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1.
BMC Surg ; 22(1): 9, 2022 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-34996403

RESUMO

BACKGROUND: Bone fibrous dysplasia is a benign disease of bone tissue dysplasia. Vision impairment is the commonest neurological complication of craniofacial fibrous dysplasia. Most of the vision loss caused by craniofacial fibrous dysplasia is usually a gradual process. Very few present with acute visual impairment as described in our case. CASE PRESENTATION: We report a patient with fibrous dysplasia presenting rapidly progressive visual loss in the left eye secondary to bone cyst formation. Transnasal endoscopic surgery guided by navigation with drainage and curettage of this bone cyst and orbital decompression resulted in progressive improvement in visual acuity that returned to normal 1 month post-operatively. CONCLUSIONS: In cases with acute visual loss due to fibrous dysplasia, emergency surgical treatment should be considered to preserve vision. In the surgical approach, navigation-guided nasal endoscopic surgery may be preferred because of its advantages.


Assuntos
Displasia Fibrosa Óssea , Complicações na Gravidez , Descompressão Cirúrgica , Endoscopia , Displasia Fibrosa Óssea/complicações , Displasia Fibrosa Óssea/cirurgia , Humanos , Acuidade Visual
2.
J Hazard Mater ; 428: 128212, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-35030491

RESUMO

The oxygen evolution reaction kinetics in industrial zinc electrowinning is sluggish, resulting in low electrocatalytic activity and substantial energy expenditure (about one-third of energy was wasted due to the strong polarization effect). Herein, the paper described a core-shell structured MnCo2O4.5@C modified PbO2 electrode through the pyrolysis and co-electrodeposition as a promising candidate for zinc electrowinning. As a result, the obtained Pb-0.2%Ag/α-PbO2/ß-PbO2-MnCo2O4.5@C composite electrode showed a sandwich-like structure, where Pb-0.2%Ag as a core, α-PbO2 as a mid-layer, and ß-PbO2-MnCo2O4.5@C served as an electrocatalytic layer. It also possessed improved OER catalytic activity, only required 680 mV to achieve a current density of 50 mA cm-2 and a Tafel slope of 216.04 mV dec-1 in an acidic solution containing 50 g L-1 Zn2+ and 150 g L-1 H2SO4. The current efficiency increased by 0.7% and the cell voltage reduced by 360 mV as compared to a conventional Pb-0.76%Ag alloy electrode, leading to a remarkable energy-consumption reduction of 283.5 kW h for producing per ton metallic zinc. Furthermore, Pb-0.2%Ag/α-PbO2/ß-PbO2-MnCo2O4.5@C exhibited a prolonged service life, which worked about 44 h under an ultra-high current density of 2 A cm-2. Hence, this paper provides the strategy to design and construct non-precious, high-performance catalyst for electrolysis and other applications.

3.
J Clin Invest ; 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34847079

RESUMO

Therapeutics targeting osteoclasts are commonly used treatments for bone metastasis; however, whether and how osteoclasts regulate pre-metastatic niche and bone tropism is largely unknown. In this study, we report that osteoclast precursors (OPs) can function as a pre-metastatic niche component that facilitates breast cancer (BCa) bone metastasis at early stages. At the molecular level, unbiased GPCR ligand/agonist screening in BCa cells suggested that R-spondin 2 (RSPO2) and RANKL, through interacting with their receptor LGR4, promoted osteoclastic pre-metastatic niche formation and enhanced BCa bone metastasis. This was achieved by RSPO2/RANKL-LGR4 signal modulating WNT inhibitor DKK1 through Gαq and ß-catenin signaling. DKK1 directly facilitated OP recruitment through suppressing its receptor low-density lipoprotein-related receptors 5 (LRP5) but not LRP6, upregulating Rnasek expression via inhibiting canonical WNT signaling. In clinical samples, RSPO2, LGR4 and DKK1 expression showed positive correlation with BCa bone metastasis. Furthermore, soluble LGR4 extracellular domain (ECD) protein, acting as a decoy receptor for RSPO2 and RANKL, significantly alleviated bone metastasis and osteolytic lesions in mouse bone metastasis model. These findings provide unique insights into the functional role of OPs as key components of pre-metastatic niche for BCa bone metastasis, indicate RSPO2/RANKL-LGR4 signaling as a promising target for inhibiting BCa bone metastasis.

