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1.
Mol Ther ; 32(2): 313-324, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38093516

RESUMO

Renal fibrosis is a characteristic hallmark of chronic kidney disease (CKD) that ultimately results in renal failure, leaving patients with few therapeutic options. TGF-ß is a master regulator of renal fibrosis and mediates progressive renal fibrosis via both canonical and noncanonical signaling pathways. In the canonical Smad signaling, Smad3 is a key mediator in tissue fibrosis and mediates renal fibrosis via a number of noncoding RNAs (ncRNAs). In this regard, targeting Smad3-dependent ncRNAs may offer a specific therapy for renal fibrosis. This review highlights the significance and innovation of TGF-ß/Smad3-associated ncRNAs as biomarkers and therapeutic targets in renal fibrogenesis. In addition, the underlying mechanisms of these ncRNAs and their future perspectives in the treatment of renal fibrosis are discussed.


Assuntos
Rim , Insuficiência Renal Crônica , Humanos , Fibrose , Rim/metabolismo , Insuficiência Renal Crônica/genética , Insuficiência Renal Crônica/terapia , Insuficiência Renal Crônica/metabolismo , RNA não Traduzido/genética , RNA não Traduzido/metabolismo , Proteína Smad3/genética , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo
2.
BMC Biol ; 22(1): 54, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38448930

RESUMO

BACKGROUND: Gut bacteria are beneficial to the host, many of which must be passed on to host offspring. During metamorphosis, the midgut of holometabolous insects undergoes histolysis and remodeling, and thus risks losing gut bacteria. Strategies employed by holometabolous insects to minimize this risk are obscure. How gut bacteria affect host insects after entering the hemocoel and causing opportunistic infections remains largely elusive. RESULTS: We used holometabolous Helicoverpa armigera as a model and found low Lactobacillus load, high level of a C-type lectin (CTL) gene CD209 antigen-like protein 2 (CD209) and its downstream lysozyme 1 (Lys1) in the midgut of the wandering stage. CD209 or Lys1 depletion increased the load of midgut Lactobacillus, which further translocate to the hemocoel. In particular, CD209 or Lys1 depletion, injection of Lactobacillus plantarum, or translocation of midgut L. plantarum into the hemocoel suppressed 20-hydroxyecdysone (20E) signaling and delayed pupariation. Injection of L. plantarum decreased triacylglycerol and cholesterol storage, which may result in insufficient energy and 20E available for pupariation. Further, Lysine-type peptidoglycan, the major component of gram-positive bacterial cell wall, contributed to delayed pupariation and decreased levels of triacylglycerols, cholesterols, and 20E, in both H. armigera and Drosophila melanogaster. CONCLUSIONS: A mechanism by which (Lactobacillus-induced) opportunistic infections delay insect metamorphosis was found, namely by disturbing the homeostasis of lipid metabolism and reducing 20E production. Moreover, the immune function of CTL - Lys was characterized for insect metamorphosis by maintaining gut homeostasis and limiting the opportunistic infections.


Assuntos
Microbioma Gastrointestinal , Lisina , Animais , Drosophila melanogaster , Disbiose , Bactérias , Imunidade
3.
J Cell Mol Med ; 28(6): e18195, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38429907

RESUMO

METTL3 has been shown to be involved in regulating a variety of biological processes. However, the relationship between METTL3 expression and glycolysis, cuproptosis-related genes and the ceRNA network in oesophageal carcinoma (ESCA) remains unclear. ESCA expression profiles from databases were obtained, and target genes were identified using differential analysis and visualization. Immunohistochemistry (IHC) staining assessed METTL3 expression differences. Functional enrichment analysis using GO, KEGG and GSEA was conducted on the co-expression profile of METTL3. Cell experiments were performed to assess the effect of METTL3 interference on tumour cells. Correlation and differential analyses were carried out to assess the relationship between METTL3 with glycolysis and cuproptosis. qRT-PCR was used to validate the effects of METTL3 interference on glycolysis-related genes. Online tools were utilized to screen and construct ceRNA networks based on the ceRNA theory. METTL3 expression was significantly higher in ESCA compared to the controls. The IHC results were consistent with the above results. Enrichment analysis revealed that METTL3 is involved in multiple pathways associated with tumour development. Significant correlations were observed between METTL3 and glycolysis-related genes and cuproptosis-related gene. Experiments confirmed that interfered with METTL3 significantly inhibited glucose uptake and lactate production in tumour cells, and affected the expression of glycolytic-related genes. Finally, two potential ceRNA networks were successfully predicted and constructed. Our study establishes the association between METTL3 overexpression and ESCA progression. Additionally, we propose potential links between METTL3 and glycolysis, cuproptosis and ceRNA, presenting a novel targeted therapy strategy for ESCA.


