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1.
Annu Rev Biochem ; 84: 739-64, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25621509

RESUMO

The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that plays a critical role in the pathogenesis of many cancers. The structure of intact forms of this receptor has yet to be determined, but intense investigations of fragments of the receptor have provided a detailed view of its activation mechanism, which we review here. Ligand binding converts the receptor to a dimeric form, in which contacts are restricted to the receptor itself, allowing heterodimerization of the four EGFR family members without direct ligand involvement. Activation of the receptor depends on the formation of an asymmetric dimer of kinase domains, in which one kinase domain allosterically activates the other. Coupling between the extracellular and intracellular domains may involve a switch between alternative crossings of the transmembrane helices, which form dimeric structures. We also discuss how receptor regulation is compromised by oncogenic mutations and the structural basis for negative cooperativity in ligand binding.


Assuntos
Receptores ErbB/metabolismo , Animais , Dimerização , Fator de Crescimento Epidérmico/metabolismo , Receptores ErbB/química , Humanos , Ligação Proteica , Estrutura Terciária de Proteína
2.
Cell ; 152(3): 543-56, 2013 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-23374349

RESUMO

How the epidermal growth factor receptor (EGFR) activates is incompletely understood. The intracellular portion of the receptor is intrinsically active in solution, and to study its regulation, we measured autophosphorylation as a function of EGFR surface density in cells. Without EGF, intact EGFR escapes inhibition only at high surface densities. Although the transmembrane helix and the intracellular module together suffice for constitutive activity even at low densities, the intracellular module is inactivated when tethered on its own to the plasma membrane, and fluorescence cross-correlation shows that it fails to dimerize. NMR and functional data indicate that activation requires an N-terminal interaction between the transmembrane helices, which promotes an antiparallel interaction between juxtamembrane segments and release of inhibition by the membrane. We conclude that EGF binding removes steric constraints in the extracellular module, promoting activation through N-terminal association of the transmembrane helices.


Assuntos
Membrana Celular/metabolismo , Fator de Crescimento Epidérmico/metabolismo , Receptores ErbB/química , Transdução de Sinais , Animais , Células COS , Membrana Celular/química , Chlorocebus aethiops , Dimerização , Receptores ErbB/metabolismo , Humanos , Modelos Moleculares
3.
Opt Express ; 32(12): 21870-21886, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38859531

RESUMO

In contrast to the passive remote sensing of global CO2 column concentrations (XCO2), active remote sensing with a lidar enables continuous XCO2 measurements throughout the entire atmosphere in daytime and nighttime. The lidar could penetrate most cirrus and is almost unaffected by aerosols. Atmospheric environment monitoring satellite (AEMS, also named DQ-1) aerosol and carbon dioxide detection Lidar (ACDL) is a novel spaceborne lidar that implements a 1572 nm integrated path differential absorption (IPDA) method to measure the global XCO2 for the first time. In this study, special methods have been developed for ACDL data processing and XCO2 retrieval. The CO2 measurement data products of ACDL, including the differential absorption optical depth between the online and offline wavelengths, the integral weighting function, and XCO2, are presented. The results of XCO2 measurements over the period from 1st June 2022 to 30th June 2022 (first month data of ACDL) are analyzed to demonstrate the measurement capabilities of the spaceborne ACDL system.

