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1.
Cell ; 185(22): 4117-4134.e28, 2022 10 27.
Artículo en Inglés | MEDLINE | ID: mdl-36306734

RESUMEN

In most sensory modalities, neuronal connectivity reflects behaviorally relevant stimulus features, such as spatial location, orientation, and sound frequency. By contrast, the prevailing view in the olfactory cortex, based on the reconstruction of dozens of neurons, is that connectivity is random. Here, we used high-throughput sequencing-based neuroanatomical techniques to analyze the projections of 5,309 mouse olfactory bulb and 30,433 piriform cortex output neurons at single-cell resolution. Surprisingly, statistical analysis of this much larger dataset revealed that the olfactory cortex connectivity is spatially structured. Single olfactory bulb neurons targeting a particular location along the anterior-posterior axis of piriform cortex also project to matched, functionally distinct, extra-piriform targets. Moreover, single neurons from the targeted piriform locus also project to the same matched extra-piriform targets, forming triadic circuit motifs. Thus, as in other sensory modalities, olfactory information is routed at early stages of processing to functionally diverse targets in a coordinated manner.


Asunto(s)
Corteza Olfatoria , Vías Olfatorias , Ratones , Animales , Bulbo Olfatorio , Neuronas/fisiología , Secuenciación de Nucleótidos de Alto Rendimiento
2.
Cell ; 179(3): 772-786.e19, 2019 10 17.
Artículo en Inglés | MEDLINE | ID: mdl-31626774

RESUMEN

Understanding neural circuits requires deciphering interactions among myriad cell types defined by spatial organization, connectivity, gene expression, and other properties. Resolving these cell types requires both single-neuron resolution and high throughput, a challenging combination with conventional methods. Here, we introduce barcoded anatomy resolved by sequencing (BARseq), a multiplexed method based on RNA barcoding for mapping projections of thousands of spatially resolved neurons in a single brain and relating those projections to other properties such as gene or Cre expression. Mapping the projections to 11 areas of 3,579 neurons in mouse auditory cortex using BARseq confirmed the laminar organization of the three top classes (intratelencephalic [IT], pyramidal tract-like [PT-like], and corticothalamic [CT]) of projection neurons. In depth analysis uncovered a projection type restricted almost exclusively to transcriptionally defined subtypes of IT neurons. By bridging anatomical and transcriptomic approaches at cellular resolution with high throughput, BARseq can potentially uncover the organizing principles underlying the structure and formation of neural circuits.


Asunto(s)
Corteza Auditiva/metabolismo , Red Nerviosa/metabolismo , Análisis de Secuencia de ARN/métodos , Análisis de la Célula Individual/métodos , Animales , Mapeo Encefálico , Humanos , Integrasas/genética , Ratones , Neuritas/metabolismo , Células Piramidales/metabolismo , Tractos Piramidales/metabolismo
3.
Nature ; 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38658747

RESUMEN

The cerebral cortex is composed of neuronal types with diverse gene expression that are organized into specialized cortical areas. These areas, each with characteristic cytoarchitecture1,2, connectivity3,4 and neuronal activity5,6, are wired into modular networks3,4,7. However, it remains unclear whether these spatial organizations are reflected in neuronal transcriptomic signatures and how such signatures are established in development. Here we used BARseq, a high-throughput in situ sequencing technique, to interrogate the expression of 104 cell-type marker genes in 10.3 million cells, including 4,194,658 cortical neurons over nine mouse forebrain hemispheres, at cellular resolution. De novo clustering of gene expression in single neurons revealed transcriptomic types consistent with previous single-cell RNA sequencing studies8,9. The composition of transcriptomic types is highly predictive of cortical area identity. Moreover, areas with similar compositions of transcriptomic types, which we defined as cortical modules, overlap with areas that are highly connected, suggesting that the same modular organization is reflected in both transcriptomic signatures and connectivity. To explore how the transcriptomic profiles of cortical neurons depend on development, we assessed cell-type distributions after neonatal binocular enucleation. Notably, binocular enucleation caused the shifting of the cell-type compositional profiles of visual areas towards neighbouring cortical areas within the same module, suggesting that peripheral inputs sharpen the distinct transcriptomic identities of areas within cortical modules. Enabled by the high throughput, low cost and reproducibility of BARseq, our study provides a proof of principle for the use of large-scale in situ sequencing to both reveal brain-wide molecular architecture and understand its development.