5.
Psychiatry Res ; 306: 114237, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34655926

RESUMO

The direct effect of genetic variations on clinical phenotypes within schizophrenia (SZ) remains elusive. We examined the previously identified association of reduced gray matter concentration in the insula - medial prefrontal cortex and a quantitative trait locus located in 12q24 in a SZ dataset. The main analysis was performed on 1461 SNPs and 830 participants. The highest contributing SNPs were localized in five genes including TMEM119, which encodes a microglial marker, that is associated with neuroinflammation and Alzheimer's disease. The gene set in 12q4 may partially explain brain alterations in SZ, but they may also relate to other psychiatric and developmental disorders.

6.
Mol Genet Genomic Med ; 9(10): e1795, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34535971

RESUMO

BACKGROUND: Cone dystrophy with supernormal rod response (CDSRR) is an autosomal recessive retinal disorder characterized by myopia, dyschromatopsia, nyctalopia, photophobia, and nystagmus. CDSRR is caused by mutations in KCNV2, the gene encoding for an electrically silent Kv subunit (Kvs) named Kv8.2. METHODS: A Chinese CDSRR family was recruited. Complete ophthalmology clinical examinations were performed to clarify the phenotype. Genetic examination was underwent using whole exome sequencing (WES). In addition, a candidate gene was validated by Sanger sequencing. Expression analysis in vitro including immunoblotting, quantitative real-time PCR (qRT-PCR), and co-immunoprecipitation experiments was performed to investigate the pathogenic mechanism of the identified gene variants. RESULTS: WES identified two KCNV2 heterozygous mutations from the proband. Sanger sequencing validated that the patient's parents had, respectively, carried those two mutations. Further in vitro functional experiments indicated that the mutated alleles had led the Kv8.2 proteins to fail in expressing and interacting with the Kv2.1 protein, respectively. CONCLUSIONS: This study expanded the KCNV2 mutation spectrum. It can also be deduced that CDSRR has a broad heterogeneity. It is further confirmed that the inability expression of Kv8.2 proteins and the failure of Kv8.2 proteins to interact with Kv2.1 may have accounted for the etiology of CDSRR based on previous studies and this study.

7.
Int J Biol Macromol ; 192: 398-406, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34571128

RESUMO

The fungus Sporidiobolus pararoseus not only produces carotenoids, but also produces bioactive extracellular polysaccharides (SPP). However, the relationship between SPP and the metabolism of gut microbiome is unclear. The aim of this study was to investigate the mechanism of SPP regulating intestinal health in vivo and in vitro. Results showed that SPP are nondigestible polysaccharides after the digestion with simulated stomach and small intestinal juice in vitro. After SPP was cultured in an in vitro intestinal simulation system for seven days, the concentration of short-chain fatty acids (SCFAs) increased; the microbial diversity changed; the relative abundance of Bifidobacterium and Streptococcus increased; and that of Escherichia Shigella and Lachnospiraceae NK4A136 decreased. In addition, metabolism of SPP by the mice colonic microbiome showed SPP decreased the relative abundance of Firmicutes and Bacteroidota, while the relative abundance of Verrucomicrobiota, Desulfobacterota, and Actinobacteriota increased. Finally, predicted Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolism results also showed that SPP can enhance the metabolism of cofactors, vitamins, amino acids, starch, and sucrose. In conclusion, SPP can multiply the intestinal beneficial bacteria of humans and mice, promote the production of SCFAs and metabolism of amino acids, and promote intestinal health.

