Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 82
Filtrar
1.
Pharmaceutics ; 13(11)2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34834192

RESUMO

Micelle is mainly used for drug delivery and is prepared from amphiphilic block copolymers. It can be formed into an obvious core-shell structure that can incorporate liposoluble drugs. However, micelles are not suitable for the encapsulation of water-soluble drugs, and it is also difficult to maintain stability in the systemic circulation. To solve these problems, a type of polymer material, Fmoc-Lys-PEG and Fmoc-Lys-PEG-RGD, was designed and synthesized. These copolymers could self-assemble into micelles driven by π-π stacking and the hydrophobic interaction of 9-fluorenylmethoxycarbony (Fmoc) and, at the same time, form a framework for a hydrogen-bonding environment in the core. Mitomycin C (MMC), as a water-soluble drug, can be encapsulated into micelles by hydrogen-bonding interactions. The interaction force between MMC and the polymers was analyzed by molecular docking simulation and Fourier transform infrared (FTIR). It was concluded that the optimal binding conformation can be obtained, and that the main force between the MMC and polymers is hydrogen bonding. Different types of MMC nanoparticles (NPs) were prepared and the physicochemical properties of them were systematically evaluated. The pharmacodynamics of the MMC NPs in vitro and in vivo were also studied. The results show that MMC NPs had a high uptake efficiency, could promote cell apoptosis, and had a strong inhibitory effect on cell proliferation. More importantly, the as-prepared NPs could effectively induce tumor cell apoptosis and inhibit tumor growth and metastasis in vivo.

2.
Sci China Life Sci ; 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34729700

RESUMO

Blood vessel dysfunction causes several retinal diseases, including diabetic retinopathy, familial exudative vitreoretinopathy, macular degeneration and choroidal neovascularization in pathological myopia. Vascular endothelial growth factor (VEGF)-neutralizing proteins provide benefits in most of those diseases, yet unsolved haemorrhage and frequent intraocular injections still bothered patients. Here, we identified endothelial CD146 as a new target for retinal diseases. CD146 expression was activated in two ocular pathological angiogenesis models, a laser-induced choroid neovascularization model and an oxygen-induced retinopathy model. The absence of CD146 impaired hypoxia-induced cell migration and angiogenesis both in cell lines and animal model. Preventive or therapeutic treatment with anti-CD146 antibody AA98 significantly inhibited hypoxia-induced aberrant retinal angiogenesis in two retinal disease models. Mechanistically, under hypoxia condition, CD146 was involved in the activation of NFκB, Erk and Akt signalling pathways, which are partially independent of VEGF. Consistently, anti-CD146 therapy combined with anti-VEGF therapy showed enhanced impairment effect of hypoxia-induced angiogenesis in vitro and in vivo. Given the critical role of abnormal angiogenesis in retinal and choroidal diseases, our results provide novel insights into combinatorial therapy for neovascular fundus diseases.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34636991

RESUMO

PURPOSE: Cyclase-associated protein 1 (CAP1) is a ubiquitous protein which regulates actin dynamics. Previous studies have shown that S308 and S310 are the two major phosphorylated sites in human CAP1. In the present study, we aimed to investigate the role of CAP1 phosphorylation in lung cancer. METHODS: Massive bioinformatics analysis was applied to determine CAP1's role in different cancers and especially in lung cancer. Lung cancer patients' serum and tissue were collected and analyzed in consideration of clinical background. CAP1 shRNA-lentivirus and siRNA were applied to CAP1 gene knockdown, and plasmids were constructed for CAP1 phosphorylation and de-phosphorylation. Microarray analysis was used for CAP1-associated difference analysis. Both in vitro and in vivo experiments were performed to investigate the roles of CAP1 phosphorylation and de-phosphorylation in lung cancer A549 cells. RESULTS: CAP1 is a kind of cancer-related protein. Its mRNA was overexpressed in most types of cancer tissues when compared with normal tissues. CAP1 high expression correlated with poor prognosis. Our results showed that serum CAP1 protein concentrations were significantly upregulated in non-small cell lung cancer (NSCLC) patients when compared with the healthy control group, higher serum CAP1 protein concentration correlated with shorter overall survival (OS) in NSCLC patients, and higher pCAP1 and CAP1 protein level were observed in lung cancer patients' tumor tissue compared with adjacent normal tissue. Knockdown CAP1 in A549 cells can inhibit proliferation and migration, and the effect is validated in H1975 cells. It can also lead to an increase ratio of F-actin/G-actin. In addition, phosphorylated S308 and S310 in CAP1 promoted lung cancer cell proliferation, migration, and metastasis both in vitro and in vivo. When de-phosphorylated, these two sites in CAP1 showed the opposite effect. Phosphorylation of CAP1 can promote epithelial-mesenchymal transition (EMT). CONCLUSION: These findings indicated that CAP1 phosphorylation can promote lung cancer proliferation, migration, and invasion. Phosphorylation sites of CAP1 might be a novel target for lung cancer treatment.

