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1.
Artigo em Inglês | MEDLINE | ID: mdl-33471184

RESUMO

PURPOSE: Recent clinical trials with agents targeting immune checkpoint pathway have emerged as an important therapeutic approach for a broad range of cancer types. Resveratrol has been shown to possess cancer preventive and therapeutic effects and has potential to be chemotherapeutic agent/adjuvant. Here, we assessed the effect of resveratrol on immune checkpoint pathways. METHODS: The expression patterns of Wnt components and PD-L1 were examined by Western blot, Chromatin immunoprecipitation (ChIP) was used for analysis of DNA-protein interaction, the promoter activity was determined by luciferase reporter assay, apoptosis was analyzed by flow cytometry and the ability of the resveratrol to modulate T cell function was assessed in a co-culture system. RESULTS: Although the dose-, and cell-type dependent effects of resveratrol on PD-L1 expression have been reported, we show here that resveratrol dose-dependently upregulates PD-L1 expression at the range of pharmacologic-achievable concentrations in lung cancer cells and that is essential for suppression of T-cell-mediated immune response. We also found that Wnt pathway is critical for mediating resveratrol-induced PD-L1 upregulation. Mechanistically, resveratrol activates SirT1 deacetylase to deacetylate and stabilize transcriptional factor Snail. Snail in turn inhibits transcription of Axin2, which leads in disassembly of destruction complex and enhanced binding of ß-catenin/TCF to PD-L1 promoter. CONCLUSION: We conclude that resveratrol is capable to suppress anti-tumor immunity by controlling mainly PD-L1 expression. This finding will extend the understanding of resveratrol in regulation of tumor immunity and is relevant to the debate on resveratrol supplements for lung cancer patients.

2.
Sci Total Environ ; 750: 141656, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32858299

RESUMO

This study provided a systematic analysis on material flow and environmental impacts of a food waste (FW) bioconversion plant using black soldier fly larvae (BSFL), with a daily capacity of 15 tons of FW (wet weight). Food waste feed (FWF) used for BSFL bioconversion consisted of 80% FW (collected from households, restaurants, and canteens) and 20% rice hull powder. Material flow analysis conducted on a dry weight basis showed that 6% of FWF was transformed into BSF pre-pupae, 51% was stored in matured compost, and 43% was emitted to the air. Emissions of high environmental concern such as methane, nitrous oxide and ammonia (NH3) were sampled and quantified by laboratory analysis. The life cycle assessment revealed that the overall impact was 17.36 kg CO2-eq/t FW for global warming potential, 5.54 kg SO2-eq/t FW for acidification, 24.05 mol N-eq/t FW for terrestrial eutrophication, 0.54 kg N-eq NH3/t FW for marine eutrophication, and 0.18 kg PM2.5-eq/t FW of particulate matter up to 2.5 µm diameter. Moreover, emissions from post-composting, energy consumptions of drying and chemical fertilizer substitution ratio were detected by contribution analysis as the main contributors to those impacts. Finally, sensitivity analysis indicated that the substitution ratio of mineral fertilizer and protein feed as well as energy consumption were the most influential parameters, therefore control of the post-composting process of residual material should be closely monitored because it was responsible for significant environmental load caused by N-related emissions.


Assuntos
Compostagem , Dípteros , Eliminação de Resíduos , Simuliidae , Animais , Alimentos , Larva
3.
Materials (Basel) ; 13(23)2020 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-33291501

RESUMO

The corrosion behavior of the Fe50Mn30Co10Cr10 high-entropy alloy (HEA) manufactured via laser melting deposition (LMD) was investigated using open circuit potential, potentiodynamic polarization, and electrochemical impedance spectroscopy measurements. The microstructure and morphology of LMD samples before and after the electrochemical tests were compared using X-ray diffraction, optical microscopy, scanning electron microscopy, and electron backscatter diffraction techniques. After the corrosion tests, a striped morphology was observed on the surface of the LMD HEA, which is mainly caused by the interval distribution of high-density and low-density grain-boundary regions. The corrosion performances varied with different planes of the LMD HEA sample, which is mainly controlled by the grain size at each plane. Local corrosion in this HEA is concentrated at the melt pool boundary, which may be due to the abundant metallurgical defects and stress concentration at this location.

