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1.
Proc Natl Acad Sci U S A ; 121(10): e2317026121, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38408250

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been detected in almost all organs of coronavirus disease-19 patients, although some organs do not express angiotensin-converting enzyme-2 (ACE2), a known receptor of SARS-CoV-2, implying the presence of alternative receptors and/or co-receptors. Here, we show that the ubiquitously distributed human transferrin receptor (TfR), which binds to diferric transferrin to traffic between membrane and endosome for the iron delivery cycle, can ACE2-independently mediate SARS-CoV-2 infection. Human, not mouse TfR, interacts with Spike protein with a high affinity (KD ~2.95 nM) to mediate SARS-CoV-2 endocytosis. TfR knock-down (TfR-deficiency is lethal) and overexpression inhibit and promote SARS-CoV-2 infection, respectively. Humanized TfR expression enables SARS-CoV-2 infection in baby hamster kidney cells and C57 mice, which are known to be insusceptible to the virus infection. Soluble TfR, Tf, designed peptides blocking TfR-Spike interaction and anti-TfR antibody show significant anti-COVID-19 effects in cell and monkey models. Collectively, this report indicates that TfR is a receptor/co-receptor of SARS-CoV-2 mediating SARS-CoV-2 entry and infectivity by likely using the TfR trafficking pathway.


Assuntos
COVID-19 , Animais , Humanos , Camundongos , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/metabolismo , Peptidil Dipeptidase A/metabolismo , Ligação Proteica , Receptores da Transferrina/genética , Receptores da Transferrina/metabolismo , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo
2.
Proc Natl Acad Sci U S A ; 119(10): e2110647119, 2022 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-35238649

RESUMO

SignificanceAn immunosuppressant protein (MTX), which facilitates virus infection by inhibiting leukotriene A4 hydrolase (LTA4H) to produce the lipid chemoattractant leukotriene B4 (LTB4), was identified and characterized from the submandibular salivary glands of the bat Myotis pilosus. To the best of our knowledge, this is a report of an endogenous LTA4H inhibitor in animals. MTX was highly concentrated in the bat salivary glands, suggesting a mechanism for the generation of immunological privilege and immune tolerance and providing evidence of viral shedding through oral secretions. Moreover, given that the immunosuppressant MTX selectively inhibited the proinflammatory activity of LTA4H, without affecting its antiinflammatory activity, MTX might be a potential candidate for the development of antiinflammatory drugs by targeting the LTA4-LTA4H-LTB4 inflammatory axis.


Assuntos
Inibidores Enzimáticos/metabolismo , Epóxido Hidrolases , Vírus da Influenza A Subtipo H1N1/metabolismo , Leucotrieno A4/metabolismo , Infecções por Orthomyxoviridae/enzimologia , Glândulas Salivares , Proteínas e Peptídeos Salivares/metabolismo , Viroses , Animais , Quirópteros , Epóxido Hidrolases/antagonistas & inibidores , Epóxido Hidrolases/metabolismo , Camundongos , Glândulas Salivares/enzimologia , Glândulas Salivares/virologia
3.
Biochem Biophys Res Commun ; 692: 149359, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38071893

RESUMO

BACKGROUND: Ferroptosis plays an important role in acute kidney injury (AKI), but the specific regulatory mechanism of ferroptosis in AKI remains unclear. This study is expected to analyze ferroptosis-related genes (FRGs) in AKI and explore their underlying mechanisms. RESULTS: A total of 479 differentially expressed genes (DEGs), including 196 up-regulated genes and 283 down-regulated genes were identified in the AKI chip GSE30718. 341 FRGs were obtained from the Genecard, OMIM and NCBI database. Totally 11 ferroptosis-related DEGs in AKI were found, in which 7 genes (CD44, TIGAR, RB1, LCN2, JUN, ARNTL, ACSL4) were up-regulated and 4 genes (FZD7, EP300, FOXC1, DLST) were down-regulated. Three core genes (FZD7, JUN, EP300) were obtained by PPI and KEGG analysis, among which the function of FZD7 in AKI is unclear. The WGCNA analysis found that FZD7 belongs to a module that was negatively correlated with AKI. Further basic experiments confirmed that FZD7 is down-regulated in mouse model of ischemia-reperfusion-AKI and cellular model of hypoxia-reoxygenation(H/R). In addition, knockdown of FZD7 could further aggravate the down-regulation of cell viability induced by H/R and Erastin, while overexpression of FZD7 can rescue its down-regulation to some extent. Furthermore, we verified that knockdown of FZD7 decreased the expression of GPX4 and overexpression of FZD7 increased the expression of GPX4, suggesting that FZD7 may inhibit ferroptosis by regulating the expression of GPX4 and plays a vital role in the onset and development of AKI. CONCLUSIONS: This article revealed the anti-ferroptosis effect of FZD7 in acute kidney injury through bioinformatics analysis and experimental validation, suggesting that FZD7 is a promising target for AKI and provided more evidence about the vital role of ferroptosis in AKI.