4.
Int J Nanomedicine ; 16: 5755-5776, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34471351

RESUMO

Background: Glioma is the most common primary malignant brain tumor with a dreadful overall survival and high mortality. One of the most difficult challenges in clinical treatment is that most drugs hardly pass through the blood-brain barrier (BBB) and achieve efficient accumulation at tumor sites. Thus, to circumvent this hurdle, developing an effectively traversing BBB drug delivery nanovehicle is of significant clinical importance. Rabies virus glycoprotein (RVG) is a derivative peptide that can specifically bind to nicotinic acetylcholine receptor (nAChR) widely overexpressed on BBB and glioma cells for the invasion of rabies virus into the brain. Inspired by this, RVG has been demonstrated to potentiate drugs across the BBB, promote the permeability, and further enhance drug tumor-specific selectivity and penetration. Methods: Here, we used the RVG15, rescreened from the well-known RVG29, to develop a brain-targeted liposome (RVG15-Lipo) for enhanced BBB permeability and tumor-specific delivery of paclitaxel (PTX). The paclitaxel-cholesterol complex (PTX-CHO) was prepared and then actively loaded into liposomes to acquire high entrapment efficiency (EE) and fine stability. Meanwhile, physicochemical properties, in vitro and in vivo delivery efficiency and therapeutic effect were investigated thoroughly. Results: The particle size and zeta potential of PTX-CHO-RVG15-Lipo were 128.15 ± 1.63 nm and -15.55 ± 0.78 mV, respectively. Compared with free PTX, PTX-CHO-RVG15-Lipo exhibited excellent targeting efficiency and safety in HBMEC and C6 cells, and better transport efficiency across the BBB in vitro model. Furthermore, PTX-CHO-RVG15-Lipo could noticeably improve the accumulation of PTX in the brain, and then promote the chemotherapeutic drugs penetration in C6luc orthotopic glioma based on in vivo imaging assays. The in vivo antitumor results indicated that PTX-CHO-RVG15-Lipo significantly inhibited glioma growth and metabasis, therefore improved survival rate of tumor-bearing mice with little adverse effect. Conclusion: Our study demonstrated that the RVG15 was a promising brain-targeted specific ligands owing to the superior BBB penetration and tumor targeting ability. Based on the outstanding therapeutic effect both in vitro and in vivo, PTX-CHO-RVG15-Lipo was proved to be a potential delivery system for PTX to treat glioma in clinic.


Assuntos
Neoplasias Encefálicas , Glioma , Animais , Barreira Hematoencefálica , Encéfalo , Neoplasias Encefálicas/tratamento farmacológico , Linhagem Celular Tumoral , Colesterol , Sistemas de Liberação de Medicamentos , Glioma/tratamento farmacológico , Lipossomos/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Paclitaxel/uso terapêutico
5.
J Clin Invest ; 131(21)2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34491908

RESUMO

Initiation of T cell receptor (TCR) signaling involves the activation of the tyrosine kinase LCK; however, it is currently unclear how LCK is recruited and activated. Here, we have identified the membrane protein CD146 as an essential member of the TCR network for LCK activation. CD146 deficiency in T cells substantially impaired thymocyte development and peripheral activation, both of which depend on TCR signaling. CD146 was found to directly interact with the SH3 domain of coreceptor-free LCK via its cytoplasmic domain. Interestingly, we found CD146 to be present in both monomeric and dimeric forms in T cells, with the dimerized form increasing after TCR ligation. Increased dimerized CD146 recruited LCK and promoted LCK autophosphorylation. In tumor models, CD146 deficiency dramatically impaired the antitumor response of T cells. Together, our data reveal an LCK activation mechanism for TCR initiation. We also underscore a rational intervention based on CD146 for tumor immunotherapy.