8.
Int J Biol Macromol ; 187: 143-156, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34293362

RESUMO

Oxidative damage and intestinal dysbiosis are regarded as crucial culprits in alcoholic liver disease (ALD). This study aimed to examine the protective effects of Echinacea purpurea polysaccharides (EPPs) against ALD and explore the underlying mechanisms based on hepatic oxidative stress, inflammation, and intestinal barrier function. Three polysaccharide fractions, namely, EPP40, EPP60, and EPP80, were obtained by stepwise ethanol precipitation, and their antioxidant activity in vitro was investigated. The results showed that EPP80 with Mw 11.82 kDa had the strongest radical-scavenging capacity against DPPH, ABTS, and •OH radicals. Besides, EPP80 comprised arabinose, galactose, glucose, mannose, galacturonic acid, and glucuronic acid in molar ratios of 13.42:25.12:10.92:8.59:2.07:0.82. The in vivo results showed that EPP80 increased the activities of antioxidant enzymes and reduced the levels of inflammatory cytokines both in mouse serum and liver. Moreover, EPP80 upregulated the expression of Occludin and ZO-1, revealing its protective effect against intestinal barrier dysfunction. Furthermore, EPP80 inhibited alcohol-induced oxidative damage by promoting the expression of Nrf2, HO-1, and NQO1 in the liver. In summary, EPP80 markedly scavenged free radicals in vitro and ameliorated alcohol-induced liver injury via Nrf2/HO-1 pathways in vivo. These findings suggested that EPP80 could provide effective supplementary support in preventing and treating ALD.

9.
Exp Eye Res ; 209: 108652, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34097904

RESUMO

Large animal model of optic nerve crush (ONC) plays an important role in translating novel therapeutic strategies developed in rodent model to clinical application. Due to the poor accessibility of the optic nerve (ON) in humans and large animals, lateral orbitotomy is needed to expose the retrobulbar ON. This study was to explore the effects of ONC and ON exposure with lateral orbitotomy (sham surgery) on the outer retinal function and structure in goats by using standard flash electroretinogram (FERG) and spectral-domain optical coherence tomography (SD-OCT). We found that ONC led to a transient reduction in FERG amplitudes at 1 week post injury (wpi), which recovered gradually over 2 months afterwards. Sham surgery alone also caused a similar pattern of amplitude reduction in FERG, although not as significantly as ONC did. Transient outer retinal thickening following ONC occurred at 4 wpi (when progressive thinning of the ganglion cell complex began), peaked at 8 wpi, then recovered gradually at 12 wpi. In contrast, outer retinal thickness remained unchanged statistically 3 months after sham surgery. Fundus fluorescein angiography showed that neither ONC nor ON exposure with lateral orbitotomy significantly caused any significant delay or absence of central retinal vascular filling. In summary, ONC with lateral orbitotomy affects outer retinal function and structure transiently.


Assuntos
Traumatismos do Nervo Óptico/fisiopatologia , Nervo Óptico/patologia , Segmento Externo das Células Fotorreceptoras da Retina/patologia , Animais , Modelos Animais de Doenças , Eletrorretinografia , Angiofluoresceinografia/métodos , Fundo de Olho , Cabras , Masculino , Procedimentos Cirúrgicos Oftalmológicos/efeitos adversos , Nervo Óptico/fisiopatologia , Traumatismos do Nervo Óptico/diagnóstico , Órbita/cirurgia , Células Ganglionares da Retina , Segmento Externo das Células Fotorreceptoras da Retina/fisiologia , Tomografia de Coerência Óptica/métodos
10.
Soc Sci Med ; 282: 114137, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34175573

