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1.
Proc Natl Acad Sci U S A ; 118(18)2021 05 04.
Artículo en Inglés | MEDLINE | ID: mdl-33858941

RESUMEN

Ferrets (Mustela putorius furo) are mustelids of special relevance to laboratory studies of respiratory viruses and have been shown to be susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and onward transmission. Here, we report the results of a natural experiment where 29 ferrets in one home had prolonged, direct contact and constant environmental exposure to two humans with symptomatic disease, one of whom was confirmed positive for SARS-CoV-2. We observed no evidence of SARS-CoV-2 transmission from humans to ferrets based on viral and antibody assays. To better understand this discrepancy in experimental and natural infection in ferrets, we compared SARS-CoV-2 sequences from natural and experimental mustelid infections and identified two surface glycoprotein Spike (S) mutations associated with mustelids. While we found evidence that angiotensin-converting enzyme II provides a weak host barrier, one mutation only seen in ferrets is located in the novel S1/S2 cleavage site and is computationally predicted to decrease furin cleavage efficiency. These data support the idea that host factors interacting with the novel S1/S2 cleavage site may be a barrier in ferret SARS-CoV-2 susceptibility and that domestic ferrets are at low risk of natural infection from currently circulating SARS-CoV-2. We propose two mechanistically grounded hypotheses for mustelid host adaptation of SARS-CoV-2, with possible effects that require additional investigation.


Asunto(s)
/transmisión , Hurones/virología , Mutación , Glicoproteína de la Espiga del Coronavirus/genética , /fisiología , Animales , Susceptibilidad a Enfermedades , Humanos
2.
Curr Treat Options Oncol ; 22(6): 47, 2021 04 17.
Artículo en Inglés | MEDLINE | ID: mdl-33866442

RESUMEN

OPINION STATEMENT: Prostate cancer is the second leading cause of cancer death in men, and cardiovascular disease is the number one cause of death in patients with prostate cancer. Androgen deprivation therapy, the cornerstone of prostate cancer treatment, has been associated with adverse cardiovascular events. Emerging data supports decreased cardiovascular risk of gonadotropin releasing hormone (GnRH) antagonists compared to agonists. Ongoing clinical trials are assessing the relative safety of different modalities of androgen deprivation therapy. Racial disparities in cardiovascular outcomes in prostate cancer patients are starting to be explored. An intriguing inquiry connects androgen deprivation therapy with reduced risk of COVID-19 infection susceptibility and severity. Recognition of the cardiotoxicity of androgen deprivation therapy and aggressive risk factor modification are crucial for optimal patient care.


Asunto(s)
Antineoplásicos Hormonales/efectos adversos , Enfermedades Cardiovasculares/epidemiología , Neoplasias de la Próstata/tratamiento farmacológico , Androstenos/uso terapéutico , Antineoplásicos Hormonales/uso terapéutico , /patología , Cardiotoxicidad , Enfermedades Cardiovasculares/inducido químicamente , Enfermedades Cardiovasculares/etnología , Susceptibilidad a Enfermedades , Hormona Liberadora de Gonadotropina/agonistas , Hormona Liberadora de Gonadotropina/antagonistas & inhibidores , Disparidades en el Estado de Salud , Humanos , Masculino , Neoplasias de la Próstata/etnología
3.
Int J Mol Sci ; 22(6)2021 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-33806895

RESUMEN

Skeletal muscle regeneration is highly dependent on the inflammatory response. A wide variety of innate and adaptive immune cells orchestrate the complex process of muscle repair. This review provides information about the various types of immune cells and biomolecules that have been shown to mediate muscle regeneration following injury and degenerative diseases. Recently developed cell and drug-based immunomodulatory strategies are highlighted. An improved understanding of the immune response to injured and diseased skeletal muscle will be essential for the development of therapeutic strategies.