6.
Chin Med J (Engl) ; 134(18): 2166-2174, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34553699

RESUMO

BACKGROUND: The effectiveness of bronchial thermoplasty (BT) has been reported in patients with severe asthma. This study compared the effects of BT and cryoballoon ablation (CBA) therapy on the airway smooth muscle (ASM). METHODS: Eight healthy male beagle dogs were included in this experiment. In the preliminary experiment, one dog received BT treatment for both lower lobe bronchus, another dog received CBA treatment for 7 s on the upper and lower lobe of right bronchus, and 30 s on the left upper and lower lobe. The treatments were performed twice at an interval of 1 month. In subsequent experiments, the right lower lobe bronchus was treated with BT, and the left lower lobe bronchus was treated with CBA. The effects of treatment were observed after 1 (n = 3) month and 6 months (n = 3). Hematoxylin-eosin staining, Masson trichrome staining, and immunohistochemical staining were used to compare the effects of BT and CBA therapy on the ASM thickness, collagen fibers synthesis, and M3 receptor expression after treatment. One-way analysis of variance with Dunnett post hoc test was used to analyze the differences among groups. RESULTS: In the preliminary experiment, the ASM ablation effect of 30-s CBA was equivalent to that of 7-s CBA (ASM thickness: 30.52 ±â€Š7.75 µm vs. 17.57 ±â€Š15.20 µm, P = 0.128), but the bronchial mucociliary epithelium did not recover, and large numbers of inflammatory cells had infiltrated the mucosal epithelium at 1-month post-CBA with 30-s freezing. Therefore, we chose 7 s as the CBA treatment time in our follow-up experiments. Compared with the control group (35.81 ±â€Š11.02 µm), BT group and CBA group (13.41 ±â€Š4.40 µm and 4.81 ±â€Š4.44 µm, respectively) had significantly decreased ASM thickness after 1 month (P < 0.001). Furthermore, the ASM thickness was significantly lower in the 1-month post-CBA group than in the 1-month post-BT group (P = 0.015). There was no significant difference in ASM thickness between the BT and CBA groups after six months (9.92 ±â€Š4.42 µm vs. 7.41 ±â€Š7.20 µm, P = 0.540). Compared with the control group (0.161 ±â€Š0.013), the average optical density of the ASM M3 receptor was significantly decreased in 6-month post-BT, 1-month post-CBA, and 6-month post-CBA groups (0.070 ±â€Š0.022, 0.072 ±â€Š0.012, 0.074 ±â€Š0.008, respectively; all P < 0.001). There was no significant difference in the average optical density of ASM M3 receptor between the BT and CBA therapy groups after six months (P = 0.613). CONCLUSIONS: CBA therapy effectively ablates the ASM, and its ablation effect is equivalent to that of BT with a shorter onset time. A neural mechanism is involved in both BT and CBA therapy.


Assuntos
Termoplastia Brônquica , Criocirurgia , Animais , Brônquios/cirurgia , Broncoscopia , Cães , Humanos , Masculino , Músculo Liso
7.
Front Psychol ; 12: 686529, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34566765

RESUMO

Background: Individuals exposed to childhood maltreatment present with a deficiency in emotional processing in later life. Most studies have focused mainly on childhood physical or sexual abuse; however, childhood emotional abuse, a core issue underlying different forms of childhood maltreatment, has received relatively little attention. The current study explored whether childhood emotional abuse is related to the impaired processing of emotional facial expressions in healthy young men. Methods: The emotional facial processing was investigated in a classical gender discrimination task while the event-related potentials (ERPs) data were collected. Childhood emotional abuse was assessed by a Childhood Trauma Questionnaire (CTQ) among 60 healthy young men. The relationship between the score of emotional abuse and the behavioral and the ERP index of emotional facial expression (angry, disgust, and happy) were explored. Results: Participants with a higher score of childhood emotional abuse responded faster on the behavioral level and had a smaller P2 amplitude on the neural level when processing disgust faces compared to neutral faces. Discussion: Individuals with a higher level of childhood emotional abuse may quickly identify negative faces with less cognitive resources consumed, suggesting altered processing of emotional facial expressions in young men with a higher level of childhood emotional abuse.

