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1.
BMC Genomics ; 21(1): 880, 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33297944

RESUMO

BACKGROUND: Late blight disease (LBD) caused by the pathogen Phytophthora infestans (PI), is the most devastating disease limiting potato (Solanum tuberosum) production globally. Currently, this disease pathogen is re-emerging and appearing in new areas at a very high intensity. A better understanding of the natural defense mechanisms against PI in different potato cultivars especially at the protein level is still lacking. Therefore, to elucidate potato proteome response to PI, we investigated changes in the proteome and leaf morphology of three potato cultivars, namely; Favorita (FA), Mira (MA), and E-malingshu N0.14 (E14) infected with PI by using the iTRAQ-based quantitative proteomics analysis. RESULTS: A total of 3306 proteins were found in the three potato genotypes, and 2044 proteins were quantified. Cluster analysis revealed MA and E14 clustered together separately from FA. The protein profile and related functions revealed that the cultivars shared a typical hypersensitive response to PI, including induction of elicitors, oxidative burst, and suppression of photosynthesis in the potato leaves. Meanwhile, MA and E14 deployed additional specific response mechanism different from FA, involving high induction of protease inhibitors, serine/threonine kinases, terpenoid, hormone signaling, and transport, which contributed to MA tolerance of LBD. Furthermore, inductions of pathogenesis-related proteins, LRR receptor-like kinases, mitogen-activated protein kinase, WRKY transcription factors, jasmonic acid, and phenolic compounds mediate E14 resistance against LBD. These proteins were confirmed at the transcription level by a quantitative polymerase chain reaction and at the translation level by western-blot. CONCLUSIONS: We found several proteins that were differentially abundant among the cultivars, that includes common and cultivar specific proteins which highlighted similarities and significant differences between FA, MA, and E14 in terms of their defense response to PI. Here the specific accumulation of mitogen-activated protein kinase, Serine/threonine kinases, WRKY transcription played a positive role in E14 immunity against PI. The candidate proteins identified reported in this study will form the basis of future studies and may improve our understanding of the molecular mechanisms of late blight disease resistance in potato.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32495070

RESUMO

PURPOSE: Hypothyroidism (HT) is associated with accelerated atherosclerosis (AS). The efficacy of traditional strategies of hypothyroid AS remains controversial. Here, we aimed to deepen the understanding of the HT-induced acceleration of AS, to decrease the residual risk of coronary artery disease (CAD) and to find a new therapeutic target. METHODS: We collected peripheral venous blood samples from 20 patients and divided them into 4 groups, namely, the normal group, the HT group, the CAD group and the HT + CAD group. Then we performed mRNA microarray analysis and bioinformatics analysis to screen the differentially expressed genes and pathways, and we also conducted validations on ApoE knockout mice models and Raw264.7 cell models. RESULTS: In short, (1) in the analysis between the CAD group and the HT + CAD group, we found a total of 1218 differentially expressed genes, 11 upregulated pathways and 40 downregulated pathways. (2) We validated that patients with HT and CAD had a significantly decreased expression of MAP3K7 (encoding transforming growth factor-ß-activated kinase 1, TAK1) gene than normal subjects. (3) In animal and cell experiments, we found the decreased expression of TAK1 and the reduced phosphorylation of AMP-activated protein kinase (AMPK) under the hypothyroid and atherosclerotic condition. (4) Changes in the expressions of TAK1 may affect the progression of AS. CONCLUSION: Taken together, these data suggest that the accelerated AS in hypothyroid patients may be due to the suppression of TAK1-AMPK pathway in macrophages. This new finding may become a novel therapeutic target in hypothyroid AS.

3.
Clin Chim Acta ; 508: 161-169, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32417211

RESUMO

BACKGROUND: Obstructive sleep apnea (OSA) is the most common type of sleep breathing disorder and is characterized by chronic intermittent hypoxia, which could cause inflammation and nuclear factor kappa B (NF-KB)-dependent inflammatory pathways activation. Circulating APRIL (a proliferation-inducing ligand) play an important role in promoting inflammation and NF-KB-dependent inflammatory pathways activation. We explored the role of APRIL as a potential mechanism of inflammation in OSA patients. METHODS: After detailed sleep evaluated, venous blood and demographic data were collected from 155 subjects with varying severity of OSA and 52 control subjects. Plasma levels of APRIL were measured by human Magnetic Luminex assay. RESULTS: Plasma APRIL levels were significantly higher in OSA subjects compared with control subjects. Categorization of the OSA subjects into mild, moderate, and severe OSA subgroups found that plasma levels of APRIL increased with the severity of OSA. After adjusting confounding factors, found that increased plasma APRIL levels were conferred a higher odds ratio of OSA. Moreover, plasma APRIL levels were positively associated with the apnea-hypopnea index, which represents the severity of OSA. Furthermore, plasma APRIL showed higher discriminatory accuracy in predicting the presence of OSA. CONCLUSIONS: Plasma APRIL levels were significantly associated with the occurrence of OSA and its severity. APRIL could be a plasma biomarker with a positive diagnostic value for inflammation and NF-KB-dependent inflammatory pathways activation in subjects with OSA. TRIAL REGISTRATION: The project was approved by the Chinese Clinical Trial Registry (No. ChiCTRROC-17011027).