4.
Nature ; 598(7879): 159-166, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34616071

RESUMEN

An essential step toward understanding brain function is to establish a structural framework with cellular resolution on which multi-scale datasets spanning molecules, cells, circuits and systems can be integrated and interpreted1. Here, as part of the collaborative Brain Initiative Cell Census Network (BICCN), we derive a comprehensive cell type-based anatomical description of one exemplar brain structure, the mouse primary motor cortex, upper limb area (MOp-ul). Using genetic and viral labelling, barcoded anatomy resolved by sequencing, single-neuron reconstruction, whole-brain imaging and cloud-based neuroinformatics tools, we delineated the MOp-ul in 3D and refined its sublaminar organization. We defined around two dozen projection neuron types in the MOp-ul and derived an input-output wiring diagram, which will facilitate future analyses of motor control circuitry across molecular, cellular and system levels. This work provides a roadmap towards a comprehensive cellular-resolution description of mammalian brain architecture.


Asunto(s)
Corteza Motora/anatomía & histología , Corteza Motora/citología , Neuronas/clasificación , Animales , Atlas como Asunto , Femenino , Neuronas GABAérgicas/citología , Neuronas GABAérgicas/metabolismo , Glutamatos/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Neuroimagen , Neuronas/citología , Neuronas/metabolismo , Especificidad de Órganos , Análisis de Secuencia de ARN , Análisis de la Célula Individual
5.
Macromol Rapid Commun ; 44(3): e2200693, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36250510

RESUMEN

Multiple and two-way reversible shape memory polymers (M/2W-SMPs) are highly promising for many fields due to large deformation, lightweight, strong recovery stress, and fast response rates. Herein, a semi-crystalline block poly(urethane-urea-amide) elastomers (PUUAs) are prepared by the copolymerization of isocyanate-terminated polyurethane (OPU) and amino-terminated oligomeric polyamide-1212 (OPA). PUUAs, composed of OPA as stationary phase and PTMEG as reversible phase, exhibit excellent rigidity, flexibility, and resilience, and cPUUA-C7 -S25 exhibits the best tensile property with strength of 10.3 MPa and elongation at break of 360.2%. Besides, all the PUUAs possess two crystallization/melting temperatures and a glass transition temperature, which endow PUUAs with multiple and reversible two-way shape memory effect (M/2W-SME). Physically crosslinked PUUA-C0 -S25 exhibits excellent dual and triple shape memory, and micro chemically crosslinked cPUUA-C7 -S25 further shows quadruple shape memory behavior. Additionally, both PUUA-C0 -S25 and cPUUA-C7 -S25 have 2W-SME. Intriguingly, cPUUA-C7 -S25 can achieve a higher temperature (up to 165 °C) SME, which makes it suitable for more complex and changeable applications. Based on the advantages of M/2W-SME, a temperature-responsive application scenario where PUUAs can transform spontaneously among different shapes is designed. These unique M/2W-SME and high-temperature SME will enable the applications of high-temperature sensors, actuators, and aerospace equipment.


Asunto(s)
Elastómeros , Polímeros , Polímeros/química , Amidas , Urea , Poliuretanos/química
6.
Int J Mol Sci ; 24(2)2023 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-36674937

