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1.
Adv Exp Med Biol ; 1303: 129-138, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33788191

RESUMEN

Dysfunction of locomotor muscles is frequent in chronic pulmonary diseases and strongly associated with worse outcomes including higher mortality. Although these associations have been corroborated over the last decades, there is poor mechanistic understanding of the process, in part due to the lack of adequate animal models to investigate this process. Most of the mechanistic research has so far been accomplished using relevant individual stimuli such as low oxygen or high CO2 delivered to otherwise healthy animals as surrogates of the phenomena occurring in the clinical setting. This review advocates for the development of a syndromic model in which skeletal muscle dysfunction is investigated as a comorbidity of a well-validated pulmonary disease model, which could potentially allow discovering meaningful mechanisms and pathways and lead to more substantial progress to treat this devastating condition.


Asunto(s)
Enfermedades Pulmonares , Insuficiencia Respiratoria , Animales , Comorbilidad , Modelos Animales , Músculo Esquelético
2.
Zhonghua Yi Xue Za Zhi ; 101(9): 647-653, 2021 Mar 09.
Artículo en Chino | MEDLINE | ID: mdl-33685047

RESUMEN

Objective: To compare the effectiveness and safety of different methods to construct animal models of aortic arch dissection (AAD), and explore safe and effective methods for constructing AAD animal models. Methods: Twenty-four healthy mongrel dogs were divided into 4 groups by random number table (n=6). Group A: Venous incision needle high pressure water flow impact method; Group B: Venous incision needle non-high pressure water flow impact method; Group C: Transarterial sheath non-high pressure water flow impact method; Group D: Two-way balloon expansion combined with elastase perfusion method. Imaging examinations were performed immediately and 7 days after operation, aortic tissue biopsy and pathological staining were performed 15 days after operation to observe the formation of AAD. The operation time, aortic blood flow block time, model construction success rate, dissection tear length, postoperative survival rate and survival time of four groups of experimental dogs were collected to compare the effectiveness and safety of different construction methods. Results: There were no significant difference of the gender, age and weight between four groups of experimental dogs (all P>0.05). The operation time of four groups of experimental dogs were (111.6±8.0), (168.0±17.4), (164.4±13.9), (202.8±21.5)min, and the difference was statistically significant (F=39.973, P<0.001). The operation time of group A was significantly lower than group B, C and D (all P<0.001). The aortic blood flow block time of four groups of experimental dogs were (5.2±1.8), (19.6±3.8), (20.6±3.9), and (18.6±3.0) min, and the difference was statistically significant (all P<0.001). The aortic blood flow block time of group A was significantly lower than group B, C and D (F=27.598, P<0.001). The four groups of experimental dogs had 5, 5, 4, and 1 model were successfully constructed, respectively, and the difference was statistically significant (P=0.008). The successful rate of model construction in group A was significantly higher than that in group D (P=0.040). The dissection tear length of four groups were (14.4±3.0), (11.3±4.2), (7.0±2.3), (4.7±0.6) cm,and the difference was statistically significant (F=8.103, P=0.003). The dissection tear length of group A was significantly longer than group C, D (all P<0.05). The postoperative survival time were 15.0(10.0, 15.0), 5.0(3.0, 10.0), 3.5(1.5, 4.8), 10.0(2.8, 15.0) days, and the difference was statistically significant (χ2=7.825,P=0.036). The postoperative survival time of group A was significantly higher than group B, C (all P<0.05). There was no significant difference in the survival rate of the four groups (P=1.000). The pathological staining results showed that the elastic fiber at the tearing point of AAD was destroyed, and the elastic fiber on the outer wall of the false cavity was over-stretched, which was consistent with the pathological changes of aortic dissection. Conclusion: Transvenous incision needle high-pressure water flow impact modeling method is easy to operate. The aortic blood flow block time is short, the dissection tear length is wide, and the postoperative survival time is long, can be used as the preferred method of animal AAD model construction.