Assuntos
Carcinoma , Neoplasias Esofágicas , Metiltransferases , Humanos , Biomarcadores , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/genética , Glicólise/genética , Ácido Láctico , Metiltransferases/genética , RNA Endógeno Competitivo
4.
Phys Chem Chem Phys ; 26(24): 17383-17395, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38860766

RESUMO

Although GaN is a promising candidate for semiconductor devices, degradation of GaN-based device performance may occur when the device is bombarded by high-energy charged particles during its application in aerospace, astronomy, and nuclear-related areas. It is thus of great significance to explore the influence of irradiation on the microstructure and electronic properties of GaN and to reveal the internal relationship between the damage mechanisms and physical characteristics. Using a combined density functional theory (DFT) and ab initio molecular dynamics (AIMD) study, we explored the low-energy recoil events in GaN and the effects of point defects on GaN. The threshold displacement energies (Eds) significantly depend on the recoil directions and the primary knock-on atoms. Moreover, the Ed values for nitrogen atoms are smaller than those for gallium atoms, indicating that the displacement of nitrogen dominates under electron irradiation and the created defects are mainly nitrogen vacancies and interstitials. The formation energy of nitrogen vacancies and interstitials is smaller than that for gallium vacancies and interstitials, which is consistent with the AIMD results. Although the created defects improve the elastic compliance of GaN, these radiation damage states deteriorate its ability to resist external compression. Meanwhile, these point defects lead the Debye temperature to decrease and thus increase the thermal expansion coefficients of GaN. As for the electronic properties of defective GaN, the point defects have various effects, i.e., VN (N vacancy), Gaint (Ga interstitial), Nint (N interstitial), and GaN (Ga occupying the N lattice site) defects induce the metallicity, and NGa (N occupying the Ga lattice site) defects decrease the band gap. The presented results provide underlying mechanisms for defect generation in GaN, and advance the fundamental understanding of the radiation resistances of semiconductor materials.

5.
Lipids Health Dis ; 23(1): 5, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38185630

RESUMO

BACKGROUND: Lipid management in clinic is critical to the prevention and treatment of Chronic kidney disease (CKD), while the manifestations of lipid indicators vary in types and have flexible association with CKD prognosis. PURPOSE: Explore the associations between the widely used indicators of lipid metabolism and their distribution in clinic and CKD prognosis; provide a reference for lipid management and inform treatment decisions for patients with non-dialysis CKD stage 3-5. METHODS: This is a retrospective cohort study utilizing the Self-Management Program for Patients with Chronic Kidney Disease Cohort (SMP-CKD) database of 794 individuals with CKD stages 3-5. It covers demographic data, clinical diagnosis and medical history collection, laboratory results, circulating lipid profiles and lipid distribution assessments. Primary endpoint was defined as a composite outcome(the initiation of chronic dialysis or renal transplantation, sustained decline of 40% or more in estimated glomerular filtration rate (eGFR), doubled of serum creatinine (SCr) from the baseline, eGFR less than 5 mL/min/1.73m2, or all-cause mortality). Exposure variables were circulating lipid profiles and lipid distribution measurements. Association were assessed using Relative risks (RRs) (95% confidence intervals (CIs)) computed by multivariate Poisson models combined with least absolute shrinkage and selection operator (LASSO) regression according to categories of lipid manifestations. The best model was selected via akaike information criterion (AIC), area under curve (AUC), receiver operating characteristic curve (ROC) and net reclassification index (NRI). Subgroup analysis and sensitivity analysis were performed to assess the interaction effects and robustness.. RESULTS: 255 individuals reached the composite outcome. Median follow-up duration was 2.03 [1.06, 3.19] years. Median age was 58.8 [48.7, 67.2] years with a median eGFR of 33.7 [17.6, 47.8] ml/min/1.73 m2. Five dataset were built after multiple imputation and five category-based Possion models were constructed for each dataset. Model 5 across five datasets had the best fitness with smallest AIC and largest AUC. The pooled results of Model 5 showed that total cholesterol (TC) (RR (95%CI) (per mmol/L) :1.143[1.023,1.278], P = 0.018) and percentage of body fat (PBF) (RR (95%CI) (per percentage):0.976[0.961,0.992], P = 0.003) were significant factors of composite outcome. The results indicated that comprehensive consideration of lipid metabolism and fat distribution is more critical in the prediction of CKD prognosis.. CONCLUSION: Comprehensive consideration of lipid manifestations is optimal in predicting the prognosis of individuals with non-dialysis CKD stages 3-5.