RESUMO

Although numerous studies have investigated the effect of green space on mental health, as yet, little is known about the association between green space and suicide. To address this deficit, we conducted the first Japan-wide study of the relationship between green space and suicide mortality. Results from spatial analyses of municipality-level panel data for the 1975-2014 period that included 886,440 suicide deaths with a fixed-effect estimator showed that green space was associated with suicide mortality, and that this relationship was conditioned by the form of greenness, level of urbanity and demographic characteristics. In densely populated cities, park density (parks per 1000 of the population) was associated with reduced suicide mortality among females aged 18 and above and among males aged 18 to 39 and aged 65 and above. In small- and medium-sized cities, park coverage (% by area) was linked to fewer suicide deaths among middle-aged and older females (aged 40 and above). In contrast, in non-cities (rural areas), parks were not associated with suicide mortality whereas woodland coverage (% by area) was linked to reduced suicide deaths among middle-aged and older males (aged 40 and above). Our findings suggest that urban green space and rural forest coverage may have a protective effect against self-harming behavior. Future suicide prevention efforts should consider an increased greening of the residential environment in terms of both availability and accessibility, especially with better designs that accommodate population needs and local conditions.


Assuntos
Parques Recreativos , Suicídio , Idoso , Cidades , Meio Ambiente , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade
11.
Behav Brain Res ; 409: 113310, 2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-33878431

RESUMO

PURPOSE: Our previous study identified a significant association between a single nucleotide polymorphism (SNP) located in the neurogenin3 (NEUROG3) gene and post-stroke depression (PSD) in Chinese populations. The present work explores whether polymorphism rs144643855 affects regional brain activity and clinical phenotypes in major depressive disorder (MDD). METHOD: A total of 182 participants were included: 116 MDD patients and 66 normal controls. All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI) scanning at baseline. Spontaneous brain activity was assessed using amplitude of low-frequency fluctuation (ALFF). The Hamilton Depression Scale-24 (HAMD-24) and Snaith-Hamilton Pleasure Scale (SHAPS) were used to assess participants at baseline. Two-way analysis of covariance (ANCOVA) was used to explore the interaction between diagnostic groups and NEUROG3 rs144643855 on regional brain activity. We performed correlation analysis to further test the association between these interactive brain regions and clinical manifestations of MDD. RESULTS: Genotype and disease significantly interacted in the left inferior frontal gyrus (IFG-L), right superior frontal gyrus (SFG-R), and left paracentral lobule (PCL-L) (P < 0.05). ALFF values of the IFG-L were found to be significantly associated with anhedonia in MDD patients. CONCLUSION: These findings suggest a potential relationship between rs144643855 variations and altered frontal brain activity in MDD. NEUROG3 may play an important role in the neuropathophysiology of MDD.

12.
Psychiatry Res Neuroimaging ; 311: 111282, 2021 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-33780745

RESUMO

A significant proportion of individuals with attention-deficit/hyperactivity disorder (ADHD) show persistence into adulthood. The genetic and neural correlates of ADHD in adolescents versus adults remain poorly characterized. We investigated ADHD polygenic risk score (PRS) in relation to previously identified gray matter (GM) patterns, neurocognitive, and symptom findings in the same ADHD sample (462 adolescents & 422 adults from the NeuroIMAGE and IMpACT cohorts). Significant effects of ADHD PRS were found on hyperactivity and impulsivity symptoms in adolescents, hyperactivity symptom in adults, but not GM volume components. A distinct PRS effect between adolescents and adults on individual ADHD symptoms is suggested.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Adolescente , Adulto , Atenção , Transtorno do Deficit de Atenção com Hiperatividade/genética , Substância Cinzenta , Humanos , Comportamento Impulsivo , Herança Multifatorial/genética
13.
Transl Psychiatry ; 11(1): 184, 2021 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-33767139

