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1.
IEEE Trans Image Process ; 33: 3778-3792, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38870000

RESUMO

Recent research on few-shot fine-grained image classification (FSFG) has predominantly focused on extracting discriminative features. The limited attention paid to the role of loss functions has resulted in weaker preservation of similarity relationships between query and support instances, thereby potentially limiting the performance of FSFG. In this regard, we analyze the limitations of widely adopted cross-entropy loss and introduce a novel Angular ISotonic (AIS) loss. The AIS loss introduces an angular margin to constrain the prototypes to maintain a certain distance from a pre-set threshold. It guides the model to converge more stably, learn clearer boundaries among highly similar classes, and achieve higher accuracy faster with limited instances. Moreover, to better accommodate the feature requirements of the AIS loss and fully exploit its potential in FSFG, we propose a Multi-Layer Integration (MLI) network that captures object features from multiple perspectives to provide more comprehensive and informative representations of the input images. Extensive experiments demonstrate the effectiveness of our proposed method on four standard fine-grained benchmarks. Codes are available at: https://github.com/Legenddddd/AIS-MLI.

2.
J Gastroenterol ; 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38864913

RESUMO

BACKGROUND: Accumulating evidence has shown that the NOD-like receptor protein 3 (NLRP3) inflammasome plays a crucial role in the inflammatory cascades involved in the development of acute pancreatitis (AP). However, the specific agonist responsible for activating the NLRP3 inflammasome in this process has not yet been identified. The purpose of this study is to clarify whether heparan sulfate (HS) works as an NLRP3 inflammasome activator to evoke inflammatory cascades in the progression of AP. METHODS: Two experimental mouse models of AP were utilized to investigate the pro-inflammatory activity of HS in the development of AP by measuring the secretion of inflammatory cytokines and the neutrophil infiltration in pancreatic tissue. The ability of HS to activate the NLRP3 inflammasome was evaluated both in vitro and in vivo. The nuclear factor kappa B (NF-κB)-mediated expression of NLRP3 inflammasome components in response to HS treatment was determined to decipher the role of HS in transcriptional priming of NLRP3 inflammasome. Furthermore, HS-triggered deubiquitination of NLRP3 was analyzed to reveal the promoting effect of HS on the NLRP3 inflammasome priming via a non-transcriptional pathway. RESULTS: High plasma level of HS was observed with a positive correlation to that of inflammatory cytokines in AP mice. Administration of HS to mice resulted in an exacerbated inflammatory profile, while reducing HS production by an inhibitor of heparanase significantly attenuated inflammatory response. Pharmacological inhibition or genetic deletion of NLRP3 substantially suppressed the HS-stimulated elevation of IL-1ß levels in AP mice. The in vitro data demonstrated that HS primarily serves as a priming signal for the activation of the NLRP3 inflammasome. HS possesses the ability to increase the transcriptional activity of NF-κB and TLR4/NF-κB-driven transcriptional pathway is employed for NLRP3 inflammasome priming. Moreover, HS-induced deubiquitination of NLRP3 is another pathway responsible for non-transcriptional priming of NLRP3 inflammasome. CONCLUSIONS: Our current work has unveiled HS as a new activator of the NLRP3 inflammasome responsible for the secondary inflammatory cascades during the development of AP, highlighting the HS-NLRP3 pathway as a potential target for future preventive and therapeutic approaches of AP.