Assuntos
Injúria Renal Aguda , Ferroptose , Animais , Camundongos , Injúria Renal Aguda/genética , Proteínas Reguladoras de Apoptose , Sobrevivência Celular , Biologia Computacional , Bases de Dados Factuais , Ferroptose/genética , Monoéster Fosfórico Hidrolases
4.
Blood ; 140(19): 2063-2075, 2022 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-36040436

RESUMO

Studies have shown significantly increased thromboembolic events at high altitude. We recently reported that transferrin could potentiate blood coagulation, but the underlying mechanism for high altitude-related thromboembolism is still poorly understood. Here, we examined the activity and concentration of plasma coagulation factors and transferrin in plasma collected from long-term human residents and short-stay mice exposed to varying altitudes. We found that the activities of thrombin and factor XIIa (FXIIa) along with the concentrations of transferrin were significantly increased in the plasma of humans and mice at high altitudes. Furthermore, both hypoxia (6% O2) and low temperature (0°C), 2 critical high-altitude factors, enhanced hypoxia-inducible factor 1α (HIF-1α) levels to promote the expression of the transferrin gene, whose enhancer region contains HIF-1α binding site, and consequently, to induce hypercoagulability by potentiating thrombin and FXIIa. Importantly, thromboembolic disorders and pathological insults in mouse models induced by both hypoxia and low temperature were ameliorated by transferrin interferences, including transferrin antibody treatment, transferrin downregulation, and the administration of our designed peptides that inhibit the potentiation of transferrin on thrombin and FXIIa. Thus, low temperature and hypoxia upregulated transferrin expression-promoted hypercoagulability. Our data suggest that targeting the transferrin-coagulation pathway is a novel and potentially powerful strategy against thromboembolic events caused by harmful environmental factors under high-altitude conditions.


Assuntos
Altitude , Trombofilia , Camundongos , Humanos , Animais , Transferrina/genética , Trombina/metabolismo , Temperatura , Hipóxia/metabolismo , Trombofilia/etiologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo
5.
Lupus ; 33(2): 172-175, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38081170

RESUMO

As a therapeutic treatment for systemic lupus erythematosus (SLE), Belimumab reduces disease relapses and minimizes organ damage. Clinical practice, however, shows that the treatment is ineffective for a number of patients. Treatments for such cases are still lacking. As a biologic agent that targets both BLys and APRIL, Telitacicept inhibits both B cells and plasma cells. This case report describes a 35-year-old female with lupus nephritis (LN) who had previously undergone 10 cycles of Belimumab treatment but remained poorly controlled. Despite this, her condition improved significantly after switching to Telitacicept. This is the first report on the efficacy of Telitacicept in an SLE patient with suboptimal response to Belimumab. Telitacicept's role in this scenario needs more investigation and attention.


Assuntos
Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Proteínas Recombinantes de Fusão , Humanos , Feminino , Adulto , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Resultado do Tratamento , Imunossupressores/uso terapêutico
6.
Int J Mol Sci ; 25(18)2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39337525

RESUMO

Weaning is one of the most challenging phases for piglets, and it is also the time when piglets are the most susceptible to diarrhea, which may result in significant economic losses for pig production. One of the dietary strategies for reducing post-weaning diarrhea (PWD) in piglets is to provide them with a pharmacological dose of zinc oxide (ZnO). However, excessive or long-term usage of high-dose ZnO has significant impacts on pig health and the ecological environment. Therefore, caution should be exercised when considering the use of high-dose ZnO for the prevention or treatment of PWD in piglets. In this paper, the significant role of zinc in animal health, the potential mode of action of ZnO in alleviating diarrhea, and the impact of innovative, highly efficient ZnO alternatives on the regulation of piglet diarrhea were reviewed to offer insights into the application of novel ZnO in pig production.