Asunto(s)
Aneurisma Disecante , Aneurisma de la Aorta Torácica , Implantación de Prótesis Vascular , Aneurisma Disecante/cirugía , Animales , Aorta Torácica , Aneurisma de la Aorta Torácica/cirugía , Disección , Perros , Humanos , Modelos Animales
3.
Zhongguo Zhong Yao Za Zhi ; 46(4): 777-781, 2021 Feb.
Artículo en Chino | MEDLINE | ID: mdl-33645081

RESUMEN

Based on the clinical characteristics of chronic atrophic gastritis in traditional Chinese and Western medicine, the domestic and foreign relevant literature reports and animal models of chronic atrophic as well as the clinical diagnostic indicators of traditional Chinese and western medicine, chronic atrophic gastritis evaluation standard was summarized to evaluate and analyze the coincidence degree of clinical symptoms of the existing chronic atrophic gastritis animal models. The statistical results found that modeling methods with a higher coincidence degree with the existing chronic atrophic gastritis animal models are disease and syndrome combination mode-ling, surgical modeling, multifactor comprehensive modeling and MNNG modeling. Although the animal models were reproduced by such methods as etiology, pathogenesis and disease and syndrome combination similar to those of human beings, there is still a big gap with the natural disease state. Further in-depth studies and improvement shall be made in clinical practice in the hope to provide refe-rence for clinical practice and experimental studies of chronic atrophic gastritis.


Asunto(s)
Medicamentos Herbarios Chinos , Gastritis Atrófica , Medicina , Animales , China , Humanos , Medicina China Tradicional , Modelos Animales
4.
Zhongguo Zhong Yao Za Zhi ; 46(4): 786-791, 2021 Feb.
Artículo en Chino | MEDLINE | ID: mdl-33645082

RESUMEN

The incidence of heart failure has increased year by year, with a negative impact on quality of life and life expectancy of patients. Reproduction of animal models that meet the characteristics of clinical symptoms is a prerequisite for conducting experimental studies relating to heart failure. Based on the characteristics of clinical symptoms of heart failure in traditional Chinese medicine(TCM) and Western medicine, the existing common animal models of heart failure were explored, and the clinical anastomosis of the existing animal models was analyzed based on the clinical diagnostic criteria of heart failure in TCM and Western medicine. After analysis and comparison, it can be seen that the existing modeling methods are mostly single-factor animal models, with certain gaps between the characteristics of clinical multi-factors and interactions that jointly lead to heart failure, and the modeling methods were mostly guided by Western medicine, with a lack of TCM pathogenic factors in the model process, which is different from the clinical diagnostic criteria of Chinese and Western medicine for heart failure. In terms of syndrome differentiation, heart failure is classified into heart and lung Qi deficiency syndrome, Qi and Yin deficiency syndrome, heart and kidney Yang deficiency syndrome, Qi deficiency and blood stasis syndrome, Yang deficiency and water flooding syndrome, phlegm-drinking obstructive lung syndrome, Yin and yang exhausted syndrome. The existing animal models mostly confused them, with no effective and recognized method for modeling at present. There are major limitations in studies of Chinese medicine. Therefore, based on clinical characteristics of heart failure in Chinese and Western medicine, this article analyzed the existing animal models, defined their advantages and disadvantages and application prospects, and then suggested further improving the corresponding animal models of heart failure and standardizing the model evaluation, so as to improve the clinical coincidence between animal models and Chinese and Western medicine, make heart failure animal models better serve scientific studies, and promote relevant mechanism studies, pathological change studies and drug screening.


Asunto(s)
Insuficiencia Cardíaca , Medicina , Animales , China , Insuficiencia Cardíaca/tratamiento farmacológico , Humanos , Medicina China Tradicional , Modelos Animales , Calidad de Vida
5.
Methods Mol Biol ; 2278: 131-139, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33649953

RESUMEN

Members of the Bifidobacterium genus are some of the earliest and most important colonizers of the human neonatal gastrointestinal tract (GIT), exerting wide-ranging effects on early development of the host. However, human isolates of bifidobacteria are very inefficient colonizers of specific-pathogen-free (SPF) mice creating a technical barrier to discovery and applied research in this area. We have developed a reproducible model to facilitate transient colonization of SPF mice with human isolates of this genus through prior depletion of the gut resident microbiota with antibiotics. This chapter outlines the technical details for performing efficient microbiota depletion with antibiotics and subsequent administration of bifidobacteria for colonization.