RESUMO

Attention-deficit/hyperactivity disorder (ADHD) is a childhood-onset neuropsychiatric disorder and may persist into adulthood. Working memory and attention deficits have been reported to persist from childhood to adulthood. How neuronal underpinnings of deficits differ across adolescence and adulthood is not clear. In this study, we investigated gray matter of two cohorts, 486 adults and 508 adolescents, each including participants from ADHD and healthy controls families. Two cohorts both presented significant attention and working memory deficits in individuals with ADHD. Independent component analysis was applied to the gray matter of each cohort, separately, to extract cohort-inherent networks. Then, we identified gray matter networks associated with inattention or working memory in each cohort, and projected them onto the other cohort for comparison. Two components in the inferior, middle/superior frontal regions identified in adults and one component in the insula and inferior frontal region identified in adolescents were significantly associated with working memory in both cohorts. One component in bilateral cerebellar tonsil and culmen identified in adults and one component in left cerebellar region identified in adolescents were significantly associated with inattention in both cohorts. All these components presented a significant or nominal level of gray matter reduction for ADHD participants in adolescents, but only one showed nominal reduction in adults. Our findings suggest although the gray matter reduction of these regions may not be indicative of persistency of ADHD, their persistent associations with inattention or working memory indicate an important role of these regions in the mechanism of persistence or remission of the disorder.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Adolescente , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Criança , Substância Cinzenta/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Transtornos da Memória/diagnóstico por imagem , Memória de Curto Prazo , Adulto Jovem
14.
Food Funct ; 12(7): 3132-3141, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33729250

RESUMO

Maca (Lepidium meyenii Walp.) has emerged as a popular functional plant food due to its various pharmacological properties, including anti-oxidation, anti-inflammation and anti-fatigue activity. In this study, we investigated the role of Maca aqueous extract (ME) on muscle during exercise-induced fatigue both in vivo and in vitro. As a result, ME significantly enhanced mouse leg grip-strength and increased exercise endurance in the rota-rod test. ME could clear the accumulation of metabolites - blood lactic acid (BLA), blood urea nitrogen (BUN) and reactive oxygen species (ROS) levels after weight-loaded forced swimming. Focusing on muscle, we found that the administration of ME strengthened mouse muscle structures so that exercise-induced metabolic stress was alleviated by upregulating NAD+/NADH. Furthermore, ME inhibited the reduction of the viability and accumulation of ROS by treatment with H2O2 in C2C12 skeletal muscle cells. ME-induced activation of energy metabolism in skeletal muscle might up-regulate mitochondrial biogenesis and function, thereby protecting against oxidative stress-induced damage. We concluded that the effects of Maca played a crucial role in the regulation of exercise-induced fatigue in mouse muscle, which could be expected to serve as a functional food supplement for improving exercise performance and alleviating physical fatigue.


Assuntos
Antioxidantes/administração & dosagem , Lepidium , Animais , Antioxidantes/farmacologia , Suplementos Nutricionais , Fadiga , Alimento Funcional , Camundongos , Camundongos Endogâmicos ICR , Músculo Esquelético/efeitos dos fármacos , Fitoterapia , Natação
15.
J Agric Food Chem ; 69(11): 3452-3465, 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33724017

RESUMO

An efficient technique using citric acid and glucose based natural deep eutectic solvent (G-C-NADES) was developed to obtain ultrahigh deamidated wheat gluten (UDWG) (deamidation degree (DD) > 90%). FTIR and 1H NMR indicated intensive hydrogen bonds (HBs) in G-C-NADES supermolecules. Quantum chemical calculations and molecular dynamic simulations demonstrated that 10 wt % diluted G-C-NADES still had a myriad of HBs. Physicochemical results showed UDWG had DD up to 92.45% after G-C-NADES deamidation, that is, 22% higher than citric-acid-DWG with a weak degree of hydrolysis (1.75%). Conformational characterization demonstrated the obvious conversion from α-helix to ß-sheet via FTIR, the least amount of disulfide bonds by Raman spectra, and more exposure of tryptophan residues by fluorescence measurement for UDWG. It is proven that enhanced accessible conformation of WG reached with HBs of G-C-NADESs could contribute to the improvement on nucleophilic attack of deamidation, declaring that G-C-NADES might be a potential solvent for obtaining an ultrahigh deamidation for WG to successfully guarantee the safety of wheat gluten based cereal food regarding to lowering its allergy.


