancers. As a lining tissue, the skin epithelium is often subject to injury and has evolutionarily adapted by acquiring the cellular plasticity necessary to repair damaged tissue. Over the years, several efforts have been made to study epithelial plasticity using in vitro and ex vivo cell-based models. However, these efforts have been limited in their capacity to recapitulate the various phases of epithelial cell plasticity. We describe here a protocol for generating 3D epidermal spheroids and epidermal spheroid-derived cells from primary neonatal human keratinocytes. This protocol outlines the capacity of epidermal spheroid cultures to functionally model distinct stages of keratinocyte generative plasticity and demonstrates that epidermal spheroid re-plating can enrich heterogenous normal human keratinocytes (NHKc) cultures for integrinα6hi/EGFRlo keratinocyte subpopulations with enhanced stem-like characteristics. Our report describes the development and maintenance of a high throughput system for the study of skin keratinocyte plasticity and epidermal regeneration.


Asunto(s)
Técnicas de Cultivo de Célula/métodos , Plasticidad de la Célula , Células Epidérmicas/citología , Queratinocitos/citología , Esferoides Celulares/citología , Células Madre/citología , Biomarcadores/metabolismo , Proliferación Celular , Separación Celular , Rastreo Celular , Células Cultivadas , Ensayo de Unidades Formadoras de Colonias , Humanos , Masculino , Transcripción Genética
18.
Yonsei Med J ; 62(3): 215-223, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33635011

RESUMEN

PURPOSE: This study aimed to elucidate whether lncRNA ZFAS1 is involved in neuronal apoptosis and inflammation in temporal lobe epilepsy (TLE). MATERIALS AND METHODS: Ninety-six TLE patients were recruited, and their peripheral venous blood was gathered to determine Zfas1 expression with polymerase chain reaction. Neurons were separated from hippocampal tissue of newborn SD rats, and si-Zfas1 or pcDNA3.1-Zfas1 was transfected into the neurons. Inflammatory cytokines released by neurons were determined, and neuronal activities were evaluated through MTT assay, colony formation assay, and flow cytometry. RESULTS: Serum levels of Zfas1 were higher in TLE patients than in healthy controls (p<0.05). Furthermore, Zfas1 expression in neurons was raised by pcDNA3.1-Zfas1 and declined after silencing of Zfas1 (p<0.05). Transfection of pcDNA-Zfas1 weakened the viability and proliferation of neurons and increased neuronal apoptosis (p<0.05). Meanwhile, pcDNA3.1-Zfas1 transfection promoted lipopolysaccharide-induced release of cytokines, including tumor necrosis factor-α, interleukin (IL)-1, IL-6, and intercellular adhesion molecule-1 (p<0.05), and boosted NF-κB activation by elevating the expression of NF-κB p65, pIκBα, and IKKß in neurons (p<0.05). CONCLUSION: Our results indicated that lncRNA ZFAS1 exacerbates epilepsy development by promoting neuronal apoptosis and inflammation, implying ZFAS1 as a promising treatment target for epilepsy.


Asunto(s)
Apoptosis/genética , Epilepsia del Lóbulo Temporal/genética , Inflamación/patología , Neuronas/patología , ARN Largo no Codificante/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Animales Recién Nacidos , Biomarcadores/metabolismo , Estudios de Casos y Controles , Supervivencia Celular/genética , Niño , Citocinas/metabolismo , Femenino , Regulación de la Expresión Génica , Hipocampo/patología , Humanos , Masculino , MicroARNs/genética , Persona de Mediana Edad , FN-kappa B/metabolismo , ARN Largo no Codificante/genética , Ratas Sprague-Dawley , Transducción de Señal/genética , Adulto Joven
19.
Int J Mol Med ; 47(4): 1, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33537825

RESUMEN

The Golgi apparatus is known to underpin many important cellular homeostatic functions, including trafficking, sorting and modifications of proteins or lipids. These functions are dysregulated in neurodegenerative diseases, cancer, infectious diseases and cardiovascular diseases, and the number of disease­related genes associated with Golgi apparatus is on the increase. Recently, many studies have suggested that the mutations in the genes encoding Golgi resident proteins can trigger the occurrence of diseases. By summarizing the pathogenesis of these genetic diseases, it was found that most of these diseases have defects in membrane trafficking. Such defects typically result in mislocalization of proteins, impaired glycosylation of proteins, and the accumulation of undegraded proteins. In the present review, we aim to understand the patterns of mutations in the genes encoding Golgi resident proteins and decipher the interplay between Golgi resident proteins and membrane trafficking pathway in cells. Furthermore, the detection of Golgi resident protein in human serum samples has the potential to be used as a diagnostic tool for diseases, and its central role in membrane trafficking pathways provides possible targets for disease therapy. Thus, we also introduced the clinical value of Golgi apparatus in the present review.


Asunto(s)
Enfermedad , Aparato de Golgi/metabolismo , Animales , Biomarcadores/metabolismo , Humanos , Membranas Intracelulares/metabolismo , Mutación/genética
20.
Nutrients ; 13(2)2021 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-33557013

RESUMEN

Post-viral fatigue syndrome (PVFS) is a widespread chronic neurological disease with no definite etiological factor(s), no actual diagnostic test, and no approved pharmacological treatment, therapy, or cure. Among other features, PVFS could be accompanied by various irregularities in creatine metabolism, perturbing either tissue levels of creatine in the brain, the rates of phosphocreatine resynthesis in the skeletal muscle, or the concentrations of the enzyme creatine kinase in the blood. Furthermore, supplemental creatine and related guanidino compounds appear to impact both patient- and clinician-reported outcomes in syndromes and maladies with chronic fatigue. This paper critically overviews the most common disturbances in creatine metabolism in various PVFS populations, summarizes human trials on dietary creatine and creatine analogs in the syndrome, and discusses new frontiers and open questions for using creatine in a post-COVID-19 world.


Asunto(s)
Creatina/administración & dosificación , Creatina/metabolismo , Síndrome de Fatiga Crónica/dietoterapia , Síndrome de Fatiga Crónica/metabolismo , Biomarcadores/metabolismo , Encéfalo/metabolismo , Creatina/análogos & derivados , Suplementos Dietéticos , Síndrome de Fatiga Crónica/diagnóstico , Humanos , Músculo Esquelético/metabolismo , Ensayos Clínicos Controlados Aleatorios como Asunto
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