Asunto(s)
Bifidobacterium/fisiología , Microbioma Gastrointestinal , Ratones/microbiología , Animales , Humanos , Ratones Endogámicos C57BL , Modelos Animales , Organismos Libres de Patógenos Específicos
6.
Nat Commun ; 12(1): 1328, 2021 02 26.
Artículo en Inglés | MEDLINE | ID: mdl-33637711

RESUMEN

Murine animal models from genetically modified pluripotent stem cells (PSCs) are essential for functional genomics and biomedical research, which require germline transmission for the establishment of colonies. However, the quality of PSCs, and donor-host cell competition in chimeras often present strong barriers for germline transmission. Here, we report efficient germline transmission of recalcitrant PSCs via blastocyst complementation, a method to compensate for missing tissues or organs in genetically modified animals via blastocyst injection of PSCs. We show that blastocysts from germline-deficient Prdm14 knockout rats provide a niche for the development of gametes originating entirely from the donor PSCs without any detriment to somatic development. We demonstrate the potential of this approach by creating PSC-derived Pax2/Pax8 double mutant anephric rats, and rescuing germline transmission of a PSC carrying a mouse artificial chromosome. Furthermore, we generate mouse PSC-derived functional spermatids in rats, which provides a proof-of-principle for the generation of xenogenic gametes in vivo. We believe this approach will become a useful system for generating PSC-derived germ cells in the future.


Asunto(s)
Blastocisto/metabolismo , Proteínas de Unión al ADN/deficiencia , Células Germinativas/fisiología , Proteínas de Unión al ARN/genética , Espermátides/metabolismo , Factores de Transcripción/deficiencia , Animales , Blastocisto/patología , Proteínas de Unión al ADN/genética , Células Madre Embrionarias , Femenino , Técnicas de Inactivación de Genes , Ingeniería Genética , Células Germinativas/trasplante , Masculino , Ratones , Modelos Animales , Células Madre Pluripotentes , Ratas , Factores de Transcripción/genética , Transcriptoma
7.
Nucleic Acids Res ; 49(4): 1859-1871, 2021 02 26.
Artículo en Inglés | MEDLINE | ID: mdl-33524155

RESUMEN

Animal models are crucial for advancing our knowledge about the molecular pathways involved in human diseases. However, it remains unclear to what extent tissue expression of pathways in healthy individuals is conserved between species. In addition, organism-specific information on pathways in animal models is often lacking. Within these limitations, we explore the possibilities that arise from publicly available data for the animal models mouse, rat, and pig. We approximate the animal pathways activity by integrating the human counterparts of curated pathways with tissue expression data from the models. Specifically, we compare whether the animal orthologs of the human genes are expressed in the same tissue. This is complicated by the lower coverage and worse quality of data in rat and pig as compared to mouse. Despite that, from 203 human KEGG pathways and the seven tissues with best experimental coverage, we identify 95 distinct pathways, for which the tissue expression in one animal model agrees better with human than the others. Our systematic pathway-tissue comparison between human and three animal modes points to specific similarities with human and to distinct differences among the animal models, thereby suggesting the most suitable organism for modeling a human pathway or tissue.


Asunto(s)
Modelos Animales , Animales , Expresión Génica , Genoma , Humanos , Ratones , Especificidad de Órganos , Mapeo de Interacción de Proteínas , Ratas , Porcinos
8.
Medicine (Baltimore) ; 100(4): e23873, 2021 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-33530181