Assuntos
Ácido Cítrico , Triticum , Glucose , Glutens , Solventes
16.
Biochem Biophys Res Commun ; 546: 40-45, 2021 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-33561747

RESUMO

The emergence of worldwide spreading drug-resistant bacteria has been a serious threat to public health during the past decades. The development of new and effective antibacterial agents to address this critical issue is an urgent action. In the present study, we investigated the antibacterial activity of two 9,10-dihydroacridine derivatives and their mechanism. Both compounds were found possessing strong antibacterial activity against some selected Gram-positive bacteria including MRSA, VISA and VRE. The biological study suggests that the compounds promoted FtsZ polymerization and also disrupted Z-ring formation at the dividing site and consequently, the bacterial cell division is interrupted and causing cell death.


Assuntos
Acridinas/química , Acridinas/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Desenho de Fármacos , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Divisão Celular/efeitos dos fármacos , Proteínas do Citoesqueleto/antagonistas & inibidores , Proteínas do Citoesqueleto/química , Proteínas do Citoesqueleto/metabolismo , Bactérias Gram-Positivas/efeitos dos fármacos , Meticilina/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos
17.
Aging (Albany NY) ; 13(4): 4811-4830, 2021 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-33581688

RESUMO

Traditional Chinese medicine (TCM) had demonstrated effectiveness in the prevention and control of COVID-19. Statistics showed that Ephedra and Glycyrrhiza were frequently used in the treatment of COVID-19. We hypothesized that the Ephedra-Glycyrrhiza drug pair is a potential choice for the treatment of COVID-19. Here, 112 active compounds were identified from Ephedra-Glycyrrhiza via network pharmacology approach. Ephedra-Glycyrrhiza pair enrichment analysis demonstrated that these compounds might participate in the cAMP, PI3K-Akt, JAK-STAT and chemokine signaling pathways, which had a high correlation with respiratory, nervous, blood circulation and digestive system-related diseases. Pathway analysis between Ephedra-Glycyrrhiza and COVID-19 showed that the key targets were TNF-α, IL2, FOS, ALB, and PTGS2. They might control PI3K-Akt signaling pathway to exert immune regulation, organ protection and antiviral effects. Molecular docking results showed that the active compounds from the Ephedra-Glycyrrhiza pair bound well to COVID-19 related targets, including the main protease (Mpro, also called 3CLpro), the spike protein (S protein), and the angiotensin-converting enzyme 2 (ACE2). The Molecular dynamics simulation was analyzed for the stability and flexibility of the complex. In conclusion, our study elucidated the potential pharmacological mechanism of Ephedra-Glycyrrhiza in the treatment of COVID-19 through multiple targets and pathways.


Assuntos
Antivirais/farmacologia , COVID-19/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Ephedra/química , Glycyrrhiza/química , SARS-CoV-2/efeitos dos fármacos , Enzima de Conversão de Angiotensina 2/metabolismo , Antivirais/química , Antivirais/uso terapêutico , COVID-19/metabolismo , Combinação de Medicamentos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Simulação de Acoplamento Molecular , Mapas de Interação de Proteínas/efeitos dos fármacos , SARS-CoV-2/fisiologia , Transdução de Sinais/efeitos dos fármacos , Glicoproteína da Espícula de Coronavírus/metabolismo
18.
Cell Death Differ ; 28(6): 1941-1954, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33469229