4.
Ecotoxicol Environ Saf ; 241: 113767, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35714486

RESUMO

With the rapid development of the seaweed industry in China, the scale and production of its commercial seaweed are ranked among the most significant worldwide. Consequently, the control of algal blooms, especially fouling diatoms, during macroalgae industrialisation is an important issue. Many diatom bloom studies have focused on physical and chemical controls, with limited economic and eco-friendly biological controls reported. In our study, Gracilaria bailiniae fresh thalli and aqueous extract profoundly suppressed Nitzschia closterium growth (50% inhibition concentration of the fourth day (IC50-4 day) was 0.667 × 10-3 g·mL-1 and 3.889 × 10-3 g·mL-1, respectively). The cellular morphology changes of N. closterium exposed to the G. bailiniae aqueous extract were severe atrophies and plasmolysis and dissolution of endocellular structures. To explore more potential allelochemicals to control N. closterium, the intracellular compounds of G. bailiniae were detected and screened. Three organic acids (citrate, hydroxyethanesulfonic acid (HA) and taurine) had allelopathic potential against N. closterium. Our results showed that citrate and HA markedly suppressed N. closterium (IC50-4 day: 1.035 mM and 1.151 mM, respectively); however, taurine poorly suppressed N. closterium (IC50-4 day: 2.500 mM). Therefore, HA is one of the main allelopathic compounds in G. bailiniae. Further, the allelopathic mechanism of HA against the N. closterium photosynthetic system broke its photosynthetic apparatus (oxygen-evolving complex, reaction centres, the effective antenna size and the donor side of photosystem II) and hindered electron transport. The experimental results provide a new and eco-friendly strategy to control diatom blooms.


Assuntos
Closterium , Diatomáceas , Gracilaria , Rodófitas , Alga Marinha , Citratos , Complexo de Proteína do Fotossistema II , Taurina
5.
J Environ Manage ; 319: 115685, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-35816963

RESUMO

Contaminated sites are a main cause of urban soil problems and have led to increasing pollution and public risk in China as a result of the rapid growth of industrial and urban land use. Because land pollution involves extensive multi-source heterogeneous information, identifying the risk of urban soil pollution efficiently and predicting pollution-related events are important for urban environmental management. Knowledge graphs (KGs) have unique advantages in dealing with massive amounts of information. This study attempts to construct a KG of contaminated sites in South China to explore its feasibility and effectiveness in urban soil environmental management. The results demonstrate that KGs have a favorable effect in information retrieval, knowledge reasoning, and visualization. Studied cases in this article demonstrate that the KG model can achieve many functions, including the display of global information of polluted sites, and discovery of regional distribution of characteristic pollutants and main pollutants of specific industries, based on special query syntax. However, this approach is limited by some technical difficulties, such as knowledge mining of natural resources, which must be overcome in future studies to improve the operability of KG technologies.


Assuntos
Poluentes Ambientais , Metais Pesados , Poluentes do Solo , China , Monitoramento Ambiental/métodos , Poluição Ambiental/análise , Metais Pesados/análise , Reconhecimento Automatizado de Padrão , Medição de Risco , Solo , Poluentes do Solo/análise
6.
J Cell Physiol ; 236(11): 7591-7604, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34041752

RESUMO

Uncontrolled recurrence and metastasis are important reasons for the high mortality rate of malignant tumors. Vimentin is positively correlated with the degree of malignancy of cancer cells. Vimentin is also highly expressed in colorectal cancer (CRC) cells and plays a critical role in the metastasis and prognosis of CRC. However, the molecular mechanism of vimentin in the progression of CRC is incompletely understood. Therefore, the most active regions (nucleotides: 785-1085 nt) of the vimentin promoter in CRC were identified using luciferase experiments. By transcription factor sequence search and mutation analysis, the activator protein 1 (AP-1) binding site in the region of 785-1085 nt was confirmed. The vimentin promoter activity was enhanced by overexpression of AP-1. The electrophoretic mobility shift assay and chromatin immunoprecipitation assay showed that the binding site was recognized by AP-1. By cell proliferation assay, colony-forming assay, scratch-wound assay, cell migration assay, and cell invasion assay, we demonstrated that the AP-1 overexpression increased CRC cell proliferation, migration, and invasion. However, when vimentin was knocked down by vimentin small hairpin RNA in the CRC cell of AP-1 overexpression, this trend disappeared. Animal experiments and immunohistochemistry showed that AP-1 promoted tumor growth by regulating the vimentin gene. In summary, AP-1 affected metastasis, invasion of CRC cells in vitro, and tumor growth in vivo by activating the vimentin promoter. This study might provide new insights into the molecular mechanisms of the development of CRC and provide potential therapeutic targets for CRC.