Assuntos
Insuficiência Renal Crônica , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Distribuição Tecidual , Prognóstico , Insuficiência Renal Crônica/terapia , Lipídeos
6.
J Transl Med ; 21(1): 574, 2023 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-37626419

RESUMO

BACKGROUND: This study investigated the correlation between the expression of DARS2 and metabolic parameters of 18F-FDG PET/CT, and explored the potential mechanisms of DARS2 affecting the proliferation and glycolysis of lung adenocarcinoma (LUAD) cells. METHODS: This study used genomics and proteomics to analyze the difference in DARS2 expression between LUAD samples and control samples. An analysis of 62 patients with LUAD who underwent 18F-FDG PET/CT examinations before surgery was conducted retrospectively. The correlation between DARS2 expression and PET/CT metabolic parameters, including SUVmax, SUVmean, MTV, and TLG, was examined by Spearman correlation analysis. In addition, the molecular mechanism of interfering with DARS2 expression in inhibiting LUAD cell proliferation and glycolysis was analyzed through in vitro cell experiments. RESULTS: DARS2 expression was significantly higher in LUAD samples than in control samples (p < 0.001). DARS2 has high specificity (98.4%) and sensitivity (95.2%) in the diagnosis of LUAD. DARS2 expression was positively correlated with SUVmax, SUVmean, and TLG (p < 0.001). At the same time, the sensitivity and specificity of SUVmax in predicting DARS2 overexpression in LUAD were 88.9% and 65.9%, respectively. In vitro cell experiments have shown that interfering with DARS2 expression can inhibit the proliferation and migration of LUAD cells, promote cell apoptosis, and inhibit the glycolytic activity of tumor cells by inhibiting the expression of glycolytic related genes SLC2A1, GPI, ALDOA, and PGAM1. CONCLUSIONS: Overexpression of DARS2 is associated with metabolic parameters on 18F-FDG PET/CT, which can improve LUAD diagnosis accuracy. DARS2 may be a useful biomarker to diagnose, prognosis, and target treatment of LUAD patients.


Assuntos
Adenocarcinoma de Pulmão , Aspartato-tRNA Ligase , Neoplasias Pulmonares , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Fluordesoxiglucose F18 , Estudos Retrospectivos , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/genética , Glicólise , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/genética
7.
J Transl Med ; 20(1): 450, 2022 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-36195940

RESUMO

BACKGROUND: The aim of this study was to determine the expression and function of heterogeneous nuclear ribonucleoprotein R (HNRNPR) in esophageal carcinoma (ESCA), the correlation between its expression and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computerized tomography scan (PET/CT)-related parameters. We also investigated whether 18F-FDG PET/CT can be used to predict the expression of HNRNPR in ESCA. METHODS: We analyzed patients with ESCA who underwent 18F-FDG PET/CT before surgery, and their tissues were stained with HNRNPR IHC. The associated parameters were derived using the 18F-FDG PET imaging data, and the correlation with the IHC score was evaluated. The Oncomine, TCGA, and GEO datasets were used to investigate HNRNPR expression in the pan- and esophageal cancers, as well as its relationship with N6-methyladenosine (m6A) modification and glycolysis. The R software, LinkedOmics, GeneMANIA, and StringOnline tools were used to perform GO/KEGG, GGI, and PPI analyses on the HNRNPR. RESULTS: HNRNPR is highly expressed in the majority of pan-cancers, including ESCA, and is associated with BMI, weight, and history of reflux in patients with ESCA. HNRNPR is somewhat accurate in predicting the clinical prognosis of ESCA. HNRNPR expression was positively correlated with SUVmax, SUVmean, and TLG in ESCA (p < 0.05). The combination of these three variables provides a strong predictive value for HNRNPR expression in ESCA. GO/KEGG analysis showed that HNRNPR played a role in the regulation of cell cycle, DNA replication, and the Fannie anemia pathway. The analysis of the TCGA and GEO data sets revealed a significant correlation between HNRNPR expression and m6A and glycolysis-related genes. GSEA analysis revealed that HNRNPR was involved in various m6A and glycolysis related-pathways. CONCLUSION: HNRNPR overexpression correlates with 18F-FDG uptake in ESCA and may be involved in the regulation of the cell cycle, m6A modification, and cell glycolysis. 18F-FDG PET/CT-related parameters can predict the diagnostic accuracy of HNRNPR expression in ESCA.


