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1.
Sensors (Basel) ; 24(6)2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38544249

RESUMO

Binocular structured light systems are widely used in 3D measurements. In the condition of complex and local highly reflective scenes, to obtain more 3D information, binocular systems are usually divided into two pairs of devices, each having a Single Camera and a Projector (SCP). In this case, the binocular system can be seen as Dual Cameras-Projector (DCP) system. In the DCP calibration, the Left-SCP and Right-SCP need to be calibrated separately, which leads to inconsistent parameters for the same projector, thus reducing the measurement accuracy. To solve this problem and improve manoeuvrability, a coupled calibration method using an orthogonal phase target is proposed. The 3D coordinates on a phase target are uniquely determined by the binocular camera in DCP, rather than being calculated separately in each SCP. This ensures the consistency of the projector parameters. The coordinates of the projector image plane are calculated through the unwrapped phase, while the parameters are calibrated by the plane calibration method. In order to extract sub-pixel accuracy feature points, a method based on polynomial fitting using an orthogonal phase target is exploited. The experimental results show that the reprojection error of our method is less than 0.033 pixels, which improves the calibration accuracy.

2.
Int J Biol Macromol ; 261(Pt 2): 129645, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38296143

RESUMO

Thyroxine-binding globulin (TBG) plays a vital role in regulating metabolism, growth, organ differentiation, and energy homeostasis, exerting significant effects in various key metabolic pathways. Halogenated thiophenols (HTPs) exhibit high toxicity and harmfulness to organisms, and numerous studies have demonstrated their thyroid-disrupting effects. To understand the mechanism of action of HTPs on TBG, a combination of competitive binding experiments, multiple fluorescence spectroscopy techniques, molecular docking, and molecular simulations was employed to investigate the binding mechanism and identify the binding site. The competition binding assay between HTPs and ANS confirmed the competition of HTPs with thyroid hormone T4 for the active site of TBG, resulting in changes in the TBG microenvironment upon the binding of HTPs to the active site. Key amino acid residues involved in the binding process of HTPs and TBG were further investigated through residue energy decomposition. The distribution of high-energy contributing residues was determined. Analysis of root-mean-square deviation (RMSD) demonstrated the stability of the HTPs-TBG complex. These findings confirm the toxic mechanism of HTPs in thyroid disruption, providing a fundamental reference for accurately assessing the ecological risk of pollutants and human health. Providing mechanistic insights into how HTPS causes thyroid diseases.


Assuntos
Fenóis , Compostos de Sulfidrila , Globulina de Ligação a Tiroxina , Tiroxina , Humanos , Globulina de Ligação a Tiroxina/metabolismo , Tiroxina/farmacologia , Proteínas de Ligação a Tiroxina/metabolismo , Simulação de Acoplamento Molecular
3.
Small ; 20(1): e2304607, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37653591

RESUMO

Micro/nano-robots are powerful tools for biomedical applications and are applied in disease diagnosis, tumor imaging, drug delivery, and targeted therapy. Among the various types of micro-robots, cell-based micro-robots exhibit unique properties because of their different cell sources. In combination with various actuation methods, particularly externally propelled methods, cell-based microrobots have enormous potential for biomedical applications. This review introduces recent progress and applications of cell-based micro/nano-robots. Different actuation methods for micro/nano-robots are summarized, and cell-based micro-robots with different cell templates are introduced. Furthermore, the review focuses on the combination of cell-based micro/nano-robots with precise control using different external fields. Potential challenges, further prospects, and clinical translations are also discussed.