4.
J Interv Card Electrophysiol ; 58(3): 369-379, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32472281

RESUMO

PURPOSE: Obstructive sleep apnea (OSA) is associated with the management of atrial fibrillation (AF). This manuscript aims to discuss the effects of continuous positive airway pressure (CPAP) in patients with rhythm control strategies and patients with different ages, weights and length of follow-up. METHODS: We searched Embase, PubMed, Cochrane, Web of Science and Ovid for relevant studies (from inception to 7 July 2019; English). The primary outcome was documented AF recurrence in CPAP users and nonusers. We assessed pooled data by use of a random-effects model. RESULTS: Nine prospective cohort studies with a total of 2134 participants met the inclusion criteria. Results showed that complementary CPAP therapy reduced AF recurrence (RR = 0.63; 95% CI, 0.56-0.72). In subgroup analyses, the benefits of CPAP were stronger in patients younger than 60 years old (< 60 years old: RR, 0.59; 95% CI, 0.50-0.68 vs. ≥ 60 years old: RR, 0.73; 95% CI, 0.59-0.91), with a body mass index (BMI) of less than 30 (< 30: RR, 0.53; 95% CI, 0.37-0.77 vs. ≥ 30: RR, 0.65; 95% CI, 0.55-0.77) or with less follow-up time (≤ 1 year: RR, 0.57; 95% CI, 0.42-0.79 vs. > 1 year: RR, 0.64; 95% CI, 0.53-0.78). CONCLUSIONS: Complementary CPAP therapy reduces the risk of AF recurrence in OSA patients with rhythm control strategies. In addition to weight control and early AF intervention, CPAP compliance should be recommended along with periodic adjustments as necessary.

5.
Nat Commun ; 10(1): 4996, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31676803

RESUMO

Plants deploy various immune receptors to recognize pathogens and defend themselves. Crosstalk may happen among receptor-mediated signal transduction pathways in the same host during simultaneous infection of different pathogens. However, the related function of the receptor-like kinases (RLKs) in thwarting different pathogens remains elusive. Here, we report that NIK1, which positively regulates plant antiviral immunity, acts as an important negative regulator of antibacterial immunity. nik1 plants exhibit dwarfed morphology, enhanced disease resistance to bacteria and increased PAMP-triggered immunity (PTI) responses, which are restored by NIK1 reintroduction. Additionally, NIK1 negatively regulates the formation of the FLS2/BAK1 complex. The interaction between NIK1 and FLS2/BAK1 is enhanced upon flg22 perception, revealing a novel PTI regulatory mechanism by an RLK. Furthermore, flg22 perception induces NIK1 and RPL10A phosphorylation in vivo, activating antiviral signalling. The NIK1-mediated inverse modulation of antiviral and antibacterial immunity may allow bacteria and viruses to activate host immune responses against each other.


Assuntos
Proteínas de Arabidopsis/genética , Arabidopsis/genética , Imunidade Vegetal/genética , Proteínas Quinases/genética , Proteínas Serina-Treonina Quinases/genética , Arabidopsis/microbiologia , Arabidopsis/virologia , Proteínas de Arabidopsis/imunologia , Proteínas de Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas/imunologia , Interações Hospedeiro-Patógeno/imunologia , Complexos Multiproteicos/imunologia , Complexos Multiproteicos/metabolismo , Doenças das Plantas/imunologia , Doenças das Plantas/microbiologia , Doenças das Plantas/virologia , Imunidade Vegetal/imunologia , Vírus de Plantas/imunologia , Vírus de Plantas/fisiologia , Plantas Geneticamente Modificadas , Ligação Proteica , Proteínas Quinases/imunologia , Proteínas Quinases/metabolismo , Proteínas Serina-Treonina Quinases/imunologia , Proteínas Serina-Treonina Quinases/metabolismo , Pseudomonas syringae/imunologia , Pseudomonas syringae/fisiologia , Transdução de Sinais/genética , Transdução de Sinais/imunologia
6.
Biochem Biophys Res Commun ; 434(4): 885-91, 2013 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-23618859

RESUMO

CCN1, a secreted matrix-associated molecule, is involved in multiple cellular processes. Accumulating evidence supports that CCN1 plays an important role in tumorigenesis and progression of breast cancer. In this study, we have developed a novel CCN1 function-blocking monoclonal antibody (mAb), designated YM1B. YM1B binds to human CCN1 with high specificity, recognizing the native CCN1 structure with undisturbed disulfide linkages. Our analyses have mapped the YM1B recognition region to domain IV of CCN1, likely in proximity to the DM site. In breast cancer cells, CCN1 can induce actin reorganization, formation of lamellipodia, and cell migration/invasion through the αV integrins/Rac1/ERK signaling axis; these CCN1-dependent activities can be effectively suppressed by YM1B. Our results also suggest that YM1B may exert its CCN1-blocking effect by perturbing the interaction of CCN1 with vitronectin and fibronectin, which are ligands of αV integrins and instrumental for integrin activation. This CCN1-specific mAb may open a new potential avenue for therapeutic intervention of breast cancer progression.