Assuntos
Diarreia , Doenças dos Suínos , Desmame , Óxido de Zinco , Animais , Óxido de Zinco/farmacologia , Diarreia/tratamento farmacológico , Diarreia/metabolismo , Diarreia/veterinária , Suínos , Doenças dos Suínos/tratamento farmacológico , Doenças dos Suínos/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Função da Barreira Intestinal
7.
Cell Mol Life Sci ; 79(1): 35, 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34989866

RESUMO

Multiple representatives of eulipotyphlan mammals such as shrews have oral venom systems. Venom facilitates shrews to hunt and/or hoard preys. However, little is known about their venom composition, and especially the mechanism to hoard prey in comatose states for meeting their extremely high metabolic rates. A toxin (BQTX) was identified from venomous submaxillary glands of the shrew Blarinella quadraticauda. BQTX is specifically distributed and highly concentrated (~ 1% total protein) in the organs. BQTX shares structural and functional similarities to toxins from snakes, wasps and snails, suggesting an evolutional relevancy of venoms from mammalians and non-mammalians. By potentiating thrombin and factor-XIIa and inhibiting plasmin, BQTX induces acute hypertension, blood coagulation and hypokinesia. It also shows strong analgesic function by inhibiting elastase. Notably, the toxin keeps high plasma stability with a 16-h half-life in-vivo, which likely extends intoxication to paralyze or immobilize prey hoarded fresh for later consumption and maximize foraging profit.


Assuntos
Analgesia/métodos , Hipocinesia/fisiopatologia , Musaranhos/metabolismo , Toxinas Biológicas/metabolismo , Peçonhas/metabolismo , Adulto , Sequência de Aminoácidos , Animais , Sequência de Bases , Pressão Sanguínea/efeitos dos fármacos , Feminino , Membro Posterior/efeitos dos fármacos , Membro Posterior/fisiopatologia , Humanos , Macaca mulatta , Masculino , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Dor/induzido quimicamente , Dor/fisiopatologia , Dor/prevenção & controle , Homologia de Sequência de Aminoácidos , Musaranhos/genética , Trombina/antagonistas & inibidores , Trombina/metabolismo , Toxinas Biológicas/administração & dosagem , Toxinas Biológicas/genética , Peçonhas/genética
8.
Circ Res ; 127(5): 651-663, 2020 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-32450779

RESUMO

RATIONALE: Epidemiological studies have identified an associate between iron deficiency (ID) and the use of oral contraceptives (CC) and ischemic stroke (IS). To date, however, the underlying mechanism remains poorly understood. Both ID and CC have been demonstrated to upregulate the level and iron-binding ability of Tf (transferrin), with our recent study showing that this upregulation can induce hypercoagulability by potentiating FXIIa/thrombin and blocking antithrombin-coagulation proteases interactions. OBJECTIVE: To investigate whether Tf mediates IS associated with ID or CC and the underlying mechanisms. METHODS AND RESULTS: Tf levels were assayed in the plasma of IS patients with a history of ID anemia, ID anemia patients, venous thromboembolism patients using CC, and ID mice, and in the cerebrospinal fluid of some IS patients. Effects of ID and estrogen administration on Tf expression and coagulability and the underlying mechanisms were studied in vivo and in vitro. High levels of Tf and Tf-thrombin/FXIIa complexes were found in patients and ID mice. Both ID and estrogen upregulated Tf through hypoxia and estrogen response elements located in the Tf gene enhancer and promoter regions, respectively. In addition, ID, administration of exogenous Tf or estrogen, and Tf overexpression promoted platelet-based thrombin generation and hypercoagulability and thus aggravated IS. In contrast, anti-Tf antibodies, Tf knockdown, and peptide inhibitors of Tf-thrombin/FXIIa interaction exerted anti-IS effects in vivo. CONCLUSIONS: Our findings revealed that certain factors (ie, ID and CC) upregulating Tf are risk factors of thromboembolic diseases decipher a previously unrecognized mechanistic association among ID, CC, and IS and provide a novel strategy for the development of anti-IS medicine by interfering with Tf-thrombin/FXIIa interactions.