5.
Adv Sci (Weinh) ; 7(21): 2002273, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33173745

RESUMO

Nuclear receptors (NRs) are a superfamily of transcription factors which sense hormonal signals or nutrients to regulate various biological events, including development, reproduction, and metabolism. Here, this study identifies nuclear receptor subfamily 2, group F, member 6 (NR2F6), as an important regulator of hepatic triglyceride (TG) homeostasis and causal factor in the development of non-alcoholic fatty liver disease (NAFLD). Adeno-associated virus (AAV)-mediated overexpression of NR2F6 in the liver promotes TG accumulation in lean mice, while hepatic-specific suppression of NR2F6 improves obesity-associated hepatosteatosis, insulin resistance, and methionine and choline-deficient (MCD) diet-induced non-alcoholic steatohepatitis (NASH). Mechanistically, the fatty acid translocase CD36 is identified as a transcriptional target of NR2F6 to mediate its steatotic role. NR2F6 is able to bind directly onto the CD36 promoter region in hepatocytes and increases the enrichment of nuclear receptor coactivator 1 (SRC-1) and histone acetylation at its promoter. Of pathophysiological significance, NR2F6 is significantly upregulated in the livers of obese mice and NAFLD patients. Moreover, treatment with metformin decreases NR2F6 expression in obese mice, resulting in suppression of CD36 and reduced hepatic TG contents. Therefore, these results provide evidence for an unpredicted role of NR2F6 that contributes to liver steatosis and suggest that NR2F6 antagonists may present a therapeutic strategy for reversing or treating NAFLD/NASH pathogenesis.

6.
Curr Microbiol ; 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33141316

RESUMO

Using black soldier fly (Hermetia illucens) larvae in treatment of livestock manure is a promising technology. In this study, high-throughput sequencing was used to analyze the microbial community in chicken manure before and after treatment with H. illucens larvae. In fresh chicken manure, the most abundant bacterial phylum was Firmicutes (55.58%) followed by Bacteroidetes (24.52%) and then Proteobacteria (12.29%). After treatment of the manure with H. illucens larvae for 15 days, the abundance of Firmicutes increased to 97.72% while that of Bacteroidetes and Proteobacteria decreased. Concomitantly, the most abundant genera of fungi in chicken manure changed from Kernia (46.19%) and Microascus (17.22%) to Penicillium (46.82%) and Aspergillus (45.22%). Correlation-network analysis showed the existence of strong and complex correlations between the dominant operational taxonomic units (OUT) of bacteria and fungi. While most of these correlations were positive, three specific genera, namely g_norank_f_Bacillaceae, Penicillium, and Aspergillus exhibited negative correlations with the remaining genera. These three genera were highly abundant in the intestines of H. illucens and in chicken manure treated with H. illucens larvae. Based on 16S rDNA microbiome-function predictions, the metabolic pathways associated with sugars, amino acids, and organic pollutants inside the intestinal tract of H. illucens were enriched versus those of the other three groups. In summary, the treatment of chicken manure with H. illucens larvae significantly reduced the microbial diversity, while strongly increasing organic metabolism in the intestinal bacteria. This technology shows the potential for applications in livestock manure treatment.