3.
Biomed Environ Sci ; 37(3): 266-277, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38582991

RESUMO

Objective: The purpose of this study was to investigate the bacterial communities of biting midges and ticks collected from three sites in the Poyang Lake area, namely, Qunlu Practice Base, Peach Blossom Garden, and Huangtong Animal Husbandry, and whether vectors carry any bacterial pathogens that may cause diseases to humans, to provide scientific basis for prospective pathogen discovery and disease prevention and control. Methods: Using a metataxonomics approach in concert with full-length 16S rRNA gene sequencing and operational phylogenetic unit (OPU) analysis, we characterized the species-level microbial community structure of two important vector species, biting midges and ticks, including 33 arthropod samples comprising 3,885 individuals, collected around Poyang Lake. Results: A total of 662 OPUs were classified in biting midges, including 195 known species and 373 potentially new species, and 618 OPUs were classified in ticks, including 217 known species and 326 potentially new species. Surprisingly, OPUs with potentially pathogenicity were detected in both arthropod vectors, with 66 known species of biting midges reported to carry potential pathogens, including Asaia lannensis and Rickettsia bellii, compared to 50 in ticks, such as Acinetobacter lwoffii and Staphylococcus sciuri. We found that Proteobacteria was the most dominant group in both midges and ticks. Furthermore, the outcomes demonstrated that the microbiota of midges and ticks tend to be governed by a few highly abundant bacteria. Pantoea sp7 was predominant in biting midges, while Coxiella sp1 was enriched in ticks. Meanwhile, Coxiella spp., which may be essential for the survival of Haemaphysalis longicornis Neumann, were detected in all tick samples. The identification of dominant species and pathogens of biting midges and ticks in this study serves to broaden our knowledge associated to microbes of arthropod vectors. Conclusion: Biting midges and ticks carry large numbers of known and potentially novel bacteria, and carry a wide range of potentially pathogenic bacteria, which may pose a risk of infection to humans and animals. The microbial communities of midges and ticks tend to be dominated by a few highly abundant bacteria.


Assuntos
Ceratopogonidae , Microbiota , Carrapatos , Animais , Humanos , Carrapatos/microbiologia , Ceratopogonidae/genética , Filogenia , RNA Ribossômico 16S/genética , Estudos Prospectivos , Coxiella/genética
4.
J Refract Surg ; 40(3): e164-e172, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38466765

RESUMO

PURPOSE: To evaluate the dynamic changes in anterior segment parameters during accommodation following Implantable Collamer Lens (ICL) implantation with swept-source optical coherence tomography (SS-OCT). METHODS: Under the accommodation of 0.00 diopters (D), 3.00 D, and maximum amplitude, SS-OCT was used to examine the anterior segment parameters, including ICL vault, ICL depth (the distance between the corneal endothelium and the posterior surface of ICL), crystalline lens thickness, anterior chamber depth, and various parameters of the anterior chamber angle, comprising angle opening distance, angle recess area, trabecular iris space area, and trabecular iris angle. RESULTS: During accommodation, the ICL vault showed a significant decrease from baseline (536 ± 278 µm) to 3.00 D (522 ± 281 µm), followed by an increase from 3.00 D to maximum amplitude (548 ± 306 µm) (analysis of variance [ANOVA], P < .001). Four eyes (2.61%) exhibited a decrease in ICL vault to less than 100 µm (47 ± 32 µm) at maximum accommodation. The ICL depth decreased significantly as accommodation increased (ANOVA, P < .001). Crystalline lens thickness increased, whereas anterior chamber depth decreased during accommodation (ANOVA, P < .001). The anterior chamber angle widened during 3.00 D of accommodation but narrowed at maximum accommodation, leading to significant changes in the angle opening distance, angle recess area, trabecular iris space area, and trabecular iris angle during accommodation (ANOVA, P < .001 for all). CONCLUSIONS: The anterior segment, including ICL vault and anterior chamber angle, undergo significant dynamic changes during accommodation. These accommodative changes may require careful monitoring for the surgery design of ICL implantation. [J Refract Surg. 2024;40(3):e164-e172.].