RESUMEN

Poria cocos polysaccharides (PCP) have been validated for several biological activities, including antitumor, anti-inflammatory, antioxidant, immunomodulatory, hepatoprotective and modulation on gut microbiota. In this research, we aim to demonstrate the potential prebiotic effects and the therapeutic efficacies of PCP in the treatment of antibiotic-associated diarrhea (AAD), and confirm the beneficial effects of PCP on gut dysbiosis. Antibiotic-associated diarrhea mice models were established by treating them with broad-spectrum antibiotics in drinking water for seven days. Mice in two groups treated with probiotics and polysaccharide were given Bifico capsules (4.2 g/kg/d) and PCP (250 mg/kg/d) for seven days using intragastric gavage, respectively. To observe the regulatory effects of PCP on gut microbiota and intestinal mucosal barrier, we conducted the following experiments: intestinal flora analysis (16S rDNA sequencing), histology (H&E staining) and tight junction proteins (immunofluorescence staining). The levels of mRNA expression of receptors associated with inflammation and gut metabolism were assessed by real-time reverse transcription-polymerase chain reaction (RT-PCR). The study revealed that PCP can comprehensively improve the clinical symptoms of AAD mice, including fecal traits, mental state, hair quality, etc., similar to the effect of probiotics. Based on histology observation, PCP significantly improved the substantial structure of the intestine of AAD mice by increasing the expression levels of colonic tight junction protein zonula-occludens 1 (ZO-1) and its mRNA. Moreover, PCP not only increased the abundance of gut microbiota, but also increased the diversity of gut microbiota in AAD mice, including alpha diversity and beta diversity. Further analysis found that PCP can modulate seven characteristic species of intestinal flora in AAD mice, including Parabacteroides_distasonis, Akkermansia_muciniphila, Clostridium_saccharolyticum, Ruminoc-occus_gnavus, Lactobacillus_salivarius, Salmonella_enterica and Mucispirillum_schaedleri. Finally, enrichment analysis predicted that PCP may affect intestinal mucosal barrier function, host immune response and metabolic function by regulating the microbiota. RT-PCR experiments showed that PCP can participate in immunomodulatory and modulation on metabolic by regulating the mRNA expression of forkhead-box protein 3 (FOXP3) and G protein-coupled receptor 41 (GPR41). These results indicated that Poria cocos polysaccharide may ameliorate antibiotic-associated diarrhea in mice by regulating the homeostasis of the gut microbiota and intestinal mucosal barrier. In addition, polysaccharide-derived changes in intestinal microbiota were involved in the immunomodulatory activities and modulation of the metabolism.


Asunto(s)
Microbioma Gastrointestinal , Wolfiporia , Ratones , Animales , Wolfiporia/genética , Diarrea/inducido químicamente , Diarrea/tratamiento farmacológico , Polisacáridos/farmacología , Antibacterianos/efectos adversos , Homeostasis , ARN Mensajero
7.
Ann Surg Oncol ; 29(3): 1868-1879, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34613537

RESUMEN

BACKGROUND: Surgery has become an accepted method for the treatment of early-stage non-small cell lung cancer (NSCLC). The purpose of this Bayesian meta-analysis was to compare the overall survival (OS), disease-free survival (DFS), and relapse-free survival (RFS) between wedge resection and lobectomy/segmentectomy for treatment of early-stage NSCLC. METHODS: Eligible studies were retrieved from Web of Science, PubMed, MEDLINE, Cochrane Library, EMBASE, CNKI, and WanFang up to July 2021 and screened based on established selection criteria. The Bayesian meta-analysis was performed with the combination of the reported survival outcomes of the individual studies using a random-effect model. The OS, DFS, and RFS of the wedge resection group was compared with the lobectomy/segmentectomy group. The hazard ratio (HR) and standard error were extracted or calculated for each study using the Kaplan-Meier method. RESULTS: This study was registered with PROSPERO (INPLASY202080090).The pooled OS hazard ratio between segmentectomy and lobectomy was 1.1 [95% confidence interval (CI) 0.92-1.4], the pooled HR between lobectomy and wedge resection was 0.71 [95% CI 0.52-0.96], and the pooled HR between segmentectomy and wedge was 0.80 [95% CI 0.56-1.10]. The pooled HR of DFS or RFS was not statistically significant among the three surgical approaches. CONCLUSIONS: Patients with early-stage NSCLC received lobectomy had the lowest hazard ratio of OS than patients received wedge resection, indicating that the overall survival of patients received lobectomy was higher than patients received wedge resection. However, regarding DFS and RFS, the three surgical approaches showed no significant difference.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Teorema de Bayes , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Neumonectomía
8.
PLoS Comput Biol ; 17(3): e1008256, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33684106

RESUMEN

Modern spatial transcriptomics methods can target thousands of different types of RNA transcripts in a single slice of tissue. Many biological applications demand a high spatial density of transcripts relative to the imaging resolution, leading to partial mixing of transcript rolonies in many voxels; unfortunately, current analysis methods do not perform robustly in this highly-mixed setting. Here we develop a new analysis approach, BARcode DEmixing through Non-negative Spatial Regression (BarDensr): we start with a generative model of the physical process that leads to the observed image data and then apply sparse convex optimization methods to estimate the underlying (demixed) rolony densities. We apply BarDensr to simulated and real data and find that it achieves state of the art signal recovery, particularly in densely-labeled regions or data with low spatial resolution. Finally, BarDensr is fast and parallelizable. We provide open-source code as well as an implementation for the 'NeuroCAAS' cloud platform.