7.
Exp Eye Res ; : 108367, 2020 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-33232710

RESUMO

The autonomic innervation in the anterior chamber (AC) structures might play an efferent role in neural intraocular pressure (IOP) regulation, the center of which is thought to be located in the hypothalamus. In this study, we identified the efferent pathway from the hypothalamus to the autonomic innervation in the AC structures. Retrograde trans-multisynaptic pseudorabies virus (PRV) expressing green or red fluorescent protein, PRV531 and PRV724, was injected into the right and left AC of five rats, respectively; PRV531 was injected into the right AC of another five rats, and a non-trans-synaptic tracer, FAST Dil, was injected into the right AC of five rats as a control. Fluorescence signals in autonomic ganglia,the spinal cord and the central nervous system (CNS) were observed. Seven days after FAST Dil right AC injection, FAST Dil-labeled neurons were observed in the ipsilateral autonomic ganglia, including the superior cervical ganglion, pterygopalatine ganglion, and ciliary ganglion, but not in the CNS. Four and a half days after PRV531 injection into the right AC, PRV531-labeled neurons could be observed in the ipsilateral autonomic ganglia and bilateral hypothalamus nuclei, especially in the suprachiasmatic nucleus, paraventricular nucleus, dorsomedial hypothalamus, perifornical hypothalamus and ventral mammillary nucleus. Fluorescence signals of PRV531 mainly located in the ipsilateral autonomic preganglionic nuclei (Edinger-Westphal nucleus, superior salivatory nucleus and intermediolateral nucleus), but not in sensory trigeminal nuclei. Four and a half days after PRV531 right AC injection and PRV724 left AC injection, PRV531-labeled, PRV724-labeled, and double-labeled neurons could be observed in the above mentioned bilateral hypothalamus nuclei; but few contralateral infection-involving neurons (including double-labeled neurons) could be detected in the autonomic preganglionic nuclei. Our results indicate that there exist a both crossed and uncrossed hypothalamo-pre-parasympathetic and -pre-sympathetic tracts in the efferent pathways between the bilateral hypothalamic nuclei and the autonomic innervation of the bilateral AC.

8.
Amino Acids ; 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33245424

RESUMO

As a promising cell therapy, neural crest-derived ectoderm mesenchymal stem cells (EMSCs) secrete high amounts of extracellular matrix (ECM) and neurotrophic factors, promoting neural stem cell (NSC) differentiation into neuronal lineages and aiding tissue regeneration. Additionally, the forced overexpression of secreted proteins can increase the therapeutic efficacy of the secretome. Tissue transglutaminase (TG2) is a ubiquitously expressed member of the transglutaminase family of calcium-dependent crosslinking enzymes, which can stabilize the ECM, inducing smart or living biomaterial to stimulate differentiation and enhance the neurogenesis of NSCs. In this study, we examined the neuronal differentiation of NSCs induced by TG2 gene-modified EMSCs (TG2-EMSCs) in a co-culture model directly. Two weeks after initiating differentiation, levels of the neuronal markers, tubulin beta 3 class III and growth-associated protein 43, were higher in NSCs in the TG2-EMSC co-culture group and those of the astrocytic marker glial fibrillary acidic protein were lower, compared with the control group. These results were confirmed by immunofluorescence, and laminin, fibronectin and sonic hedgehog (Shh) contributed to this effect. The results of western blot analysis and the enzyme-linked immunoassay showed that after TG2-EMSCs were co-cultured for 2 weeks, they expressed much higher levels of Shh than the control group. Moreover, the sustained release of Shh was observed in the TG2-EMSC co-culture group. Overall, our findings indicate that EMSCs can induce the differentiation of NSCs, of which TG2-EMSCs can promote the differentiation of NSCs compared with EMSCs.

10.
Mol Brain ; 13(1): 138, 2020 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-33054827

RESUMO

Recombinant adeno-associated viruses (rAAVs), particularly those that permit efficient gene transfer to neurons from axonal terminals or across the blood-brain barrier, are useful vehicles for structural and functional studies of the neural circuit and for the treatment of many gene-deficient brain diseases that need to compensate for the correct genes in every cell in the whole brain. However, AAVs with these two advantages have not been reported. Here, we describe a new capsid engineering method, which exploits the combination of different capsids and aims to yield a capsid that can provide more alternative routes of administration that are more suitable for the wide-scale transduction of the central nervous system (CNS). A new AAV variant, AAV9-Retro, was developed by inserting the 10-mer peptide fragment from AAV2-Retro into the capsid of AAV9, and the biodistribution properties were evaluated in mice. By intracranial and intravenous injection in the mice, we found that AAV9-Retro can retrogradely infect projection neurons with an efficiency comparable to that of AAV2-Retro and retains the characteristic of AAV9, which can be transported across the nervous system. Our strategy provides a new tool for the manipulation of neural circuits and future preclinical and clinical treatment of some neurological and neurodegenerative disorders.

