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1.
Fish Shellfish Immunol ; 102: 350-360, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32371258

RESUMO

Succinate dehydrogenase (SDH) is a mitochondrial enzyme with the unique ability to participate in both the tricarboxylic acid cycle and the electron transport chain to produce reactive oxygen species (ROS). The B subunit of SDH is required for succinate oxidation, which is critical for pro-inflammatory response. In this study, we cloned the iron-sulfur protein subunit of SDH from Apostichopus japonicus (denoted as AjSDHB) via RACE technology and explored its role in the immune system as a response to pathogen infection. The full-length cDNA of AjSDHB was 1442 bp with a complete open reading frame of 858 bp encoding 286 amino acids. Simple modular architecture research tool analysis revealed that AjSDHB contained two conserved domains, including a 2Fe-2S iron-sulfur cluster binding domain and a 4Fe-4S dicluster domain, without a signal peptide. Multiple sequence alignment demonstrated that AjSDHB shared a high degree of structural conservation and sequence identities with other counterparts from invertebrates and vertebrates. Phylogenetic analysis supported the finding that AjSDHB is a new member of the SDHB protein subfamily. Tissue distribution analysis revealed that AjSDHB was expressed in all examined tissues and particularly highly expressed in the muscles. AjSDHB transcripts were markedly induced in coelomocytes both by Vibrio splendidus challenge in vivo and lipopolysaccharide exposure in vitro. Function analysis showed that siRNA-mediated AjSDHB knockdown could substantially reduce the mitochondrial membrane potential (ΔΨm) and further decrease mitochondrial ROS production in A. japonicus coelomocytes. By contrast, AjSDHB overexpression considerably increased ΔΨm and mitochondrial ROS production of A. japonicus coelomocytes. These results supported the idea that AjSDHB is involved in the innate immunity of A. japonicus through its participation in mitochondrial ROS generation.

2.
Dev Comp Immunol ; 109: 103694, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32283109

RESUMO

The sedoheptulose kinase carbohydrate kinase-like protein (CARKL) is critical for immune cell activation, reactive oxygen species (ROS) production, and cell polarization by restricting flux through the pentose phosphate pathway (PPP). To date, little is known about CARKL in regulating immune responses in marine invertebrates. In this study, we first cloned and characterized the CARKL gene from Apostichopus japonicus (designated as AjCARKL). Time-course analysis revealed that Vibrio splendidus challenge in vivo and lipopolysaccharide stimulation in vitro significantly downregulated AjCARKL mRNA expression. Furthermore, AjCARKL overexpression in cultured coelomocytes not only significantly inhibited the mRNA expression level of the rate-limiting enzyme glucose-6-phosphate dehydrogenase of the PPP but sharply decreased coelomocyte proliferation, ROS production, and phagocytic rate. Additionally, AjCARKL overexpression in mouse peritoneal macrophages (RAW264.7 cells) significantly attenuated the intracellular ROS production and sensitized the M2 phenotype macrophage polarization. These results revealed that AjCARKL serves as a rheostat for cellular metabolism and is required for proper immune response by negatively regulating PPP in pathogen-challenged A. japonicus.

3.
Chemistry ; 26(19): 4246-4250, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32012367

RESUMO

The radical-radical coupling reaction is an important synthetic strategy. In this study, the iron-catalyzed radical-radical cross-coupling reaction based on the decarboxylation of keto acids and decarbonylation of aliphatic aldehydes to obtain valuable aryl ketones is reported for the first time. Remarkably, when tertiary aldehydes were used as carbonyl sources, ketone esters were selectively obtained instead of ketones. The gram-scale preparation of aryl ketone through this strategy was easily achieved by using only 3 mol % of the iron catalyst. As a proof-of-concept, the bioactive molecule flurprimidol was synthesized in two steps by using this strategy.

4.
Front Psychol ; 10: 2547, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31781010

RESUMO

The present study aimed to investigate whether acute moderate-intensity exercise led to a selective effect on executive function tasks or general effect on cognitive tasks that involve executive function and basic information processing in young adults. Besides, we also aimed to examine acute exercise's effect on multiple ERP components (e.g., P2, N2, P3b, and N450) to expand previous research. Seventy-two young adults were randomly assigned to the exercise or control groups. The Stroop task was administrated before and after treatments (exercise or reading), and the P2, N2, P3b, and N450 components of the Event-Related Potential (ERP) waveform were recorded and analyzed. Larger P2 amplitudes on both congruent and incongruent tasks were observed following acute exercise. Acute exercise did not influence accuracy or response time, and no effects on N2, P3b, and N450 components were found. These findings suggest that acute moderate-intensity exercise may have a generally beneficial effect on mobilization of attentional resources related to perceptual processing and exercise-related physiological arousal.