Asunto(s)
Inmunidad Adaptativa , Inmunidad Innata , Músculo Esquelético/fisiología , Regeneración/inmunología , Factores de Edad , Animales , Diferenciación Celular/genética , Diferenciación Celular/inmunología , Susceptibilidad a Enfermedades , Humanos , Inmunomodulación , Leucocitos/inmunología , Leucocitos/metabolismo , Macrófagos/inmunología , Macrófagos/metabolismo , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Desarrollo de Músculos/genética , Desarrollo de Músculos/inmunología , Linfocitos T/inmunología , Linfocitos T/metabolismo
4.
Int J Mol Sci ; 22(6)2021 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-33806981

RESUMEN

Infectious diseases occur worldwide with great frequency in both adults and children. Both infections and their treatments trigger mitochondrial interactions at multiple levels: (i) incorporation of damaged or mutated proteins to the complexes of the electron transport chain, (ii) mitochondrial genome (depletion, deletions, and point mutations) and mitochondrial dynamics (fusion and fission), (iii) membrane potential, (iv) apoptotic regulation, (v) generation of reactive oxygen species, among others. Such alterations may result in serious adverse clinical events with great impact on children's quality of life, even resulting in death. As such, bacterial agents are frequently associated with loss of mitochondrial membrane potential and cytochrome c release, ultimately leading to mitochondrial apoptosis by activation of caspases-3 and -9. Using Rayyan QCRI software for systematic reviews, we explore the association between mitochondrial alterations and pediatric infections including (i) bacterial: M. tuberculosis, E. cloacae, P. mirabilis, E. coli, S. enterica, S. aureus, S. pneumoniae, N. meningitidis and (ii) parasitic: P. falciparum. We analyze how these pediatric infections and their treatments may lead to mitochondrial deterioration in this especially vulnerable population, with the intention of improving both the understanding of these diseases and their management in clinical practice.


Asunto(s)
Infecciones Bacterianas/metabolismo , Infecciones Bacterianas/microbiología , Interacciones Huésped-Patógeno , Mitocondrias/metabolismo , Enfermedades Parasitarias/metabolismo , Enfermedades Parasitarias/parasitología , Factores de Edad , Apoptosis , Infecciones Bacterianas/diagnóstico , Biomarcadores , Niño , Susceptibilidad a Enfermedades , Interacciones Huésped-Parásitos , Humanos , Potencial de la Membrana Mitocondrial , Oxidación-Reducción , Enfermedades Parasitarias/diagnóstico
5.
Int J Mol Sci ; 22(6)2021 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-33807010

RESUMEN

Glycine N-methyltransferase (GNMT) regulates S-adenosylmethionine (SAMe), a methyl donor in methylation. Over-expressed SAMe may cause neurogenic capacity reduction and memory impairment. GNMT knockout mice (GNMT-KO) was applied as an experimental model to evaluate its effect on neurons. In this study, proteins from brain tissues were studied using proteomic approaches, Haemotoxylin and Eosin staining, immunohistochemistry, Western blotting, and ingenuity pathway analysis. The expression of Receptor-interacting protein 1(RIPK1) and Caspase 3 were up-regulated and activity-dependent neuroprotective protein (ADNP) was down-regulated in GNMT-KO mice regardless of the age. Besides, proteins related to neuropathology, such as excitatory amino acid transporter 2, calcium/calmodulin-dependent protein kinase type II subunit alpha, and Cu-Zn superoxide dismutase were found only in the group of aged wild-type mice; 4-aminobutyrate amino transferase, limbic system-associated membrane protein, sodium- and chloride-dependent GABA transporter 3 and ProSAAS were found only in the group of young GNMT-KO mice and are related to function of neurons; serum albumin and Rho GDP dissociation inhibitor 1 were found only in the group of aged GNMT-KO mice and are connected to neurodegenerative disorders. With proteomic analyses, a pathway involving Gonadotropin-releasing hormone (GnRH) signal was found to be associated with aging. The GnRH pathway could provide additional information on the mechanism of aging and non-aging related neurodegeneration, and these protein markers may be served in developing future therapeutic treatments to ameliorate aging and prevent diseases.