Assuntos
Movimento Celular , Proliferação de Células , Neoplasias Colorretais/metabolismo , Fator de Transcrição AP-1/metabolismo , Vimentina/metabolismo , Animais , Sítios de Ligação , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Células HEK293 , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Metástase Neoplásica , Regiões Promotoras Genéticas , Transdução de Sinais , Fator de Transcrição AP-1/genética , Carga Tumoral , Vimentina/genética
7.
World J Surg ; 45(12): 3623-3632, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34494162

RESUMO

BACKGROUND: Parastomal hernia and fecal incontinence cause severe distress to the rectal cancer patients with stoma after abdominoperineal resection. We attempted a new colostomy technique through the gap between the abdominal oblique internal and external muscles to prevent parastomal hernia and improve quality of life. METHODS: This cohort study retrospectively examined clinical data from a total of 114 consecutive rectal cancer patients who underwent laparoscopic abdominoperineal resection in our center from March 2016 to March 2018 after propensity score matching. Group A included 57 patients who underwent colostomy through the gap between the abdominal oblique internal and oblique external muscles, while group B included 57 patients who underwent extraperitoneal colostomy. Patients' quality of life was evaluated using Fecal Incontinence Quality of Life (FIQL) Scale. RESULTS: Group A had a lower incidence of parastomal hernia (0% vs. 15.7%, p = 0.004) and higher quality of life, especially in lifestyle, coping/behavior and embarrassment domains (all p values < 0.05) than group B both during the follow-up period. The incidence of other outcomes did not differ between the groups. CONCLUSIONS: Colostomy through the gap between the abdominal oblique internal and oblique external muscle is a new technique showing both safety and effectiveness for preventing parastomal hernia and improving quality of life after laparoscopic abdominoperineal resection.


Assuntos
Hérnia Ventral , Hérnia Incisional , Neoplasias Retais , Estudos de Coortes , Colostomia , Hérnia Ventral/epidemiologia , Hérnia Ventral/cirurgia , Humanos , Incidência , Hérnia Incisional/epidemiologia , Hérnia Incisional/etiologia , Hérnia Incisional/prevenção & controle , Músculos , Qualidade de Vida , Neoplasias Retais/cirurgia , Estudos Retrospectivos , Telas Cirúrgicas
8.
Biol Chem ; 401(2): 285-296, 2020 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-31188741

RESUMO

The gene encoding transmembrane protein 100 (TMEM100) was first discovered to be transcribed by the murine genome. It has been recently proven that TMEM100 contributes to hepatocellular carcinoma and non-small-cell lung carcinoma (NSCLC). This study investigates the impact of TMEM100 expression on gastric cancer (GC). TMEM100 expression was remarkably downregulated in GC samples compared to the surrounding non-malignant tissues (p < 0.01). Excessive TMEM100 expression prohibited the migration and invasion of GC cells without influencing their growth. However, TMEM100 knockdown restored their migration and invasion potential. Additionally, TMEM100 expression restored the sensitivity of GC cells to chemotherapeutic drugs such as 5-fluouracil (5-FU) and cisplatin. In terms of TMEM100 modulation, it was revealed that BMP9 rather than BMP10, is the upstream modulator of TM3M100. HIF1α downregulation modulated the impact of TMEM100 on cell migration, chemotherapy sensitivity and invasion in GC cells. Eventually, the in vivo examination of TMEM100 activity revealed that its upregulation prohibits the pulmonary metastasis of GC cells and increases the sensitivity of xenograft tumors to 5-FU treatment. In conclusion, TMEM100 serves as a tumor suppressor in GC and could be used as a promising target for the treatment of GC and as a predictor of GC clinical outcome.