Assuntos
Carcinoma , Neoplasias Esofágicas , Biomarcadores/metabolismo , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/genética , Fluordesoxiglucose F18/metabolismo , Glicólise/genética , Ribonucleoproteínas Nucleares Heterogêneas/metabolismo , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia por Emissão de Pósitrons/métodos , Prognóstico , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Carga Tumoral
8.
BMC Nephrol ; 23(1): 93, 2022 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-35247988

RESUMO

BACKGROUND: Chronic kidney disease (CKD) is a major global health problem. Short-term self-management has been considered to effect some renal and psychological endpoints. However, there are currently very few studies about self-management for CKD that a) have been scientifically designed by a theory-based framework and b) that evaluate the long-term effects and working mechanism. This study presents the rationale and design of a theory-based cohort study to explore how this self-management intervention works and its effectiveness on the Chinese CKD population. METHODS: In this ambispective intervention cohort study,1,200 patients with CKD stages 1-5 will be recruited from July 2015 to July 2024 in 3 branches of Guangdong Provincial Hospital of Chinese Medicine (GPHCM) in Guangdong province, China. The patients in the self-management cohort will choose to receive an intervention that consists of education, nutrition/diet modification, lifestyle change recommendation, medication review, and psychology support based on Social Cognition Theory (SCT). The patients in the control cohort will do regular follow-ups based on the clinic rules. All the patients will be followed up for 5 years, or until the occurrence of a primary outcome. Detailed clinical, laboratory markers, nutritional status, psychological exposures and outcome questionaries will be collected semiannually in CKD stage 1-2 and trimonthly in stage 3-5 patients. The primary outcome is the occurrence of composite clinical endpoints (doubling of serum creatinine level, ESKD, loss of renal function (≥ 40% decline in GFR from baseline), death, major cardiovascular or cerebrovascular events). The main secondary outcomes include the absolute change and slope of eGFR, absolute changes of urinary protein creatinine ratio, 24-h urine proteinuria, intact parathyroid hormone level, and self-management adherence rate and quality of life from baseline to end of the study. The effectiveness of self-management will be analyzed and the association between longitudinal trajectories of self-management and renal outcomes will be evaluated. DISCUSSION: This study aims to provide further evidence for the effectiveness of theory-based self-management in CKD patients and to improve the lives of patients with CKD by slowing progression, improving psychological well-being and overall quality of life. TRIAL REGISTRATION: Chinese Clinical Trial Register (ChiCTR1900024633). 19 July, 2019. http://www.chictr.org.cn/showproj.aspx?proj=38378.


Assuntos
Insuficiência Renal Crônica , Autogestão , Biomarcadores , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , Masculino , Qualidade de Vida , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/terapia
9.
Magn Reson Chem ; 60(3): 407-413, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34823270

RESUMO

On the basis of the higher order perturbation formulas of g factors for a 4d1 group in tetragonally compressed octahedra, the g factors, optical absorption, local structure, and their concentration dependences of pentavalent molybdenum in 40PbO-(10 - x)Y2 O3 -50P2 O5 :xMoO3 (1 ≤ x ≤ 5 mol%) glass are uniformly investigated. The experimental optical absorption spectra and g factors for Mo5+ at various concentrations x are reasonably regenerated by using the reasonable exponential concentration functions of the cubic field parameter Dq , covalent factor N, and relative tetragonal compression ratio ρ. The tetragonal compression ratio ρ due to the Jahn-Teller effect was found in the range of 3.8% to 4.2%. The decreasing trend of Dq and N and the increasing trend of ρ with concentration can be interpreted as the fact that the variations of MoO3 and Y2 O3 concentrations lead to the modulations of local structure and electron cloud distribution around Mo5+ , associated with the adjustment of the glass network. The concentration dependence of optical basicity is also analyzed for the above glass systems.

10.
Eur J Nucl Med Mol Imaging ; 48(3): 904-912, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32856112

RESUMO

PURPOSE: This study investigated the correlation of nucleophosmin 1 (NPM1) expression with 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computerised tomography scan (PET/CT)-related parameters and compared the diagnostic value of NPM1 with that of the positive biomarker TTF1 in lung adenocarcinoma patients. METHODS: Forty-six lung adenocarcinoma patients who underwent 18F-FDG PET/CT before pulmonary surgery were retrospectively analysed. Metabolic parameters including SUVmax, SUVmean, metabolic tumour volume (MTV) and total lesion glycolysis (TLG) were calculated from 18F-FDG PET imaging data. The expression levels of NPM1 and TTF1 were assessed using The Cancer Genome Atlas (TCGA) database and immunohistochemistry of tumour tissues and adjacent normal lung tissues. We examined the association between the frequency of NPM1 and TTF1 expression and the metabolic parameters. RESULTS: Lung adenocarcinoma samples expressed higher levels of NPM1 than adjacent normal lung epithelial tissues. NPM1 showed higher specificity and sensitivity for lung adenocarcinoma compared with TTF1 (p < 0.001). SUVmax, SUVmean and TLG correlated with NPM1 expression (p < 0.001). MTV was inversely correlated with TTF1 (p < 0.01). SUVmax was the primary predictor of NPM1 expression by lung adenocarcinoma (p < 0.01). A cutoff value for the SUVmax of 3.93 allowed 90.9% sensitivity and 84.6% specificity for predicting NPM1 overexpression in lung adenocarcinoma. CONCLUSION: NPM1 overexpression correlated with 18F-FDG PET/CT metabolic parameters and improved diagnostic accuracy in lung adenocarcinoma. SUVmax on 18F-FDG PET/CT may estimate NPM1 expression for targeted therapy of lung adenocarcinoma.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/genética , Fluordesoxiglucose F18 , Glicólise , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Proteínas Nucleares , Nucleofosmina , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Prognóstico , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Carga Tumoral
11.
Arch Insect Biochem Physiol ; 106(3): e21769, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33590536