8.
Int J Chron Obstruct Pulmon Dis ; 16: 2023-2037, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34262271

RESUMO

Introduction: Diaphragm dysfunction is a significant extrapulmonary effect in chronic obstructive pulmonary disease (COPD), which is manifested by changes in diaphragm structure and reduced diaphragm strength. Acupuncture is a traditional rehabilitation technique in China, which has been used in rehabilitation for COPD. But whether acupuncture can improve the diaphragm function of COPD patients remains to be verified. Objective: The objective of this study was to evaluate the rehabilitation effects of acupuncture on diaphragm dysfunction in patients with COPD. Methods: The authors retrieved in CNKI, VIP, SinoMed, PubMed, Ebsco, Web of Science, from inception to November 2020, for relevant randomized control trials. Two researchers independently screened the articles and extracted the data. The quality of the included studies was evaluated by Physiotherapy Evidence Database scale. The primary outcome measures were maximal inspiratory pressure and the scale for accessory respiratory muscle mobilization, the secondary outcome measures were pulmonary function-related indicators and arterial blood gas indicators. Results: Nine articles were finally obtained. Seven studies added acupuncture to standard treatment for patients with diaphragm dysfunction in COPD and found statistically significant changes in the maximum inspiratory pressure and the scale for accessory respiratory muscle mobilization. Two studies have proved that use acupuncture combined with other Traditional Chinese Medicine methods in the rehabilitation for COPD can effectively improve the diaphragm strength and diaphragmatic motor performance. Seven studies showed that acupuncture has obvious improvement in pulmonary ventilation function. Seven studies reported significant differences in arterial blood gas pre- to post-intervention. Conclusion: This systematic review found that acupuncture can effectively enhance the diaphragm strength, relieve respiratory muscle fatigue, it can also play a promoting role in improving lung function, hypoxia, and carbon dioxide retention, as well as preventing and alleviating respiratory failure. The generalizability of these results is limited by the design of the included studies.


Assuntos
Terapia por Acupuntura , Doença Pulmonar Obstrutiva Crônica , Diafragma , Humanos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/terapia , Respiração , Músculos Respiratórios
9.
Cryobiology ; 102: 76-81, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34310910

RESUMO

Spray cryotherapy (SCT) is a new transbronchial approach that disrupts epithelial cells by freezing. However, there are limited data addressing the effect of SCT on airway secretion. The aim of this study was to evaluate if SCT effect on airway secretion and the possible mechanism in canines. Fifteen labradors were randomly scheduled SCT or sham operation. Six labradors were scheduled SCT for a short-time observation, and six for a long-time observation, the remaining three received sham operation as control. Lung tissues were harvested for PAS staining. Mucin, MUC5AC and acetylcholine in bronchoalveolar lavage fluid (BALF) were analyzed by enzyme-linked immunosorbent assay (ELISA). CHRM3 and Mucin 5AC (MUC5AC) expressions in the lung tissues were analyzed by immunohistochemistry. MUC5AC mRNA expression was analyzed by rt-PCR. From 0 day to 30 days after SCT, the ratio of PAS positive cells to total bronchial epithelial cells, the average optical density of MUC5AC + by immunohistochemistry, the protein expression of MUC5AC, acetylcholine in BALF decreased compared with that of control group (p < 0.05). The average optical density of CHRM3+ by immunohistochemistry were decreased from 0 day to 7 days after SCT (p < 0.05) compared with control group. In conclusion, SCT was able to reduce the PAS-, MUC5AC- and CHRM3-positive cells in the lung tissue and acetylcholine in BALF, suggesting that SCT may prove to be a beneficial way in mucus excessive production in airway and acetylcholine-CHRM3 pathway may one possible mechanism.