Assuntos
Anticorpos Monoclonais/farmacologia , Movimento Celular/efeitos dos fármacos , Proteína Rica em Cisteína 61/antagonistas & inibidores , Citoesqueleto/efeitos dos fármacos , Proteínas rac1 de Ligação ao GTP/metabolismo , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/metabolismo , Especificidade de Anticorpos/imunologia , Sítios de Ligação de Anticorpos , Western Blotting , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proteína Rica em Cisteína 61/imunologia , Proteína Rica em Cisteína 61/metabolismo , Citoesqueleto/metabolismo , Epitopos/imunologia , Epitopos/metabolismo , Feminino , Fibronectinas/metabolismo , Humanos , Integrina alfaV/metabolismo , Células MCF-7 , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Ligação Proteica/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Vitronectina/metabolismo
7.
World J Gastroenterol ; 12(41): 6715-21, 2006 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-17075991

RESUMO

AIM: To observe the efficiency and safety of thymosin-alpha1 treatment in patients with hepatitis B e antigen (HBeAg) and HBV DNA positive chronic hepatitis. METHODS: Sixty-two patients were randomly divided into groups A and B. The patients in group A received subcutaneous injection of 1.6 mg thymosin-alpha1, twice a week (T-alpha1 group) for six months, and the patients in group B received 5 MU interferon alpha (IFN-alpha) each day for fifteen days, then three times weekly (IFN-alpha group) for six months. The results between two groups treated with and the group untreated with IFN-alpha which was followed up for 12 mo (historical control group consisting of 30 patients) were compared, and three groups were comparable between each other (P>0.05) at baseline (age, sex, clinical history, biochemical, and serological parameters). RESULTS: At the end of treatment, complete response, which was defined as alanine aminotransferase (ALT) normalization and HBV DNA and HBeAg loss, occurred in 9 of 29 (31.0%) patients in the T-alpha1 group and in 15 of 33 (45.5%) patients in the IFN-alpha group (chi2=1.36, P>0.05). After a follow-up period of six months, a complete response was observed in 14 of 29 (48.3%) patients in the T-alpha1 group and in 9 of 33 (27.3%) patients in the IFN-alpha group (chi2=2.93, P>0.05). Compared with the results observed in the historical control (HC) group untreated with IFN-alpha which was followed up for 12 mo, the rate of complete response was significantly higher in IFN-alpha group at the end of therapy (1 of 30 vs 15 of 33, chi2=14.72, P<0.001) and in the T-alpha1 group at the end of follow-up (1 of 30 vs 14 of 29, chi2=15.71, P<0.001). In T-alpha1 and IFN-alpha treatment groups, the area under (the plasma concentration time) curve (AUC) of negative HBV DNA and HBeAg was 34%, 17%, 31% and 19% smaller than that in the HC group. By the end of the follow-up period, the proportions of ALT normalization and negative HBV DNA in the T-alpha1 group were significantly higher than those in the IFN-alpha and HC groups. The odds of ALT normalization and negative HBV DNA at the end of the follow-up was three-fold higher in the T-alpha1 group than in the IFN-alpha group. Unlike IFN-alpha, T-alpha1 was well tolerated by all patients, and no side effects appeared in T-alpha1 group. CONCLUSION: The results suggest that a 6-mo course of T-alpha1 therapy is effective and safe in patients with chronic hepatitis B. T-alpha1 is able to reduce HBV replication in patients with chronic hepatitis B. Furthermore, T-alpha1 is better tolerated than IFN-alpha and can gradually induce more sustained ALT normalization and HBV DNA and HBeAg loss. However, a response rate of 48.3% is still less ideal. A more effective therapeutic approach warrants further study.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Timosina/análogos & derivados , Adjuvantes Imunológicos/efeitos adversos , Adjuvantes Imunológicos/farmacologia , Adulto , Alanina Transaminase/sangue , Antivirais/efeitos adversos , Antivirais/farmacologia , DNA Viral/sangue , Relação Dose-Resposta a Droga , Feminino , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/genética , Hepatite B Crônica/sangue , Hepatite B Crônica/imunologia , Humanos , Interferon-alfa/efeitos adversos , Interferon-alfa/farmacologia , Masculino , Pessoa de Meia-Idade , Timalfasina , Timosina/efeitos adversos , Timosina/farmacologia , Timosina/uso terapêutico , Replicação Viral/efeitos dos fármacos
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