Asunto(s)
Envejecimiento/metabolismo , Biomarcadores , Enfermedades Neurodegenerativas/metabolismo , Animales , Biomarcadores/metabolismo , Encéfalo , Senescencia Celular , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades , Inmunohistoquímica , Ratones , Proteínas del Tejido Nervioso/metabolismo , Enfermedades Neurodegenerativas/diagnóstico , Enfermedades Neurodegenerativas/etiología , Neuronas/metabolismo , Pronóstico , Proteoma , Proteómica/métodos , Transducción de Señal/efectos de los fármacos
6.
Int J Mol Sci ; 22(6)2021 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-33807045

RESUMEN

Breast cancer is very heterogenous and the most common gynaecological cancer, with various factors affecting its development. While its impact on human lives and national health budgets is still rising in almost all global areas, many molecular mechanisms affecting its onset and development remain unclear. Conventional treatments still prove inadequate in some aspects, and appropriate molecular therapeutic targets are required for improved outcomes. Recent scientific interest has therefore focused on the non-coding RNAs roles in tumour development and their potential as therapeutic targets. These RNAs comprise the majority of the human transcript and their broad action mechanisms range from gene silencing to chromatin remodelling. Many non-coding RNAs also have altered expression in breast cancer cell lines and tissues, and this is often connected with increased proliferation, a degraded extracellular environment, and higher endothelial to mesenchymal transition. Herein, we summarise the known abnormalities in the function and expression of long non-coding RNAs, Piwi interacting RNAs, small nucleolar RNAs and small nuclear RNAs in breast cancer, and how these abnormalities affect the development of this deadly disease. Finally, the use of RNA interference to suppress breast cancer growth is summarised.


Asunto(s)
Biomarcadores de Tumor , Neoplasias de la Mama/genética , Regulación Neoplásica de la Expresión Génica , ARN no Traducido/genética , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/metabolismo , Manejo de la Enfermedad , Susceptibilidad a Enfermedades , Femenino , Humanos , Biopsia Líquida/métodos , Interferencia de ARN , ARN no Traducido/química
7.
Int J Mol Sci ; 22(6)2021 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-33807071

RESUMEN

Hepatocellular carcinoma (HCC), the most common malignant tumor in the liver, grows and metastasizes rapidly. Despite advances in treatment modalities, the five-year survival rate of HCC remains less than 30%. We sought genetic mutations that may affect the oncogenic properties of HCC, using The Cancer Genome Atlas (TCGA) data analysis. We found that the GNAQ T96S mutation (threonine 96 to serine alteration of the Gαq protein) was present in 12 out of 373 HCC patients (3.2%). To examine the effect of the GNAQ T96S mutation on HCC, we transfected the SK-Hep-1 cell line with the wild-type or the mutant GNAQ T96S expression vector. Transfection with the wild-type GNAQ expression vector enhanced anchorage-independent growth, migration, and the MAPK pathways in the SK-Hep-1 cells compared to control vector transfection. Moreover, cell proliferation, anchorage-independent growth, migration, and the MAPK pathways were further enhanced in the SK-Hep-1 cells transfected with the GNAQ T96S expression vector compared to the wild-type GNAQ-transfected cells. In silico structural analysis shows that the substitution of the GNAQ amino acid threonine 96 with a serine may destabilize the interaction between the regulator of G protein signaling (RGS) protein and GNAQ. This may reduce the inhibitory effect of RGS on GNAQ signaling, enhancing the GNAQ signaling pathway. Single nucleotide polymorphism (SNP) genotyping analysis for Korean HCC patients shows that the GNAQ T96S mutation was found in only one of the 456 patients (0.22%). Our data suggest that the GNAQ T96S hotspot mutation may play an oncogenic role in HCC by potentiating the GNAQ signal transduction pathway.


Asunto(s)
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Mutación , Transducción de Señal , Alelos , Sustitución de Aminoácidos , Carcinoma Hepatocelular/patología , Movimiento Celular/genética , Proliferación Celular , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/metabolismo , Susceptibilidad a Enfermedades , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/química , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/metabolismo , Expresión Génica , Genotipo , Humanos , Neoplasias Hepáticas/patología , Sistema de Señalización de MAP Quinasas , Modelos Moleculares , Oncogenes , Conformación Proteica , Relación Estructura-Actividad
8.
Int J Mol Sci ; 22(6)2021 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-33807043