Asunto(s)
Regresión Espacial , Algoritmos , Simulación por Computador , Transcriptoma
9.
Dermatol Ther ; 35(8): e15599, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35614844

RESUMEN

Although secukinumab has demonstrated high efficacy and favorable safety in moderate-to-severe psoriasis and psoriatic arthritis, patients developing adverse events of special interest (AESI) were reported increasingly in real-world practice. A systematic literature search of the PubMed database was conducted to identify clinical studies or case reports on secukinumab-induced AESI. More than 1077 patients (aged 18-74 years) from 55 studies were reported to have 24 AESI 3 days to 96 weeks after secukinumab treatment. The four most common AESI was inflammatory bowel disease (n > 1000), eczematous drug eruption (n > 30), drug-associated vasculitis (n = 8), and drug-induced lupus erythematosus (n = 4). Most of these AESI were only mild to moderately severe and resolved after secukinumab discontinuation without or with symptomatic treatment. Secukinumab has the potential to develop a number of AESI by probably dysregulating the different expression of polar T-cell axes (Th1, Th2, Th17, Th22, and/or Treg) and driving various cytokines in some patients. Physicians should be aware of these AESI for timely diagnosis and proper treatment.


Asunto(s)
Artritis Psoriásica , Psoriasis , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Artritis Psoriásica/tratamiento farmacológico , Humanos , Psoriasis/inducido químicamente , Psoriasis/diagnóstico , Psoriasis/tratamiento farmacológico , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
10.
Dermatol Ther ; 34(5): e15048, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34212464

RESUMEN

Psoriasis is a systemic inflammatory disease commonly associated with postinflammatory hyper- and hypo-pigmentation. Psoriasis-related cytokines such as IL-17 and TNF can contribute to these pigmentation changes by regulating both the growth and pigment production of melanocytes. Here, we present the first reported the case of a patient with a 10-year history of severe psoriasis vulgaris, who developed multiple lentigines in areas of resolved psoriatic plaques during anti-IL-17A antibody secukinumab.


Asunto(s)
Lentigo , Trastornos de la Pigmentación , Psoriasis , Anticuerpos Monoclonales Humanizados , Humanos , Psoriasis/inducido químicamente , Psoriasis/diagnóstico , Psoriasis/tratamiento farmacológico
11.
Nucleic Acids Res ; 46(4): e22, 2018 02 28.
Artículo en Inglés | MEDLINE | ID: mdl-29190363

RESUMEN

Cellular DNA/RNA tags (barcodes) allow for multiplexed cell lineage tracing and neuronal projection mapping with cellular resolution. Conventional approaches to reading out cellular barcodes trade off spatial resolution with throughput. Bulk sequencing achieves high throughput but sacrifices spatial resolution, whereas manual cell picking has low throughput. In situ sequencing could potentially achieve both high spatial resolution and high throughput, but current in situ sequencing techniques are inefficient at reading out cellular barcodes. Here we describe BaristaSeq, an optimization of a targeted, padlock probe-based technique for in situ barcode sequencing compatible with Illumina sequencing chemistry. BaristaSeq results in a five-fold increase in amplification efficiency, with a sequencing accuracy of at least 97%. BaristaSeq could be used for barcode-assisted lineage tracing, and to map long-range neuronal projections.