11.
Cell Commun Signal ; 18(1): 167, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33097055

RESUMO

BACKGROUND: Metabolic reprogramming contributes significantly to tumor development and is tightly linked to drug resistance. The chemotherapeutic agent etoposide (VP-16) has been used clinically in the treatment of lung cancer but possess different sensitivity and efficacy towards SCLC and NSCLC. Here, we assessed the impact of etoposide on glycolytic metabolism in SCLC and NSCLC cell lines and investigated the role of metabolic rewiring in mediating etoposide resistance. METHODS: glycolytic differences of drug-treated cancer cells were determined by extracellular acidification rate (ECAR), glucose consumption, lactate production and western blot. DNA damage was evaluated by the comet assay and western blot. Chemoresistant cancer cells were analyzed by viability, apoptosis and western blot. Chromatin immunoprecipitation (ChIP) was used for analysis of DNA-protein interaction. RESULTS: Here we showed that exposure to chemotherapeutic drug etoposide induces an exacerbation of ROS production which activates HIF-1α-mediated the metabolic reprogramming toward increased glycolysis and lactate production in non-small cell lung cancer (NSCLC). We identified lactic acidosis as the key that confers multidrug resistance through upregulation of multidrug resistance-associated protein 1 (MRP1, encoded by ABCC1), a member of ATP-binding cassette (ABC) transporter family. Mechanistically, lactic acid coordinates TGF-ß1/Snail and TAZ/AP-1 pathway to induce formation of Snail/TAZ/AP-1 complex at the MRP1/ABCC1 promoter. Induction of MRP1 expression inhibits genotoxic and apoptotic effects of chemotherapeutic drugs by increasing drug efflux. Furthermore, titration of lactic acid with NaHCO3 was sufficient to overcome resistance. CONCLUSIONS: The chemotherapeutic drug etoposide induces the shift toward aerobic glycolysis in the NSCLC rather than SCLC cell lines. The increased lactic acid in extracellular environment plays important role in etoposide resistance through upregulation of MRP expression. These data provide first evidence for the increased lactate production, upon drug treatment, contributes to adaptive resistance in NSCLC and reveal potential vulnerabilities of lactate metabolism and/or pathway suitable for therapeutic targeting. Video Abstract The chemotherapeutic drug etoposide induces metabolic reprogramming towards glycolysis in the NSCLC cells. The secreted lactic acid coordinates TGF-ß1/Snail and TAZ/AP-1 pathway to activate the expression of MRP1/ABCC1 protein, thus contributing to chemoresistance in NSCLC.

12.
Sensors (Basel) ; 20(21)2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33114199

RESUMO

In robot teaching for contact tasks, it is necessary to not only accurately perceive the traction force exerted by hands, but also to perceive the contact force at the robot end. This paper develops a tandem force sensor to detect traction and contact forces. As a component of the tandem force sensor, a cylindrical traction force sensor is developed to detect the traction force applied by hands. Its structure is designed to be suitable for humans to operate, and the mechanical model of its cylinder-shaped elastic structural body has been analyzed. After calibration, the cylindrical traction force sensor is proven to be able to detect forces/moments with small errors. Then, a tandem force sensor is developed based on the developed cylindrical traction force sensor and a wrist force sensor. The robot teaching experiment of drawer switches were made and the results confirm that the developed traction force sensor is simple to operate and the tandem force sensor can achieve the perception of the traction and contact forces.