Assuntos
Criopreservação , Mucina-5AC , Animais , Criopreservação/métodos , Crioterapia , Cães , Pulmão , Mucina-5AC/genética , Projetos Piloto
10.
Nano Today ; 40: 101243, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34249143

RESUMO

The outbreak of SARS-coronavirus 2 (SARS-CoV2) has become a global health emergency. Although enormous efforts have been made, there is still no effective treatment against the new virus. Herein, a TiO2 supported single-atom nanozyme containing atomically dispersed Ag atoms (Ag-TiO2 SAN) is designed to serve as a highly efficient antiviral nanomaterial. Compared with traditional nano-TiO2 and Ag, Ag-TiO2 SAN exhibits higher adsorption (99.65%) of SARS-CoV2 pseudovirus. This adsorption ability is due to the interaction between SAN and receptor binding domain (RBD) of spike 1 protein of SARS-CoV2. Theoretical calculation and experimental evidences indicate that the Ag atoms of SAN strongly bind to cysteine and asparagine, which are the most abundant amino acids on the surface of spike 1 RBD. After binding to the virus, the SAN/virus complex is typically phagocytosed by macrophages and colocalized with lysosomes. Interestingly, Ag-TiO2 SAN possesses high peroxidase-like activity responsible for reactive oxygen species production under acid conditions. The highly acidic microenvironment of lysosomes could favor oxygen reduction reaction process to eliminate the virus. With hACE2 transgenic mice, Ag-TiO2 SAN showed efficient anti-SARS-CoV2 pseudovirus activity. In conclusion, Ag-TiO2 SAN is a promising nanomaterial to achieve effective antiviral effects for SARS-CoV2.

11.
J Agric Food Chem ; 69(27): 7534-7544, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34185539

RESUMO

The insect chitinase OfChtI from the agricultural pest Ostrinia furnacalis (Asian corn borer) is a promising target for green insecticide design. OfChtI is a critical chitinolytic enzyme for the cuticular chitin degradation at the stage of molting. In this study, piperine, a natural amide compound isolated from black pepper, Piper nigrum L., was discovered for the first time to have inhibitory activity toward OfChtI. The compound-enzyme interaction was presumed to take place between the piperine benzo[d][1,3] dioxole skeleton and subsite -1 of the substrate-binding pocket of OfChtI. Hence, on the basis of the deduced inhibitory mechanism and crystal structure of the substrate-binding cavity of OfChtI, compounds 5a-f were designed and synthesized by introducing a butenolide scaffold into the lead compound piperine. The enzymatic activity assay indicated that compounds 5a-f (Ki = 1.03-2.04 µM) exhibited approximately 40-80-fold higher inhibitory activity than the lead compound piperine (I) (Ki = 81.45 µM) toward OfChtI. The inhibitory mechanism of the piperonyl butenolide compounds was elucidated by molecular dynamics, which demonstrated that the introduced butenolide skeleton improved the binding affinity to OfChtI. Moreover, the in vivo activity assay indicated that these compounds also displayed moderate insecticidal activity toward O. furnacalis. This work introduces the natural product piperine as a starting point for the development of novel insecticides targeting OfChtI.


Assuntos
Quitinases , Mariposas , Piper nigrum , Alcaloides , Animais , Benzodioxóis/farmacologia , Piperidinas , Alcamidas Poli-Insaturadas/farmacologia
12.
iScience ; 24(5): 102417, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-33997697

RESUMO

CD146 is an adhesion molecule that plays important roles in angiogenesis, cancer metastasis, and immune response. It exists as a monomer or dimer on the cell surface. AA98 is a monoclonal antibody that binds to CD146, which abrogates the activation of CD146-mediated signaling pathways and shows inhibitory effects on tumor growth. However, how AA98 inhibits the function of CD146 remains unclear. Here, we describe a crystal structure of the CD146/AA98 Fab complex at a resolution of 2.8 Å. Monomeric CD146 is stabilized by AA98 Fab binding to the junction region of CD146 domains 4 and 5. A higher-affinity AA98 variant (here named HA98) was thus rationally designed. Better binding to CD146 and prominent inhibition on cell migration were achieved with HA98. Further experiments on xenografted melanoma in mice with HA98 revealed superior inhibitory effects on tumor growth to those of AA98, which suggested future applications of this antibody in cancer therapy.