Assuntos
Anemia Ferropriva/complicações , Coagulação Sanguínea , Anticoncepcionais Orais Hormonais/efeitos adversos , Estrogênios/toxicidade , AVC Isquêmico/etiologia , Trombofilia/etiologia , Transferrina/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia Ferropriva/sangue , Anemia Ferropriva/diagnóstico , Animais , Biomarcadores/sangue , Estudos de Casos e Controles , Linhagem Celular , Modelos Animais de Doenças , Fator XIIa/metabolismo , Feminino , Humanos , AVC Isquêmico/sangue , AVC Isquêmico/diagnóstico , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Trombina/metabolismo , Trombofilia/sangue , Trombofilia/diagnóstico , Regulação para Cima , Adulto Jovem
9.
J Craniofac Surg ; 33(5): e476-e481, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34775442

RESUMO

BACKGROUND: For completely impacted teeth, it is of great significance to locate teeth accurately, preserve hard tissue and recovering the height of alveolar ridge. This can be effectively solved by the digital three-dimensional printing guide technology. METHODS: Ten patients with completely impacted tooth were selected in this experiment. After cone-beam computed tomography scan, the dicom formal computed tomography data was analyzed for threedimensional reconstruction by mimics 17.0 software. Then determining the surgical plan and making surgical guide plate. Threedimensional printing guide plate assisted piezosurgery was used to remove bone and extract impacted teeth. After that, the removed bone cap was back to the original position. Cone-beam computed tomography was used for each operated patients after 1 week and 6 months. RESULT: The surgical guide plates can locate teeth accurately and the surgery time was reduced for all patients. A week later, all patients healed well and removed the stitches on time. Cone-beam computed tomography showed that the retention of bone caps was good and there was no displacement. All patients showed a normal parameter of pain. Six months later, cone-beam computed tomography showed good bone formation in the extraction area, which filled with new bones completely. The recovery of bone outline and height of alveolar crest at the surgical site were basically consistent with those before the operation. CONCLUSIONS: Three-dimensional printing guide plates combining with fenestration and bone-cap restoration can locate impacted teeth accurately, reduce the extraction volume of bone, shorten surgery time, and alleviate complications. This was conducive to preserve and restore hard tissue and had great prospective.


Assuntos
Perda do Osso Alveolar , Dente Impactado , Processo Alveolar/diagnóstico por imagem , Processo Alveolar/cirurgia , Tomografia Computadorizada de Feixe Cônico/métodos , Humanos , Impressão Tridimensional , Estudos Prospectivos , Preservação de Tecido , Extração Dentária
10.
J Pathol ; 247(2): 266-278, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30357833

RESUMO

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) deficiency in primary human glioblastoma (GBM) is associated with increased invasiveness and poor prognosis with unknown mechanisms. Therefore, how loss of PTEN promotes GBM progression remains to be elucidated. Herein, we identified that ADP-ribosylation factor like-4C (ARL4C) was highly expressed in PTEN-deficient human GBM cells and tissues. Mechanistically, loss of PTEN stabilized ARL4C protein due to AKT/mTOR pathway-mediated inhibition of ARL4C ubiquitination. Functionally, ARL4C enhanced the progression of GBM cells in vitro and in vivo. Moreover, microarray profiling and GST pull-down assay identified that ARL4C accelerated tumor progression via RAC1-mediated filopodium formation. Importantly, targeting PTEN potently inhibited GBM tumor progression in vitro and in vivo, whereas overexpression of ARL4C reversed the tumor progression impaired by PTEN overexpression. Clinically, analyses with patients' specimens validated a negative correlation between PTEN and ARL4C expression. Elevated ARL4C expression but PTEN deficiency in tumor was associated with poorer disease-free survival and overall survival of GBM patients. Taken together, ARL4C is critical for PTEN-deficient GBM progression and acts as a novel prognostic biomarker and a potential therapeutic candidate. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Assuntos
Fatores de Ribosilação do ADP/metabolismo , Neoplasias Encefálicas/enzimologia , Glioblastoma/enzimologia , PTEN Fosfo-Hidrolase/deficiência , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Fatores de Ribosilação do ADP/genética , Animais , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/terapia , Movimento Celular , Proliferação de Células , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Glioblastoma/genética , Glioblastoma/patologia , Humanos , Camundongos Endogâmicos NOD , Camundongos SCID , Invasividade Neoplásica , PTEN Fosfo-Hidrolase/genética , Estabilidade Proteica , Pseudópodes/enzimologia , Pseudópodes/genética , Pseudópodes/patologia , Transdução de Sinais , Células Tumorais Cultivadas , Ubiquitinação , Proteínas rac1 de Ligação ao GTP/genética , Proteínas rac1 de Ligação ao GTP/metabolismo
11.
Lab Invest ; 99(2): 191-199, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30291323