RESUMEN

Numerous studies have assembled a complex picture, in which extracellular stimuli and intracellular signaling pathways modulate the chondrocyte phenotype. Because many diseases are mechanobiology-related, this review asked to what extent phenotype regulators control chondrocyte function through the cytoskeleton and cytoskeleton-regulating signaling processes. Such information would generate leverage for advanced articular cartilage repair. Serial passaging, pro-inflammatory cytokine signaling (TNF-α, IL-1α, IL-1ß, IL-6, and IL-8), growth factors (TGF-α), and osteoarthritis not only induce dedifferentiation but also converge on RhoA/ROCK/Rac1/mDia1/mDia2/Cdc42 to promote actin polymerization/crosslinking for stress fiber (SF) formation. SF formation takes center stage in phenotype control, as both SF formation and SOX9 phosphorylation for COL2 expression are ROCK activity-dependent. Explaining how it is molecularly possible that dedifferentiation induces low COL2 expression but high SF formation, this review theorized that, in chondrocyte SOX9, phosphorylation by ROCK might effectively be sidelined in favor of other SF-promoting ROCK substrates, based on a differential ROCK affinity. In turn, actin depolymerization for redifferentiation would "free-up" ROCK to increase COL2 expression. Moreover, the actin cytoskeleton regulates COL1 expression, modulates COL2/aggrecan fragment generation, and mediates a fibrogenic/catabolic expression profile, highlighting that actin dynamics-regulating processes decisively control the chondrocyte phenotype. This suggests modulating the balance between actin polymerization/depolymerization for therapeutically controlling the chondrocyte phenotype.


Asunto(s)
Actinas/metabolismo , Condrocitos/metabolismo , Condrogénesis , Citoesqueleto/metabolismo , Fenotipo , Transducción de Señal , Animales , Desdiferenciación Celular , Diferenciación Celular , Susceptibilidad a Enfermedades , Humanos , Unión Proteica , Isoformas de Proteínas , Multimerización de Proteína , Transporte de Proteínas , Fibras de Estrés/metabolismo
9.
Int J Mol Sci ; 22(6)2021 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-33809827

RESUMEN

With the burgeoning interest in hyaluronic acid (HA) in recent years, hyaluronidases (HYALs) have come to light for their role in regulating catabolism of HA and its molecular weight (MW) distribution in various tissues. Of the six hyaluronidase-like gene sequences in the human genome, HYALs 1 and 2 are of particular significance because they are the primary hyaluronidases active in human somatic tissue. Perhaps more importantly, for the sake of this review, they cleave anti-inflammatory and anti-fibrotic high-molecular-weight HA into pro-inflammatory and pro-fibrotic oligosaccharides. With this, HYALs regulate HA degradation and thus the development and progression of various diseases. Given the dearth of literature focusing specifically on HYALs in the past decade, this review seeks to expound their role in human diseases of the skin, heart, kidneys, and more. The review will delve into the molecular mechanisms and pathways of HYALs and discuss current and potential future therapeutic benefits of HYALs as a clinical treatment.


Asunto(s)
Susceptibilidad a Enfermedades , Hialuronoglucosaminidasa/genética , Hialuronoglucosaminidasa/metabolismo , Animales , Manejo de la Enfermedad , Desarrollo de Medicamentos , Regulación de la Expresión Génica , Humanos , Ácido Hialurónico/metabolismo , Hialuronoglucosaminidasa/química , Hialuronoglucosaminidasa/uso terapéutico , Familia de Multigenes , Especificidad de Órganos/genética
10.
Int J Mol Sci ; 22(6)2021 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-33809908

RESUMEN

Endoglin (CD105) is a type-1 integral transmembrane glycoprotein and coreceptor for transforming growth factor-ß (TGF-ß) ligands. The endoglin/TGF-ß signaling pathway regulates hemostasis, cell proliferation/migration, extracellular matrix (ECM) synthesis and angiogenesis. Angiogenesis contributes to early progression, invasion, postoperative recurrence, and metastasis in hepatocellular carcinoma (HCC), one of the most widespread malignancies globally. Endoglin is overexpressed in newly formed HCC microvessels. It increases microvessel density in cirrhotic and regenerative HCC nodules. In addition, circulating endoglin is present in HCC patients, suggesting potential for use as a diagnostic or prognostic factor. HCC angiogenesis is dynamic and endoglin expression varies by stage. TRC105 (carotuximab) is an antibody against endoglin, and three of its clinical trials were related to liver diseases. A partial response was achieved when combining TRC105 with sorafenib. Although antiangiogenic therapy still carries some risks, combination therapy with endoglin inhibitors or other targeted therapies holds promise.