Assuntos
Cristalino , Miopia , Lentes Intraoculares Fácicas , Humanos , Implante de Lente Intraocular/métodos , Miopia/cirurgia , Acomodação Ocular , Câmara Anterior/diagnóstico por imagem , Pseudofacia/cirurgia , Tomografia de Coerência Óptica , Biometria
5.
Ying Yong Sheng Tai Xue Bao ; 35(2): 439-446, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38523102

RESUMO

Aglaia duperreana, a species with a long cultivation history, is of high ornamental value. To understand the growth and photosynthetic changes of A. duperreana seedlings under variable environmental conditions, we conducted an experiment with light intensities adjusted at 70%, 50% and 30%, crossed with three moisture treatments at 70%, 50% and 30% of field capacity, and a control group which maintained 90% light intensity and 90% field capacity. The results showed that both drought stress and shading propensity significantly inhibited the growth of A. duperreana seedlings, with stronger impacts from drought stress. The increments in stem height and ground diameter, net photosynthetic rate, transpiration rate, stomatal conductance, and chlorophyll content were decreased with the maximum declines by 71.4%, 81.2%, 93.2%, 71.5%, 70.6% and 30.4%, respectively. Under severe drought stress (30% of field capacity), partial shading (50% of translucency) appeared to lessen the detrimental effects of drought. The combination of 70% translucency and 70% field capacity was optimal, resulting in higher increments in stem height, leaf area, net photosynthetic rate, transpiration rate, and stomatal conductance. The maximum fluorescence, variable fluorescence, PSⅡ potential activity, and PSⅡ maximum light energy conversion efficiency increased and then decreased with decreasing moisture. These findings suggested that A. duperreana could adapt to drought and shading stress by modulating growth, enhancing chlorophyll content, and adjusting photosynthetic system. Maintaining translucency at 70% and field moisture capacity at 70% could promote photosynthesis, with positive consequences on growth of A. duperreana.


Assuntos
Aglaia , Plântula , Água , Fotossíntese , Clorofila , Secas , Folhas de Planta
6.
Inorg Chem ; 62(43): 17577-17582, 2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-37843583

RESUMO

Our research demonstrated that novel pentamethylcyclopentadienyl (Cp*) iridium pyridine sulfonamide complex PySO2NPh-Ir (7) could highly specifically catalyze nicotinamide adenine dinucleotide (NAD+) into the corresponding reducing cofactor NADH in cell growth media containing various biomolecules. The structures and catalytic mechanism of 7 were studied by single-crystal X-ray, NMR, electrochemical, and kinetic methods, and the formation of iridium hydride species Ir-H was confirmed to be the plausible hydride-transfer intermediate of 7. Moreover, benefiting from its high hydrogen-transfer activity and selectivity for NADH regeneration, 7 was used as an optimal metal catalyst to establish a chem-enzyme cascade catalytic hydrogen-transfer system, which realized the high-efficiency preparation of l-glutamic acid by combining with l-glutamate dehydrogenase (GLDH).


Assuntos
Hidrogênio , NAD , NAD/química , Hidrogênio/química , Irídio/química , Catálise , Regeneração
7.
Inflamm Res ; 72(9): 1919-1932, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37725105

RESUMO

OBJECTIVE: Nafamostat mesilate (NM), a synthetic broad-spectrum serine protease inhibitor, has been commonly used for treating acute pancreatitis (AP) and other inflammatory-associated diseases in some East Asia countries. Although the potent inhibitory activity against inflammation-related proteases (such as thrombin, trypsin, kallikrein, plasmin, coagulation factors, and complement factors) is generally believed to be responsible for the anti-inflammatory effects of NM, the precise target and molecular mechanism underlying its anti-inflammatory activity in AP treatment remain largely unknown. METHODS: The protection of NM against pancreatic injury and inhibitory effect on the NOD-like receptor protein 3 (NLRP3) inflammasome activation were investigated in an experimental mouse model of AP. To decipher the molecular mechanism of NM, the effects of NM on nuclear factor kappa B (NF-κB) activity and NF-κB mediated NLRP3 inflammasome priming were examined in lipopolysaccharide (LPS)-primed THP-1 cells. Additionally, the potential of NM to block the activity of histone deacetylase 6 (HDAC6) and disrupt the association between HDAC6 and NLRP3 was also evaluated. RESULTS: NM significantly suppressed NLRP3 inflammasome activation in the pancreas, leading to a reduction in pancreatic inflammation and prevention of pancreatic injury during AP. NM was found to interact with HDAC6 and effectively inhibit its function. This property allowed NM to influence HDAC6-dependent NF-κB transcriptional activity, thereby blocking NF-κB-driven transcriptional priming of the NLRP3 inflammasome. Furthermore, NM exhibited the potential to interfere the association between HDAC6 and NLRP3, impeding HDAC6-mediated intracellular transport of NLRP3 and ultimately preventing NLRP3 inflammasome activation. CONCLUSIONS: Our current work has provided valuable insight into the molecular mechanism underlying the immunomodulatory effect of NM in the treatment of AP, highlighting its promising application in the prevention of NLRP3 inflammasome-associated inflammatory pathological damage.