Assuntos
Antineoplásicos/farmacologia , Biomarcadores Tumorais/genética , Proteínas de Membrana/genética , Neoplasias Gástricas/tratamento farmacológico , Animais , Biomarcadores Tumorais/metabolismo , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Fluoruracila/farmacologia , Humanos , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Células Tumorais Cultivadas
9.
Cell Physiol Biochem ; 39(5): 1665-1678, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27639612

RESUMO

BACKGROUND AND AIM: Lipopolysaccharide(LPS) could promote the progression of colorectal cancer, but the specific regulatory mechanisms are largely unknown. So, this study aim to clarify the mechanisms that LPS upregulated VEGFR-3, which promotes colorectal cancer cells migration and invasion with a mechanism of increased NF-κB bind to the promoter of VEGFR-3. METHODS: The present study examined the VEGFR-3 expression in colorectal cancer tissues and analyzed the relationship between the VEGFR-3 expression with clinical parameters. PCR, Western blot, CCK-8, colone formation assay, and Transwell assay detected that LPS promoted the migration and invasion and the role of VEGFR-3 in the process of colorectal carcinoma in vitro. Used the methods of promoter analysis, EMSA assay and ChIP assay to explore the mechanisms LPS increased the expression of VEGFR-3. RESULTS: VEGFR-3 was significantly high expression in the colorectal cancer tissues. And the high expression was associated with the TNM stage and lymph node metastasis of colorectal cancer. LPS could promote the migration and invasion, which could be blocked by the neutralizing antibody IgG of VEGFR-3. And found that -159 nt to +65 nt was the crucial region of VEGFR-3 promoter. And detected that the NF-κB was important transcription factor for the VEGFR-3 promoter. And LPS could increase NF-κB binding to VEGFR-3 promoter and upregulated the expression of VEGFR-3 to exert biological functions. CONCLUSION: We have elucidated the relationship between LPS and the VEGFR-3 expression and revealed that VEGFR-3 play very important role in the process of LPS promoting the migration and invasion of colorectal cancer cells. Further illuminated the mechanism that LPS upregulated VEGFR-3 expression via increased NF-κB bind to the promoter of VEGFR-3.


Assuntos
Movimento Celular/efeitos dos fármacos , Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , Lipopolissacarídeos/farmacologia , NF-kappa B/genética , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/genética , Idoso , Anticorpos Neutralizantes/farmacologia , Sítios de Ligação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia , Feminino , Células HCT116 , Humanos , Imunoglobulina G/farmacologia , Masculino , Pessoa de Meia-Idade , NF-kappa B/imunologia , Invasividade Neoplásica , Estadiamento de Neoplasias , Regiões Promotoras Genéticas , Ligação Proteica , Transdução de Sinais , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/imunologia
10.
Nature ; 467(7316): 734-8, 2010 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-20877283

RESUMO

The major facilitator superfamily (MFS) transporters are an ancient and widespread family of secondary active transporters. In Escherichia coli, the uptake of l-fucose, a source of carbon for microorganisms, is mediated by an MFS proton symporter, FucP. Despite intensive study of the MFS transporters, atomic structure information is only available on three proteins and the outward-open conformation has yet to be captured. Here we report the crystal structure of FucP at 3.1 Å resolution, which shows that it contains an outward-open, amphipathic cavity. The similarly folded amino and carboxyl domains of FucP have contrasting surface features along the transport path, with negative electrostatic potential on the N domain and hydrophobic surface on the C domain. FucP only contains two acidic residues along the transport path, Asp 46 and Glu 135, which can undergo cycles of protonation and deprotonation. Their essential role in active transport is supported by both in vivo and in vitro experiments. Structure-based biochemical analyses provide insights into energy coupling, substrate recognition and the transport mechanism of FucP.