RESUMEN

BACKGROUND: Ischemic stroke is a huge threat to human health globally. Rescuing neurons in the ischemic penumbra (IP) is pivotal after the onset of ischemic stroke, and autophagy is essential to the survival of IP neurons and the development of related pathological processes. As the most common autophagy inhibitor, 3-Methyladenine (3-MA) is widely used in studies related to the mechanism of neuronal autophagy in ischemic stroke; however, there is no consensus has been reached on its effects of neuroprotection or neurodamage, which hinders the development and clinical application of autophagy-targeted therapy strategies for the treatment of ischemic stroke. METHODS: We will search the following electronic bibliographic databases: PubMed, EMBASE, Scopus, Science Direct, and Web of Science. Participant intervention comparator outcomes of this study are as flowing: P, animal models of ischemic stroke; I, received 3-MA treatment merely; C, received only vehicle or sham treatment, or no treatment; O, Primary outcomes are infarct volume; neuro-behavioral scores. Secondary outcomes are cerebral blood flow, blood-brain barrier permeability, cerebral hemorrhage, brain water content. Review Manager 5.3 and Stata 15.1 will be used in data analysis. The characteristics of the studies, the experimental model, and the main results will be described, the quality assessment and the risk of bias assessment will be conducted. A narrative synthesis will be made for the included studies. Besides, if sufficient qualitative data is available, a meta-analysis will be conducted. I2 statistics will be used to assess heterogeneity. DISCUSSION: This systematic review and meta-analysis of the autophagy inhibitor 3-MAs effects on animal models of ischemic stroke can help us to understand whether inhibiting autophagy brings protection or damage to IP neurons; in addition, it also helps to clarify the specific role of autophagy in cerebral infarction. Therefore, this study can provide evidence for the future development of therapy strategies targeting autophagy and bring more hope to patients with ischemic stroke. PROSPERO REGISTRATION NUMBER: CRD42020194262.


Asunto(s)
Adenina/análogos & derivados , Autofagia/efectos de los fármacos , Metaanálisis como Asunto , Revisiones Sistemáticas como Asunto , Adenina/uso terapéutico , Animales , Infarto Encefálico/tratamiento farmacológico , Infarto Encefálico/patología , Infarto Encefálico/fisiopatología , Protocolos Clínicos , /fisiopatología , Modelos Animales , Neuronas/patología , Proyectos de Investigación
9.
Arch Environ Contam Toxicol ; 80(2): 499-506, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33523258

RESUMEN

Infant skin is highly absorptive and sensitive to exposure from external agents (microbes, toxicants, heat, cold, etc.). Many specialized infant skincare products are currently commercially available. Although the manufacturers claim that their products are mild enough to suit the infant skin, these products need to be studied for their safety. Using animal models to examine the safety of the ever-increasing number of skincare products is not economically or logistically feasible. To overcome this problem, we suggest using a battery of microbial bioassays as a robust system for monitoring the mutagenic potential of skincare products. We picked popular infant skincare products from the Indian market and assessed them by using a battery of three microbial mutagenicity bioassays. Most of them showed significant and reproducible mutagenic potential. Our study results raise concerns about regular use of infant products and emphasize the need to enforce strict regulations for the manufacturing and safety assessment of infant products.


Asunto(s)
Bioensayo , Cosméticos/toxicidad , Exposición a Riesgos Ambientales/estadística & datos numéricos , Mutágenos/toxicidad , Animales , Humanos , Lactante , Modelos Animales , Cuidados de la Piel/métodos , Pruebas Cutáneas
10.
J Frailty Aging ; 10(2): 86-93, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33575696

RESUMEN

Aging is the most important risk factor for the onset of several chronic diseases and functional decline. Understanding the interplays between biological aging and the biology of diseases and functional loss as well as integrating a function-centered approach to the care pathway of older adults are crucial steps towards the elaboration of preventive strategies (both pharmacological and non-pharmacological) against the onset and severity of burdensome chronic conditions during aging. In order to tackle these two crucial challenges, ie, how both the manipulation of biological aging and the implementation of a function-centered care pathway (the Integrated Care for Older People (ICOPE) model of the World Health Organization) may contribute to the trajectories of healthy aging, a new initiative on Gerosciences was built: the INSPIRE research program. The present article describes the scientific background on which the foundations of the INSPIRE program have been constructed and provides the general lines of this initiative that involves researchers from basic and translational science, clinical gerontology, geriatrics and primary care, and public health.