Assuntos
Nanotecnologia , Neoplasias , Humanos , Nanotecnologia/métodos , Sistemas de Liberação de Medicamentos/métodos , Neoplasias/diagnóstico , Neoplasias/terapia
4.
Quant Imaging Med Surg ; 13(7): 4676-4686, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37456292

RESUMO

Background: The most common cause of lower motor neuron facial palsy is Bell's palsy (BP). BP results in partial or complete inability to automatically move the facial muscles on the affected side and, in some cases, to close the eyelids, which can cause permanent eye damage. This study investigated changes in brain function and connectivity abnormalities in patients with BP. Methods: This study included 46 patients with unilateral BP and 34 healthy controls (HCs). Resting-state brain functional magnetic resonance imaging (fMRI) images were acquired, and Toronto Facial Grading System (TFGS) scores were obtained for all participants. The fractional amplitude of low-frequency fluctuation (fALFF) was estimated, and the relationship between the TFGS and fALFF was determined using correlation analysis for brain regions with changes in fALFF in those with BP versus HCs. Brain regions associated with TFGS were used as seeds for further functional connectivity (FC) analysis; relationships between FC values of abnormal areas and TFGS scores were also analyzed. Results: Activation of the right precuneus, right angular gyrus, left supramarginal gyrus, and left middle occipital gyrus was significantly decreased in the BP group. fALFF was significantly higher in the right thalamus, vermis, and cerebellum of the BP group compared with that in the HC group (P<0.05). The FC between the left middle occipital gyrus and right angular gyrus, left precuneus, and right middle frontal gyrus increased sharply, but decreased in the left angular gyrus, left posterior cingulate gyrus, left middle frontal gyrus, inferior cerebellum, and left middle temporal gyrus. Furthermore, the fALFF in the left middle occipital gyrus was negatively correlated with TFGS score (R=0.144; P=0.008). Conclusions: The pathogenesis of BP is closely related to functional reorganization of the cerebral cortex. Patients with BP have altered fALFF activity in cortical regions associated with facial motion feedback monitoring.

5.
Molecules ; 28(14)2023 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-37513327

RESUMO

The purpose was to screen type III secretory system (T3SS) inhibitors of Salmonella enterica serovar Typhimurium (S. Typhimurium) from natural compounds. The pharmacological activities and action mechanisms of candidate compounds in vivo and in vitro were systematically studied and analyzed. Using a SipA-ß-lactamase fusion reporting system, we found that quercitrin significantly blocked the translocation of SipA into eukaryotic host cells without affecting the growth of bacteria. Adhesion and invasion assay showed that quercitrin inhibited S. Typhimurium invasion into host cells and reduced S. Typhimurium mediated host cell damage. ß-galactosidase activity detection and Western blot analysis showed that quercitrin significantly inhibited the expression of SPI-1 genes (hilA and sopA) and effectors (SipA and SipC). The results of animal experiments showed that quercitrin significantly reduced colony colonization and alleviated the cecum pathological injury of the infected mice. Small molecule inhibitor quercitrin directly inhibited the function of T3SS and provided a potential antibiotic alternative against S. Typhimurium infection. Importance: T3SS plays a crucial role in the bacterial invasion and pathogenesis of S. Typhimurium. Compared with conventional antibiotics, small molecules could inhibit the virulence factors represented by S. Typhimurium T3SS. They have less pressure on bacterial vitality and a lower probability of producing drug resistance. Our results provide strong evidence for the development of novel inhibitors against S. Typhimurium infection.


Assuntos
Salmonella typhimurium , Sistemas de Secreção Tipo III , Animais , Camundongos , Sorogrupo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo
6.
Ageing Res Rev ; 87: 101911, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36931328

RESUMO

Alzheimer's disease (AD) is a degenerative neurological disease in elderly individuals. Subjective cognitive decline (SCD), mild cognitive impairment (MCI) and further development to dementia (d-AD) are considered to be major stages of the progressive pathological development of AD. Diffusion tensor imaging (DTI), one of the most important modalities of MRI, can describe the microstructure of white matter through its tensor model. It is widely used in understanding the central nervous system mechanism and finding appropriate potential biomarkers for the early stages of AD. Based on the multilevel analysis methods of DTI (voxelwise, fiberwise and networkwise), we summarized that AD patients mainly showed extensive microstructural damage, structural disconnection and topological abnormalities in the corpus callosum, fornix, and medial temporal lobe, including the hippocampus and cingulum. The diffusion features and structural connectomics of specific regions can provide information for the early assisted recognition of AD. The classification accuracy of SCD and normal controls can reach 92.68% at present. And due to the further changes of brain structure and function, the classification accuracy of MCI, d-AD and normal controls can reach more than 97%. Finally, we summarized the limitations of current DTI-based AD research and propose possible future research directions.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Substância Branca , Humanos , Idoso , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Imagem de Tensor de Difusão/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/patologia
7.
J Pharm Pharmacol ; 75(5): 693-702, 2023 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-36964741