5.
Sci Immunol ; 4(37)2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31300478

RESUMO

Immunological tolerance of tumors is characterized by insufficient infiltration of cytotoxic T lymphocytes (CTLs) and immunosuppressive microenvironment of tumor. Tumor resistance to immune checkpoint inhibitors due to immunological tolerance is an ongoing challenge for current immune checkpoint blockade (ICB) therapy. Here, we report the development of tumor microenvironment-activatable anti-PDL1 antibody (αPDL1) nanoparticles for combination immunotherapy designed to overcome immunological tolerance of tumors. Combination of αPDL1 nanoparticle treatment with near-infrared (NIR) laser irradiation-triggered activation of photosensitizer indocyanine green induces the generation of reactive oxygen species, which promotes the intratumoral infiltration of CTLs and sensitizes the tumors to PDL1 blockade therapy. We showed that the combination of antibody nanoparticles and NIR laser irradiation effectively suppressed tumor growth and metastasis to the lung and lymph nodes in mouse models. The nanoplatform that uses the antibody nanoparticle alone both for immune stimulation and PDL1 inhibition could be readily adapted to other immune checkpoint inhibitors for improved ICB therapy.

6.
J Immunol ; 203(3): 760-768, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31201236

RESUMO

A T cell clone is able to distinguish Ags in the form of peptide-MHC complexes with high specificity and sensitivity; however, how subtle differences in peptide-MHC structures translate to distinct T cell effector functions remains unknown. We hypothesized that mitochondrial positioning and associated calcium responses play an important role in T cell Ag recognition. We engineered a microfluidic system to precisely manipulate and synchronize a large number of cell-cell pairing events, which provided simultaneous real-time signaling imaging and organelle tracking with temporal precision. In addition, we developed image-derived metrics to quantify calcium response and mitochondria movement. Using myelin proteolipid altered peptide ligands and a hybridoma T cell line derived from a mouse model of experimental autoimmune encephalomyelitis, we observed that Ag potency modulates calcium response at the single-cell level. We further developed a partial least squares regression model, which highlighted mitochondrial positioning as a strong predictor of calcium response. The model revealed T cell mitochondria sharply alter direction within minutes following exposure to agonist peptide Ag, changing from accumulation at the immunological synapse to retrograde movement toward the distal end of the T cell body. By quantifying mitochondria movement as a highly dynamic process with rapidly changing phases, our result reconciles conflicting prior reports of mitochondria positioning during T cell Ag recognition. We envision applying this pipeline of methodology to study cell interactions between other immune cell types to reveal important signaling phenomenon that is inaccessible because of data-limited experimental design.

7.
Nat Mater ; 18(7): 760-769, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30911119

RESUMO

Integrins are membrane receptors that mediate cell adhesion and mechanosensing. The structure-function relationship of integrins remains incompletely understood, despite the extensive studies carried out because of its importance to basic cell biology and translational medicine. Using a fluorescence dual biomembrane force probe, microfluidics and cone-and-plate rheometry, we applied precisely controlled mechanical stimulations to platelets and identified an intermediate state of integrin αIIbß3 that is characterized by an ectodomain conformation, ligand affinity and bond lifetimes that are all intermediate between the well-known inactive and active states. This intermediate state is induced by ligand engagement of glycoprotein (GP) Ibα via a mechanosignalling pathway and potentiates the outside-in mechanosignalling of αIIbß3 for further transition to the active state during integrin mechanical affinity maturation. Our work reveals distinct αIIbß3 state transitions in response to biomechanical and biochemical stimuli, and identifies a role for the αIIbß3 intermediate state in promoting biomechanical platelet aggregation.