Asunto(s)
Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/metabolismo , Susceptibilidad a Enfermedades , Endoglina/genética , Endoglina/metabolismo , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/metabolismo , Animales , Biomarcadores de Tumor , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Endoglina/sangre , Endoglina/química , Células Endoteliales/metabolismo , Regulación Neoplásica de la Expresión Génica , Hepacivirus/fisiología , Hepatitis C/metabolismo , Hepatitis C/virología , Humanos , Neoplasias Hepáticas/patología , Técnicas de Diagnóstico Molecular , Terapia Molecular Dirigida , Neovascularización Patológica/genética , Neovascularización Patológica/metabolismo , Transducción de Señal , Relación Estructura-Actividad , Proteínas del Núcleo Viral/metabolismo
11.
Int J Mol Sci ; 22(6)2021 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-33809910

RESUMEN

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficient social interaction and communication besides repetitive, stereotyped behaviours. A characteristic feature of ASD is altered dendritic spine density and morphology associated with synaptic plasticity disturbances. Since microtubules (MTs) regulate dendritic spine morphology and play an important role in spine development and plasticity the aim of the present study was to investigate the alterations in the content of neuronal α/ß-tubulin and Tau protein level as well as phosphorylation state in the valproic acid (VPA)-induced rat model of autism. Our results indicated that maternal exposure to VPA induces: (1) decrease the level of α/ß-tubulin along with Tau accumulation in the hippocampus and cerebral cortex; (2) excessive Tau phosphorylation and activation of Tau-kinases: CDK5, ERK1/2, and p70S6K in the cerebral cortex; (3) up-regulation of mTOR kinase-dependent signalling in the hippocampus and cerebral cortex of adolescent rat offspring. Moreover, immunohistochemical staining showed histopathological changes in neurons (chromatolysis) in both analysed brain structures of rats prenatally exposed to VPA. The observed changes in Tau protein together with an excessive decrease in α/ß-tubulin level may suggest destabilization and thus dysfunction of the MT cytoskeleton network, which in consequence may lead to the disturbance in synaptic plasticity and the development of autistic-like behaviours.


Asunto(s)
Trastorno Autístico/etiología , Trastorno Autístico/metabolismo , Encéfalo/metabolismo , Exposición Materna/efectos adversos , Efectos Tardíos de la Exposición Prenatal , Ácido Valproico/efectos adversos , Proteínas tau/metabolismo , Animales , Trastorno Autístico/patología , Biomarcadores , Encéfalo/patología , Susceptibilidad a Enfermedades , Activación Enzimática , Femenino , Inmunohistoquímica , Fosforilación , Embarazo , Ratas , Transducción de Señal , Tubulina (Proteína)/metabolismo
12.
Int J Mol Sci ; 22(6)2021 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-33810172

RESUMEN

The relationship between autoimmunity and changes in intestinal microbiota is not yet fully understood. In this study, the role of intestinal microbiota in the onset and progression of autoimmune lesions in non-obese diabetic (NOD) mice was evaluated by administering antibiotics to alter their intestinal microenvironment. Flow cytometric analysis of spleen cells showed that antibiotic administration did not change the proportion or number of T and B cells in NOD mice, and pathological analysis demonstrated that autoimmune lesions in the salivary glands and in the pancreas were also not affected by antibiotic administration. These results suggest that the onset and progression of autoimmunity may be independent of enteral microbiota changes. Our findings may be useful for determining the appropriate use of antibiotics in patients with autoimmune diseases who are prescribed drugs to maintain systemic immune function.