Assuntos
Proteínas de Escherichia coli/química , Escherichia coli/química , Proteínas de Transporte de Monossacarídeos/química , Simportadores/química , Cristalografia por Raios X , Proteínas de Escherichia coli/metabolismo , Fucose/metabolismo , Interações Hidrofóbicas e Hidrofílicas , Modelos Biológicos , Modelos Moleculares , Proteínas de Transporte de Monossacarídeos/metabolismo , Conformação Proteica , Prótons , Rotação , Eletricidade Estática , Simportadores/metabolismo
11.
Nature ; 462(7272): 467-72, 2009 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-19940917

RESUMO

FocA is a representative member of the formate-nitrite transporter family, which transports short-chain acids in bacteria, archaea, fungi, algae and parasites. The structure and transport mechanism of the formate-nitrite transporter family remain unknown. Here we report the crystal structure of Escherichia coli FocA at 2.25 A resolution. FocA forms a symmetric pentamer, with each protomer consisting of six transmembrane segments. Despite a lack of sequence homology, the overall structure of the FocA protomer closely resembles that of aquaporin and strongly argues that FocA is a channel, rather than a transporter. Structural analysis identifies potentially important channel residues, defines the channel path and reveals two constriction sites. Unlike aquaporin, FocA is impermeable to water but allows the passage of formate. A structural and biochemical investigation provides mechanistic insights into the channel activity of FocA.


Assuntos
Aquaporinas/química , Proteínas de Escherichia coli/química , Proteínas de Membrana Transportadoras/química , Aquaporinas/metabolismo , Cristalografia por Raios X , Escherichia coli/química , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Formiatos/metabolismo , Lipossomos/química , Lipossomos/metabolismo , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Modelos Moleculares , Mimetismo Molecular , Mutação , Permeabilidade , Estrutura Quaternária de Proteína , Relação Estrutura-Atividade , Água/análise , Água/metabolismo
12.
Ecol Evol ; 14(5): e11424, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38779531

RESUMO

Monostroma nitidum, a monostromatic green algae (MGA) with high economic value, is distributed worldwide. Life cycle often serves as a fundamental criterion for taxonomic classification. Most researchers consider the life cycle of M. nitidum to involve dimorphic alternation of generations, although the possibility of a monomorphic asexual life cycle remains unclear. In this study, tufA and 18S rDNA sequences were employed as molecular markers, complemented by morphological analysis, to classify and identify MGA in two distinct habitats: Hailing Island reefs (YJ) and Naozhou Island reefs (ZJ). The results of tufA and 18S rDNA sequence analysis revealed that all samples from YJ and ZJ clustered to the same branch (M. nitidum clade) with high bootstrap support and genetic distances of less than 0.000 and 0.005, respectively. However, morphological observations indicated significant differences in the external morphology of the YJ and ZJ samples, although both initially exhibited a filament-blade form during early development. The life cycle of the ZJ samples exhibited typical dimorphic alternation of generations, whereas the YJ samples only produced biflagellate asexual gametes with negative phototaxis. Gametes of the YJ samples directly developed into new gametophytes without undergoing the sporophyte stage. Consequently, the YJ and ZJ samples were classified as monomorphic asexual and dimorphic sexual M. nitidum, respectively. These findings provide evidence supporting the monomorphic asexual life cycle of M. nitidum for the classification of MGA.

13.
Eur J Med Res ; 29(1): 160, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38475928

RESUMO

BACKGROUND: He long noncoding RNA small nucleolar host RNA 5 (SNHG5) is highly expressed in many cancers, and there is a notable correlation between the elevated expression of SNHG5 and survival outcome in cancer patients. The objective of this study was to conduct a meta-analysis to evaluate the correlation between SNHG5 expression and the clinical outcome of cancer patients. METHODS: Six relevant electronic databases were exhaustively searched, and, depending on the inclusion and exclusion criteria, appropriate literature was obtained. The Newcastle-Ottawa Scale (NOS) score was utilized to evaluate the quality of the research for every article included, and pertinent data from each study were carefully extracted. Hazard ratios (HRs), odds ratios (ORs) and 95% confidence intervals (CIs) were combined to explore the association of SNHG5 expression levels with cancer prognosis, and sensitivity analyses and assessments of publication bias were also conducted to investigate any possibility in the publication of the studies. RESULTS: Eleven studies encompassing 721 patients were ultimately collected. When combined, the hazard ratios (HRs) revealed a substantial direct correlation between elevated SNHG5 expression and an unfavourable prognosis for cancer patients (HR = 1.90, 95% CI 0.87-4.15); however, the correlation did not reach statistical significance. Furthermore, high SNHG5 expression was predictive of advanced TNM stage (OR: 1.988, 95% CI 1.205-3.278) and larger tumour size (OR: 1.571, 95% CI 1.090-2.264); moreover, there were nonsignificant relationships between SNHG5 expression and DM (OR: 0.449, 95% CI 0.077-2.630), lymph node metastasis (OR: 1.443, 95% CI 0.709-2.939), histological grade (OR: 2.098, 95% CI 0.910-4.838), depth of invasion (OR: 1.106, 95% CI 0.376-3.248), age (OR: 0.946, 95% CI 0.718-1.247) and sex (OR: 0.762, 95% CI 0.521-1.115). CONCLUSION: SNHG5 expression is typically increased in the majority of tumour tissues. Elevated SNHG5 expression may indicate poor prognosis in cancer patients. Therefore, SNHG5 is a promising potential therapeutic target for tumours and a reliable prognostic biomarker.