Assuntos
Fenômenos Mecânicos , Agregação Plaquetária , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo , Fenômenos Biomecânicos , Humanos , Ligantes , Transdução de Sinais
8.
Adv Mater ; 31(14): e1805888, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30762908

RESUMO

Chemoimmunotherapy is reported to activate a robust T cell antitumor immune response by triggering immunogenic cell death (ICD), which has initiated a number of clinical trials. However, current chemoimmunotherapy is restricted to a small fraction of patients due to low drug delivery efficacy and immunosuppression within the tumor microenvironment. A tumor microenvironment-activatable prodrug vesicle for cancer chemoimmunotherapy using ICD is herein reported. The prodrug vesicles are engineered by integrating an oxaliplatin (OXA) prodrug and PEGylated photosensitizer (PS) into a single nanoplatform, which show tumor-specific accumulation, activation, and deep penetration in response to the tumoral acidic and enzymatic microenvironment. It is demonstrated that codelivery of OXA prodrug and PS can trigger ICD of the tumor cells by immunogenic cells killing. The combination of prodrug vesicle-induced ICD with Î ± CD47-mediated CD47 blockade further facilitates dendritic cell (DC) maturation, promotes antigen presentation by DCs, and eventually propagates the antitumor immunity of ICD. CD47 blockade and ICD induction efficiently inhibit the growth of both primary and abscopal tumors, suppress tumor metastasis, and prevent tumor recurrence. Collectively, these results imply that boosting antitumor immunity using ICD induction and suppressing tumor immune evasion via CD47 blockade might be promising for improved cancer chemoimmunotherapy.


Assuntos
Antígeno CD47/antagonistas & inibidores , Morte Celular/efeitos dos fármacos , Morte Celular/imunologia , Imunoterapia/métodos , Nanoestruturas/química , Pró-Fármacos/metabolismo , Microambiente Tumoral/efeitos dos fármacos , Animais , Humanos , Pró-Fármacos/química , Microambiente Tumoral/imunologia
9.
Pest Manag Sci ; 75(1): 170-179, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29797399

RESUMO

BACKGROUND: Insects form both mutualistic and antagonistic relationships with microbes, and some antagonistic microbes have been used as biocontrol agents (BCAs) in pest management. Contextually, BCAs may be inhibited by beneficial insect symbionts, which can become potential barriers to entomopathogen-dependent pest biocontrol. Using the symbioses formed by one devastating dipteran pest, Delia antiqua, and its associated microbes as a model system, we sought to determine whether the antagonistic interaction between BCAs and microbial symbionts could affect the outcome of entomopathogen-dependent pest biocontrol. RESULTS: The result showed that in contrast to non-axenic D. antiqua larvae, i.e., onion maggots, axenic larvae lost resistance to the entomopathogenic Beauveria bassiana, and the re-inoculation of microbiota increased the resistance of axenic larvae to B. bassiana. Furthermore, bacteria frequently isolated from larvae, including Citrobacter freundii, Enterobacter ludwigii, Pseudomonas protegens, Serratia plymuthica, Sphingobacterium faecium and Stenotrophomonas maltophilia, suppressed B. bassiana conidia germination and hyphal growth, and the re-inoculation of specific individual bacteria enhanced the resistance of axenic larvae to B. bassiana. CONCLUSION: Bacteria associated with larvae, including C. freundii, E. ludwigii, P. protegens, S. plymuthica, S. faecium and S. maltophilia, can inhibit B. bassiana infection. Removing the microbiota can suppress larval resistance to fungal infection. © 2018 Society of Chemical Industry.


Assuntos
Beauveria/fisiologia , Dípteros/microbiologia , Microbiota , Controle Biológico de Vetores , Animais , China , Dípteros/crescimento & desenvolvimento , Larva/crescimento & desenvolvimento , Larva/microbiologia
10.
Mol Pain ; 14: 1744806918796057, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30152258

RESUMO

Extracellular regulated protein kinase (ERK) pathway activation in astrocytes and neurons has been reported to be critical for neuropathic pain development after chronic constriction injury. TGN-020 was found to be the most potent aquaporin 4 inhibitor among the agents studied. The present study aimed to assess whether the inhibition of aquaporin 4 had an analgesic effect on neuropathic pain and whether the inhibition of astrocytic activation and ERK pathway was involved in the analgesic effect of TGN-020. We thus found that TGN-020 upregulated the threshold of thermal and mechanical allodynia, downregulated the expression of interleukin-1ß, interleukin-6, and tumor necrosis factor-α, attenuated the astrocytic activation and suppressed the activation of mitogen-activated protein kinase pathways in the spinal dorsal horn and dorsal root ganglion. Additionally, TGN-020 suppressed ERK phosphorylation in astrocytes and neurons after injury. The findings suggested that the analgesic effects of TGN-020 in neuropathic pain were mediated mainly by the downregulation of chronic constriction injury-induced astrocytic activation and inflammation, which is via the inhibition of ERK pathway in the spinal dorsal horn and dorsal root ganglion.