RESUMO

OBJECTIVES: Nephrotic syndrome (NS) remains a therapeutic challenge for nephrologists. Piceatannol-3'-O-ß-d-glucopyranoside (PG) is a major active ingredient in Quzha. The purpose of the study was to assess the renoprotection of PG. METHODS: In vitro, the podocyte protection of PG was assessed in MPC-5. SD rats were injected with adriamycin to induce nephropathy in vivo. The determination of biochemical changes and inflammatory cytokines was performed, and pathological changes were examined by histopathological examination. Immunostaining and western blot analyses were used to analyse expression levels of proteins. KEY FINDINGS: The results showed that PG improved adriamycin-induced podocyte injury, attenuated nephropathy, improved hypoalbuminemia and hyperlipidaemia, and lowered cytokine levels. The podocyte protection of PG was further verified by reduction of desmin and increasing synaptopodin expression. Furthermore, treatment with PG down-regulated the expression of HMGB1, TLR4 and NF-κB along with its upstream regulator, IKKß and yet up-regulated IκBα expression by western blot analysis. CONCLUSIONS: Overall, our data showed that PG has a favourable renoprotection in experimental nephrosis, apparently by amelioration of podocyte injury. PG might mediate these effects via modulation of the HMGB1/TLR4/NF-κB signalling pathway. The study first provides a promising leading compound for the treatment of NS.


Assuntos
Proteína HMGB1 , NF-kappa B , Transdução de Sinais , Animais , Ratos , Citocinas , Doxorrubicina , NF-kappa B/metabolismo , Ratos Sprague-Dawley , Receptor 4 Toll-Like/metabolismo
8.
Tissue Cell ; 82: 102038, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36870313

RESUMO

BACKGROUND: Clusterin and transient receptor potential melastatin 2 (TRPM2) play significant roles in acute myocardial infarction (AMI), but their interactions in AMI are unclear. METHODS: Myocardial infarction was induced by ligation of the left anterior descending coronary artery in wild-type C57BL/6J male mice. Infarct size and myocardium pathology were evaluated after 6, 12, and 24 h of ischemia. The expression levels of clusterin and TRPM2 were measured in the myocardium. Furthermore, myocardial infarction was induced in TRPM2 knockout (TRPM2-/-) C57BL/6J male mice to evaluate the expression of clusterin. H9C2 cells with various levels of TRPM2 expression were used to analyze the effects of clusterin under hypoxic conditions. RESULTS: Following AMI, myocardial hypertrophy and TRPM2 expression increased in a time-dependent manner. In contrast, the expression of clusterin decreased in an infarct time-dependent manner. Knockout of TRPM2 protected against myocardial injury and resulted in upregulation of clusterin. In the H9C2 cells, cultured under hypoxic conditions treatment with clusterin or silencing of TRPM2 significantly increased cell viability and decreased TRPM2 expression. Treatment with clusterin protected against TRPM2 overexpression-induced damage in hypoxia-treated H9C2 cells. CONCLUSION: This study characterized the effects of clusterin on TRPM2 in AMI, which may guide development of new treatment strategies for AMI.


