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Microplastic is globally regarded as an important factor impacting biogeochemical cycles, yet our understanding of such influences is limited by the uncertainties of intricate microbial processes. By multiomics analysis, coupled with soil chemodiversity characterization and microbial carbon use efficiency (CUE), we investigated how microbial responses to microplastics impacted soil carbon cycling in a long-term field experiment. We showed that biodegradable microplastics promoted soil organic carbon accrual by an average of 2.47%, while nondegradable microplastics inhibited it by 17.4%, as a consequence of the virus-bacteria coadaptations to the microplastics disturbance. In the relevant functional pathways, nondegradable microplastics significantly (P < 0.05) enhanced the abundance and transcriptional activity related to complex carbohydrate metabolism, whereas biodegradable microplastics significantly (P < 0.05) promoted functions involved in amino acid metabolism and glycolysis. Accordingly, viral lysis enhanced in nondegradable microplastics treatments to introduce more complex organic compounds to soil dissolved organic matters, thus benefiting the oligotrophs with high carbon metabolic capabilities in exploitation competition. In contrast, biodegradable microplastics enriched viral auxiliary metabolic genes of carbon metabolism through "piggyback-the-winner" strategy, conferring to dominant copiotrophs, enhanced substrate utilization capabilities. These virus-host interactions were also demonstrated in the corresponding soil plastisphere, which would alter microbial resource allocation and metabolism via CUE, affecting carbon storage consequently. Overall, our results underscore the importance of viral-host interactions in understanding the microplastics-dependent carbon storage in the soil ecosystem.
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Carbono , Microplásticos , Microbiologia do Solo , Solo , Microplásticos/metabolismo , Solo/química , Carbono/metabolismo , Ciclo do Carbono , Poluentes do Solo/metabolismo , Bactérias/metabolismo , Bactérias/genéticaRESUMO
The development of targeted chemotherapeutic agents against colorectal cancer (CRC), one of the most common cancers with a high mortality rate, is in a constant need. Nannocystins are a family of myxobacterial secondary metabolites featuring a 21-membered depsipeptide ring. The in vitro anti-CRC activity of natural and synthetic nannocystins was well documented, but little is known about their in vivo efficacy and if positive, the underlying mechanism of action. In this study we synthesized a nitroaromatic nannocystin through improved preparation of a key fragment, and characterized its in vitro activity and in vivo efficacy against CRC. We first described the total synthesis of compounds 2-4 featuring Heck macrocyclization to forge their 21-membered macrocycle. In a panel of 7 cancer cell lines from different tissues, compound 4 inhibited the cell viability with IC values of 1-6 nM. In particular, compound 4 (1, 2, 4 nM) inhibited the proliferation of CRC cell lines (HCT8, HCT116 and LoVo) in both concentration and time dependent manners. Furthermore, compound 4 concentration-dependently inhibited the colony formation and migration of CRC cell lines. Moreover, compound 4 induced cell cycle arrest at sub-G1 phase, apoptosis and cellular senescence in CRC cell lines. In three patient-derived CRC organoids, compound 4 inhibited the PDO with IC values of 3.68, 28.93 and 11.81 nM, respectively. In a patient-derived xenograft mouse model, injection of compound 4 (4, 8 mg/kg, i.p.) every other day for 12 times dose-dependently inhibited the tumor growth without significant change in body weight. We conducted RNA-sequencing, molecular docking and cellular thermal shift assay to elucidate the anti-CRC mechanisms of compound 4, and revealed that it exerted its anti-CRC effect at least in part by targeting AKT1.