Assuntos
Analgésicos/uso terapêutico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Neuralgia/tratamento farmacológico , Niacinamida/análogos & derivados , Tiadiazóis/uso terapêutico , Animais , Aquaporina 4/antagonistas & inibidores , Aquaporina 4/metabolismo , Modelos Animais de Doenças , Hiperalgesia/tratamento farmacológico , Hiperalgesia/etiologia , Masculino , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Niacinamida/uso terapêutico , Limiar da Dor/efeitos dos fármacos , Fosfopiruvato Hidratase/metabolismo , Ratos , Ratos Sprague-Dawley , Regulação para Cima/efeitos dos fármacos
11.
Adv Mater ; 30(38): e1803001, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30063262

RESUMO

Checkpoint blockade immunotherapy is promising for clinical treatment of various malignant tumors. However, checkpoint blockade immunotherapy suffers from a low response rate due to insufficient tumor immunogenicity and the immunosuppressive tumor microenvironment (ITM). In this study, a tumor-microenvironment-activatable binary cooperative prodrug nanoparticle (BCPN) is rationally designed to improve immunotherapy by synergistically modulating the immune tumor microenvironment. BCPN is purely constructed from a tumor acidity and reduction dual-responsive oxaliplatin (OXA) prodrug for triggering immunogenic cell death (ICD) and eliciting antitumor immunity, and a reduction-activatable homodimer of NLG919 for inactivating indoleamine 2,3-dioxygenase 1, which is a key regulator for ITM. Upon tumor-acidity-triggered cleavage of the poly(ethylene glycol) shell, PN shows negative to positive charge switch for enhanced tumor accumulation and deep penetration. OXA and NLG919 are then activated in the tumor cells via glutathione-mediated reduction. It is demonstrate that activated OXA promotes intratumoral accumulation of cytotoxic T lymphocytes by triggering ICD of cancer cells. Meanwhile, NLG919 downregulates IDO-1-mediated immunosuppression and suppresses regulatory T cells. Most importantly, PN shows much higher efficiency than free OXA or the combination of free OXA and NLG919 to regress tumor growth and prevent metastasis of mouse models of both breast and colorectal cancer.


Assuntos
Nanopartículas , Animais , Imunoterapia , Camundongos , Neoplasias , Pró-Fármacos , Microambiente Tumoral
12.
Front Microbiol ; 9: 1251, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29963021

RESUMO

Insects harbor a community of gut bacteria, ranging from pathogenic to obligate mutualistic organisms. Both biotic and abiotic factors can influence species composition and structure of the insect gut bacterial communities. Dendroctonus valens is a destructive forest pest in China. To overcome host pine defenses, beetles mass-attack the pine to a threshold density that can exhaust pine defenses. The intensity of pine chemical defenses and carbohydrate concentrations of pines can be influenced by beetle attack, both of which are known factors that modify beetle's gut microbiota. However, little is known to what extent variation exists in the beetle's gut communities, and host monoterpenes and carbohydrates at different attack densities. In this study, the gut bacterial microbiota of D. valens at low and high attack densities were analyzed, and monoterpenes and carbohydrates in host pine phloem were assayed in parallel. The results showed that no significant changes of gut bacterial communities of the beetles and concentrations of D-glucose, D-pinitol, and D-fructose in pine phloem were found between low and high attack densities. The concentrations of α-pinene, ß-pinene, limonene at high attack densities were significantly higher than those at low attack densities. Our results suggested that different attack densities of D. valens influence monoterpenes concentration of host pines' phloem but have no significant impact on gut bacterial community structures of D. valens and carbohydrate concentration of host trees' phloem in early attack phase. Similar gut bacterial community structures of D. valens between low and high attack densities might be due to the quick adaptation of gut microbiota to high monoterpenes concentrations.