Asunto(s)
Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Animales , Linaje de la Célula , Células Cultivadas , Neuronas/citología , Análisis de Secuencia de ARN/métodos
12.
J Cell Physiol ; 234(10): 17839-17853, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-30972748

RESUMEN

Sepsis is a systemic inflammatory response that may be induced by trauma, infection, surgery, and burns. With the aim of discovering novel treatment targets for sepsis, this current study was conducted to investigate the effect and potential mechanism by which microRNA-30a (miR-30a) controls sepsis-induced liver cell proliferation and apoptosis. Rat models of sepsis were established by applying the cecal ligation and puncture (CLP) method to simulate sepsis models. The binding site between miR-30a and suppressor of cytokine signaling protein 1 (SOCS-1) was determined by dual luciferase reporter gene assay. The gain-of-and-loss-of-function experiments were applied to analyze the effects of miR-30a and SOCS-1 on liver cell proliferation and apoptosis of the established sepsis rat models. The expression of miR-30a, SOCS-1, Janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), Bcl-2 associated X protein (Bax), B cell lymphoma-2 (Bcl-2), toll-like receptor 4 (TLR4), and high-mobility group box 1 (HMGB1), and the extent of JAK2 and STAT3 phosphorylation were all determined. Sepsis led to an elevation of miR-30a and also a decline of SOCS-1 in the liver cells. SOCS-1 was negatively regulated by miR-30a. Upregulated miR-30a and downregulated SOCS-1 increased the expression of JAK2, STAT3, Bax, TLR4, and HMGB1 as well as the extent of JAK2 and STAT3 phosphorylation whereas impeding the expression of SOCS-1 and Bcl-2. More important, either miR-30a elevation or SOCS-1 silencing suppressed liver cell proliferation and also promoted apoptosis. On the contrary, the inhibition of miR-30a exhibited the opposite effects. Altogether, we come to the conclusion that miR-30a inhibited the liver cell proliferation and promoted cell apoptosis by targeting and negatively regulating SOCS-1 via the JAK/STAT signaling pathway in rats with sepsis.


Asunto(s)
Apoptosis/genética , Proliferación Celular/genética , Janus Quinasa 2/genética , MicroARNs/genética , Factor de Transcripción STAT3/genética , Sepsis/genética , Proteína 1 Supresora de la Señalización de Citocinas/genética , Animales , Regulación hacia Abajo/genética , Hepatocitos/fisiología , Hígado/fisiología , Masculino , Fosforilación/genética , Ratas , Ratas Wistar , Transducción de Señal/genética , Regulación hacia Arriba/genética
13.
Phytother Res ; 32(12): 2560-2567, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30306659

RESUMEN

Berberine, a natural isoquinoline alkaloid isolated from the berberis species, has a wide array of biological properties such as anti-inflammatory, antibacterial, antifungal, and antihelminthic effects. We evaluated the antiviral effect of berberine against influenza A/FM1/1/47 (H1N1) in vivo and in vitro. The results showed that berberine strongly suppressed viral replication in A549 cells and in mouse lungs. Meanwhile, berberine relieved pulmonary inflammation and reduced necrosis, inflammatory cell infiltration, and pulmonary edema induced by viral infection in mice when compared with vehicle-treated mice. Berberine suppressed the viral infection-induced up-regulation of TLR7 signaling pathway, such as TLR7, MyD88, and NF-κB (p65), at both the mRNA and protein levels. Furthermore, berberine significantly inhibited the viral infection-induced increase in Th1/Th2 and Th17/Treg ratios as well as the production of inflammatory cytokines. Our data provide new insight into the potential of berberine as a therapeutic agent for viral infection via its antiviral activity.


Asunto(s)
Antivirales/farmacología , Berberina/farmacología , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Replicación Viral/efectos de los fármacos , Células A549 , Animales , Antivirales/uso terapéutico , Berberina/uso terapéutico , Embrión de Pollo , Humanos , Subtipo H1N1 del Virus de la Influenza A/fisiología , Gripe Humana/diagnóstico , Gripe Humana/tratamiento farmacológico , Gripe Humana/virología , Ratones , Ratones Endogámicos C57BL , Infecciones por Orthomyxoviridae/diagnóstico , Infecciones por Orthomyxoviridae/tratamiento farmacológico , Infecciones por Orthomyxoviridae/virología , Neumonía/diagnóstico , Neumonía/tratamiento farmacológico , Neumonía/virología , Pronóstico , Transducción de Señal/efectos de los fármacos
14.
Molecules ; 23(12)2018 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-30513647