Asunto(s)
Investigación Biomédica , Geriatría , Envejecimiento Saludable , Anciano , Animales , Prestación de Atención de Salud , Humanos , Modelos Animales
11.
J Vis Exp ; (168)2021 02 05.
Artículo en Inglés | MEDLINE | ID: mdl-33616107

RESUMEN

Fetal tracheal occlusion (TO), an established treatment modality, promotes fetal lung growth and survival in severe congenital diaphragmatic hernia (CDH). Following TO, retention of the secreted epithelial fluid increases luminal pressure and induces lung growth. Various animal models have been defined to understand the pathophysiology of CDH and TO. All have their own advantages and disadvantages such as the difficulty of the technique, the size of the animal, cost, high mortality rates, and the availability of genetic tools. Herein, a novel transuterine model of murine fetal TO is described. Pregnant mice were anesthetized, and the uterus exposed via a midline laparotomy. The trachea of selected fetuses were ligated with a single transuterine suture placed behind the trachea, one carotid artery, and one jugular vein. The dam was closed and allowed to recover. Fetuses were collected just before parturition. Lung to body weight ratio in TO fetuses was higher than that in control fetuses. This model provides researchers with a new tool to study the impact of both TO and increased luminal pressure on lung development.


Asunto(s)
Embrión de Mamíferos/cirugía , Fetoscopía/métodos , Feto/cirugía , Hernias Diafragmáticas Congénitas/cirugía , Pulmón/crecimiento & desarrollo , Modelos Animales , Tráquea/cirugía , Animales , Femenino , Pulmón/embriología , Ratones , Embarazo
12.
Cell ; 184(5): 1188-1200.e19, 2021 03 04.
Artículo en Inglés | MEDLINE | ID: mdl-33577765

RESUMEN

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is continuing to disrupt personal lives, global healthcare systems, and economies. Hence, there is an urgent need for a vaccine that prevents viral infection, transmission, and disease. Here, we present a two-component protein-based nanoparticle vaccine that displays multiple copies of the SARS-CoV-2 spike protein. Immunization studies show that this vaccine induces potent neutralizing antibody responses in mice, rabbits, and cynomolgus macaques. The vaccine-induced immunity protects macaques against a high-dose challenge, resulting in strongly reduced viral infection and replication in the upper and lower airways. These nanoparticles are a promising vaccine candidate to curtail the SARS-CoV-2 pandemic.


Asunto(s)
/administración & dosificación , Macaca fascicularis , Glicoproteína de la Espiga del Coronavirus/química , Animales , Anticuerpos Neutralizantes , Linfocitos B/inmunología , /prevención & control , Ratones , Ratones Endogámicos BALB C , Modelos Animales , Nanopartículas/administración & dosificación , Conejos , Glicoproteína de la Espiga del Coronavirus/sangre , Linfocitos T/inmunología , Carga Viral
13.
Methods Mol Biol ; 2224: 1-27, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33606203

RESUMEN

Recent development of Easi-CRISPR (Efficient additions with ssDNA inserts-CRISPR) that utilizes long single-stranded DNA (lssDNA) of 0.2-2 kbases in length as donor templates to insert large segments of novel DNA sequences or to replace endogenous genes at precise locations in the genome has enabled CRISPR-assisted genome editing to make strides toward a more simple and rapid workflow. By leveraging the notion that short single-stranded DNA oligo (<200 bases) serves as efficient donor in mouse zygotes for facilitating HDR-mediated genome editing, Easi-CRISPR expands to use lssDNA as the donor which accelerates the timeline to as little as 2 months for creating most types of genetically engineered mouse models (F0). Our lab (CGERC) has adopted Easi-CRISPR for multiple loci to generate mouse models over the past three plus years since its introduction. Here, we use two genes as examples to illustrate a step-by-step protocol for generating two commonly used models, including a knock-in (insertion of a reporter gene plus GOI) as well as a conditional knock-out model (via exon floxing). This protocol will focus more on molecular biology aspect, particularly we demonstrate two recently developed methods for lssDNA procuration: (1) PCR-based Takara Bio kit with modifications; (2) plasmid-retrieval-based CRISPR-CLIP (CRISPR-Clipped LssDNA via Incising Plasmid). Both methods are devised to retain sequence fidelity in lssDNA generated. In addition, CRISPR-CLIP directly retrieves lssDNA from DNA plasmid without using restriction enzymes through a PCR-free system hence carries virtually no restriction on sequence complexity, further mitigating limitations discussed in the original Easi-CRISPR protocol. We have alternated the use between both methods when suitable and successfully generated lssDNA templates via CRISPR-CLIP up to 3.5 kbases patched with multiple highly repetitive sequences, which is otherwise challenging to maneuver. Along with certain other modified workflow presented herein, Easi-CRISPR can be adapted to be more straightforward while applicable to generate mouse models in broader scope. (Certain figures and text passages presented in this chapter are reproduced from Shola et al. (The CRISPR J 3(2):109-122, 2020), published by Mary Ann Libert, Inc).