Assuntos
Neoplasias , RNA Longo não Codificante , Masculino , Humanos , Neoplasias/genética , Prognóstico , Modelos de Riscos Proporcionais , RNA Longo não Codificante/genética , Biomarcadores Tumorais/genética
14.
Nat Struct Mol Biol ; 31(3): 424-435, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38177685

RESUMO

Clamp loaders are AAA+ ATPases that facilitate high-speed DNA replication. In eukaryotic and bacteriophage clamp loaders, ATP hydrolysis requires interactions between aspartate residues in one protomer, present in conserved 'DEAD-box' motifs, and arginine residues in adjacent protomers. We show that functional defects resulting from a DEAD-box mutation in the T4 bacteriophage clamp loader can be compensated by widely distributed single mutations in the ATPase domain. Using cryo-EM, we discovered an unsuspected inactive conformation of the clamp loader, in which DNA binding is blocked and the catalytic sites are disassembled. Mutations that restore function map to regions of conformational change upon activation, suggesting that these mutations may increase DNA affinity by altering the energetic balance between inactive and active states. Our results show that there are extensive opportunities for evolution to improve catalytic efficiency when an inactive intermediate is involved.


Assuntos
Adenosina Trifosfatases , Replicação do DNA , Adenosina Trifosfatases/metabolismo , Microscopia Crioeletrônica , DNA , ATPases Associadas a Diversas Atividades Celulares/metabolismo , Mutagênese , Trifosfato de Adenosina/metabolismo
15.
J Med Virol ; 85(3): 493-500, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23341371

RESUMO

This study investigated the effects of allitridin compound on murine cytomegalovirus (MCMV)-induced regulatory T cell (Treg; CD4(+) CD25(+) Foxp3(+) ) amplification in vivo and in vitro. One hundred twenty MCMV-infected mice were allocated at random into two groups for treatment with allitridin or placebo. Another 120 mock-infected mice were randomly allocated as controls for the allitridin treatment and placebo treatment groups. The mice were euthanized at various time points after infection (out to 120 days) to evaluate the effects of treatment on Treg presence and function, as well as MCMV infective load. Co-culture with mouse embryo fibroblasts (MEF) and MCMV was performed to evaluate allitridin-mediated Treg and anti-CMV effects. The maximum tolerance concentration (MTC) of allitridin was used to treat cells for 3 days. Changes in Foxp3 mRNA and protein levels, percentages of T cell subsets, and Treg-related cytokines (IL-10 and TGF-ß) were measured. Allitridin treatment did not influence Foxp3 expression and Treg proportion in uninfected mice, but did down-regulate each in infected mice during the chronic infection period. Additionally, allitridin treatment reduced the MCMV load in salivary glands. MTC allitridin treatment of co-cultures partially blocked MCMV induction of Foxp3 mRNA and protein expression. In vitro treatment with allitridin also increased significantly the percentages of Tc1, Tc2, and Th1, reduced the secreted levels of IL-10 and TGF-ß1, and significantly suppressed viral loads. In conclusion, allitridin can promote MCMV-induced Treg expansion and Treg-mediated anti-MCMV immunosuppression. Therefore, allitridin may be useful as a therapeutic agent to enhance the specific cellular immune responses against CMV.