Assuntos
Clusterina , Infarto do Miocárdio , Canais de Cátion TRPM , Animais , Masculino , Camundongos , Clusterina/genética , Clusterina/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infarto do Miocárdio/genética , Canais de Cátion TRPM/genética , Canais de Cátion TRPM/metabolismo
9.
BMC Pharmacol Toxicol ; 23(1): 83, 2022 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-36289546

RESUMO

BACKGROUND: Toxicological problem associated with herbal medicine is a significant public health problem. Hence, it is necessary to elaborate on the safety of herbal medicine. Salvianolic acid A (SAA) is a major active compound isolated from Danshen, a popular herbal drug and medicinal food plant in China. The aim of the present study was to explore the toxicological profile of SAA. METHODS: The acute toxicity studies were performed in mice and Beagle dogs with single administration with SAA. A 4-week subchronic toxicity was test in dogs. SAA was intravenously administered at doses of 20, 80 and 300 mg/kg. Clinical observation, laboratory testing and necropsy and histopathological examination were performed. The genotoxic potential of SAA was evaluated by 2 types of genotoxicity tests: a reverse mutation test in bacteria and bone marrow micronucleus test in mice. RESULTS: In acute toxicities, the LD50 of SAA is 1161.2 mg/kg in mice. The minimum lethal dose (MLD) and maximal non-lethal dose (MNLD) of SAA were 682 mg/kg and 455 mg/kg in dogs, respectively. The approximate lethal dose range was 455-682 mg/kg. In the study of 4-week repeated-dose toxicity in dogs, focal necrosis in liver and renal tubular epithelial cell, the decrease in relative thymus weight, as well as abnormal changes in biochemical parameters, were observed in SAA 80 or 300 mg/kg group. The no observed adverse effect level (NOAEL) of SAA was 20 mg/kg. Thymus, liver and kidneys were the toxic targets. These toxic effects were transient and reversible. These results indicated that it should note examination of liver and kidney function during the administration of SAA in clinic. Furthermore, SAA had no mutagenic effect at any tested doses. CONCLUSION: These results provide new toxicological information of SAA for its clinical application and functional food consumption.


Assuntos
Ácidos Cafeicos , Lactatos , Camundongos , Animais , Cães , Nível de Efeito Adverso não Observado , Dano ao DNA , Testes de Mutagenicidade
10.
Front Aging Neurosci ; 14: 978611, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36212042

RESUMO

The relationship between geriatric depression and dementia has been widely debated, and the neurological mechanisms underlying subjective cognitive decline (SCD) associated with social relationships remain elusive. Subclinical geriatric depression (SGD) is common in patients with SCD, and close friends (CFs) have a great influence on a person's social life. Studies have proven that communication or leisure activities with CFs can improve the cognitive performance of elderly. However, it remains unclear whether the engagement of specific brain regions mediates having CFs, SGD, and SCD. In this study, we aimed to assess the association between social relationships (that is, CFs), SGD, and SCD from the perspective of brain function. We examined the data of 66 patients with SCD and 63 normal controls (NC). Compared with NC, SGD was significantly inversely correlated with the number of CFs in the SCD group. We calculated regional homogeneity (ReHo) of functional magnetic resonance imaging (MRI) data of each subject. At a corrected threshold, the right occipital gyrus (SOG.R) and right fusiform gyrus (FFG.R) exhibited positive correlation with SGD in patients with SCD. Mediation analyses to query the inter-relationships between the neural markers and clinical variables exhibited a best fit of the model with CFs → FFG.R → SGD → SOG.R → SCD. These findings suggested a pathway whereby social relationships alter the function of specific brain regions, and SGD may be an early symptom of SCD. We observed that the FFG.R mediate social relationships and SGD, and the abnormality of the SOG.R may be a key factor in the SCD caused by depression. Moreover, a greater number of CFs may reduce the risk of developing SGD.

11.
Children (Basel) ; 9(6)2022 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-35740719

RESUMO

Neuroimaging studies have associated brain changes in children with future reading and language skills, but few studies have investigated the association between language skills and white matter structure in preschool-aged children. Using 208 data sets acquired in 73 healthy children aged 2-7 years, we investigated the relationship between developmental brain microstructure and phonological processing ability as measured using their phonological processing raw score (PPRS). The correlation analysis showed that across the whole age group, with increasing age, PPRS increased, fractional anisotropy (FA) of the internal capsule and inferior fronto-occipital fasciculus and some other regions increased, and mean diffusivity (MD) of the corpus callosum and internal capsule and some other regions decreased. The results of the mediation analysis suggest that increased FA may be the basis of phonological processing ability development during this period, and the increased number of fiber connections between the right inferior parietal lobule and right supramarginal gyrus may be a key imaging feature of phonological processing ability development. Our study reflects the changes in brain microstructure and contributes to understanding the underlying neural mechanisms of language development in preschool children.