13.
EBioMedicine ; 33: 57-67, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30045829

RESUMO

BACKGROUND: Long non-coding RNAs (lncRNAs) show great potential as diagnostic tools in many diseases. We aimed to develop sensitive and noninvasive biomarkers in saliva for detecting early hepatocellular carcinoma (HCC). METHODS: Candidate lncRNA biomarkers identified by Agilent microarray were subjected to validation using qPCR for the quantification of their expression levels in independent tissue, plasma and saliva sample sets, including healthy controls, HBsAg carriers, patients with chronic Hepatitis B, liver cirrhosis, early HCC, and advanced HCC. Levels of candidate biomarkers were also measured in totally 108 saliva samples from patients with any one of other nine leading causes of cancer death in men and women. FINDINGS: Lnc-PCDH9-13:1 was significantly elevated in HCC tissues, plasma and saliva of HCC patients compared with healthy controls and groups of several benign liver diseases and other leading cancers. Its level was significantly reduced after curative hepatectomy but significantly elevated again if HCC recurrence occurred. Salivary lnc-PCDH9-13:1 showed reasonable specificities and sensitivities for detecting HCC compared with several control groups. Furthermore, the overexpression of lnc-PCDH9-13:1 promotes cell proliferation and migration in vitro. INTERPRETATION: Salivary lnc-PCDH9-13:1 is a desirable biomarker for early HCC. It may help warrant prospective validation with larger sample sizes in multi-centers.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , RNA Longo não Codificante/genética , Regulação para Cima , Idoso , Linhagem Celular Tumoral , Detecção Precoce de Câncer , Feminino , Regulação Neoplásica da Expressão Gênica , Células Hep G2 , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Estudos Prospectivos , Saliva/química
14.
Nat Commun ; 9(1): 1532, 2018 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-29670088

RESUMO

Vaccines to induce effective and sustained antitumor immunity have great potential for postoperative cancer therapy. However, a robust cancer vaccine simultaneously eliciting tumor-specific immunity and abolishing immune resistance continues to be a challenge. Here we present a personalized cancer vaccine (PVAX) for postsurgical immunotherapy. PVAX is developed by encapsulating JQ1 (a BRD4 inhibitor) and indocyanine green (ICG) co-loaded tumor cells with a hydrogel matrix. Activation of PVAX by 808 nm NIR laser irradiation significantly inhibits the tumor relapse by promoting the maturation of dendritic cells and eliciting tumor infiltration of cytotoxic T lymphocytes. A mechanical study reveals that NIR light-triggered antigen release and JQ1-mediated PD-L1 checkpoint blockade cumulatively contribute to the satisfied therapeutic effect. Furthermore, PVAX prepared from the autologous tumor cells induces patient-specific memory immune response to prevent tumor recurrence and metastasis. The PVAX model might provide novel insights for postoperative immunotherapy.


Assuntos
Vacinas Anticâncer/uso terapêutico , Imunoterapia , Metástase Neoplásica , Neoplasias/imunologia , Neoplasias/terapia , Animais , Células Dendríticas/citologia , Feminino , Humanos , Hidrogéis/química , Hidrogênio/química , Verde de Indocianina/química , Lasers , Camundongos , Camundongos Endogâmicos BALB C , Células NIH 3T3 , Transplante de Neoplasias , Neoplasias/cirurgia , Peptídeos/química , Período Pós-Operatório , Recidiva , Linfócitos T Citotóxicos/citologia
15.
Horm Metab Res ; 50(1): 65-72, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29329467

RESUMO

Several groups have reported the important role of estradiol (E2) and testosterone (T) in postmenopausal osteoporosis (PMOP). Because aromatase catalyzes the conversion of T to E2, the purpose of this study was to determine the influence of aromatase activity on the bone mineral density (BMD) in postmenopausal women. A total of 344 postmenopausal women were selected for this study. Serum E2, T, sex hormone-binding globulin (SHBG), calcium (Ca), alkaline phosphatase (ALP), C-terminal telopeptide of type I collagen (CTX), and procollagen type I amino-terminal propeptide (PINP) were examined. The E2/T was positively associated with total hip BMD and PINP (p<0.05). When E2/T was divided into quartiles, participants in lower quartiles of E2/T were likely to have higher PINP and lower BMD (p<0.05). The prevalence of osteoporosis significantly increased as E2/T ratio decreased. The receiver operating characteristic (ROC) curves were constructed for serum E2, free E2 index (FEI), and E2/T, to assess their diagnostic accuracy in PMOP. The overall area under the curve (AUC) were 0.83 (95% CI=0.77-0.88) for E2, 0.87 (95% CI=0.82-0.92) for FEI, and 0.89 (95% CI=0.85-0.94), respectively. In conclusion, the study suggests that in postmenopausal women, aromatase activity could be an important determinant of skeletal health. The women with lower aromatase activity may have greater likelihood of PMOP and the E2/T was expected to be a valuable indicator for the prediction of PMOP and to monitor the process of osteoporosis.