RESUMEN

The intestinal flora may be an important and modifiable factor that contributes to the immune response in influenza. To investigate the effect of intestinal flora alteration induced by antibiotic interference on microRNA (miRNA) communication in antiviral immunity, BALB/c mice received two weeks of antibiotic treatment before infection with the influenza A virus. The changes in intestinal flora and pulmonary flora were detected and analyzed by 16S ribosomal RNA (rRNA) gene sequencing. The amplification of the influenza virus in the lungs was measured by RT-PCR. The involvement of pulmonary miRNA was explored using miRNA microarray analysis. The results showed that the antibiotics destroyed the symbiotic relationship of the intestinal flora, resulting in a reduction in bacterial diversity, but they did not affect the pulmonary flora. The alteration of intestinal flora affected the expression of pulmonary miRNAs and resulted in an enhancement of pulmonary influenza virus amplification. The conclusion is that alteration of intestinal flora induced by antibiotic interference affected the expression of pulmonary miRNAs to interfere with host antiviral immunity, of which miR-146b and miR-29c might be good resources of resistance to influenza under antibiotic abuse.


Asunto(s)
Antivirales/inmunología , Microbioma Gastrointestinal , Interacciones Huésped-Patógeno/genética , Inmunidad , Pulmón/metabolismo , MicroARNs/metabolismo , Infecciones por Orthomyxoviridae/genética , Infecciones por Orthomyxoviridae/inmunología , Animales , Biodiversidad , Femenino , Perfilación de la Expresión Génica , Pulmón/patología , Pulmón/virología , Masculino , Ratones Endogámicos BALB C , MicroARNs/genética , Infecciones por Orthomyxoviridae/virología , ARN Viral/genética , ARN Viral/metabolismo , Especificidad de la Especie
15.
J Neurosci ; 35(5): 2200-12, 2015 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-25653375

RESUMEN

In Caenorhabditis elegans, gentle touch is sensed by the anterior (ALM and AVM) and posterior (PLM) touch receptor neurons. Anterior, but not posterior, touch is affected by several stress conditions via the action of AKT kinases and the DAF-16/FOXO transcription factor. Here we show that a ubiquitination-dependent mechanism mediates such effects. AKT-1/AKT kinase and DAF-16 alter the transcription of mfb-1, which encodes an E3 ubiquitin ligase needed for the ubiquitination of the mechanosensory channel subunit MEC-4. Ubiquitination of MEC-4 reduces the amount of MEC-4 protein in the processes of ALM neurons and, consequently, the mechanoreceptor current. Even under nonstress conditions, differences in the amount of MFB-1 appear to cause the PLM neurons to be less sensitive to touch than the ALM neurons. These studies demonstrate that modulation of surface mechanoreceptors can regulate the sensitivity to mechanical signals.


Asunto(s)
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Mecanotransducción Celular , Proteínas de la Membrana/metabolismo , Ubiquitinación , Animales , Caenorhabditis elegans/fisiología , Factores de Transcripción Forkhead , Mecanorreceptores/metabolismo , Mecanorreceptores/fisiología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Tacto , Factores de Transcripción/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo
16.
Molecules ; 21(5)2016 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-27128889

RESUMEN

OBJECTIVE: The objective of this study was to observe the effects of forsythoside A on controlling influenza A virus (IAV) infection and improving the prognosis of IAV infection. METHODS: Forty-eight SPF C57BL/6j mice were randomly divided into the following four groups: Group A: normal control group (normal con); Group B: IAV control group (V con); Group C: IAV+ oseltamivir treatment group (V oseltamivir; 0.78 mg/mL, 0.2 mL/mouse/day); Group D: IAV+ forsythoside A treatment group (V FTA; 2 µg/mL, 0.2 mL/mouse/day). Real-time fluorescence quantitative PCR (RT-qPCR) was used to measure mRNA expression of the TLR7, MyD88, TRAF6, IRAK4 and NF-κB p65 mRNA in TLR7 signaling pathway and the virus replication level in lung. Western blot was used to measure TLR7, MyD88 and NF-κB p65 protein. Flow cytometry was used to detect the proportion of the T cell subsets Th1/Th2 and Th17/Treg. RESULTS: The body weight began to decrease after IAV infection, while FTA and oseltamivir could reduce the rate of body weight loss. The pathological damages in the FTA and oseltamivir group were less serious. TLR7, MyD88, TRAF6, IRAK4 and NF-κB p65 mRNA were up-regulated after virus infection (p < 0.01) while down-regulated after oseltamivir and FTA treatment (p < 0.01). The results of TLR7, MyD88 and NF-κB p65 protein consisted with correlative mRNA. Flow cytometry showed the Th1/Th2 differentiated towards Th2, and the Th17/Treg cells differentiated towards Treg after FTA treatment. CONCLUSIONS: Our study suggests forsythoside A can control influenza A virus infection and improve the prognosis of IAV infection by inhibiting influenza A virus replication.