Assuntos
Inflamassomos , Pancreatite , Camundongos , Animais , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Pancreatite/induzido quimicamente , Pancreatite/tratamento farmacológico , Pancreatite/prevenção & controle , NF-kappa B/metabolismo , Ceruletídeo/efeitos adversos , Proteínas NLR , Desacetilase 6 de Histona/uso terapêutico , Doença Aguda , Inflamação/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico
8.
Int J Mol Med ; 51(6)2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37114562

RESUMO

Diabetic cardiomyopathy (DCM) is a cardiovascular disease which has been reported as a major cause of mortality worldwide for several years. Berberine (BBR) is a natural compound extracted from a Chinese herb, with a clinically reported anti­DCM effect; however, its molecular mechanisms have not yet been fully elucidated. The present study indicated that BBR markedly alleviated DCM by inhibiting IL­1ß secretion and the expression of gasdermin D (Gsdmd) at the post­transcriptional level. Considering the importance of microRNAs (miRNAs/miRs) in the regulation of the post­transcriptional process of specific genes, the ability of BBR to upregulate the expression levels of miR­18a­3p by activating its promoter (­1,000/­500) was examined. Notably, miR­18a­3p targeted Gsdmd and abated pyroptosis in high glucose­treated H9C2 cells. Moreover, miR­18a­3p overexpression inhibited Gsdmd expression and improved biomarkers of cardiac function in a rat model of DCM. On the whole, the findings of the present study indicate that BBR alleviates DCM by inhibiting miR­18a­3p­mediated Gsdmd activation; thus, BBR may be considered a potential therapeutic agent for the treatment of DCM.


Assuntos
Berberina , Diabetes Mellitus , Cardiomiopatias Diabéticas , MicroRNAs , Animais , Ratos , Berberina/farmacologia , Berberina/uso terapêutico , Cardiomiopatias Diabéticas/tratamento farmacológico , Cardiomiopatias Diabéticas/genética , Cardiomiopatias Diabéticas/metabolismo , Inflamassomos/metabolismo , MicroRNAs/genética , MicroRNAs/farmacologia , Piroptose
9.
Sci Rep ; 13(1): 16, 2023 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-36604433

RESUMO

Sauropterygia is the largest, most successful group of Mesozoic marine diapsids, spanning from the late Early Triassic to the Late Cretaceous. Plesiomorphic for sauropterygians, pachypleurosauroids are important for our understanding on the early evolution of this group. Here, we present a new pachypleurosaurid, Luopingosaurus imparilis gen. et sp. nov., based on an exceptionally preserved skeleton from the early Middle Triassic Luoping Lagerstätte in Yunnan, China. The discovery documents the first long-snouted pachypleurosaurid with an unexpected hyperphalangy in the manus, providing new insights into the morphological diversification, ecological adaption and biogeographic evolution of this clade. The discovery further indicates that there is a morphological divergence between short-snouted (brevirostrine) keichousaurids and relatively long-snouted (longirostrine) pachypleurosaurids, which was probably driven by ecological specializations related to feeding and foraging. Additionally, an evolutionary trend towards the reduction of the ratio of the hyoid length to mandibular length (HM ratio) is recognized in pachypleurosauroids. This reduction of HM ratio, associated with the increase of the snout length, might implicate a gradual recession of suction feeding in pachypleurosauroid evolution. Phylogenetic studies incorporating Luopingosaurus recover European pachypleurosaurids as successive sister groups to Chinese derived pachypleurosaurids, supporting a western Tethyan origin for this family.