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Antineoplásicos , Proliferação de Células , Neoplasias Colorretais , Depsipeptídeos , Compostos Macrocíclicos , Proteínas Proto-Oncogênicas c-akt , Animais , Humanos , Camundongos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Depsipeptídeos/farmacologia , Depsipeptídeos/uso terapêutico , Depsipeptídeos/química , Depsipeptídeos/síntese química , Descoberta de Drogas , Ensaios de Seleção de Medicamentos Antitumorais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Relação Estrutura-Atividade , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: A large number of new causative and risk genes for amyotrophic lateral sclerosis (ALS) have been identified mostly in patients of European ancestry. In contrast, we know relatively little regarding the genetics of ALS in other ethnic populations. This study aims to provide a comprehensive analysis of the genetics of ALS in an unprecedented large cohort of Chinese mainland population and correlate with the clinical features of rare variants carriers. METHODS: A total of 1587 patients, including 64 familial ALS (FALS) and 1523 sporadic ALS (SALS), and 1866 in-house controls were analysed by whole-exome sequencing and/or testing for G4C2 repeats in C9orf72. Forty-one ALS-associated genes were analysed. FINDINGS: 155 patients, including 26 (40.6%) FALS and 129 (8.5%) SALS, carrying rare pathogenic/likely pathogenic (P/LP) variants of ALS causative genes were identified. SOD1 was the most common mutated gene, followed by C9orf72, FUS, NEK1, TARDBP and TBK1. By burden analysis, rare variants in SOD1, FUS and TARDBP contributed to the collective risk for ALS (p<2.5e-6) at the gene level, but at the allelic level TARDBP p.Gly294Val and FUS p.Arg521Cys and p.Arg521His were the most important single variants causing ALS. Clinically, P/LP variants in TARDBP and C9orf72 were associated with poor prognosis, in FUS linked with younger age of onset, and C9orf72 repeats tended to affect cognition. CONCLUSIONS: Our data provide essential information for understanding the genetic and clinical features of ALS in China and for optimal design of genetic testing and evaluation of disease prognosis.
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Esclerose Lateral Amiotrófica , Esclerose Lateral Amiotrófica/epidemiologia , Esclerose Lateral Amiotrófica/genética , Proteína C9orf72/genética , Estudos de Coortes , Predisposição Genética para Doença , Humanos , Mutação/genética , Superóxido Dismutase-1/genéticaRESUMO
BACKGROUND AND PURPOSE: Recent genetic progress has shown many causative/risk genes linked to Parkinson's disease (PD), mainly in patients of European ancestry. The study aimed to investigate the PD-related genes and determine the mutational spectrum of early-onset PD in ethnic Chinese. METHODS: In this study, whole-exome sequencing and/or gene dosage analysis were performed in 704 early-onset PD (EOPD) patients (onset age ≤45 years) and 1866 controls. Twenty-six PD-related genes and 20 other genes linked to neurodegenerative and lysosome diseases were analysed. RESULTS: Eighty-two (11.6%, 82/704) EOPD patients carrying rare pathogenic/likely pathogenic variants in PD-related genes were identified. The mutation frequency in autosomal recessive inheritance EOPD (42.9%, 27/63) was much higher than that in autosomal dominant inheritance EOPD (0.9%, 12/110) or sporadic EOPD (8.1%, 43/531). Bi-allelic mutations in PRKN were the most frequent, accounting for 5.1% of EOPD cases. Three common pathogenic variants, p.A53V in SNCA, p.G284R in PRKN and p.P53Afs*38 in CHCHD2, occur exclusively in Asians. The putative damaging variants from GBA, PRKN, DJ1, PLA2G6 and GCH1 contributed to the collective risk for EOPD. Notably, the protein-truncating variants in CHCHD2 were enriched in EOPD, especially for p.P53Afs*38, which was also found in three patients from an independent cohort of patients with late-onset PD (n = 1300). Functional experiments confirmed that truncated CHCHD2 variants cause loss of function and are linked to mitochondrial dysfunction. CONCLUSIONS: Our study reveals that the genetic spectrum of EOPD in Chinese, which may help develop genetic scanning strategies, provided more evidence supporting CHCHD2 in PD.