13.
Waste Manag ; 118: 270-280, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32919346

RESUMO

With the economy growing rapidly, as well as the increasing diversification of human material and cultural needs, waste management poses a pressing challenge for local authorities in China. The primary aim of the present study is to examine the determinants of household waste-related behaviors, especially focusing on the roles of two important social interaction-based factors, social norms and networks, and their combinations. Specifically, this paper adopted the method of principal component analysis to capture social interactions and leveraged ordered logit models to explore their influences on the behaviors involving waste sorting, bringing their own shopping bags and reusing plastic bags in other aspects. Using the data from the Chinese General Social Survey in 2013 (CGSS2013), the results reveal that both social norms and social networks exert a significant positive influence on pure altruistic waste sorting while only social norms are positively associated with bringing their own shopping bags to store and reusing bags in other aspects with the nature of impure altruism. Meanwhile, there is no convincing evidence for the interaction effect between social norms and social networks on waste sorting, yet the interaction item does work together negatively influencing bringing their own bags and reusing bags behaviors. Moreover, the results show that social norms have a much larger effect on waste-related behaviors in males than females while social networks lead to significant promotion in waste sorting only for females. For people with higher education levels, the impacts of social norms and social networks on waste sorting and bringing their own bags behaviors are insignificant, while the higher income groups are weakly affected by social networks as well, partly because of time constraints and opportunity cost. Lastly, this paper provides new insight into waste management from the perspective of social interaction.


Assuntos
Reciclagem , Gerenciamento de Resíduos , China , Humanos , Relações Interpessoais
14.
J Clin Invest ; 130(12): 6539-6554, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32910804

RESUMO

Homeostasis of bone metabolism is regulated by the central nervous system, and mood disorders such as anxiety are associated with bone metabolism abnormalities, yet our understanding of the central neural circuits regulating bone metabolism is limited. Here, we demonstrate that chronic stress in crewmembers resulted in decreased bone density and elevated anxiety in an isolated habitat mimicking a space station. We then used a mouse model to demonstrate that GABAergic neural circuitry in the ventromedial hypothalamus (VMH) mediates chronic stress-induced bone loss. We show that GABAergic inputs in the dorsomedial VMH arise from a specific group of somatostatin neurons in the posterior region of the bed nucleus of the stria terminalis, which is indispensable for stress-induced bone loss and is able to trigger bone loss in the absence of stressors. In addition, the sympathetic system and glutamatergic neurons in the nucleus tractus solitarius were employed to regulate stress-induced bone loss. Our study has therefore identified the central neural mechanism by which chronic stress-induced mood disorders, such as anxiety, influence bone metabolism.

15.
Clin Exp Nephrol ; 24(12): 1162-1176, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32779058

RESUMO

BACKGROUND: ESRD (End-stage renal disease) treatment is a comprehensive medical process and requires numerous serological biochemical tests (SBTs) in diagnosis. To reduce these invasive, expensive, cumbersome, and time-consuming SBTs, there is a need to develop an alternative serological biochemical composition evaluation method. Bioelectrical impedance analysis (BIA) is affected by body's chemical and physical components, which might be correlated with serological biochemical composition and can be potentially used to evaluate biochemical composition in hemodialysis patient treatments. In this work, the relationship of classic and specific bioelectrical impedance vector analysis (BIVA) with major serological biochemical indexes in maintenance hemodialysis (MHD) patients was examined. METHODS: Bioelectrical and biochemical datasets were measured from 280 women and 408 men and formed 3872 effective biochemical-bioelectrical records in total. Statistical analysis was performed. RESULTS: The results show that BIVA vectors have strong relationship with phosphorus, hemoglobin, and PTH in both male and female groups. Strong correlation was also observed between Ca, albumin, CHOL, LDLC, and BIVA vectors in the male group. In the female group, a significant correlation was observed between classic BIVA values and NT-proBNP. SVM models are effective for classifying biochemical indexes. CONCLUSIONS: The obtained correlations and SVM classification models imply that BIVA can be used as a preliminary tool to evaluate and classify the degree of anemia, malnutrition, fluid overload, and mineral and bone disorder (MBD) in MHD patients by reducing the number of SBTs.