Asunto(s)
Antivirales/administración & dosificación , Glicósidos/administración & dosificación , Virus de la Influenza A/fisiología , Glicoproteínas de Membrana/genética , Infecciones por Orthomyxoviridae/tratamiento farmacológico , Receptor Toll-Like 7/genética , Replicación Viral/efectos de los fármacos , Animales , Antivirales/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Glicósidos/farmacología , Virus de la Influenza A/efectos de los fármacos , Pulmón/virología , Ratones , Ratones Endogámicos C57BL , Infecciones por Orthomyxoviridae/genética , Infecciones por Orthomyxoviridae/veterinaria , Oseltamivir/administración & dosificación , Oseltamivir/farmacología , Pronóstico , Distribución Aleatoria , Reacción en Cadena en Tiempo Real de la Polimerasa/veterinaria , Transducción de Señal/efectos de los fármacos , Pérdida de Peso/efectos de los fármacos
17.
J Neurosci ; 34(19): 6522-36, 2014 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-24806678

RESUMEN

Sensory systems can adapt to different environmental signals. Here we identify four conditions that modulate anterior touch sensitivity in Caenorhabditis elegans after several hours and demonstrate that such sensory modulation is integrated at multiple levels to produce a single output. Prolonged vibration involving integrin signaling directly sensitizes the touch receptor neurons (TRNs). In contrast, hypoxia, the dauer state, and high salt reduce touch sensitivity by preventing the release of long-range neuroregulators, including two insulin-like proteins. Integration of these latter inputs occurs at upstream neurohormonal cells and at the insulin signaling cascade within the TRNs. These signals and those from integrin signaling converge to modulate touch sensitivity by regulating AKT kinases and DAF-16/FOXO. Thus, activation of either the integrin or insulin pathways can compensate for defects in the other pathway. This modulatory system integrates conflicting signals from different modalities, and adapts touch sensitivity to both mechanical and non-mechanical conditions.


Asunto(s)
Caenorhabditis elegans/fisiología , Percepción del Tacto/fisiología , Animales , Conducta Animal/fisiología , Proteínas de Caenorhabditis elegans/fisiología , Calcio/fisiología , Factores de Transcripción Forkhead , Hipoxia/fisiopatología , Integrinas/fisiología , Rayos Láser , Mecanorreceptores/fisiología , Músculos/inervación , Músculos/fisiología , Neuroimagen , Proteína Oncogénica v-akt/fisiología , Estimulación Física , Interferencia de ARN , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Transducción de Señal/fisiología , Estrés Fisiológico , Factores de Transcripción/fisiología , Vibración
18.
J Tradit Chin Med ; 34(1): 10-4, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25102684

RESUMEN

OBJECTIVE: To observe the effect of the Traditional Chinese Medicine, modified Taohongsiwu decoction, versus pyridoxine on patients with hand-foot syndrome (HFS) from capecitabine, sorafenib, and gefitinib chemotherapy for gastric, lung, breast, colon, or rectal cancer. Also, to compare quality of life of patients in each group. METHODS: Patients were assigned randomly to group A or B. Group A was given modified Taohongsiwu decoction to soak hands and feet for 30 min, once daily. Group B was given 100 mg pyridoxine orally, twice daily. After a 2-week treatment, the therapeutic effect was assessed by observing three major symptoms, including pain, ulceration, and muscular atrophy. This was assessed with the HFS-14 questionnaire. RESULTS: Significant differences were observed between the two groups in pain relief, and improvement of daily life, walking, and interpersonal communication (P < 0.01). No significant differences in driving ability or interpersonal relationships were found. After 2 weeks, the effective rate was 88.3% in group A, which was significantly higher than the 50% in group B (P = 0.00). CONCLUSION: Modified Taohongsiwu decoction is effective in the treatment of patients with HFS. It improves patients' quality of life according to the HFS-14.