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Doença de Parkinson , Idade de Início , Povo Asiático/genética , China , Proteínas de Ligação a DNA/genética , Humanos , Pessoa de Meia-Idade , Mutação , Doença de Parkinson/genética , Fatores de Transcrição/genéticaRESUMO
In patients with sepsis, lipopolysaccharide (LPS) from the outer membrane of gram-negative bacteria triggers cardiac dysfunction and heart failure, but target therapy for septic cardiomyopathy remains unavailable. In this study we evaluated the beneficial effects of cardamonin (CAR), a flavone existing in Alpinia plant, on endotoxemia-induced cardiac dysfunction and the underlying mechanisms with focus on oxidative stress and apoptosis. Adult mice were exposed to LPS (4 mg/kg, i.p. for 6 h) prior to functional or biochemical assessments. CAR (20 mg/kg, p.o.) was administered to mice immediately prior to LPS challenge. We found that LPS challenge compromised cardiac contractile function, evidenced by compromised fractional shortening, peak shortening, maximal velocity of shortening/relengthening, enlarged LV end systolic diameter and prolonged relengthening in echocardiography, and induced apoptosis, overt oxidative stress (O2- production and reduced antioxidant defense) associated with inflammation, phosphorylation of NF-κB and cytosolic translocation of transcriptional factor Nrf2. These deteriorative effects were greatly attenuated or mitigated by CAR administration. However, H&E and Masson's trichrome staining analysis revealed that neither LPS challenge nor CAR administration significantly affected cardiomyocyte cross-sectional area and interstitial fibrosis. Mouse cardiomyocytes were treated with LPS (4 µg/mL) for 6 h in the absence or presence of CAR (10 µM) in vitro. We found that addition of CAR suppressed LPS-induced defect in cardiomyocyte shortening, which was nullified by the Nrf2 inhibitor ML-385 or the NF-κB activator prostratin. Taken together, our results suggest that CAR administration protects against LPS-induced cardiac contractile abnormality, oxidative stress, apoptosis, and inflammation through Nrf2- and NF-κB-dependent mechanism.
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Cardiomiopatias/prevenção & controle , Cardiotônicos/uso terapêutico , Chalconas/uso terapêutico , Contração Miocárdica/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Animais , Apoptose/efeitos dos fármacos , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/complicações , Cardiomiopatias/patologia , Feminino , Coração/efeitos dos fármacos , Inflamação/induzido quimicamente , Inflamação/complicações , Inflamação/tratamento farmacológico , Lipopolissacarídeos , Masculino , Camundongos , Miocárdio/patologia , Miócitos Cardíacos/efeitos dos fármacos , Subunidade p50 de NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacosRESUMO
Three Legionella-like strains, designed km488T, km489 and km521, were isolated from freshwater samples in China. Cells were Gram-stain-negative, rod-shaped and non-spore-forming. Growth was observed on BCYEα agar, but not on BCYEα agar without l-cysteine, chocolate agar with PolyViteX or Columbia blood agar. The major fatty acids (>5â%) of strains km488T, km489 and km521 were C16â:â0, anteiso-C15â:â0, iso-C16â:â0 and anteiso-C17â:â0. The mip gene sequences (574 nt) showed the isolates were almost identical with more than 99.7â% sequence similarities, and closely matched to L. gormanii ATCC 33297T with 95.4-95.6â% sequence similarities. Phylogenetic analyses based on concatenated gene (16S rRNA, mip, rpoB and rnpB) sequences indicated that the isolates formed a distinct cluster along with L. gormanii within the genus Legionella. Matrix-assisted laser desorption ionization time-of-flight analyses also demonstrated a clear separation between the isolates and other closely and distantly related Legionella species. DNA-DNA hybridization studies demonstrated that the isolates were closely related (92.0â-95.0â% DNA-DNA relatedness) but differentiated from their phylogenetic neighbours (<70â% DNA-DNA relatedness). The whole genome of km488T was sequenced, and showed a G+C content of 37.8âmol%. Based on the findings from this polyphasic taxonomic study, the isolates are considered to represent a single novel species, for which the name Legionella qingyii sp. nov. is proposed. The type strain is km488T (KCTC 15636T=CCTCC AB 2018025T=NRBC 113223T).