Assuntos
Compostos Alílicos/administração & dosagem , Infecções por Herpesviridae/imunologia , Fatores Imunológicos/administração & dosagem , Muromegalovirus/imunologia , Sulfetos/administração & dosagem , Linfócitos T Reguladores/efeitos dos fármacos , Compostos Alílicos/isolamento & purificação , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Fatores de Transcrição Forkhead/biossíntese , Alho/química , Perfilação da Expressão Gênica , Fatores Imunológicos/isolamento & purificação , Camundongos , Camundongos Endogâmicos BALB C , Placebos/administração & dosagem , Sulfetos/isolamento & purificação , Subpopulações de Linfócitos T/imunologia , Carga Viral
16.
Transl Pediatr ; 12(6): 1278-1287, 2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37427056

RESUMO

Background: The neurite extension and migration factor (NEXMIF) gene encodes the neurite growth-directed factor whose main function is to play a role in neurite extension and migration for nerve development. It is associated with X-linked intellectual disability 98 and X-linked dominant inheritance, and its clinical manifestations mainly include intellectual disability, autistic behavior, poor development, dysmorphic features, gastroesophageal reflux, renal infection, and early seizures. Few cases of patients with NEXMIF variants had been reported, and to date, no deaths have been reported to our knowledge. Case Description: We present a clinical report of a female child who had a history of epilepsy, and was diagnosed with multiple organ failure (MOF), sepsis, hemophagocytic lymphohistiocytosis, severe pneumonia, and pulmonary hemorrhaging. Genetic testing identified the NEXMIF variant c.937C>T (p.R313*) in this patient. Despite aggressive treatment with anti-inflammation drugs with methylprednisolone, plasma exchange, hemodialysis and mechanical ventilation, the patient died. Conclusions: We reported the first case of the NEXMIF variant in a patient with the symptom of MOF, including acute liver failure and acute kidney injury (Grade 3). In addition, some complications, such as sepsis, hemophagocytic syndrome, pneumonia, and pulmonary hemorrhage, can also occur with this disease. All of these complications may have contributed to the patient's death. This report not only broadens the phenotype for NEXMIF variants but may also help physicians involved in the care of patients with this syndrome and enhance their understanding of this variant.

17.
Front Oncol ; 13: 1134723, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37361602

RESUMO

Background: Anastomotic leakage (AL) is the most serious complication that can arise during colorectal surgery. Indocyanine green (ICG) angiography offers an intraoperative assessment of colonic vascular perfusion in real time. We aimed to assess ICG's effects on the AL rate in patients who have undergone transanal total mesorectal excision (TaTME) for rectal cancer. Methods: This retrospective cohort study was conducted at our center from October 2018 to March 2022 to analyze the clinical data of patients with rectal cancer who have undergone TaTME after propensity score matching (PSM). The primary outcome was the proximal colonic transection line modification and clinical AL rate. Results: A total of 143 patients in the non-ICG group and 143 patients in the ICG group were included after PSM. The proximal colonic transection line of seven patients in the non-ICG group was modified, while 18 were in the ICG group (4.9% vs. 12.5%, p = 0.023). Twenty-three patients (16.1%) in the non-ICG group and five patients (3.5%) in the ICG group were diagnosed with AL (p < 0.001). The ICG group had a less hospital readmission rate than the non-ICG group (0.7% vs. 7.7%, p = 0.003). The between-group differences in basic line and other outcomes were not significant. Conclusions: ICG angiography is a safe and feasible method to help surgeons identify potentially poor colonic vascular perfusion and modify the proximal colonic transection line, resulting in a significant reduction in AL and hospital readmission rates.