RESUMO

Upon entry into the hemocoel of host insects, entomopathogenic fungi switch to yeast-like hyphal bodies that are not recognized by host hemocytes and replicate extensively in the hemolymph. The mechanism by which hyphal bodies evade host cellular immunity is not well understood. This study compares Metarhizium rileyi conidia and hyphal bodies with respect to elicitation of the immune response of Helicoverpa armigera and recognition by host pattern recognition receptors (PRRs). We found that the ability of host hemocytes to phagocytize and nodulate hyphal bodies was weaker than those responses against conidia, suggesting that hyphal bodies are more able to evade host cellular immunity. Additionally, we found that the binding affinity of H. armigera ß-1,3-glucan recognition proteins was much lower for hyphal bodies than for conidia. We observed no agglutination response of H. armigera C-type lectin 3 (HaCTL3) against hyphal bodies, and HaCTL3 bound significantly less to hyphal bodies than to conidia, indicating that host PRRs have a lower affinity for hyphal bodies than for conidia. This study provides direct evidence that the mechanism whereby entomopathogenic fungi escape host cellular immunity involves the inability of host PRRs to sufficiently recognize hyphal bodies to elicit the cellular immune response.


Assuntos
Interações entre Hospedeiro e Microrganismos , Imunidade Celular , Metarhizium/imunologia , Mariposas/imunologia , Receptores de Reconhecimento de Padrão/metabolismo , Aglutinação/fisiologia , Animais , Hemócitos/metabolismo , Hemolinfa/citologia , Hemolinfa/metabolismo , Hifas/imunologia , Evasão da Resposta Imune , Lectinas Tipo C/metabolismo , Mariposas/microbiologia , Fagocitose , Esporos Fúngicos/imunologia
12.
Magn Reson Chem ; 59(4): 439-446, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33084084

RESUMO

The local structure, d-d transition band, and spin Hamiltonian parameters (SHPs) are theoretically studied for the V4+ probe in Na2 O-PbO-Bi2 O3 -SiO2 (NPBS) glass ceramics containing V2 O5 dopant with various concentration x (0 ≤ x ≤ 5 mol%) by using the perturbation formulas of the SHPs for tetragonally compressed octahedral 3d1 clusters. The first decreasing (or increasing) and then increasing (or decreasing) d-d transition band (= 10 Dq ) and hyperfine structure constants A// and A⊥ (or g factors g// and g⊥ ) with x can be suitably simulated with the similarly varying Fourier type concentration functions of cubic field parameter Dq , covalence factor N, core polarization constant κ, and reduction factor H (or relative tetragonal compression ratio ρ), with the minima (or maxima) at the middle concentration x = 3 mol%, respectively. The above concentration variations of SHPs and the related quantities may originate from the modifications of local crystal field strength, tetragonal compression, and electron cloud distribution near the impurity V4+ with x, corresponding to the highest [V4+ ]/[V5+ ] ratio at 3 mol%. Present studies would be helpful to explore novel sodium lead bismuth silicate glass ceramics by modifying the concentration of V2 O5 dopant.