Asunto(s)
Antibacterianos/farmacología , Enfermedades Autoinmunes/etiología , Autoinmunidad , Susceptibilidad a Enfermedades , Animales , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Enfermedades Autoinmunes/tratamiento farmacológico , Autoinmunidad/efectos de los fármacos , Citocinas/metabolismo , Modelos Animales de Enfermedad , Sistema Inmunológico/efectos de los fármacos , Sistema Inmunológico/inmunología , Sistema Inmunológico/metabolismo , Ratones , Ratones Endogámicos NOD , Sialadenitis/etiología , Sialadenitis/metabolismo , Sialadenitis/patología
13.
J Infect Dev Ctries ; 15(3): 333-341, 2021 03 31.
Artículo en Inglés | MEDLINE | ID: mdl-33839706

RESUMEN

INTRODUCTION: The study of epidemiological outcomes of COVID-19 in the affected countries needs to be conducted to implement an effective strategy. METHODOLOGY: Our study included age and sex-based analysis of epidemiological data of infected and deceased patients from various countries. The patient data was graphically depicted with the slope's calculation to describe a gradual or steep spread of the disease along with subsequent rise or fall in the death reports. RESULTS: Population groups of 20-49 years of age and 50 years-above were highly vulnerable to infection. Interestingly, 20-49 years of age group was most affected in India. However, higher population of the deceased were reported in the 50 years-above in all countries. India and South Korea demonstrated a gradual appearance of COVID-19 positive cases than other countries illustrated by reduced slope %. Further the highest percentage of infected people and deaths were reported from the densely populated states of India. We observed a sex independent prevalence of COVID-19. The BCG and JE vaccine are unique in the vaccination regime of India and South Korea. CONCLUSIONS: Reduced ACE-2 expression in the children's nasal epithelium may be responsible for reduced SARS-CoV-2 susceptibility. Countries showed varying patterns in COVID-19 spread and associated mortality. It may be influenced by factors, such as screening strategy, countries demography, implementation of lockdown, etc. Due to limited evidence, it would be difficult to point to the influence of the virus on either sexes. Although vaccines may stimulate non-specific immunity, experimental proofs are needed to demonstrate the potential of any vaccine against SARS-CoV-2.


Asunto(s)
/epidemiología , Brotes de Enfermedades , Adolescente , Adulto , Distribución por Edad , Niño , Preescolar , Susceptibilidad a Enfermedades , Europa (Continente)/epidemiología , Femenino , Humanos , India/epidemiología , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Prevalencia , República de Corea/epidemiología , Distribución por Sexo , Adulto Joven
14.
Front Immunol ; 12: 645741, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33854510

RESUMEN

Particulate matter (PM) induces neutrophilic inflammation and deteriorates the prognosis of diseases such as cardiovascular diseases, cancers, and infections, including COVID-19. Here, we addressed the role of γδ T cells and intestinal microbiome in PM-induced acute neutrophilia. γδ T cells are a heterogeneous population composed of Tγδ1, Tγδ2, Tγδ17, and naïve γδ T cells (TγδN) and commensal bacteria promote local expansion of Tγδ17 cells, particularly in the lung and gut without affecting their Vγ repertoire. Tγδ17 cells are more tissue resident than Tγδ1 cells, while TγδN cells are circulating cells. IL-1R expression in Tγδ17 cells is highest in the lung and they outnumber all the other type 17 cells such as Th17, ILC3, NKT17, and MAIT17 cells. Upon PM exposure, IL-1ß-secreting neutrophils and IL-17-producing Tγδ17 cells attract each other around the airways. Accordingly, PM-induced neutrophilia was significantly relieved in γδ T- or IL-17-deficient and germ-free mice. Collectively, these findings show that the commensal microbiome promotes PM-induced neutrophilia in the lung via Tγδ17 cells.