RESUMO

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies and cause of death from cancer in China. Previous studies showed that autophagy and apoptosis inhibition are critical for the survival of ESCC cells. However, the underlying mechanisms remain to be clarified. Recently, we found that PIWIL2, a novel cancer testis protein, is highly expressed in ESCC and associated with high T-stage and poor 5-year survival rate in patients. Our further study showed that PIWIL2 can directly bind to IKK and promote its phosphorylation, leading to phosphorylation of IκB and subsequently nuclear translocation of NF-κB for apoptosis inhibition. Meanwhile, PIWIL2 competitively inhibits binding of IKK to TSC1, and thus deactivate mTORC1 pathway which suppresses ULK1 phosphorylation and initiation of autophagy. The mouse xenograft model suggested that PIWIL2 can promote ESCC growth in an IKK-dependent manner. This present work firstly revealed that PIWIL2 can play a role in regulating autophagy and apoptosis, and is associated with poor prognosis in ESCC patients, providing novel insights into the roles of PIWIL2 in tumorigenesis.

19.
J Med Internet Res ; 23(1): e13556, 2021 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-33480851

RESUMO

BACKGROUND: Health care professionals are required to maintain accurate health records of patients. Furthermore, these records should be shared across different health care organizations for professionals to have a complete review of medical history and avoid missing important information. Nowadays, health care providers use electronic health records (EHRs) as a key to the implementation of these goals and delivery of quality care. However, there are technical and legal hurdles that prevent the adoption of these systems, such as concerns about performance and privacy issues. OBJECTIVE: This study aimed to build and evaluate an experimental blockchain for EHRs, named HealthChain, which overcomes the disadvantages of traditional EHR systems. METHODS: HealthChain is built based on consortium blockchain technology. Specifically, three organizations, namely hospitals, insurance providers, and governmental agencies, form a consortium that operates under a governance model, which enforces the business logic agreed by all participants. Every peer node hosts an instance of the distributed ledger consisting of EHRs and an instance of chaincode regulating the permissions of participants. Designated orderers establish consensus on the order of EHRs and then disseminate blocks to peers. RESULTS: HealthChain achieves functional and nonfunctional requirements. It can store EHRs in a distributed ledger and share them among different participants. Moreover, it demonstrates superior features, such as privacy preservation, security, and high throughput. These are the main reasons why HealthChain is proposed. CONCLUSIONS: Consortium blockchain technology can help to build new EHR systems and solve the problems that prevent the adoption of traditional systems.


Assuntos
Blockchain/normas , Atenção à Saúde/métodos , Registros Eletrônicos de Saúde/normas , Humanos
20.
EMBO Mol Med ; 13(1): e12798, 2021 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-33283987

RESUMO

Immune checkpoint blockade (ICB) has a limited effect on colorectal cancer, underlining the requirement of co-targeting the complementary mechanisms. Here, we identified prostaglandin E2 (PGE2 ) receptor 4 (EP4) as the master regulator of immunosuppressive myeloid cells (IMCs), which are the major driver of resistance to ICB therapy. PGE2 -bound EP4 promotes the differentiation of immunosuppressive M2 macrophages and myeloid-derived suppressor cells (MDSCs) and reduces the expansion of immunostimulated M1 macrophages. To explore the immunotherapeutic role of EP4 signaling, we developed a novel and selective EP4 antagonist TP-16. TP-16 effectively blocked the function of IMCs and enhanced cytotoxic T-cell-mediated tumor elimination in vivo. Cell co-culture experiments revealed that TP-16 promoted T-cell proliferation, which was impaired by tumor-derived CD11b+ myeloid cells. Notably, TP-16 and anti-PD-1 combination therapy significantly impeded tumor progression and prolonged mice survival. We further demonstrated that TP-16 increased responsiveness to anti-PD-1 therapy in an IMC-related spontaneous colorectal cancer mouse model. In summary, this study demonstrates that inhibition of EP4-expressing IMCs may offer a potential strategy for enhancing the efficacy of immunotherapy for colorectal cancer.


Assuntos
Neoplasias Colorretais , Células Supressoras Mieloides , Animais , Neoplasias Colorretais/tratamento farmacológico , Imunoterapia , Camundongos , Células Mieloides , Receptores de Prostaglandina E Subtipo EP4
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