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1.
Cancer Immunol Res ; 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39269772

RESUMEN

Accumulating evidence indicates that the gut microbiome influences cancer progression and therapy. We recently showed that progressive changes in gut microbial diversity and composition are closely associated with tobacco-associated lung adenocarcinoma (LUAD) in a human-relevant mouse model. Furthermore, we demonstrated that the loss of the antimicrobial protein Lcn2 in these mice, exacerbates pro-tumor inflammatory phenotypes while further reducing microbial diversity. Yet, how gut microbiome alterations impinge on LUAD development remains poorly understood. Here, we investigated the role of gut microbiome changes in LUAD development using fecal microbiota transfer and delineated a pathway by which gut microbiome alterations incurred by loss of Lcn2 fostered the proliferation of pro-inflammatory bacteria of the genus Alistipes, triggering gut inflammation. This inflammation propagated systemically, exerting immunosuppression within the tumor microenvironment, augmenting tumor growth through an IL-6-dependent mechanism and dampening response to immunotherapy. Corroborating our preclinical findings, we found that patients with LUAD with a higher relative abundance of Alistipes species in the gut showed diminished response to neoadjuvant immunotherapy. These insights reveal the role of microbiome-induced inflammation in LUAD and present new potential targets for interception and therapy.

2.
Nat Commun ; 14(1): 6878, 2023 10 28.
Artículo en Inglés | MEDLINE | ID: mdl-37898601

RESUMEN

Wastewater is a discarded human by-product, but its analysis may help us understand the health of populations. Epidemiologists first analyzed wastewater to track outbreaks of poliovirus decades ago, but so-called wastewater-based epidemiology was reinvigorated to monitor SARS-CoV-2 levels while bypassing the difficulties and pit falls of individual testing. Current approaches overlook the activity of most human viruses and preclude a deeper understanding of human virome community dynamics. Here, we conduct a comprehensive sequencing-based analysis of 363 longitudinal wastewater samples from ten distinct sites in two major cities. Critical to detection is the use of a viral probe capture set targeting thousands of viral species or variants. Over 450 distinct pathogenic viruses from 28 viral families are observed, most of which have never been detected in such samples. Sequencing reads of established pathogens and emerging viruses correlate to clinical data sets of SARS-CoV-2, influenza virus, and monkeypox viruses, outlining the public health utility of this approach. Viral communities are tightly organized by space and time. Finally, the most abundant human viruses yield sequence variant information consistent with regional spread and evolution. We reveal the viral landscape of human wastewater and its potential to improve our understanding of outbreaks, transmission, and its effects on overall population health.


Asunto(s)
Poliovirus , Viroma , Humanos , Viroma/genética , Aguas Residuales , Ciudades , Brotes de Enfermedades , SARS-CoV-2/genética
3.
Vaccines (Basel) ; 9(11)2021 Nov 19.
Artículo en Inglés | MEDLINE | ID: mdl-34835293

RESUMEN

Vaccine uptake is a multifactor measure of successful immunization outcomes that includes access to healthcare and vaccine hesitancy for both healthcare workers and communities. The present coronavirus disease (COVID-19) pandemic has highlighted the need for novel strategies to expand vaccine coverage in underserved regions. Mobile clinics hold the promise of ameliorating such inequities, although there is a paucity of studies that validate environmental infection in such facilities. Here, we describe community-based management of COVID-19 through a Smart Pod mobile clinic deployed in an underserved community area in the United States (Aldine, Harris County, TX, USA). In particular, we validate infection control and biological decontamination of the Smart Pod by testing surfaces and the air-filtration system for the COVID-19 virus and bacterial pathogens. We show the Smart Pod to be efficacious in providing a safe clinical environment for vaccine delivery. Moreover, in the Smart Pod, up-to-date education of community healthcare workers was provided to reduce vaccine hesitancy and improve COVID-19 vaccine uptake. The proposed solution has the potential to augment existing hospital capacity and combat the COVID-19 pandemic locally and globally.

4.
Ticks Tick Borne Dis ; 11(3): 101368, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-31917128

RESUMEN

The cattle tick, Rhipicephalus annulatus (Say) is a vector of bovine babesiosis and responsible for direct and indirect losses to cattle producing areas located in temperate and subtropical dry regions. Resistance against pyrethroids has been reported for this species in Asia and Africa, but never before in North America. An outbreak strain, Rio Lado, collected close to the border between Mexico and the United States, in Maverick County, Texas, showed low level of resistance to permethrin, a pyrethroid pesticide. We used genomic material from different strains of cattle ticks collected within the Permanent Quarantine Zone (Rio Lado, Vega and Klein Grass strains) to partially characterize the coding gene of the voltage-gated sodium channel (Na-channel), target-site of pyrethroid pesticides, and search for putative mutations associated with resistance using quantitative PCR high resolution melt (HRM) analysis. The two amplified fragments, corresponding to domains II and III of the Na-channel, were 100 % identical to its ortholog in Rhipicephalus microplus (Canestrini). No nucleotide polymorphisms in the Na-channel gene were observed in the pyrethroid-resistant Rio Lado strain, when compared to the susceptible strains Klein Grass and Vega. This study reports the first case of pyrethroid resistance in R. annulatus collected in the United States. Also, we provide new genomic data for this species of tick that allows for the development of a new method to screen for mutations associated with pyrethroid resistance.


Asunto(s)
Acaricidas/farmacología , Proteínas de Artrópodos/genética , Resistencia a Medicamentos/genética , Permetrina/farmacología , Rhipicephalus/fisiología , Canales de Sodio Activados por Voltaje/genética , Secuencia de Aminoácidos , Animales , Proteínas de Artrópodos/química , Proteínas de Artrópodos/metabolismo , Secuencia de Bases , Femenino , Larva/genética , Larva/crecimiento & desarrollo , Larva/fisiología , Rhipicephalus/genética , Rhipicephalus/crecimiento & desarrollo , Canales de Sodio Activados por Voltaje/química , Canales de Sodio Activados por Voltaje/metabolismo
5.
J Autism Dev Disord ; 50(5): 1800-1808, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-30076499

RESUMEN

This brief report examines the implementation of dietary intervention utilizing the specific carbohydrate diet (SCD) for the management of gastrointestinal issues in a 4 year old boy diagnosed with Autism Spectrum Disorder (ASD) and Fragile X Syndrome (FXS). Data relating to anthropometrics, dietary intake, blood markers, gastrointestinal (GI) symptoms, sleep issues, and behavioral concerns were gathered at baseline and after 4 months of dietary intervention. The dietary intervention was well tolerated. Improvements in nutrient status, GI symptoms, and behavioral domains were reported. The use of the SCD protocol in children with ASD/FXS and GI symptoms warrants further investigation.


Asunto(s)
Trastorno del Espectro Autista/complicaciones , Dieta Baja en Carbohidratos , Síndrome del Cromosoma X Frágil/complicaciones , Enfermedades Gastrointestinales/complicaciones , Enfermedades Gastrointestinales/dietoterapia , Trastorno del Espectro Autista/dietoterapia , Preescolar , Dieta Baja en Carbohidratos/efectos adversos , Síndrome del Cromosoma X Frágil/dietoterapia , Enfermedades Gastrointestinales/diagnóstico , Humanos , Masculino , Estado Nutricional , Trastornos del Sueño-Vigilia/complicaciones , Trastornos del Sueño-Vigilia/diagnóstico , Trastornos del Sueño-Vigilia/dietoterapia
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