13.
J Biol Chem ; 294(26): 10172-10181, 2019 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-31088910

RESUMO

The Toll signaling pathway in Drosophila melanogaster regulates several immune-related functions, including the expression of antimicrobial peptide (AMP) genes. The canonical Toll receptor (Toll-1) is activated by the cytokine Spätzle (Spz-1), but Drosophila encodes eight other Toll genes and five other Spz genes whose interactions with one another and associated functions are less well-understood. Here, we conducted in vitro assays in the Drosophila S2 cell line with the Toll/interleukin-1 receptor (TIR) homology domains of each Toll family member to determine whether they can activate a known target of Toll-1, the promoter of the antifungal peptide gene drosomycin. All TIR family members activated the drosomycin promoter, with Toll-1 and Toll-7 TIRs producing the highest activation. We found that the Toll-1 and Toll-7 ectodomains bind Spz-1, -2, and -5, and also vesicular stomatitis virus (VSV) virions, and that Spz-1, -2, -5, and VSV all activated the promoters of drosomycin and several other AMP genes in S2 cells expressing full-length Toll-1 or Toll-7. In vivo experiments indicated that Toll-1 and Toll-7 mutants could be systemically infected with two bacterial species (Enterococcus faecalis and Pseudomonas aeruginosa), the opportunistic fungal pathogen Candida albicans, and VSV with different survival times in adult females and males compared with WT fly survival. Our results suggest that all Toll family members can activate several AMP genes. Our results further indicate that Toll-1 and Toll-7 bind multiple Spz proteins and also VSV, but they differentially affect adult survival after systemic infection, potentially because of sex-specific differences in Toll-1 and Toll-7 expression.


Assuntos
Peptídeos Catiônicos Antimicrobianos/metabolismo , Infecções Bacterianas/microbiologia , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/crescimento & desenvolvimento , Drosophila melanogaster/metabolismo , Regulação da Expressão Gênica , Receptores Toll-Like/metabolismo , Animais , Peptídeos Catiônicos Antimicrobianos/genética , Bactérias/isolamento & purificação , Infecções Bacterianas/genética , Infecções Bacterianas/metabolismo , Proteínas de Drosophila/genética , Drosophila melanogaster/microbiologia , Feminino , Masculino , Regiões Promotoras Genéticas , Transdução de Sinais , Receptores Toll-Like/genética
14.
BMC Genomics ; 20(1): 161, 2019 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-30813894

RESUMO

BACKGROUND: Mermithid nematodes, such as Ovomermis sinensis, display a broad host range including some lepidopteran pests. Infective juveniles penetrate their host through the cuticle, complete their growth within the hemocoel and eventually kill the host upon their emergence. Hence, mermithid nematodes are considered potential biological control agents of insect pests. Our previous data indicate that the infection rate of O. sinensis on cotton bollworm (Helicoverpa armigera) is low, which may be largely due to the strong immune system of the host. However, current knowledge on the interactions of mermithid nematodes with their hosts and the mechanisms employed by hosts to defend themselves against mermithid nematodes is limited. RESULTS: Here, we investigated the response of H. armigera to O. sinensis infection. Parasitism by O. sinensis caused a sharp decline in the survival rate of H. armigera. The hemocytic phagocytosis ability, antibacterial activity, and phenoloxidase (PO) activity in plasma of H. armigera increased at 1 d post parasitism (dpp) but decreased at 3 dpp. Further, we investigated gene expression in the fat body of parasitized and non-parasitized H. armigera larvae at 1, 3, and 5 dpp using a digital gene expression system. In total, 41, 60 and 68 immune-related differentially expressed genes were identified at 1, 3, and 5 dpp, respectively. These genes encoded pattern recognition receptors (PRRs), antimicrobial peptides (AMPs), serine proteases (SPs), SP inhibitors, mucins and other immune-related proteins. The expression of most PRRs, AMPs, SPs, and mucins was upregulated in the fat body of larvae at 1 dpp, downregulated at 3 dpp, and then again upregulated at 5 dpp by O. sinensis. The increased expression of SP inhibitors may contribute to the inhibited PO activity at 5 dpp. CONCLUSIONS: This study demonstrates that parasitism by O. sinensis modulates the immune reaction of the host H. armigera by altering the expression of immune-related genes. Our data provide a basis for future investigation of the molecular mechanisms employed by the mermithid nematode O. sinensis to modulate the immunity of the host H. armigera. These data will also likely facilitate the improvement of success in parasitism of H. armigera by O. sinensis.


Assuntos
Mermithoidea/fisiologia , Mariposas/imunologia , Mariposas/parasitologia , Animais , Perfilação da Expressão Gênica , Larva/imunologia , Larva/parasitologia , Mariposas/genética , Mariposas/metabolismo , Receptores de Reconhecimento de Padrão/genética , Receptores de Reconhecimento de Padrão/metabolismo , Análise de Sequência de RNA , Serina Proteases/genética , Serina Proteases/metabolismo , Análise de Sobrevida
15.
Artigo em Inglês | MEDLINE | ID: mdl-28643953

RESUMO

In this study, we investigated the effect of the entomopathogenic fungus Nomuraea rileyi on Helicoverpa armigera cellular immune responses. Nomuraea rileyi infection had no effect on total hemocyte count (THC), but impaired hemocyte-mediated phagocytosis, nodulation, and encapsulation responses. Nomuraea rileyi infection led to a significant reduction in hemocyte spreading. An in vitro assay revealed that plasma from N. rileyi infected H. armigera larvae suppressed the spreading ability of hemocytes from naïve larvae. We infer that N. rileyi suppresses the cellular immune response of its host, possibly by secreting exogenous, cytotoxic compounds into the host's hemolymph.