Asunto(s)
Sistemas CRISPR-Cas/genética , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas/genética , ADN de Cadena Simple/genética , Animales , Exones/genética , Femenino , Edición Génica/métodos , Técnicas de Sustitución del Gen , Genes Reporteros/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Modelos Animales , ARN Guia/genética , Cigoto/fisiología
14.
Methods Mol Biol ; 2224: 61-74, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33606206

RESUMEN

The mammalian hippocampus shows a remarkable capacity for continued neurogenesis throughout life. Newborn neurons, generated by the radial neural stem cells (NSCs), are important for learning and memory as well as mood control. During aging, the number and responses of NSCs to neurogenic stimuli diminish, leading to decreased neurogenesis and age-associated cognitive decline and psychiatric disorders. Thus, adult hippocampal neurogenesis has been the subject of intense investigation, generating both excitement and controversy. Identifying the core molecular machinery responsible for NSC preservation is of fundamental importance if we are to use neurogenesis to halt or reverse hippocampal age-related pathology. Here, we briefly overview the most frequently used mouse models to study hippocampal neurogenesis and then focus on a unique mouse model that allows NSC-specific studies based on their unique expression of lunatic fringe (Lfng). The Lfng-eGFP and Lfng(BAC)-CreERT2;RCL-tdT transgenic mice provide us with an excellent tool to resolve long-standing questions regarding the properties of NSCs, such as their specific molecular composition, potency, and plasticity, in isolation from any other cell in the hippocampal neurogenic niche.


Asunto(s)
Hipocampo/fisiología , Células-Madre Neurales/fisiología , Células Madre Adultas/fisiología , Envejecimiento/fisiología , Animales , Biología , Disfunción Cognitiva/fisiopatología , Ratones , Ratones Transgénicos , Modelos Animales , Neurogénesis/fisiología , Neuronas/fisiología
15.
Methods Mol Biol ; 2224: 183-193, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33606215

RESUMEN

The availability of mouse models that allow inducible long-term hematopoietic stem cell (LT-HSC)-specific gene deletion in adult mice has been limited. Therefore, analysis of gene function in adult LT-HSCs has mostly relied on models such as the interferon inducible Mx1-Cre model. Unfortunately, the Mx1-Cre strain has significant drawbacks due to lack of specificity towards the hematopoietic system, adverse effects of interferon induction on the interpretation of data, and Cre expression leakage. In this chapter, we will describe the use of other inducible models, the tamoxifen-inducible Cre-ERT and Cre-ERT2 strains, and how these mice can be used to study gene function in LT-HSC.


Asunto(s)
Células Madre Adultas/fisiología , Silenciador del Gen/fisiología , Células Madre Adultas/efectos de los fármacos , Animales , Eliminación de Gen , Silenciador del Gen/efectos de los fármacos , Células Madre Hematopoyéticas/efectos de los fármacos , Células Madre Hematopoyéticas/fisiología , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Modelos Animales , Tamoxifeno/farmacología
16.
Int Immunopharmacol ; 93: 107406, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33601246