Asunto(s)
Leucocitosis/etiología , Pulmón/inmunología , Microbiota , Neutrófilos/patología , Material Particulado/efectos adversos , Receptores de Antígenos de Linfocitos T gamma-delta/metabolismo , Células Th17/inmunología , Células Th17/metabolismo , Animales , Asma/etiología , Asma/metabolismo , Asma/patología , Biomarcadores , Citocinas/metabolismo , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades , Técnica del Anticuerpo Fluorescente , Inmunidad Innata , Inmunofenotipificación , Leucocitosis/metabolismo , Leucocitosis/patología , Pulmón/metabolismo , Pulmón/patología , Ratones , Neutrófilos/metabolismo , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo
15.
Front Immunol ; 12: 666983, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33854516

RESUMEN

The emergence of viruses with pandemic potential such as the SARS-CoV-2 coronavirus causing COVID-19 poses a global health challenge. There is remarkable progress in vaccine technology in response to this threat, but their design often overlooks the innate arm of immunity. Gamma Delta (γδ) T cells are a subset of T cells with unique features that gives them a key role in the innate immune response to a variety of homeostatic alterations, from cancer to microbial infections. In the context of viral infection, a growing body of evidence shows that γδ T cells are particularly equipped for early virus detection, which triggers their subsequent activation, expansion and the fast deployment of antiviral functions such as direct cytotoxic pathways, secretion of cytokines, recruitment and activation of other immune cells and mobilization of a trained immunity memory program. As such, γδ T cells represent an attractive target to stimulate for a rapid and effective resolution of viral infections. Here, we review the known aspects of γδ T cells that make them crucial component of the immune response to viruses, and the ways that their antiviral potential can be harnessed to prevent or treat viral infection.


Asunto(s)
/inmunología , Interacciones Huésped-Patógeno , Receptores de Antígenos de Linfocitos T gamma-delta/metabolismo , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Inmunidad Adaptativa , Animales , Terapia Combinada , Citotoxicidad Inmunológica , Manejo de la Enfermedad , Susceptibilidad a Enfermedades/inmunología , Interacciones Huésped-Patógeno/inmunología , Humanos , Inmunidad Innata , Receptores Inmunológicos/metabolismo
16.
Artículo en Inglés | MEDLINE | ID: mdl-33808395

RESUMEN

AirRater is a free smartphone app developed in 2015, supporting individuals to protect their health from environmental hazards. It does this by providing (i) location-specific and near real-time air quality, pollen and temperature information and (ii) personal symptom tracking functionality. This research sought to evaluate user perceptions of AirRater's usability and effectiveness. We collected demographic data and completed semi-structured interviews with 42 AirRater users, identified emergent themes, and used two frameworks designed to understand and support behavior change-the Behavior Change Wheel (BCW) and the Protective Action Decision Model (PADM)-to interpret results. Of the 42 participants, almost half indicated that experiencing symptoms acted as a prompt for app use. Information provided by the app supported a majority of the 42 participants to make decisions and implement behaviors to protect their health irrespective of their location or context. The majority of participants also indicated that they shared information provided by the app with family, friends and/or colleagues. The evaluation also identified opportunities to improve the app. Several study limitations were identified, which impacts the generalizability of results beyond the populations studied. Despite these limitations, findings facilitated new insights into motivations for behavior change, and contribute to the existing literature investigating the potential for smartphone apps to support health protection from environmental hazards in a changing climate.


Asunto(s)
Aplicaciones Móviles , Teléfono Inteligente , Susceptibilidad a Enfermedades , Humanos , Motivación , Polen
17.
Int J Mol Sci ; 22(5)2021 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-33807915

RESUMEN

Coronavirus disease 2019 (COVID-19) is induced by SARS-CoV-2 and may arise as a variety of clinical manifestations, ranging from an asymptomatic condition to a life-threatening disease associated with cytokine storm, multiorgan and respiratory failure. The molecular mechanism behind such variability is still under investigation. Several pieces of experimental evidence suggest that genetic variants influencing the onset, maintenance and resolution of the immune response may be fundamental in predicting the evolution of the disease. The identification of genetic variants behind immune system reactivity and function in COVID-19 may help in the elaboration of personalized therapeutic strategies. In the frenetic look for universally shared treatment plans, those genetic variants that are common to other diseases/models may also help in addressing future research in terms of drug repurposing. In this paper, we discuss the most recent updates about the role of immunogenetics in determining the susceptibility to and the history of SARS-CoV-2 infection. We propose a narrative review of available data, speculating about lessons that we have learnt from other viral infections and immunosenescence, and discussing what kind of aspects of research should be deepened in order to improve our knowledge of how host genetic variability impacts the outcome for COVID-19 patients.