Assuntos
Interações Hospedeiro-Patógeno , Imunidade Celular , Fungos Mitospóricos/fisiologia , Mariposas/imunologia , Animais , Mariposas/microbiologia
16.
Magn Reson Chem ; 55(11): 972-978, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28543855

RESUMO

The copper electron paramagnetic resonance gyromagnetic factors are theoretically studied for three novel Cu2+ coordination polymers [Cu(XL)(NO3 )2 ]n (1), {[Cu(XL)(4,4'-bpy)(NO3 )2 ]•CH3 CN}n (1a) and {[Cu(XL)3 ](NO3 )2 •3.5H2 O}n (2) with bi-triazole ligand (XL) = N,N'-bicyclo[2.2.2]oct-7-ene-2,3,5,6-tetracarboxdiimide bi(1,2,4-triazole) from the high-order perturbation calculations of the g factors for a rhombically elongated octahedral 3d9 group. The order (1 ≤ 1a < 2) of gz can be illustrated by the dominant second-order perturbation term roughly proportional to the square of the covalency factor N. gx (and gy ) relies on the combination of the contributions from N, cubic field parameter Dq , and axial elongation of the copper sites and exhibits the sequence (1 ≤ 2 < 1a). As regards the axiality (gx  ≈ gy ) of g factors, this is because the perpendicular rhombic contribution from the deviations of the bond lengths and bond angles for the planar ligands with respect to an ideal octahedron and that from the discrepancies between the crystal fields of the planar ligands O2- and N3- largely cancel each other. The present theoretical studies on the copper electron paramagnetic resonance g factors would be helpful to understand the structures and properties of some promising coordination polymers containing copper with the novel bi-triazole ligand XL.

17.
Arch Insect Biochem Physiol ; 92(4): 225-41, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27226059

RESUMO

Autophagy is not only involved in development, but also has been proved to attend immune response against invading pathogens. Autophagy protein 5 (ATG5) is an important autophagic protein, which plays a crucial role in autophagosome elongation. Although ATG5 has been well studied in mammal, yeast, and Drosophila, little is known about ATG5 in lepidopteran insects. We cloned putative SeAtg5 gene from Spodoptera exigua larvae by the rapid amplification of cDNA ends method, and its characteristics and the influences of multiple exogenous factors on its expression levels were then investigated. The results showed that the putative S. exigua SeATG5 protein is highly homologous to other insect ATG5 proteins, which has a conserved Pfm domain and multiple phosphorylation sites. Next, fluorescence microscope observation showed that mCherry-SeATG5 was distributed in both nucleus and cytoplasm of Spodoptera litura Sl-HP cells and partially co-localized with BmATG6-GFP, but it almost has no significant co-localization with GFP-HaATG8. Then, the Western blot analysis demonstrated that GFP-SeATG5 conjugated with ATG12. Moreover, real-time PCR revealed that its expression levels significantly increased at the initiation of pupation and the stage of adult. In addition, the expression levels of SeAtg5 can be enhanced by the starvation, UV radiation, and infection of baculovirus and bacterium. However, the expression levels of SeAtg5 decreased at 24 h post treatments in all these treatments except in starvation. These results suggested that SeATG5 might be involved in response of S. exigua under various stress conditions.


Assuntos
Proteína 5 Relacionada à Autofagia/genética , Regulação da Expressão Gênica , Proteínas de Insetos/genética , Spodoptera/genética , Sequência de Aminoácidos , Animais , Proteína 5 Relacionada à Autofagia/química , Proteína 5 Relacionada à Autofagia/metabolismo , Sequência de Bases , Clonagem Molecular , DNA Complementar/genética , DNA Complementar/metabolismo , Perfilação da Expressão Gênica , Proteínas de Insetos/química , Proteínas de Insetos/metabolismo , Larva/genética , Larva/crescimento & desenvolvimento , Larva/metabolismo , Filogenia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Alinhamento de Sequência , Spodoptera/classificação , Spodoptera/crescimento & desenvolvimento , Spodoptera/metabolismo
18.
Arch Insect Biochem Physiol ; 86(4): 240-58, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25044262