RESUMEN

In patients with COVID-19,type 2 diabetes mellitus (T2DM) can impair the function of nasal-associated lymphoid tissue (NALT) and result in olfactory dysfunction. Exploring the causative alterations of T2DM within the nasal mucosa and NALT could provide insight into the pathogenic mechanisms and bridge the gap between innate immunity and adaptive immunity for virus clearance. Here, we designed a case-control study to compare the olfactory function (OF) among the groups of normal control (NC), COVID-19 mild pneumonia (MP), and MP patients with T2DM (MPT) after a 6-8 months' recovery, in which MPT had a higher risk of hyposmia than MP and NC. No significant difference was found between the MP and NC. This elevated risk of hyposmia indicated that T2DM increased COVID-19 susceptibility in the nasal cavity with unknown causations. Therefore, we used the T2DM animal model (db/db mice) to evaluate how T2DM increased COVID-19 associated susceptibilities in the nasal mucosa and lymphoid tissues. Db/db mice demonstratedupregulated microvasculature ACE2 expression and significant alterations in lymphocytes component of NALT. Specifically, db/db mice NALT had increased immune-suppressive TCRγδ+ CD4-CD8- T and decreased immune-effective CD4+/CD8+ TCRß+ T cells and decreased mucosa-protective CD19+ B cells. These results indicated that T2DM could dampen the first-line defense of nasal immunity, and further mechanic studies of metabolic damage and NALT restoration should be one of the highest importance for COVID-19 healing.


Asunto(s)
/inmunología , /inmunología , Diabetes Mellitus Tipo 2/inmunología , Diabetes Mellitus Tipo 2/virología , Adulto , Animales , Linfocitos B/inmunología , /fisiopatología , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Humanos , Inmunidad Mucosa/inmunología , Tejido Linfoide/inmunología , Macrófagos/inmunología , Masculino , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , Modelos Animales , Mucosa Nasal/inmunología , Mucosa Olfatoria/metabolismo , Factores de Riesgo , Serina Endopeptidasas/metabolismo , Linfocitos T/inmunología
17.
Int J Mol Sci ; 22(3)2021 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-33540898

RESUMEN

The mechanisms of how obesity contributes to the development of cardio-metabolic diseases are not entirely understood. Obesity is frequently associated with adipose tissue dysfunction, characterized by, e.g., adipocyte hypertrophy, ectopic fat accumulation, immune cell infiltration, and the altered secretion of adipokines. Factors secreted from adipose tissue may induce and/or maintain a local and systemic low-grade activation of the innate immune system. Attraction of macrophages into adipose tissue and altered crosstalk between macrophages, adipocytes, and other cells of adipose tissue are symptoms of metabolic inflammation. Among several secreted factors attracting immune cells to adipose tissue, chemotactic C-C motif chemokine ligand 2 (CCL2) (also described as monocyte chemoattractant protein-1 (MCP-1)) has been shown to play a crucial role in adipose tissue macrophage infiltration. In this review, we aimed to summarize and discuss the current knowledge on CCL2 with a focus on its role in linking obesity to cardio-metabolic diseases.


Asunto(s)
Quimiocina CCL2/fisiología , Inflamación/complicaciones , Obesidad/etiología , Adipocitos/fisiología , Tejido Adiposo/metabolismo , Animales , Enfermedades Autoinmunes/genética , Enfermedades Autoinmunes/metabolismo , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/metabolismo , Quimiocina CCL2/deficiencia , Quimiocina CCL2/genética , Quimiocinas/metabolismo , Humanos , Inflamación/genética , Inflamación/fisiopatología , Resistencia a la Insulina , Macrófagos/fisiología , Células Madre Mesenquimatosas/metabolismo , Síndrome Metabólico/genética , Síndrome Metabólico/metabolismo , Ratones , Ratones Noqueados , Modelos Animales , Terapia Molecular Dirigida , Proteínas de Neoplasias/metabolismo , Neoplasias/metabolismo , Neoplasias/patología , Defectos del Tubo Neural/genética , Defectos del Tubo Neural/metabolismo , Obesidad/genética , Obesidad/fisiopatología , Polimorfismo de Nucleótido Simple , Transducción de Señal
18.
Spine (Phila Pa 1976) ; 46(3): E146-E152, 2021 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-33399436