13.
Int J Chron Obstruct Pulmon Dis ; 16: 1287-1297, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34007168

RESUMO

Background: Pulmonary and activation-regulated chemokine (PARC) also named CC-chemokine ligand 18 (CCL18) is a lung-predominant inflammatory protein that is found in serum. The relationship of PARC/CCL18 with the chronic obstructive pulmonary disease (COPD) is not fully understood. The aim of the present study is to analyze the expression of PARC/CCL18 in COPD. Methods: Ninety-eight hospitalized COPD patients and 60 healthy volunteers from January 2019 to December 2019 were recruited in this retrospective study. Gender, age, height, weight, disease duration, smoking status, blood cell classification and count, length of hospital stay (LOS), symptom score, including COPD Assessment Test (CAT) score, modified British Medical Research Council (mMRC) score, lung function and therapy were recorded and serum PARC/CCL18 was analyzed by ELISA. The correlation between symptom score, blood cell classification and count, CRP, lung function parameters and serum levels of PARC/CCL18 and ROC curves of PARC/CCL18 levels and inhaled corticosteroids (ICS) were accessed. Results: It was found that serum PARC/CCL18 level in hospitalized COPD population was significantly higher than that in healthy people (p=0.003). COPD patients with emphysema had significantly higher serum level of PARC/CCL18 than those without emphysema (p=0.049). Total lung capacity (TLC) and residual volume (RV)/TLC had positive correlation with serum level of PARC/CCL18 (p=0.001, 0.020, respectively). Furthermore, serum PARC/CCL18 level was predictive for the application ICS (p=0.003) and related to C-reactive protein (p <0.0001) in hospitalized COPD patients. Conclusion: PARC/CCL18 is associated with the severity of inflammation and emphysema in COPD. Furthermore, PARC/CCL18 is a predictor of ICS application in the treatment of hospitalized COPD patients.


Assuntos
Quimiocina CCL18 , Enfisema , Doença Pulmonar Obstrutiva Crônica , Corticosteroides/efeitos adversos , Quimiocinas CC , Humanos , Inflamação , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Estudos Retrospectivos
14.
Pest Manag Sci ; 77(9): 3910-3920, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33871901

RESUMO

BACKGROUND: Succinate dehydrogenase inhibitors (SDHIs) play an increasingly important role in controlling plant diseases. However, the similar structures of SDHIs result in rapid development of cross-resistance development and a clear bottleneck of poor activity against oomycetes, therefore the need to seek new SDHI fungicides with novel structures is urgent. RESULTS: Innovative pyrazolyl oxime ethers were designed by replacing amide with oxime ether based on the succinate dehydrogenase (SDH) structure, and 19 pairs of Z- and E-isomers were efficiently prepared for the discovery of SDHI compounds with a novel bridge. Their biological activities against four fungi and two oomycetes were evaluated, and substantial differences were observed between the Z- and E- isomers of the title compounds. Furthermore, most of these compounds exhibited remarkable activities against Rhizoctonia solani with EC50 values of less than 10 mg L-1 in vitro, and bioassay in vivo further confirmed that E-I-6 exhibited good protective efficacy (76.12%) at 200 mg L-1 . In addition, Z-I-12 provided better activity against the oomycetes Pythium aphanidermatum and Phytophthora capsici (EC50  = 1.56 and 0.93 mg L-1 ) than those of boscalid. Moreover, E-I-12 exhibited excellent SDH inhibition (IC50  = 0.21 mg L-1 ) thanks to its good binding ability to the SDH by hydrogen-bonding interactions, π-cation interaction and hydrophobic interactions. CONCLUSION: Novel pyrazolyl oxime ethers have the potential as SDHI compounds for future development, and the strategy of replacing an amide bond with oxime ether may offer an alternative option in SDHI fungicide discovery.