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Água Doce/microbiologia , Legionella/classificação , Filogenia , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Genes Bacterianos , Legionella/isolamento & purificação , Hibridização de Ácido Nucleico , RNA Ribossômico 16S/genética , Análise de Sequência de DNARESUMO
Aspirin can efficiently inhibit liver cancer growth, but the mechanism is poorly understood. In this study, we report that aspirin modulates glucose uptake through downregulating glucose transporter 1 (GLUT1), leading to the inhibition of hepatoma cell proliferation. Our data showed that aspirin significantly decreased the levels of reactive oxygen species (ROS) and glucose consumption in hepatoma cells. Interestingly, we identified that GLUT1 and HIF1α could be decreased by aspirin. Mechanically, we demonstrated that the -1008/-780 region was the regulatory element of transcriptional factor NF-κB in GLUT1 promoter by luciferase report gene assays. PDTC, an inhibitor of NF-κB, could suppress the expression of GLUT1 in HepG2 and H7402 cells, followed by affecting the levels of ROS and glucose consumption. CoCl2-activated HIF1α expression could slightly rescue the GLUT1 expression inhibited by aspirin or PDTC, suggesting that aspirin depressed GLUT1 through targeting NF-κB or NF-κB/HIF1α signaling. Moreover, we found that GLUT1 was highly expressed in clinical HCC tissues relating to their paired adjacent normal tissues. Importantly, we observed that high level of GLUT1 was significantly correlated with the poor relapse-free survival of HCC patients by analysis of public data. Functionally, overexpression of GLUT1 blocked the PDTC-induced or aspirin-induced inhibition of glucose metabolism in HepG2 cells. Conversely, aspirin failed to work when GLUT1 was stably knocked down in the cells. Administration of aspirin could depress the growth of hepatoma cells through controlling GLUT1 in vitro and in vivo. Thus, our finding provides new insights into the mechanism by which aspirin depresses liver cancer.
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Aspirina/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Transportador de Glucose Tipo 1/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Animais , Carcinoma Hepatocelular/diagnóstico , Linhagem Celular Tumoral , Regulação para Baixo , Glucose/metabolismo , Transportador de Glucose Tipo 1/genética , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Hepáticas/diagnóstico , Masculino , Camundongos Endogâmicos BALB C , Prognóstico , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
Aberrant expression of miR-511 is involved in the development of cancer, but the role of miR-511 in hepatocellular carcinoma (HCC) is not well documented. In this study, we explored the molecular mechanisms of miR-511 in hepatocarcinogenesis. Our results of bioinformatics analysis suggested that B cell translocation gene 1 (BTG1), a member of anti-proliferative gene family, was one of the putative targets of miR-511. The expression levels of miR-511 were significantly higher in 30 clinical HCC tissues than in corresponding peritumor tissues, and were negatively correlated with those of BTG1 in the HCC tissues (r=-0.6105, P<0.01). In human hepatoma cell lines HepG2 and H7402, overexpression of miR-511 dose-dependently inhibited the expression of BTG1, whereas knockdown of miR-511 dose-dependently increased the expression of BTG1. Luciferase reporter gene assays verified that miR-511 targeted the 3'UTR of BTG1 mRNA. In the hepatoma cells, overexpression of miR-511 significantly decreased BTG1-induced G1 phase arrest, which was rescued by overexpression of BTG1. Furthermore, overexpression of miR-511 promoted the proliferation of the hepatoma cells, which was rescued by overexpression of BTG1. Conversely, knockdown of miR-511 inhibited cell proliferation, which was reversed by knockdown of BTG1. In conclusion, miR-511 promotes the proliferation of human hepatoma cells in vitro by targeting the 3'UTR of BTG1 mRNA.
Assuntos
Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , MicroRNAs/metabolismo , Proteínas de Neoplasias/metabolismo , Regiões 3' não Traduzidas , Western Blotting , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Citometria de Fluxo , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
A new in-fiber Mach-Zehnder interferometer (MZI) based on lateral-offset and peanut shape structure is proposed and demonstrated for the measure of curvature and liquid level. The sensor consists of lateral-offset structure and peanut shape structure. A section of single mode fiber (SMF) is spliced between them. A part of core mode in the single mode fiber is excited to cladding modes by lateral-offset. The cladding modes are re-coupled to the core mode by peanut-shape structure and get interference with the core mode. A high-quality interference spectrum with a fringe visibility of about 12 dB is observed. The effective refractive indices of cladding mode would change with the external environment parameters, which further bring about a shift of the interference fringes. The liquid level or curvature can be measured by record the shift of the valley, because the shift of the valley shows a linear dependence with the variation of the liquid level or curvature theoretically. In the water level experiment, the water level changes from 1.00 to 5.00 cm and the wavelength valley shows a red shift. The sensitivity of the MZI with a length of 6.10 cm is -0.68 nm·cm-1. In the curvature experiment, the curvature changes from 0.3 to 1.2 and the wavelength valley shows a blue shift. The sensitivity of the MZI with a length of 2.10 cm is 22.47 nm·m. The lateral-offset structure and peanut shape structure are spliced to fabricate the MZI. The sensitivity of the MZI is high, especially in the curvature measurement, it is higher than that of other fiber curvature sensors. Moreover the MZI presented in this paper has advantages of low cost and easy fabrication, which can be a potential application in the liquid level and curvature measurement.