RESUMO

Peptidoglycan recognition proteins (PGRPs) specifically bind to peptidoglycans, and play crucial roles as pattern recognition receptors (PRRs) in mediating innate immune responses. In this study, we identified and characterized a PGRP (HaPGRP-D) from the cotton bollworm, Helicoverpa armigera. Sequence analysis indicated that HaPGRP-D is an amidase-type PGRP. Expression of HaPGRP-D was upregulated in the hemocytes of H. armigera larvae after injecting Gram-negative Escherichia coli, Gram-positive Staphylococcus aureus, or chromatography beads. To test the biological activity of HaPGRP-D, purified recombinant protein was prepared. Subsequent analysis showed that rHaPGRP-D (i) could bind and agglutinate Gram-negative E. coli and Gram-positive S. aureus in a zinc-dependent manner, (ii) functioned as an amidase to degrade peptidoglycans in the presence of Zn(2+) , (iii) strongly inhibited the growth of E. coli and S. aureus in the presence of Zn(2+) , (iv) could bind to the surface of hemocytes, (v) increased the phagocytosis of E. coli cells by hemocytes in vitro, and (vi) promoted hemocyte encapsulation on chromatography beads in vitro. These results suggest that HaPGRP-D plays important roles as PRR, amidase, and opsonin in H. armigera humoral and cellular immune responses.


Assuntos
Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Regulação da Expressão Gênica/imunologia , Imunidade Inata/genética , Mariposas/genética , Mariposas/imunologia , Animais , Sequência de Bases , Primers do DNA/genética , Escherichia coli/imunologia , Perfilação da Expressão Gênica , Hemócitos/metabolismo , Dados de Sequência Molecular , Mariposas/metabolismo , Peptidoglicano/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNA , Staphylococcus aureus/imunologia , Zinco
19.
Onco Targets Ther ; 17: 41-44, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38298550

RESUMO

Burkitt lymphoma is a highly invasive non-Hodgkin lymphoma. Sporadic Burkitt's lymphoma is commonly found in the abdomen. However, Burkitt lymphoma infiltrating the uterus is uncommon in occurrence. We report the results of 18F-FDG PET/CT examination of a 36-year-old woman. The report indicates that in addition to the strong uptake of FDG imaging agent in the uterus, bilateral cervical and abdominal lymph nodes also have strong activity. At the same time, it was also found that bilateral small breast nodules, sacral canal and multiple bones in the whole body showed a radiation uptake pattern similar to that of the uterus. 18F-FDG PET/CT imaging can help determine the extent of the disease and the affected body area, which is helpful to guide the treatment decision. This case report shows the application of 18F-FDG PET/CT imaging in the diagnosis, staging and post-treatment evaluation of Burkitt lymphoma of the uterus. It provides very useful information for clinicians and helps to improve the accuracy of diagnosis and treatment effect.

20.
Aging (Albany NY) ; 16(4): 3934-3954, 2024 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-38382106

RESUMO

OBJECTIVE: The enzyme Aspartyl tRNA synthetase 2 (DARS2) is a crucial enzyme in the mitochondrial tRNA synthesis pathway, playing a critical role in maintaining normal mitochondrial function and protein synthesis. However, the role of DARS2 in ESCA is unclear. MATERIALS AND METHODS: Transcriptional data of pan-cancer and ESCA were downloaded from UCSC XENA, TCGA, and GEO databases to analyze the differential expression of DARS2 between tumor samples and normal samples, and its correlation with clinicopathological features of ESCA patients. R was used for GO, KEGG, and GSEA functional enrichment analysis of DARS2 co-expression and to analyze the connection of DARS2 with glycolysis and m6A-related genes. In vitro experiments were performed to assess the effects of interfering with DARS2 expression on ESCA cells. TarBase v.8, mirDIP, miRTarBase, ENCORI, and miRNet databases were used to analyze and construct a ceRNA network containing DARS2. RESULTS: DARS2 was overexpressed in various types of tumors. In vitro experiments confirmed that interfering with DARS2 expression significantly affected the proliferation, migration, apoptosis, cell cycle, and glycolysis of ESCA cells. DARS2 may be involved in multiple biological pathways related to tumor development. Furthermore, correlation and differential analysis revealed that DARS2 may regulate ESCA m6A modification through its interaction with METTL3 and YTHDF1. A ceRNA network containing DARS2, DLEU2/has-miR-30a-5p/DARS2, was successfully predicted and constructed. CONCLUSIONS: Our findings reveal the upregulation of DARS2 in ESCA and its association with clinical features, glycolysis pathway, m6A modification, and ceRNA network. These discoveries provide valuable insights into the molecular mechanisms underlying ESCA.


Assuntos
Aspartato-tRNA Ligase , Carcinoma , Neoplasias Esofágicas , Humanos , Neoplasias Esofágicas/genética , Apoptose/genética , Ciclo Celular , Metiltransferases
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