12.
J Colloid Interface Sci ; 614: 247-255, 2022 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-35101672

RESUMO

The practical applications of perovskite solar cells (PSCs) are limited by the further improvement of their stability and performance. Interface engineering is a promising strategy to solve these pain points. Herein, we design (R)-(-)-1-cyclohexylethylamine iodide (R-CEAI), composed of positively charged hydrophobic R-CEA+ and negatively charged I-, to post-treat the interface of 3D mixed-cation/halide perovskite with assist one of isopropyl alcohol (IPA). R-CEAI treatment not only passivates the defects at surface and grain boundaries of perovskite, but also in-situ grows quasi 2D Ruddlesden-Popper perovskite at the interface between 3D perovskite and hole transport layer, which reduces trap density of states, tunes energy level and alleviates lattice distortion. As a result, R-CEAI treated 2D/3D PSCs yield a champion PCE of 22.52%, with an improved open-circuit voltage of 1.195 V and retain 84.34% of their initial efficiency in long-term stability test, while the pristine device provides a PCE of 19.43% with only 54.30% retention.

14.
Small Methods ; 5(12): e2101000, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34928027

RESUMO

The 2D/3D composite structure possesses both the excellent stability of 2D perovskite and the excellent performance of 3D perovskite, which recently have attracted special attention. Different from the popular isopropanol, a novel additive solvent-polypropylene glycol bis (2-aminopropyl ether) (A-PPG) is introduced here to dissolve excess PbI2 and perovskite, and then reconstruct and in situ form the quasi-2D perovskite layer on 3D perovskite bulk. The lone electron pairs of the ether-oxygen and amino in A-PPG can form coordination bonds with Pb2+ . The introduction of A-PPG tunes the energy array of functional layers, passivates defects, and mitigates carrier nonradiative recombination. Consequently, the 2D/3D perovskite device exhibits a championship efficiency of 22.24% with a distinguished open-circuit voltage of 1.21 V (the thermodynamic limit of 1.30 V). Moreover, the 2D/3D device still maintains 90% of the original efficiency in the ambient atmosphere with a relative humidity of 30 ± 10% after 50 days.

15.
Int J Mol Sci ; 22(23)2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34884846

RESUMO

Pesticides have been used extensively in the field of plant protection to maximize crop yields. However, the long-term, unmanaged application of pesticides has posed severe challenges such as pesticide resistance, environmental contamination, risk in human health, soil degradation, and other important global issues. Recently, the combination of nanotechnology with plant protection strategies has offered new perspectives to mitigate these global issues, which has promoted a rapid development of NCs-based pesticides. Unlike certain conventional pesticides that have been applied inefficiently and lacked targeted control, pesticides delivered by nanocarriers (NCs) have optimized formulations, controlled release rate, and minimized or site-specific application. They are receiving increasing attention and are considered as an important part in sustainable and smart agriculture. This review discussed the limitation of traditional pesticides or conventional application mode, focused on the sustainable features of NCs-based pesticides such as improved formulation, enhanced stability under harsh condition, and controlled release/degradation. The perspectives of NCs-based pesticides and their risk assessment were also suggested in this view for a better use of NCs-based pesticides to facilitate sustainable, smart agriculture in the future.