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Helicobacter pylori (H. pylori), known for causing gastric inflammation, gastritis and gastric cancer, prompted our study to investigate the differential expression of cytokines in gastric tissues, which is crucial for understanding H. pylori infection and its potential progression to gastric cancer. Focusing on Il-1ß, IL-6, IL-8, IL-12, IL-18, and TNF-α, we analysed gene and protein levels to differentiate between H. pylori-infected and non-infected gastritis. We utilised real-time quantitative polymerase chain reaction (RT-qPCR) for gene quantification, immunohistochemical staining, and ELISA for protein measurement. Gastric samples from patients with gastritis were divided into three groups: (1) non-gastritis (N-group) group, (2) gastritis without H. pylori infection (G-group), and (3) gastritis with H. pylori infection (GH-group), each consisting of 8 samples. Our findings revealed a statistically significant variation in cytokine expression. Generally, cytokine levels were higher in gastritis, but in H. pylori-infected gastritis, IL-1ß, IL-6, and IL-8 levels were lower compared to H. pylori-independent gastritis, while IL-12, IL-18, and TNF-α levels were higher. This distinct cytokine expression pattern in H. pylori-infected gastritis underscores a unique inflammatory response, providing deeper insights into its pathogenesis.
Assuntos
Gastrite , Infecções por Helicobacter , Helicobacter pylori , Helicobacter , Neoplasias Gástricas , Humanos , Citocinas/metabolismo , Helicobacter pylori/metabolismo , Interleucina-18/genética , Interleucina-18/metabolismo , Helicobacter/metabolismo , Interleucina-8/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Gastrite/patologia , Interleucina-12/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Infecções por Helicobacter/genética , Infecções por Helicobacter/metabolismo , Mucosa Gástrica/metabolismoRESUMO
Assessing failure pressure is critical in determining pipeline integrity. Current research primarily concerns the buckling performance of pressurized pipelines subjected to a bending load or axial compression force, with some also looking at the failure pressure of corroded pipelines. However, there is currently a lack of limit state models for pressurized pipelines with bending moments and axial forces. In this study, based on the unified yield criterion, we propose a limit state equation for steel pipes under various loads. The most common operating loads on buried pipelines are bending moment, internal pressure, and axial force. The proposed limit state equation for intact pipelines is based on a three-dimensional pipeline stress model with complex load coupling. Using failure data, we investigate the applicability of various yield criteria in assessing the failure pressure of pipelines with complex loads. We show that the evaluation model can be effectively used as a theoretical solution for assessing the failure pressure in such circumstances and for selecting appropriate yield criteria based on load condition differences.
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The presence of water strongly influences structure, dynamics and properties of ion-containing soft matter. Yet, the hydration of such matter is not well understood. Here, we show through a large study of monovalent π-conjugated polyelectrolytes that their reversible hydration, up to several water molecules per ion pair, occurs chiefly at the interface between the ion clusters and the hydrophobic matrix without disrupting ion packing. This establishes the appropriate model to be surface hydration, not the often-assumed internal hydration of the ion clusters. Through detailed analysis of desorption energies and O-H vibrational frequencies, together with OPLS4 and DFT calculations, we have elucidated key binding motifs of the sorbed water. Type-I water, which desorbs below 50 °C, corresponds to hydrogen-bonded water clusters constituting secondary hydration. Type-II water, which typically desorbs over 50-150 °C, corresponds to water bound to the anion under the influence of a proximal cation, or to a cationâanion pair, at the cluster surface. This constitutes primary hydration. Type-III water, which irreversibly desorbs beyond 150 °C, corresponds to water kinetically trapped between ions. Its amount varies strongly with processing and heat treatment. As a consequence, hygroscopicity-which is the water sorption capacity per ion pair-depends not only on the ions, but also their cluster morphology.