16.
J Autoimmun ; 112: 102464, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32381456

RESUMO

Pirfenidone has been widely used in the treatment of idiopathic pulmonary fibrosis (IPF). However, the role of pirfenidone in LPS-induced acute lung injury (ALI) remains unclear. This study aims to investigate the protective effects of pirfenidone in ALI and to explore its underlying mechanism. Pirfenidone clearly reduces LPS-triggered ALI as indicated by significant pathological alterations, reduced oxidative stress and inflammatory responses in vivo. Furthermore, pirfenidone also blocks apoptosis of LPS-induced alveolar epithelial type II (ATII) cells through inhibition of endoplasmic reticulum (ER) stress and mitochondrial injury in vivo and in vitro. A lower expression level of BAP31, an ER transmembrane protein, was found to be associated with ALI followed LPS challenge. The reintroduction of BAP31 blunted LPS induced ER stress and mitochondrial damage and therefore alleviated ATII cell apoptosis, which correlated with pirfenidone treatment. Knockdown of BAP31 expression in pirfenidone treated ATII cells re-activated ER stress, mitochondrial damage and followed cellular apoptosis. In summary, this study confirms the beneficial effect of pirfenidone on ER stress and mitochondrial dysfunction mediated apoptosis via upregulation of BAP31. Our results demonstrated that pirfenidone may be considered as a potential agent for the treatment of ALI in the future.

17.
Head Neck ; 42(6): 1202-1208, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32338807

RESUMO

The practices of head and neck surgical oncologists must evolve to meet the unprecedented needs placed on our health care system by the Coronavirus disease 2019 (COVID-19) pandemic. Guidelines are emerging to help guide the provision of head and neck cancer care, though in practice, it can be challenging to operationalize such recommendations. Head and neck surgeons at Wuhan University faced significant challenges in providing care for their patients. Similar challenges were faced by the University of Toronto during the severe acute respiratory syndrome (SARS) pandemic in 2003. Herein, we outline our combined experience and key practical considerations for maintaining an oncology service in the midst of a pandemic.


Assuntos
Controle de Doenças Transmissíveis/normas , Infecções por Coronavirus/prevenção & controle , Neoplasias de Cabeça e Pescoço/cirurgia , Pandemias/estatística & dados numéricos , Pneumonia Viral/prevenção & controle , Guias de Prática Clínica como Assunto , Oncologia Cirúrgica/normas , Canadá , China , Infecções por Coronavirus/epidemiologia , Assistência à Saúde/normas , Feminino , Neoplasias de Cabeça e Pescoço/diagnóstico , Humanos , Masculino , Monitorização Intraoperatória/métodos , Saúde do Trabalhador , Avaliação de Resultados em Cuidados de Saúde , Pandemias/prevenção & controle , Segurança do Paciente , Pneumonia Viral/epidemiologia , Padrões de Prática Médica/normas
18.
ACS Omega ; 5(13): 7361-7368, 2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32280877

RESUMO

Vitamin D deficiency is a serious global health problem. Edible mushrooms are a good source of vitamin D for human health. The objective of this experiment was to investigate the efficiency of converting its precursor ergosterol to vitamin D2 in shiitake mushroom (Lentinus edodes) and oyster mushroom (Pleurotus ostreatus) powder in ethanol suspension under ultraviolet (UV) irradiation. UV irradiation conditions were optimized for several parameters, such as material form, wavelength, wavelength combination, and exposure time. Under the optimal conditions, UV irradiation increased the concentrations of vitamin D2 from undetectable to 40.59 ± 1.16 µg/g (dw) in dry shiitake mushroom powder and to 677.28 ± 40.42 µg/g (dw) (an approximately 16.69-fold increase) in ethanol suspension. The concentration of vitamin D2 increased from undetectable to 23.71 ± 5.72 µg/g (dw) in the dry oyster mushroom powder upon UV irradiation, whereas UV irradiation increased the concentration to 275.32 ± 48.45 µg/g (dw) (an approximately 11.61-fold increase) in the ethanol suspension. Comparing the effects of varying combinations of wavelengths showed that irradiation with UV-A, UV-C, or a combination of both is more effective than UV-B irradiation. In addition, the increase in vitamin D2 in shiitake mushrooms irradiated by UV-C was time-dependent, that is, dose-dependent. Nevertheless, the increase rates decreased with time. The concentration of ergosterol decreased with the increase in vitamin D2, but ergosterol was only partially converted to vitamin D2, whereas most of the ergosterol was probably UV-degraded. Exposure to ultraviolet light in ethanol suspension offers an effective way to increase the concentration of vitamin D2 and thus improve the nutritional value of edible mushrooms, as well as make them more functional as a source of vitamin D to improve the consumer health.