Asunto(s)
/inmunología , Inmunogenética , Sistema del Grupo Sanguíneo ABO/inmunología , /epidemiología , Susceptibilidad a Enfermedades/inmunología , Predisposición Genética a la Enfermedad , Antígenos HLA/sangre , Antígenos HLA/genética , Antígenos HLA/inmunología , Humanos , Inmunidad/genética , Índice de Severidad de la Enfermedad
19.
Med Sci Monit ; 27: e930278, 2021 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-33833211

RESUMEN

The high infectivity and severity of SARS-CoV-2 infection (COVID-19), and our limited understanding of the biology of the novel coronavirus, as well as the lack of an effective treatment for COVID-19, have created a global pandemic. Those most likely to become seriously ill with COVID-19 are adults, especially the elderly and those who are already weak or sick. At present, a specific drug for treatment of COVID-19 has not been developed. This, combined with the typical coexistence of a variety of chronic diseases in elderly patients, makes treatment challenging at present. In addition, for elderly patients, COVID-19 isolation measures during the epidemic can easily lead to psychological problems. Thus, how to manage elderly patients has become a focus of social attention in the current circumstances. This article reviews the effects of COVID-19 and makes management suggestions for elderly patients during this epidemic period. In addition to the elderly, critically ill people are also highly susceptible to this novel coronavirus. For elderly COVID-19 patients, antiviral therapy, immune regulation, and even auxiliary respiratory therapy can be given after a comprehensive evaluation of the disease. With the approval and use of COVID-19 vaccines, it is reasonable to expect that we can conquer SARS-CoV-2.


Asunto(s)
Antivirales/uso terapéutico , Enfermedad Crónica/epidemiología , Terapia Respiratoria/métodos , Factores de Edad , Anciano , Envejecimiento/inmunología , /epidemiología , /administración & dosificación , Terapia Combinada/métodos , Comorbilidad , Enfermedad Crítica/epidemiología , Susceptibilidad a Enfermedades , Humanos , Factores de Riesgo , /inmunología , Índice de Severidad de la Enfermedad
20.
G Ital Nefrol ; 38(2)2021 Apr 14.
Artículo en Italiano | MEDLINE | ID: mdl-33852219

RESUMEN

The SARS-CoV-2 (Covid-19) has infected about 124 million people worldwide and the total amount of casualties now sits at a staggering 2.7 million. One enigmatic aspect of this disease is the protean nature of the clinical manifestations, ranging from total absence of symptoms to extremely severe cases with multiorgan failure and death. Chronic Kidney Disease (CKD) has emerged as the primary risk factor in the most severe patients, apart from age. Kidney disease and acute kidney injury have been correlated with a higher risk of death. Notably the Italian Society of Nephrology have reported a 10-fold increase in mortality in patients undergoing dialysis compared to the rest of the population, especially during the second phase of the pandemic (26% vs 2.4). These dramatic numbers require an immediate response. At the moment of writing, three Covid-19 vaccines are being administered already , two of which, Pfizer-BioNTech and Moderna, share the same mRNA mechanism and Vaxzevria (AstraZeneca) based on a more traditional approach. All of them are completely safe and reliable. The AIFA scientific commission has suggested that the mRNA vaccines should be administered to older and more fragile patients, while the Vaxzevria (AstraZeneca) vaccine should be reserved for younger subjects above the age of 18. The near future looks bright: there are tens of other vaccines undergoing clinical and preclinical validation, whose preliminary results look promising. The high mortality of CKD and dialysis patients contracting Covid-19 should mandate top priority for their vaccination.


Asunto(s)
/provisión & distribución , Insuficiencia Renal Crónica/complicaciones , Factores de Edad , /etiología , /psicología , Susceptibilidad a Enfermedades/etiología , Miedo , Humanos , Riñón/metabolismo , Diálisis Renal/efectos adversos , Diálisis Renal/mortalidad , Insuficiencia Renal Crónica/mortalidad , Factores de Riesgo , Vacunación
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