Assuntos
Aromatase/metabolismo , Grupo com Ancestrais do Continente Asiático , Densidade Óssea , Estradiol/metabolismo , Quadril/fisiopatologia , Osteoporose Pós-Menopausa/metabolismo , Osteoporose Pós-Menopausa/fisiopatologia , Globulina de Ligação a Hormônio Sexual/metabolismo , Idoso , Biomarcadores/metabolismo , Doenças Ósseas Metabólicas/epidemiologia , Remodelação Óssea , Feminino , Humanos , Funções Verossimilhança , Modelos Lineares , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/epidemiologia , Pós-Menopausa , Prevalência , Curva ROC
16.
ISME J ; 11(12): 2809-2820, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28800134

RESUMO

Interactions among microbial symbionts have multiple roles in the maintenance of insect-microbe symbiosis. However, signals mediating microbial interactions have been scarcely studied. In the classical model system of bark beetles and fungal associates, fungi increase the fitness of insects. However, not all interactions are mutualistic, some of these fungal symbionts compete for sugars with beetle larvae. How this antagonistic effect is alleviated is unknown, and recent research suggests potential roles of bacterial symbionts. Red turpentine beetle (RTB), Dendroctonus valens LeConte, is an invasive pest in China, and it leads to wide spread, catastrophic mortality to Chinese pines. In the symbiotic system formed by RTB, fungi and bacteria, volatiles from predominant bacteria regulate the consumption sequence of carbon sources d-pinitol and d-glucose in the fungal symbiont Leptographium procerum, and appear to alleviate the antagonistic effect from the fungus against RTB larvae. However, active components of these volatiles are unknown. We detected 67 volatiles by Gas Chromatography-Mass Spectrometer (GC-MS). Seven of them were identified as candidate chemicals mediating bacteria-fungus interactions, among which ammonia made L. procerum consume its secondary carbon source D-pinitol instead of its preferred carbohydrate D-glucose. In conclusion, ammonia regulated the consumption sequence of these two carbon sources in the fungal symbiont.


Assuntos
Amônia/metabolismo , Bactérias/metabolismo , Glucose/metabolismo , Inositol/análogos & derivados , Ophiostomatales/metabolismo , Pinus/parasitologia , Gorgulhos/microbiologia , Amônia/análise , Animais , Bactérias/química , China , Inositol/metabolismo , Simbiose , Gorgulhos/fisiologia
17.
Nano Lett ; 17(9): 5429-5436, 2017 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-28753017

RESUMO

The success of cancer chemotherapy is impeded by poor drug delivery efficiency due to the existence of a series of pathophysiological barriers in the tumor. In this study, we reported a tumor acidity-triggered ligand-presenting (ATLP) nanoparticle for cancer therapy. The ATLP nanoparticles were composed of an acid-responsive diblock copolymer as a sheddable matrix and an iRGD-modified polymeric prodrug of doxorubicin (iPDOX) as an amphiphilic core. A PEG corona of the polymer matrix protected the iRGD ligand from serum degradation and nonspecific interactions with the normal tissues while circulating in the blood. The ATLP nanoparticles specifically accumulated at the tumor site through the enhanced permeability and retention (EPR) effect, followed by acid-triggered dissociation of the polymer matrix within the tumoral acidic microenvironment (pH ∼ 6.8) and subsequently exposing the iRGD ligand for facilitating tumor penetration and cellular uptake of the PDOX prodrug. Additionally, the acid-triggered dissociation of the polymer matrix induced a 4.5-fold increase of the fluorescent signal for monitoring nanoparticle activation in vivo. Upon near-infrared (NIR) laser irradiation, activation of Ce6-induced significant reactive oxygen species (ROS) generation, promoted drug diffusion inside the tumor mass and circumvented the acquired drug resistance by altering the gene expression profile of the tumor cells. The ATLP strategy might provide a novel insight for cancer nanomedicine.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Preparações de Ação Retardada/química , Doxorrubicina/administração & dosagem , Nanopartículas/química , Ácidos/química , Animais , Antibióticos Antineoplásicos/farmacocinética , Antibióticos Antineoplásicos/uso terapêutico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Doxorrubicina/farmacocinética , Doxorrubicina/uso terapêutico , Sistemas de Liberação de Medicamentos , Feminino , Humanos , Concentração de Íons de Hidrogênio , Ligantes , Células MCF-7 , Camundongos Nus , Microambiente Tumoral/efeitos dos fármacos
19.
J Microbiol Methods ; 141: 28-31, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28754446