Asunto(s)
Antimetabolitos Antineoplásicos/efectos adversos , Antineoplásicos/efectos adversos , Medicamentos Herbarios Chinos/uso terapéutico , Síndrome Mano-Pie/tratamiento farmacológico , Neoplasias/complicaciones , Adulto , Anciano , Antimetabolitos Antineoplásicos/uso terapéutico , Antineoplásicos/uso terapéutico , Capecitabina , Desoxicitidina/efectos adversos , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapéutico , Femenino , Fluorouracilo/efectos adversos , Fluorouracilo/análogos & derivados , Fluorouracilo/uso terapéutico , Síndrome Mano-Pie/etiología , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico
19.
Artículo en Inglés | MEDLINE | ID: mdl-38621822

RESUMEN

Comprehensive maps of neuronal connectivity provide a foundation for understanding the structure of neural circuits. In a circuit, neurons are diverse in morphology, electrophysiology, gene expression, activity, and other neuronal properties. Thus, constructing a comprehensive connectivity map requires associating various properties of neurons, including their connectivity, at cellular resolution. A commonly used approach is to use the gene expression profiles as an anchor to which all other neuronal properties are associated. Recent advances in genomics and anatomical techniques dramatically improved the ability to determine and associate the long-range projections of neurons with their gene expression profiles. These studies revealed unprecedented details of the gene-projection relationship, but also highlighted conceptual challenges in understanding this relationship. In this article, I delve into the findings and the challenges revealed by recent studies using state-of-the-art neuroanatomical and transcriptomic techniques. Building upon these insights, I propose an approach that focuses on understanding the gene-projection relationship through basic features in gene expression profiles and projections, respectively, that associate with underlying cellular processes. I then discuss how the developmental trajectories of projections and gene expression profiles create additional challenges and necessitate interrogating the gene-projection relationship across time. Finally, I explore complementary strategies that, together, can provide a comprehensive view of the gene-projection relationship.

20.
Transl Pediatr ; 13(6): 946-962, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38984024

RESUMEN

Background and Objective: Sleep influences the interaction between infants and their environment, as well as the achievement of crucial milestones in motor and language development. This is particularly significant for preterm infants in vulnerable positions. However, prematurely born infants in the neonatal intensive care unit (NICU) are exposed to various stimuli such as noise and light, which disrupt their normal sleep patterns. This study assesses and consolidates the existing evidence on non-pharmacological strategies for protecting and promoting sleep in preterm infants. By providing an evidence-based data repository, it offers a valuable reference for clinical interventions. Methods: We conducted computer-based searches using various databases and resources, including UpToDate, BMJ Best Practice, Guidelines International Network (GIN), National Institute for Health and Clinical Excellence (NICE), Scottish Intercollegiate Guidelines Network (SIGN), National Guideline Clearinghouse (NGC), Registered Nurses Association of Ontario (RNAO), Joanna Briggs Institute (JBI), World Health Organization (WHO), Cochrane Library, Web of Science, PubMed, China National Knowledge Infrastructure (CNKI), Wanfang Data, and China Biology Medicine disc (CBM). The search period spanned from January 2014 to May 2024. Key Content and Findings: We have included a total of 22 articles in our review, comprising two guidelines, 11 systematic reviews, 1 evidence summary, 1 technical report, 2 practice recommendations, and 5 randomized controlled trials. The evidence was synthesized from eight domains: sleep team construction, risk factor assessment, sleep assessment tools, positional management, noise control, light management, sensory stimulation, and hospital-home transition sleep management, resulting in 27 pieces of evidence. Conclusions: This study summarizes the optimal evidence for the management of sleep in premature infants, providing empirical support for standardizing the management of sleep in premature infants. It is recommended that healthcare professionals judiciously apply the best evidence while considering the clinical context, thus promoting safe sleep for premature infants.

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