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The persistent bloom of the brown tide alga Aureoumbra lagunensis has been reported in coastal embayments along southern Texas, but the molecular mechanisms that sustain such algal bloom are unknown. We compared the proteome and physiological parameters of A. lagunensis grown in phosphate (P)-depleted, P- and nitrogen (N)-depleted, and nutrient-replete cultures. For the proteomic analysis, samples from three conditions were subjected to two-dimensional electrophoresis and tandem mass spectrometry analysis. Because of the paucity of genomic resources in this species, a de novo cross-species protein search was used to identify the differentially expressed proteins, which revealed their involvement in several key biological processes, such as chlorophyll synthesis, antioxidative protection, and protein degradation, suggesting that A. lagunensis may adopt intracellular nutrient compensation, extracellular organic nutrient regeneration, and damage protection to thrive in P-depleted environments. A highly abundant P limitation-specific protein, tentatively identified as a putative alkaline phosphatase, was further characterized by enzyme activity assay on nondenaturing gel and confocal microscopy, which confirmed that this protein has alkaline phosphatase activity, is a cytoplasmic protein, and is closely associated with the cell membrane. The abundance, location, and functional expression of this alkaline phosphatase all indicate the importance of organic P utilization for A. lagunensis under P limitation and the possible role of this alkaline phosphatase in regenerating phosphate from extra- or intracellular organic phosphorus.
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Fosfatase Alcalina/metabolismo , Nitrogênio/metabolismo , Fosfatos/metabolismo , Proteoma/análise , Estramenópilas/química , Estramenópilas/metabolismo , Eletroforese em Gel Bidimensional , Espectrometria de Massas , Água do Mar/microbiologia , TexasRESUMO
Objective: To elucidate the clinical, radiologic characteristics of Leber's hereditary optic neuropathy (LHON) associated with the other diseases. Materials and methods: Clinical data were retrospectively collected from hospitalized patients with LHON associated with the other diseases at the Neuro-Ophthalmology Department at the Chinese People's Liberation Army General Hospital (PLAGH) from December 2014 to October 2018. Results: A total of 13 patients, 24 eyes (10 men and 3 women; mean age, 30.69 ± 12.76 years) with LHON mitochondrial DNA (mtDNA) mutations, were included in the cohort. 14502(5)11778(4)11778 &11696(1)12811(1)11696(1)3460(1). One patient was positive for aquaporin-4 antibody (AQP4-Ab), and two were positive for myelin oligodendrocyte glycoprotein antibody (MOG-Ab). Three patients were associated with idiopathic optic neuritis (ON). Two patients were with compression optic neuropathy. Three patients were with the central nervous system (CNS) diseases. One patient was with proliferative diabetic retinopathy (PDR) and one with idiopathic orbital inflammatory syndrome (IOIS). At the onset, visual acuity (VA) in eighteen eyes was below 0.1, one eye was 0.5, five eyes were above 0.5, while VA in sixteen eyes was below a 0.1 outcome, three eyes experienced moderate vision loss. MRI images showed T2 lesions and enhancement in nine patients who received corticosteroids treatment; additional immune modulators treatment was performed on two patients. None of the patients had relapse during the follow-up time. Conclusion: Leber's hereditary optic neuropathy can be accompanied with multiple-related diseases, especially different subtypes of ON, which were also exhibited with IOIS and compression optic neuropathy for the first time in this cohort. This condition may be a distinct entity with an unusual clinical and therapeutic profile.
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OBJECTIVE: To investigate the effects of Aurantii Fructus Immaturus (Zhishi, ZS) and Atractylodis Macrocephalae Rhizoma (Baizhu, BZ)-containing serum on glutamate-induced autophagy in rat colonic interstitial cells of Cajal (ICCs) and to analyze the underlying mechanism. METHODS: Rat colonic ICCs cultured in vitro were identified by fluorescence and then stimulated with glutamic acid (5 mmol/L) for 24 h to establish a cell model of autophagy. The cells were then treated with different concentrations of ZSBZ-containing serum or rat serum. The viability of the ICCs was detected with cell counting kit-8 assays, and cell apoptosis rates were examined with flow cytometry. The ultrastructure and autophagosomes in the ICCs were observed using transmission electron microscopy. The effects of ZSBZ-containing serum on apoptosis-associated mediators were assessed by Western blotting and real-time quantitative polymerase chain reaction. In addition, microtubule-associated protein light chain 3 (LC3), p-phosphoinositide 3-kinase (p-PI3K), p-Akt and p-mammalian target of rapamycin (p-mTOR) expression was detected via Western blotting analysis. RESULTS: Compared to those in the model group, ICC viability and apoptosis rates were significantly increased by ZSBZ-containing serum (P < 0.05). In addition, the expression levels of Beclin-1, LC3, p-PI3K, p-Akt and p-mTOR were significantly lower (P < 0.05) and Bcl-2 expression was higher in the ZSBZ-containing serum treatment groups than in the model group (P < 0.05). CONCLUSION: Our findings demonstrated that ZSBZ protects glutamic acid-stimulated ICCs, and this beneficial effect may be mediated by a reduction in autophagy via inhibition of the PI3K/Akt/mTOR pathway.