RESUMO

Invasion and subsequent metastasis are major characteristics of malignant human renal cell carcinoma (RCC), though the mechanisms remain elusive. Mitochondrial pyruvate carrier (MPC), a key factor that controls pyruvate transportation in mitochondria, is frequently dysregulated in tumor cells and loss of MPC predicts poor prognosis in various types of cancer. However, the clinical relevance and functional significance of MPC in RCC remain to be elucidated. In this study, we investigated the expression of MPC1 and MPC2 in specimens from RCC patients and observed downregulation of MPC1, but not MPC2, in RCC tissues compared with adjacent non-cancerous tissue. Moreover, RCC patients with higher MPC1 expression exhibited longer overall survival rate than those with lower MPC1. Functionally, MPC1 suppressed the invasion of RCC cells in vitro and reduced the growth of RCC cells in vivo, possibly through inhibition of MMP7 and MMP9. Further studies revealed that loss of MPC1 was induced by hypoxia in RCC cells, and notably, MPC1 expression, was negatively correlated with HIF1α expression in RCC cells and patient samples. Taken together, our results identify anti-tumor function of MPC1 in RCC and revealed MPC1 as a novel prognostic biomarker to predict better patient survival.


Assuntos
Carcinoma de Células Renais/metabolismo , Neoplasias Renais/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Animais , Carcinoma de Células Renais/diagnóstico , Hipóxia Celular , Linhagem Celular , Feminino , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Rim/metabolismo , Neoplasias Renais/diagnóstico , Metaloproteinases da Matriz/análise , Metaloproteinases da Matriz/metabolismo , Camundongos , Camundongos SCID , Proteínas de Transporte da Membrana Mitocondrial/análise , Transportadores de Ácidos Monocarboxílicos , Neoplasias Experimentais , Prognóstico
12.
J Craniofac Surg ; 30(2): e127-e131, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30531282

RESUMO

The reconstruction of orbital-maxillary-zygomatic complex (OMZC) on patients suffering from trauma and space-occupying lesions is challenging due to the irregularity of craniomaxillofacial bones. To overcome the challenge in precise OMZC reconstruction, individual three-dimensional (3D) disease models and mirror-imaged 3D reconstruction models were printed on the basis of the computer tomography. Preoperative planning by rehearsing surgical procedures was made on the 3D disease models and the scaffolds including titanium and absorbable meshes or plates were anatomically premolded using the mirror-imaged 3D models as guide. Many benefits were achieved including more precise OMZC reconstruction, fluent and smooth procedures of surgeries, shorter operation time, less blood loss, and improved cosmetic outcomes of craniomaxillofacial shapes. There were no complications such as diplopia, infection, foreign body reaction, exophthalmos, enophthalmos, disordered occlusal relationship, and hematoma. And patients were satisfied with the functional and esthetic outcome during the following-up time. Therefore, OMZC reconstruction can be optimized and successful through preoperative planning and premolded scaffolds with 3D printing bone model by computer-aid design and manufacturing.


Assuntos
Doenças Orbitárias/cirurgia , Fraturas Orbitárias/cirurgia , Modelagem Computacional Específica para o Paciente , Procedimentos de Cirurgia Plástica , Hemorragia Pós-Operatória/prevenção & controle , Impressão Tridimensional , Adulto , China , Feminino , Humanos , Masculino , Maxila/diagnóstico por imagem , Maxila/cirurgia , Órbita/diagnóstico por imagem , Órbita/cirurgia , Planejamento de Assistência ao Paciente , Procedimentos de Cirurgia Plástica/efeitos adversos , Procedimentos de Cirurgia Plástica/métodos , Tomografia Computadorizada por Raios X/efeitos adversos , Zigoma/diagnóstico por imagem , Zigoma/cirurgia
13.
Int J Mol Sci ; 19(3)2018 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-29538305