19.
Artigo em Inglês | MEDLINE | ID: mdl-32116571

RESUMO

The piriform cortex (PC) is a key brain area involved in both processing and coding of olfactory information. It is implicated in various brain disorders, such as epilepsy, Alzheimer's disease, and autism. The PC consists of the anterior (APC) and posterior (PPC) parts, which are different anatomically and functionally. However, the direct input networks to specific neuronal populations within the APC and PPC remain poorly understood. Here, we mapped the whole-brain direct inputs to the two major neuronal populations, the excitatory glutamatergic principal neurons and inhibitory γ-aminobutyric acid (GABA)-ergic interneurons within the APC and PPC using the rabies virus (RV)-mediated retrograde trans-synaptic tracing system. We found that for both types of neurons, APC and PPC share some similarities in input networks, with dominant inputs originating from the olfactory region (OLF), followed by the cortical subplate (CTXsp), isocortex, cerebral nuclei (CNU), hippocampal formation (HPF) and interbrain (IB), whereas the midbrain (MB) and hindbrain (HB) were rarely labeled. However, APC and PPC also show distinct features in their input distribution patterns. For both types of neurons, the input proportion from the OLF to the APC was higher than that to the PPC; while the PPC received higher proportions of inputs from the HPF and CNU than the APC did. Overall, our results revealed the direct input networks of both excitatory and inhibitory neuronal populations of different PC subareas, providing a structural basis to analyze the diverse PC functions.

20.
EBioMedicine ; 51: 102603, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31901862

RESUMO

BACKGROUND: Tumor necrosis factor α-induced protein 1 (TNFAIP1) is frequently downregulated in cancer cell lines and promotes cancer cell apoptosis. However, its role, clinical significance and molecular mechanisms in hepatocellular carcinoma (HCC) are unknown. METHODS: The expression of TNFAIP1 in HCC tumor tissues and cell lines was measured by Western blot and immunohistochemistry. The effects of TNFAIP1 on HCC proliferation, apoptosis, metastasis, angiogenesis and tumor formation were evaluated by Cell Counting Kit-8 (CCK8), Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling (TUNEL), transwell, tube formation assay in vitro and nude mice experiments in vivo. The interaction between TNFAIP1 and CSNK2B was validated by liquid chromatography-tandem mass spectrometry (LC-MS/MS), Co-immunoprecipitation and Western blot. The mechanism of how TNFAIP1 regulated nuclear factor-kappaB (NF-κB) pathway was analyzed by dual-luciferase reporter, immunofluorescence, quantitative Real-time polymerase chain reaction (RT-qPCR) and Western blot. FINDINGS: The TNFAIP1 expression is significantly decreased in HCC tissues and cell lines, and negatively correlated with the increased HCC histological grade. Overexpression of TNFAIP1 inhibits HCC cell proliferation, metastasis, angiogenesis and promotes cancer cell apoptosis both in vitro and in vivo, whereas the knockdown of TNFAIP1 in HCC cell displays opposite effects. Mechanistically, TNFAIP1 interacts with CSNK2B and promotes its ubiquitin-mediated degradation with Cul3, causing attenuation of CSNK2B-dependent NF-κB trans-activation in HCC cell. Moreover, the enforced expression of CSNK2B counteracts the inhibitory effects of TNFAIP1 on HCC cell proliferation, migration, and angiogenesis in vitro and in vivo. INTERPRETATION: Our results support that TNFAIP1 can act as a tumor suppressor of HCC by modulating TNFAIP1/CSNK2B/NF-κB pathway, implying that TNFAIP1 may represent a potential marker and a promising therapeutic target for HCC.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Carcinoma Hepatocelular/metabolismo , Caseína Quinase II/genética , Regulação para Baixo , Neoplasias Hepáticas/metabolismo , NF-kappa B/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Apoptose , Carcinogênese/genética , Carcinogênese/patologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Neovascularização Patológica/genética , Proteólise , Ubiquitina/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
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