Assuntos
Fungicidas Industriais , Oomicetos , Antifúngicos/farmacologia , Éteres/farmacologia , Fungicidas Industriais/farmacologia , Oximas/farmacologia , Rhizoctonia , Relação Estrutura-Atividade , Succinato Desidrogenase/metabolismo
15.
Soc Cogn Affect Neurosci ; 16(9): 937-949, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-33830244

RESUMO

Childhood adversity is a major risk factor for emotional and cognitive disorders later in adulthood. Behavior monitoring, one of the most important components of cognitive control, plays a crucial role in flexible interaction with the environment. Here, we test a novel conceptual model discriminating between two distinct dimensions of childhood adversity (i.e. deprivation and threat) and examine their relations to dynamic stages of behavior monitoring. Sixty young healthy adults participated in this study using event-related potentials and the dynamic stages of behavior monitoring including response inhibition, error detection and post-error adjustments were investigated in a classical Go/NoGo task. Multiple regression analyses revealed that participants with higher severity of childhood adversity recruited more controlled attention, as indicated by larger (more negative) conflict detection-related NoGo-N2 amplitudes and larger (more negative) error detection-related error-related negativity amplitudes. Higher severity of childhood abuse (an indicator of threat) was related to smaller (less positive) error appraisal-related error positivity amplitudes on the neural level and subsequently lower post-error accuracy on the behavioral level. These results suggested that prefrontal-supported controlled attention is influenced by universal adversity in childhood while the error-related behavioral adjustment is mainly affected by childhood abuse, indicating the dimensions of deprivation and threat are at least partially distinct.


Assuntos
Maus-Tratos Infantis , Potenciais Evocados , Adulto , Atenção , Criança , Eletroencefalografia , Humanos
16.
Adv Sci (Weinh) ; 8(6): 2004032, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33747748

RESUMO

Obesity and its related complications pose an increasing threat to human health; however, targetable obesity-related membrane receptors are not yet elucidated. Here, the membrane receptor CD146 is demonstrated to play an essential role in obesity. In particular, CD146 acts as a new adipose receptor for angiopoietin-like protein 2 (ANGPTL2), which is thought to act on endothelial cells to activate adipose inflammation. ANGPTL2 binds to CD146 to activate cAMP response element-binding protein (CREB), which then upregulates CD146 during adipogenesis and adipose inflammation. CD146 is present in preadipocytes and mature adipocytes, where it is mediated by its ligands ANGPTL2 and galectin-1. In preadipocytes, CD146 ablation suppresses adipogenesis, whereas the loss of CD146 in mature adipocytes suppresses lipid accumulation and enhances energy expenditure. Moreover, anti-CD146 antibodies inhibit obesity by disrupting the interactions between CD146 and its ligands. Together, these findings demonstrate that ANGPTL2 directly affects adipocytes via CD146 to promote obesity, suggesting that CD146 can be a potential target for treating obesity.

17.
Acta Pharm Sin B ; 11(1): 55-70, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33532180

RESUMO

Cancer stem cells (CSCs) are a subpopulation of cancer cells with functions similar to those of normal stem cells. Although few in number, they are capable of self-renewal, unlimited proliferation, and multi-directional differentiation potential. In addition, CSCs have the ability to escape immune surveillance. Thus, they play an important role in the occurrence and development of tumors, and they are closely related to tumor invasion, metastasis, drug resistance, and recurrence after treatment. Therefore, specific targeting of CSCs may improve the efficiency of cancer therapy. A series of corresponding promising therapeutic strategies based on CSC targeting, such as the targeting of CSC niche, CSC signaling pathways, and CSC mitochondria, are currently under development. Given the rapid progression in this field and nanotechnology, drug delivery systems (DDSs) for CSC targeting are increasingly being developed. In this review, we summarize the advances in CSC-targeted DDSs. Furthermore, we highlight the latest developmental trends through the main line of CSC occurrence and development process; some considerations about the rationale, advantages, and limitations of different DDSs for CSC-targeted therapies were discussed.