RESUMO

The epidermal growth factor (EGF) has been widely used for protection of stress-induced intestinal mucosa dysfunction. However, whether EGF would alleviate oxidative injury and reduce apoptosis in porcine intestine is not yet known. Therefore, the aim of this study was to investigate the effect of EGF on lipopolysaccharides (LPS)-induced induction of oxidative stress and ensuing apoptosis in the porcine intestinal epithelial cell line, IPEC-J2. The present study showed that EGF significantly increased cell viability and decreased the LPS-induced induction of apoptosis, dehydrogenase (LDH) release and malonaldehyde (MDA) production. EGF also (i) decreased expression of the pro-apoptotic genes Fas, Bax, Cascase-3, Cascase-8, Cascase-9, and proteins such as P53, Fas, Bax, Caspase3; (ii) increased antiapoptotic protein B-cell lymphoma 2 (Bcl2) expression; (iii) increased mRNA levels of the nuclear factor erythroid 2-related factor 2 (Nrf2) related genes Nrf2, manganese superoxide dismutase (SOD2), catalase (CAT), glutathione peroxidase (GSH-Px), heme oxygenase (HO-1) and quinone oxidoreductase (NQO1); (iv) protein level of Nrf2-realeted proteins Nrf2, HO-1, NQO1; and (v) total antioxidant capacity (T-AOC), CAT, SOD, GSH-Px concentrations. Collectively, our results indicated that EGF enhanced Nrf2 protein expression, and upregulated the expression of phase II metabolizing enzymes (such as HO-1 and NQO1) and antioxidative enzymes (SOD, CAT and GSH-Px) to alleviate oxidative injury, and then protect IPEC-J2 cells from apoptosis induced by LPS.


Assuntos
Antioxidantes/farmacologia , Apoptose , Enterócitos/metabolismo , Fator de Crescimento Epidérmico/farmacologia , Estresse Oxidativo , Animais , Linhagem Celular , Enterócitos/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Suínos
14.
Hepatology ; 62(6): 1731-41, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26095812

RESUMO

UNLABELLED: Hepatic copper determination is an important test for the diagnosis of Wilson's disease (WD). However, the method has not been standardized, the diagnostic accuracy has not been evaluated prospectively, and the optimal cut-off value remains controversial. Accordingly, we aimed to prospectively evaluate the diagnostic accuracy of hepatic copper content, as determined using the entire core of a liver biopsy sample. Patients for whom a liver biopsy was indicated were consecutively enrolled. Hepatic copper content was determined with atomic absorption spectroscopy. All assays were performed using careful quality control by a single technician. WD diagnosis was based on WD score or its combination with clinical follow-up results. A total of 3,350 consecutive patients underwent liver biopsy. Six hundred ninety-one patients, including 178 with WD, underwent two passes of liver biopsy with hepatic copper determination. Mean hepatic content in WD patients was 770.6 ± 393.2 µg/g dry weight (wt). Sensitivity, specificity, and positive and negative predictive values of hepatic copper content for WD diagnosis in the absence of primary biliary cirrhosis (PBC) or primary sclerosing cholangitis at the cut-off value of 250 µg/g dry wt. were 94.4%, 96.8%, 91.8%, and 97.8%, respectively. The most useful cut-off value was 209 µg/g dry wt, with a sensitivity and specificity of 99.4% and 96.1%, respectively. A total of 23.3% of patients without WD and PBC had hepatic copper content >75 µg/g dry wt. CONCLUSION: A liver biopsy sample of more than 1 mg dry wt may reliably reflect hepatic copper content and should be used for hepatic copper determination. Hepatic copper determination is a very valid procedure for the diagnosis of WD, and the most useful cut-off value is 209 µg/g dry wt.