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Atractylodes/química , Autofagia , Medicamentos de Ervas Chinesas/farmacologia , Células Intersticiais de Cajal , Animais , Apoptose , Ácido Glutâmico , Células Intersticiais de Cajal/efeitos dos fármacos , Células Intersticiais de Cajal/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Proteína Oncogênica v-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Ratos , Rizoma/química , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismoRESUMO
AIM: To compare uncut Roux-en-Y (U-RY) gastrojejunostomy with Roux-en-Y (RY) gastrojejunostomy after distal gastrectomy (DG) for gastric cancer. METHODS: A literature search was conducted in Pubmed, Embase, Web of Science, Cochrane Library, Science Direct, Chinese National Knowledge Infrastructure, Wanfang, and China Science and Technology Journal Database to identify studies comparing U-RY with RY after DG for gastric cancer until the end of December 2017. Pooled odds ratio or weighted mean difference with 95% confidence interval was calculated using either fixed- or random-effects models. Perioperative outcomes such as operative time, intraoperative blood loss, and hospital stay; postoperative complications such as anastomotic bleeding, stricture and ulcer, reflux gastritis/esophagitis, delayed gastric emptying, and Roux stasis syndrome; and postoperative nutritional status (serum hemoglobin, total protein, and albumin levels) were the main outcomes assessed. Meta-analyses were performed using RevMan 5.3 software. RESULTS: Two randomized controlled trials and four nonrandomized observational clinical studies involving 403 and 488 patients, respectively, were included. The results of the meta-analysis showed that operative time [weighted mean difference (WMD): -12.95; 95%CI: -22.29 to -3.61; P = 0.007] and incidence of reflux gastritis/esophagitis (OR: 0.40; 95%CI: 0.20-0.80; P = 0.009), delayed gastric emptying (OR: 0.29; 95%CI: 0.14-0.61; P = 0.001), and Roux stasis syndrome (OR: 0.14; 95%CI: 0.04-0.50; P = 0.002) were reduced; and the level of serum albumin (WMD: 0.71; 95%CI: 0.24-1.19; P = 0.003) was increased in patients undergoing U-RY reconstruction compared with those undergoing RY reconstruction. No differences were found with respect to intraoperative blood loss, hospital stay, anastomotic bleeding, anastomotic stricture, anastomotic ulcer, the levels of serum hemoglobin, and serum total protein. CONCLUSION: U-RY reconstruction has some clinical advantages over RY reconstruction after DG.
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Gastrectomia/efeitos adversos , Derivação Gástrica/efeitos adversos , Gastroenterostomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Neoplasias Gástricas/cirurgia , Gastrectomia/métodos , Derivação Gástrica/métodos , Gastroenterostomia/métodos , Humanos , Tempo de Internação/estatística & dados numéricos , Estado Nutricional , Duração da Cirurgia , Período Perioperatório , Complicações Pós-Operatórias/etiologia , Resultado do TratamentoRESUMO
Cold acclimation improves freezing tolerance in plants. In higher plants, many advances have been made toward identifying the signaling and regulatory pathways that direct the low-temperature stress response; however, similar insights have not yet been gained for simple nonvascular plants, such as bryophytes. To elucidate the pathways that regulate cold acclimation in bryophytes, we used two PCR-based differential screening techniques, cDNA amplified fragment length polymorphism (cDNA-AFLP) and suppression subtractive hybridization (SSH), to isolate 510 ESTs that are differentially expressed during cold acclimation in Physcomitrella patens. We used realtime RT-PCR to further analyze expression of 29 of these transcripts during cold acclimation. Our results show that cold acclimation in the bryophyte Physcomitrella patens is not only largely similar to higher plants but also displays distinct differences, suggests significant alteration during the evolution of land plants.