Assuntos
Agricultura , Portadores de Fármacos/química , Nanoestruturas/química , Controle de Pragas/métodos , Praguicidas/química , Quitosana/química , Praguicidas/metabolismo , RNA de Cadeia Dupla/química , RNA de Cadeia Dupla/metabolismo , Solubilidade
16.
ACS Chem Neurosci ; 12(22): 4209-4223, 2021 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-34723463

RESUMO

The neuroimaging method of multimodal magnetic resonance imaging (MRI) can identify the changes in brain structure and function caused by Alzheimer's disease (AD) at different stages, and it is a practical method to study the mechanism of AD progression. This paper reviews the studies of methods and biomarkers for predicting AD progression based on multimodal MRI. First, different approaches for predicting AD progression are analyzed and summarized, including machine learning, deep learning, regression, and other MRI analysis methods. Then, the effective biomarkers of AD progression under structural magnetic resonance imaging, diffusion tensor imaging, functional magnetic resonance imaging, and arterial spin labeling modes of MRI are summarized. It is believed that the brain changes shown on MRI may be related to the cognitive decline in different prodrome stages of AD, which is conducive to the further realization of early intervention and prevention of AD. Finally, the deficiencies of the existing studies are analyzed in terms of data set size, data heterogeneity, processing methods, and research depth. More importantly, future research directions are proposed, including enriching data sets, simplifying biomarkers, utilizing multimodal magnetic resonance, etc. In the future, the study of AD progression by multimodal MRI will still be a challenge but also a significant research hotspot.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Doença de Alzheimer/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Imagem de Tensor de Difusão , Progressão da Doença , Humanos , Imageamento por Ressonância Magnética , Neuroimagem
17.
Cell Rep ; 36(10): 109688, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34496242

RESUMO

There is broad consensus that RecQ family helicase is a high-order oligomer that dissociates into a dimer upon ATP binding. This conclusion is based mainly on studies of highly purified recombinant proteins, and the oligomeric states of RecQ helicases in living cells remain unknown. We show here that, in contrast to current models, monomeric RECQL helicase is more abundant than oligomer/dimer forms in living cells. Further characterization of endogenous BtRECQL and isolated monomeric BtRECQL using various approaches demonstrates that both endogenous and recombinant monomeric BtRECQL effectively function as monomers, displaying higher helicase and ATPase activities than dimers and oligomers. Furthermore, monomeric BtRECQL unfolds intramolecular G-quadruplex DNA as efficiently as human RECQL and BLM helicases. These discoveries have implications for understanding endogenous RECQL oligomeric structures and their regulation. It is worth revisiting oligomeric states of the other members of the RecQ family helicases in living cells.


Assuntos
Neoplasias da Mama/metabolismo , DNA/metabolismo , Predisposição Genética para Doença/genética , RecQ Helicases/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Neoplasias da Mama/genética , Bovinos , Quadruplex G , Proteínas Recombinantes/metabolismo
18.
Mater Sci Eng C Mater Biol Appl ; 124: 112054, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33947548

RESUMO

Breast cancer is the most common cancer among women worldwide, of which 10-20% accounts for triple-negative breast cancer (TNBC). TNBC is more aggressive, lacks an effective treatment target, and has a higher metastasis rate compared to other types of breast cancers. These characteristics result in poor therapeutic and prognostic outcomes in patients with TNBC. Sonodynamic therapy (SDT) is an emerging non-invasive procedure with high-tissue penetration properties to treat cancer. Therefore, we designed a new sonosensitizer, PEG-IR780@Ce6 for SDT, which showed excellent performance in inhibiting cancer cells and in simultaneously suppressing the migration and invasion of cancer cells. In vitro and in vivo experiments showed that PEG-IR780@Ce6 as a sonosensitizer could generate higher levels of reactive oxygen species (ROS) than IR780 and free Ce6 alone, thereby resulting in better anti-cancer effects. Besides, PEG-IR780@Ce6 inhibited the migration and invasion of MDA-MB-231 cells, both in vitro and in vivo, which indicated that it could suppress the metastasis of TNBC. Moreover, the long circulation time and the mitochondria-targeting ability of PEG-IR780@Ce6 guaranteed its accumulation in the tumor. In addition, both in vitro and in vivo experiments indicated the biocompatibility and biosafety of PEG-IR780@Ce6. In conclusion, our results collectively suggested that the newly designed sonosensitizer, PEG-IR780@Ce6, is a promising treatment option for TNBC with excellent therapeutic effects and low side effects.