RESUMO

An appropriate reference gene is required to get reliable results from gene expression analysis by quantitative real-time reverse transcription PCR (qRT-PCR). In order to identify stable and reliable reference genes in Trichoderma afroharzianum under oxalic acid (OA) stress, six commonly used housekeeping genes, i.e., elongation factor 1, ubiquitin, ubiquitin-conjugating enzyme, glyceraldehyde-3-phosphate dehydrogenase, α-tubulin, actin, from the effective biocontrol isolate T. afroharzianum strain LTR-2 were tested for their expression during growth in liquid culture amended with OA. Four in silico programs (comparative ΔCt, NormFinder, geNorm and BestKeeper) were used to evaluate the expression stabilities of six candidate reference genes. The elongation factor 1 gene EF-1 was identified as the most stably expressed reference gene, and was used as the normalizer to quantify the expression level of the oxalate decarboxylase coding gene OXDC in T. afroharzianum strain LTR-2 under OA stress. The result showed that the expression of OXDC was significantly up-regulated as expected. This study provides an effective method to quantify expression changes of target genes in T. afroharzianum under OA stress.


Assuntos
Expressão Gênica , Reação em Cadeia da Polimerase em Tempo Real/métodos , Estresse Fisiológico/genética , Trichoderma/genética , Trichoderma/fisiologia , Genes Essenciais , Genes de Plantas , Ácido Oxálico/metabolismo , Fator 1 de Elongação de Peptídeos/genética , Padrões de Referência , Ubiquitina/genética
20.
Sci Rep ; 7(1): 3249, 2017 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-28607407

RESUMO

Garlic, a widely cultivated global vegetable crop, is threatened by the underground pest Bradysia odoriphaga in China. Previous reports indicated that garlic essential oil, of which the dominant components are sulfides or thiosulfinates, exhibits insecticidal activity against pests. However, it is unclear whether the resistance of garlic to B. odoriphaga is related to thiosulfinates. Here, we compared the resistance of 10 garlic cultivars at various growth stages to B. odoriphaga by field investigation and indoor life-table data collection. Furthermore, the relationship between thiosulfinates content and resistance, as well as the toxicity of garlic oil and allicin against B. odoriphaga larvae was determined. Field surveys demonstrated that the garlic cultivars Qixian and Cangshan possessed the highest resistance, while Siliuban and Yishui were the most sensitive. When reared on Qixian, B. odoriphaga larval survival and fecundity declined by 26.2% and 17.7% respectively, but the development time was prolonged by 2.8 d compared with Siliuban. A positive correlation was detected between thiosulfinates content and resistance. Furthermore, garlic oil and allicin exhibited strong insecticidal activity. We screened out 2 pest-resistant cultivars, for which thiosulfinate content was highest. Additionally, the insecticidal activity displayed by sulfides and allcin suggests their potential for exploitation as botanical insecticides.


Assuntos
Alho/química , Nematóceros/efeitos dos fármacos , Compostos Alílicos/análise , Compostos Alílicos/farmacologia , Animais , Feminino , Fertilidade/efeitos dos fármacos , Alho/genética , Inseticidas/farmacologia , Larva/efeitos dos fármacos , Masculino , Nematóceros/crescimento & desenvolvimento , Melhoramento Vegetal , Sulfetos/análise , Sulfetos/farmacologia , Ácidos Sulfínicos/análise , Ácidos Sulfínicos/farmacologia
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