Assuntos
Aclimatação/genética , Aclimatação/fisiologia , Bryopsida/genética , Bryopsida/fisiologia , Genes de Plantas , Análise do Polimorfismo de Comprimento de Fragmentos Amplificados , Arabidopsis/genética , Arabidopsis/fisiologia , Sequência de Bases , Membrana Celular/fisiologia , Clima Frio , Primers do DNA/genética , DNA de Plantas/genética , Congelamento , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Dados de Sequência Molecular , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais , Esteroides/biossínteseRESUMO
AIM: To investigate the effect of activating transcription factor-3 (ATF3)-deletion on apoptosis of cultured retinal ganglion cells (RGCs). METHODS: Three ATF3 siRNA (ATF3-rat-651, ATF3-rat-319, ATF3-rat-520) were constructed, and were transiently transfected into RGC-5 cells. Quantitative real-time polymerase chain reaction (PCR) was used to examine ATF3 expression and the most effective ATF3 siRNA was selected for further studies. Flow cytometry was applied to investigate the effects of ATF3 deletion on RGC-5 apoptosis under elevated hydrostatic pressure. Quantitative real-time PCR and Western blot were performed to validate differentially expressed genes and proteins in ATF3-knockdown RGC-5 cells. RESULTS: ATF3 specific siRNA effectively down-regulated ATF3 expression and significantly inhibited cell apoptosis in RGC-5 cells. Quantitative real-time PCR and Western blot confirmed that ATF3 knockdown remarkably decreased Jun-B and increased c-Jun at both mRNA and protein levels in RGC-5 cells. CONCLUSION: ATF/cAMP-response element-binding family of transcription factors may be involved in the development of glaucoma and could be novel treatment targets for glaucoma.
RESUMO
BACKGROUND: Appendiceal mucinous adenocarcinoma is an extremely rare disease in clinical practice. Here, we report a case of unprecedented size that occupied the entire abdomen of a man. CASE PRESENTATION: A 49-year-old Chinese Han man presented with symptoms of abdominal distension. During a computed tomography imaging examination, a cystic-solid mass that occupied his entire abdominal cavity was detected. During exploratory laparotomy, an appendiceal tumor in his abdominal-pelvic cavity measuring 27.6 × 14.2 cm was found, and he underwent tumor resection. The pathology of the tumor identified a well-differentiated appendiceal mucinous adenocarcinoma with mucin infiltrating into the soft tissue of the lump edge and omentum tissue. After surgery, our patient accepted intraperitoneal infusion chemotherapy. At present, he has had no recurrence for 15 months. CONCLUSIONS: To the best of our knowledge, the present case is the largest appendiceal mucinous adenocarcinoma reported. Surgical tumor resection is the preferred treatment for appendiceal mucinous adenocarcinoma. This is supplemented by chemotherapy which can further prolong survival.
Assuntos
Adenocarcinoma Mucinoso/patologia , Neoplasias do Apêndice/patologia , Abdome/diagnóstico por imagem , Adenocarcinoma Mucinoso/diagnóstico por imagem , Adenocarcinoma Mucinoso/terapia , Adulto , Neoplasias do Apêndice/diagnóstico por imagem , Neoplasias do Apêndice/terapia , Biópsia , Quimiorradioterapia Adjuvante , Humanos , Masculino , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
The topologies of data distributions are very important for data description. Usually, it is not easy to find a description that can give us an intuitional understanding of the topologies for general distributions. In this paper, a novel concept, a topology graph, is proposed as a description for the principal topology of data distribution. The topology graph builds a one-to-one correspondence between the principal topology of the distribution and the topology itself: annularity features of the principal topology correspond to the loops of the graph, and the divarication features correspond to the branches of the graph. In general, the topology graph can be considered as the skeleton of the data distribution. A divide-and-combine learning strategy is developed to find the topology graphs for general data distributions. The learning strategy is focused on the constrained local description learning and automatic topology generation. Following the learning strategy, a cluster growing algorithm is developed. Experimental results on both artificial datasets and real-world applications show good performance of the proposed algorithm.