Assuntos
Cobre/análise , Degeneração Hepatolenticular/patologia , Fígado/química , Fígado/patologia , Adolescente , Adulto , Biópsia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Prospectivos , Reprodutibilidade dos Testes , Adulto Jovem
15.
Mediators Inflamm ; 2016: 1927348, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27524860

RESUMO

Epidermal growth factor (EGF) is a 53-amino acid peptide that plays an important role in regulating cell growth, survival, migration, apoptosis, proliferation, and differentiation. In addition, EGF has been established to be an effective intestinal regulator helping to protect intestinal barrier integrity, which was essential for the absorption of nutrients and health in humans and animals. Several researches have demonstrated that EGF via binding to the EGF receptor and subsequent activation of Ras/MAPK, PI3K/AKT, PLC-γ/PKC, and STATS signal pathways regulates intestinal barrier function. In this review, the relationship between epidermal growth factor and intestinal development and intestinal barrier is described, to provide a better understanding of the effects of EGF on intestine development and health.


Assuntos
Fator de Crescimento Epidérmico/metabolismo , Mucosa Intestinal/metabolismo , Animais , Receptores ErbB/metabolismo , Humanos , Fatores de Transcrição STAT/metabolismo , Transdução de Sinais/fisiologia
16.
J Craniofac Surg ; 26(3): 700-5, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25915672

RESUMO

OBJECTIVE: To investigate the clinical immediate load at an angle after immediate placement of the implant. METHODS: Select 4 adult dogs; through establishing the angle loading animal experiment model, perform lateral loading on 32 implants respectively at vertical and 0°, 10°, and 20°, with which as a basis for grouping, determine the osseointegration index and new bone growth rate; and observe the peri-implant bone remodeling conditions. RESULTS: The 20° group is found with the most obvious bone absorption, and compared with other groups, its osseointegration index and new bone growth rate are statistically significant (P < 0.01); bone remodeling under 0° load stress is the best, with the formation of new bone and the highest bone contact ratio, which is the most reasonable under this the stress distribution compared with other angles. CONCLUSIONS: The implant stress distribution at 0° against the occlusal force direction is closer to physiologic optimum stress on the implant bone interface, and it is permitted for the long axis of the immediately implanted and immediately loaded implant to be tilted within about 10° against the load angle.


Assuntos
Implantes Dentários , Análise do Estresse Dentário/métodos , Osseointegração/fisiologia , Animais , Força de Mordida , Implantação Dentária Endóssea , Cães , Feminino , Masculino
17.
Animals (Basel) ; 14(7)2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38612308

RESUMO

China, as the global leader in pork production and consumption, is faced with challenges in ensuring sustainable and wholesome growth of the pig industry while also guaranteeing meat food safety amidst the ban on antibiotics usage in animal feed. The focus of the pig industry lies in guaranteeing piglet health and enhancing overall production performance through nutrition regulation. Clostridium butyricum (C. butyricum), a new type of probiotic, possesses characteristics such as heat resistance, acid resistance, and bile-salt tolerance, meaning it has potential as a feed additive. Previous studies have demonstrated that C. butyricum has a probiotic effect on piglets and can serve as a substitute for antibiotics. The objective of this study was to review the probiotic role of C. butyricum in the production of piglets, specifically focusing on intestinal barrier function. Through this review, we explored the probiotic effects of C. butyricum on piglets from the perspective of intestinal health. That is, C. butyricum promotes intestinal health by regulating the functions of the mechanical barrier, chemical barrier, immune barrier, and microbial barrier of piglets, thereby improving the growth of piglets. This review can provide a reference for the rational utilization and application of C. butyricum in swine production.