19.
BMC Infect Dis ; 21(1): 62, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33435894

RESUMO

BACKGROUND: Although traditional diagnostic techniques of infection are mature and price favorable at present, most of them are time-consuming and with a low positivity. Metagenomic next⁃generation sequencing (mNGS) was studied widely because of identification and typing of all pathogens not rely on culture and retrieving all DNA without bias. Based on this background, we aim to detect the difference between mNGS and traditional culture method, and to explore the relationship between mNGS results and the severity, prognosis of infectious patients. METHODS: 109 adult patients were enrolled in our study in Shanghai Tenth People's Hospital from October 2018 to December 2019. The diagnostic results, negative predictive values, positive predictive values, false positive rate, false negative rate, pathogen and sample types were analyzed by using both traditional culture and mNGS methods. Then, the samples and clinical information of 93 patients in the infected group (ID) were collected. According to whether mNGS detected pathogens, the patients in ID group were divided into the positive group of 67 cases and the negative group of 26 cases. Peripheral blood leukocytes, C-reactive protein (CRP), procalcitonin (PCT) and neutrophil counts were measured, and the concentrations of IL-2, IL-4, IL-6, TNF-α, IL-17A, IL-10 and INF-γ in the serum were determined by ELISA. The correlation between the positive detection of pathogens by mNGS and the severity of illness, hospitalization days, and mortality were analyzed. RESULTS: 109 samples were assigned into infected group (ID, 92/109, 84.4%), non-infected group (NID, 16/109, 14.7%), and unknown group (1/109, 0.9%). Blood was the most abundant type of samples with 37 cases, followed by bronchoalveolar lavage fluid in 36 cases, tissue, sputum, pleural effusion, cerebrospinal fluid (CSF), pus, bone marrow and nasal swab. In the ID group, the majority of patients were diagnosed with lower respiratory system infections (73/109, 67%), followed by bloodstream infections, pleural effusion and central nervous system infections. The sensitivity of mNGS was significantly higher than that of culture method (67.4% vs 23.6%; P < 0.001), especially in sample types of bronchoalveolar lavage fluid (P = 0.002), blood (P < 0.001) and sputum (P = 0.037), while the specificity of mNGS was not significantly different from culture method (68.8% vs 81.3%; P = 0.41). The number of hospitals stays and 28-day-motality in the positive mNGS group were significantly higher than those in the negative group, and the difference was statistically significant (P < 0.05). Age was significant in multivariate logistic analyses of positive results of mNGS. CONCLUSIONS: The study found that mNGS had a higher sensitivity than the traditional method, especially in blood, bronchoalveolar lavage fluid and sputum samples. And positive mNGS group had a higher hospital stay, 28-day-mortality, which means the positive of pathogen nucleic acid sequences detection may be a potential high-risk factor for poor prognosis of adult patients and has significant clinical value. MNGS should be used more in early pathogen diagnosis in the future.


Assuntos
Doenças Transmissíveis/diagnóstico , Testes Diagnósticos de Rotina/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Metagenômica/métodos , Índice de Gravidade de Doença , Adulto , Idoso , Idoso de 80 Anos ou mais , Hemocultura/métodos , Líquido da Lavagem Broncoalveolar/microbiologia , China , Doenças Transmissíveis/mortalidade , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Sensibilidade e Especificidade , Escarro/microbiologia
20.
J Anxiety Disord ; 77: 102328, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33160275

RESUMO

The outbreak of a novel coronavirus (COVID-19) pandemic was a great threat to the physical and mental health of the general population. Our research aimed to investigate the relationship between perceived stress and emotional distress during the initial outbreak. Furthermore, potential risks and protective factors, i.e., coping and boredom proneness, of stress-related emotional distress were also explored. Data from 3233 participants in China were collected through an online survey platform during the initial outbreak of the COVID-19 from January 31 to February 9 in 2020. Results showed that higher perceived stress was associated with more emotional distress including depression, fear, compulsion-anxiety, neurasthenia, and hypochondria. Boredom proneness significantly and positively mediated the relationship between perceived stress and emotional distress. Moreover, coping style moderated the stress-emotional distress relationship, i.e., individuals who mainly adopted positive coping strategies suffered fewer symptoms of depression, compulsion-anxiety, and neurasthenia under stress, while negative coping strategies aggravated emotional distress. These results from the present study provide practical value for mental health intervention during the emergent public health events.


Assuntos
Adaptação Psicológica , Tédio , COVID-19/psicologia , Saúde Mental/estatística & dados numéricos , Percepção , Angústia Psicológica , Estresse Psicológico/epidemiologia , Adulto , Ansiedade/epidemiologia , Ansiedade/psicologia , COVID-19/epidemiologia , China/epidemiologia , Depressão/epidemiologia , Surtos de Doenças , Medo , Feminino , Humanos , Masculino , Estresse Psicológico/psicologia , Inquéritos e Questionários
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...