Assuntos
Neoplasias de Mama Triplo Negativas , Linhagem Celular Tumoral , Feminino , Humanos , Micelas , Mitocôndrias , Espécies Reativas de Oxigênio , Neoplasias de Mama Triplo Negativas/tratamento farmacológico
19.
Nucleic Acids Res ; 49(8): 4768-4781, 2021 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-33856462

RESUMO

Telomerase plays critical roles in cellular aging, in the emergence and/or development of cancer, and in the capacity for stem-cell renewal, consists of a catalytic telomerase reverse transcriptase (TERT) and a template-encoding RNA (TER). TERs from diverse organisms contain two conserved structural elements: the template-pseudoknot (T-PK) and a helical three-way junction (TWJ). Species-specific features of the structure and function of telomerase make obtaining a more in-depth understanding of the molecular mechanism of telomerase particularly important. Here, we report the first structural studies of N-terminally truncated TERTs from Candida albicans and Candida tropicalis in apo form and complexed with their respective TWJs in several conformations. We found that Candida TERT proteins perform only one round of telomere addition in the presence or absence of PK/TWJ and display standard reverse transcriptase activity. The C-terminal domain adopts at least two extreme conformations and undergoes conformational interconversion, which regulates the catalytic activity. Most importantly, we identified a conserved tertiary structural motif, called the U-motif, which interacts with the reverse transcriptase domain and is crucial for catalytic activity. Together these results shed new light on the structure and mechanics of fungal TERTs, which show common TERT characteristics, but also display species-specific features.


Assuntos
Motivos de Aminoácidos , Candida albicans/química , Candida tropicalis/química , Domínio Catalítico , Telomerase/química , Motivos de Aminoácidos/genética , Candida albicans/enzimologia , Candida tropicalis/enzimologia , Catálise , Domínio Catalítico/genética , Cromatografia em Gel , Cristalografia por Raios X , Difusão Dinâmica da Luz , Escherichia coli/metabolismo , Técnicas In Vitro , Modelos Moleculares , Mutação , Proteínas Recombinantes , Telomerase/genética
20.
Brain Imaging Behav ; 15(5): 2606-2615, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33723811

RESUMO

Schizophrenia is a severe psychiatric disease while its etiology and effective treatment are not completely clear. A rat model of schizophrenia was previously established by transfecting EGR3 gene into the hippocampus of rats. This study aimed to investigate the behavioral and cerebral alterations of the schizophrenic model rats and the risperidone effects. Twenty-six rats were divided into 3 groups: schizophrenia model group (E group), risperidone treatment group (T group), and healthy control group (H group). Morris water maze and open field test were used as behavioral tests, resting-state functional magnetic resonance imaging (fMRI) was performed after EGR3 gene transfection and risperidone therapy. Graph analyses were used for examining cerebral alterations of the rats. Behavioral tests demonstrated reduced spatial working memory and exploring unfamiliar space ability in schizophrenic model rats. Graph analyses revealed reduced regional architectures in the olfactory bulb, nucleus accumbens, and pineal gland in group E compared to group H (p < 0.05), while group T showed increased regional architecture in pineal gland compared to group E (p < 0.05). Besides, the regional architectures in the olfactory bulb, nucleus accumbens were lower in group T than group H, while the hippocampus showed increased regional architecture in group T compared to group H (p < 0.05). Schizophrenia induced several regional alterations in the cerebrum while risperidone can reverse part of these alterations. This study lends support for future research on the pathology of schizophrenia and provides new insights on the role of risperidone in schizophrenia.


Assuntos
Antipsicóticos , Proteína 3 de Resposta de Crescimento Precoce/genética , Esquizofrenia , Animais , Antipsicóticos/uso terapêutico , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética , Memória de Curto Prazo , Ratos , Risperidona/uso terapêutico , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/tratamento farmacológico , Esquizofrenia/genética , Transfecção
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