18.
J Anim Sci ; 1022024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38619320

RESUMO

The present study aimed to investigate the effects of deoxynivalenol (DON) stimulation on inflammatory injury and the expression of the glucose transporters sodium-dependent glucose transporter 1 (SGLT1) and glucose transporter protein 2 (GLU2) in porcine small intestinal epithelial cells (IPEC-J2). Additionally, the study aimed to provide initial insights into the connection between the expression of glucose transporters and the inflammatory injury of IPEC-J2 cells. DON concentration and DON treatment time were determined using the CCK­8 assay. Accordingly, 1.0 µg/mL DON and treatment for 24 h were chosen for subsequent experiments. Then IPEC-J2 cells were treated without DON (CON, N = 6) or with 1 µg/mL DON (DON, N = 6). Lactate dehydrogenase (LDH) content, apoptosis rate, and proinflammatory cytokines including interleukin (IL)-1ß, Il-6, and tumor necrosis factor α (TNF-α) were measured. Additionally, the expression of AMP-activated protein kinase α1 (AMPK-α1), the content of glucose, intestinal alkaline phosphatase (AKP), and sodium/potassium-transporting adenosine triphosphatase (Na+/K+-ATPase) activity, and the expression of SGLT1 and GLU2 of IPEC-J2 cells were also analyzed. The results showed that DON exposure significantly increased LDH release and apoptosis rate of IPEC-J2 cells. Stimulation with DON resulted in significant cellular inflammatory damage, as evidenced by a significant increase in proinflammatory cytokines (IL-1ß, IL-6, and TNF-α). Additionally, DON caused damage to the glucose absorption capacity of IPEC-J2 cells, indicated by decreased levels of glucose content, AKP activity, Na+/K+-ATPase activity, AMPK-α1 protein expression, and SGLT1 expression. Correlation analysis revealed that glucose absorption capacity was negatively correlated with cell inflammatory cytokines. Based on the findings of this study, it can be preliminarily concluded that the cell inflammatory damage caused by DON may be associated with decreased glucose absorption.


Glucose is one of the most basic nutrients necessary to sustain animal life and plays a crucial role in animal body composition and energy metabolism. Previous studies suggested a link between glucose absorption and inflammatory injury. In the present study, deoxynivalenol (DON) stimulation caused severe inflammatory injury and reduced the glucose absorption capacity of IPEC-J2 cells. Pearson's correlation analysis revealed a negative correlation between glucose absorption capacity and cell inflammatory cytokines. Ultimately, it can be speculated that the cellular inflammatory response triggered by DON may be related to the altered expression of glucose transporters.


Assuntos
Células Epiteliais , Glucose , Intestino Delgado , Transportador 1 de Glucose-Sódio , Tricotecenos , Animais , Tricotecenos/toxicidade , Suínos , Glucose/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Transportador 1 de Glucose-Sódio/metabolismo , Transportador 1 de Glucose-Sódio/genética , Linhagem Celular , Intestino Delgado/efeitos dos fármacos , Inflamação/induzido quimicamente , Citocinas/metabolismo , Citocinas/genética , Transporte Biológico/efeitos dos fármacos , Transportador de Glucose Tipo 2/metabolismo , Transportador de Glucose Tipo 2/genética , Apoptose/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo
19.
Front Vet Sci ; 11: 1429233, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39132437

RESUMO

The application of Bacillus spp. as probiotics in the swine industry, particularly for piglet production, has garnered significant attention in recent years. This review aimed to summarized the role and mechanisms of Bacillus spp. in promoting growth and maintaining gut health in piglets. Bacillus spp. can enhance intestinal barrier function by promoting the proliferation and repair of intestinal epithelial cells and increasing mucosal barrier integrity, thereby reducing the risk of pathogenic microbial invasion. Additionally, Bacillus spp. can activate the intestinal immune system of piglets, thereby enhancing the body's resistance to diseases. Moreover, Bacillus spp. can optimize the gut microbial community structure, enhance the activity of beneficial bacteria such as Lactobacillus, and inhibit the growth of harmful bacteria such as Escherichia coli, ultimately promoting piglet growth performance and improving feed efficiency. Bacillus spp. has advantages as well as challenges as an animal probiotic, and safety evaluation should be conducted when using the newly isolated Bacillus spp. This review provides a scientific basis for the application of Bacillus spp. in modern piglet production, highlighting their potential in improving the efficiency of livestock production and animal welfare.

20.
Adv Sci (Weinh) ; 11(6): e2305315, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38081795

RESUMO

The service life of large battery packs can be significantly influenced by only one or two abnormal cells with faster aging rates. However, the early-stage identification of lifetime abnormality is challenging due to the low abnormal rate and imperceptible initial performance deviations. This work proposes a lifetime abnormality detection method for batteries based on few-shot learning and using only the first-cycle aging data. Verified with the largest known dataset with 215 commercial lithium-ion batteries, the method can identify all abnormal batteries, with a false alarm rate of only 3.8%. It is also found that any capacity and resistance-based approach can easily fail to screen out a large proportion of the abnormal batteries, which should be given enough attention. This work highlights the opportunities to diagnose lifetime abnormalities via "big data" analysis, without requiring additional experimental effort or battery sensors, thereby leading to extended battery life, increased cost-benefit, and improved environmental friendliness.

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