18.
Front Plant Sci ; 14: 1125324, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37123824

RESUMO

Global warming causes great thermal stress to macroalgae and those species that can adapt to it are thought to be better able to cope with warmer oceans. Gracilaria bailinae, a macroalgae with high economic and ecological values, can survive through the hot summer in the South China Sea, but the molecular mechanisms underlying its adaptation to high temperatures are unclear. To address this issue, the present study analyzed the growth and transcriptome of G. bailinae after a 7-day exposure to 15°C (LT: low temperature), 25°C (MT: middle temperature), and 35°C (HT: high temperature). Growth analysis showed that the HT group had the highest relative growth rate (RGR = 2.1%) with the maximum photochemical quantum yield of PSII (F v/F m = 0.62) remaining within the normal range. Transcriptome analysis showed more differentially expressed genes (DEGs) in the comparison between MT and HT groups than in that between MT and LT, and most of these DEGs tended to be downregulated at higher temperatures. The KEGG pathway enrichment analysis showed that the DEGs were mainly enriched in the carbohydrate, energy, and lipid metabolisms. In addition, the genes involved in NADPH and ATP synthesis, which are associated with photosynthesis, the Calvin cycle, pyruvate metabolism, and the citrate cycle, were downregulated. Downregulation was also observed in genes that encode enzymes involved in fatty acid desaturation and alpha-linolenic acid metabolism. In summary, G. bailinae regulated the synthesis of NADPH and ATP, which are involved in the above-mentioned processes, to reduce unnecessary energy consumption, and limited the synthesis of enzymes in the metabolism of unsaturated fatty acids and alpha-linolenic acid to adapt to high environmental temperatures. The results of this study improve our understanding of the molecular mechanisms underlying the adaptation of G. bailinae to high temperatures.

19.
Int J Mach Learn Cybern ; : 1-16, 2022 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-36212087

RESUMO

The pressure prediction technology whereby represents the rock pressure law in the excavation is fundamental to safety in production and industrial intelligentization. A growing number of researchers dedicate that machine learning is used to accurate prediction of underground pressure changes. However, the existing research which based on the classical machine learning rarely considers the cause between inducement of underground pressure and the underground pressure change. In this paper, we propose a novel Reinforced and Causal Graph Neural Network, namely RC-GNN, for the prediction task, to overcome the shortage of causal logic. First, we build a causal graph by considering internal relations between inducement and display of pressure and employ prior knowledge to erect the early and properties of the graph. Second, we construct the prediction network for underground pressure by graph convolutional networks and long short-term memory. Finally, we use the performance index of underground pressure prediction to design a reinforcement learning algorithm, which achieves optimization of the causal graph. Compared to six representative methods, experimental results with 18-60% increases in performance on the real prediction task.

20.
J Huazhong Univ Sci Technolog Med Sci ; 31(3): 285-289, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21671165

RESUMO

Murine cytomegalovirus (MCMV) IE3 protein is a multifunctional viral protein that interacts with several target proteins of both viral and host cellular origin. To investigate the biological function of IE3 in the pathogenesis of the brain disorders caused by CMV, a screening for host cellular proteins that could interact with IE3 was performed. By yeast two-hybrid screening, ankyrin repeats domain 17 (Ankrd17, also known as Gtar) was identified as a host factor that could interact with IE3. This interaction was verified by yeast two-hybrid assay and chemiluminescent co-immunoprecipitaion. Mapping analysis suggested that the 1-148 residues of IE3 were responsible for the interaction. These results suggested that the interaction between Ankrd17 and IE3 may play a key role in the pathogenesis of MCMV-associated disease.


Assuntos
Infecções por Herpesviridae/virologia , Proteínas Imediatamente Precoces/metabolismo , Muromegalovirus/metabolismo , Proteínas de Ligação a RNA/metabolismo , Animais , Encefalopatias/virologia , Células HEK293 , Infecções por Herpesviridae/metabolismo , Humanos , Proteínas Imediatamente Precoces/genética , Medições Luminescentes , Camundongos , Muromegalovirus/patogenicidade , Proteínas de Ligação a RNA/genética , Técnicas do Sistema de Duplo-Híbrido
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