RESUMEN

STUDY DESIGN: Experimental in-vivo animal study. OBJECTIVE: The aim of this study was to evaluate an Artificial Intelligence (AI)-enabled ultrasound imaging system's ability to detect, segment, classify, and display neural and other structures during trans-psoas spine surgery. SUMMARY OF BACKGROUND DATA: Current methodologies for intraoperatively localizing and visualizing neural structures within the psoas are limited and can impact the safety of lateral lumbar interbody fusion (LLIF). Ultrasound technology, enhanced with AI-derived neural detection algorithms, could prove useful for this task. METHODS: The study was conducted using an in vivo porcine model (50 subjects). Image processing and machine learning algorithms were developed to detect neural and other anatomic structures within and adjacent to the psoas muscle while using an ultrasound imaging system during lateral lumbar spine surgery (SonoVision,™ Tissue Differentiation Intelligence, USA). The imaging system's ability to detect and classify the anatomic structures was assessed with subsequent tissue dissection. Dice coefficients were calculated to quantify the performance of the image segmentation. RESULTS: The AI-trained ultrasound system detected, segmented, classified, and displayed nerve, psoas muscle, and vertebral body surface with high sensitivity and specificity. The mean Dice coefficient score for each tissue type was >80%, indicating that the detected region and ground truth were >80% similar to each other. The mean specificity of nerve detection was 92%; for bone and muscle, it was >95%. The accuracy of nerve detection was >95%. CONCLUSION: This study demonstrates that a combination of AI-derived image processing and machine learning algorithms can be developed to enable real-time ultrasonic detection, segmentation, classification, and display of critical anatomic structures, including neural tissue, during spine surgery. AI-enhanced ultrasound imaging can provide a visual map of important anatomy in and adjacent to the psoas, thereby providing the surgeon with critical information intended to increase the safety of LLIF surgery.Level of Evidence: N/A.


Asunto(s)
Inteligencia Artificial/normas , Monitorización Neurofisiológica Intraoperatoria/normas , Vértebras Lumbares/diagnóstico por imagen , Modelos Animales , Músculos Psoas/diagnóstico por imagen , Algoritmos , Animales , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Procesamiento de Imagen Asistido por Computador/normas , Monitorización Neurofisiológica Intraoperatoria/métodos , Vértebras Lumbares/cirugía , Aprendizaje Automático/normas , Músculos Psoas/cirugía , Reproducibilidad de los Resultados , Fusión Vertebral/métodos , Fusión Vertebral/normas , Porcinos , Ultrasonografía/métodos , Ultrasonografía/normas
19.
Nat Commun ; 12(1): 157, 2021 01 08.
Artículo en Inglés | MEDLINE | ID: mdl-33420038

RESUMEN

The vagus nerve supports diverse autonomic functions and behaviors important for health and survival. To understand how specific components of the vagus contribute to behaviors and long-term physiological effects, it is critical to modulate their activity with anatomical specificity in awake, freely behaving conditions using reliable methods. Here, we introduce an organ-specific scalable, multimodal, wireless optoelectronic device for precise and chronic optogenetic manipulations in vivo. When combined with an advanced, coil-antenna system and a multiplexing strategy for powering 8 individual homecages using a single RF transmitter, the proposed wireless telemetry enables low cost, high-throughput, and precise functional mapping of peripheral neural circuits, including long-term behavioral and physiological measurements. Deployment of these technologies reveals an unexpected role for stomach, non-stretch vagal sensory fibers in suppressing appetite and demonstrates the durability of the miniature wireless device inside harsh gastric conditions.


Asunto(s)
Apetito/fisiología , Ensayos Analíticos de Alto Rendimiento/instrumentación , Optogenética/instrumentación , Estómago/fisiología , Nervio Vago/fisiología , Animales , Técnicas de Observación Conductual/instrumentación , Péptido Relacionado con Gen de Calcitonina/genética , Células Quimiorreceptoras/fisiología , Diseño de Equipo , Femenino , Masculino , Ratones Transgénicos , Modelos Animales , Vías Nerviosas/fisiología , Tecnología de Sensores Remotos/instrumentación , Estómago/citología , Estómago/inervación , Nervio Vago/citología , Tecnología Inalámbrica/instrumentación
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