Assuntos
Evolução Biológica , Fósseis , Animais , Filogenia , China , Répteis/anatomia & histologia
10.
Transpl Immunol ; 76: 101763, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36436796

RESUMO

OBJECTIVES: Gout (GT) belongs to a group of diseases caused by a purine metabolic disorder. GT is an inflammatory disease caused by the local deposition of uric acid in joints or adjacent tissues. The mechanism of GT is not fully explained, especially the involvement of an immune system. The objective of this study was to investigate the change in peripheral CD4+T subsets in acute and chronic GT patients. METHODS: A total of 205 patients with acute and chronic GT and 87 healthy controls (HCs) were enrolled. The medical history improvement, clinical indicators, immune function, and peripheral CD4+T-lymphocyte detected by modified flow cytometry were collected in all subjects. RESULTS: Compared with healthy controls, acute and chronic GT patients remarkably increased the absolute counts of T helper type 1 (Th1) cells (P < 0.05) and decreased the absolute number of Treg cells without significant difference (P > 0.05). In addition, the absolute number and percentage of Th1 cells and Th1/T helper type 2 (Th2) ratio increased significantly, and the ratio of Th2 cells decreased in patients with chronic GT compared to patients with acute GT (P < 0.05). The results of Spearman correlation analysis showed a notably negative correlation between the level of CRP and the absolute counts of peripheral Th1 and Th17 cells in patients with GT, while the levels of CD4+T sunsets had no significant correlation with ESR and uric acid. The course of the disease, the absolute number of Th1 cells, the percentage of Th1 cells and the ratio of Th1/Th2 cells were significantly associated with the progression of the disease, and the course of the disease was an independent risk factor for patients with chronic GT. CONCLUSION: The balance of Th1 and Th2 were involved throughout the whole stages of GT, Th17 cells then become involved in the disease process as the disease progresses.


Assuntos
Gota , Ácido Úrico , Humanos , Células Th1 , Células Th2 , Linfócitos T Reguladores , Células Th17
11.
Food Res Int ; 159: 111599, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35940762

RESUMO

Although collagen is widely used as an emulsifier in the food industry, its emulsifying properties are strongly influenced by processing conditions. This research investigated the effects of NaCl on the emulsifying properties of type I collagen after heating. Before heating, the solubility, emulsifying activity index (EAI), emulsifying stability index (ESI), and viscosity of type I collagen initially increased after adding NaCl (0.2 M), after which decreased with increasing NaCl concentration (0.4 M and 0.6 M) due to salt-in effect and the salt-out effects of the protein. While after heating (90℃, 30 min), the collagen became more soluble, with improved EAI and ESI, viscosity, and reduced particle size in response to increasing NaCl concentrations. It was found that NaCl increased the EAI of type I collagen twice after heating, and the EAI reached its maximum at 0.6 M NaCl concentration. We concluded that the improved emulsifying properties may due to thermal denaturation of the protein, resulting in an unfolded and disordered structure with increase of hydrogen bonds with water, rupture of disulfide bonds, and exposure of hydrophobic groups, leading to the increase of adsorption at the oil/water interface. Meanwhile, the Raman spectra analysis and Atomic Force Microscope (AFM) images showed that unfolding of the collagen triple helix was gradually destroyed after NaCl addition and heating, with emulsifying properties improved. The specific outcomes of present study can be adapted towards the requirements to improve the quality of emulsified meat products in the food industry.


Assuntos
Temperatura Alta , Cloreto de Sódio , Colágeno Tipo I , Emulsificantes/química , Emulsões/química , Proteínas
12.
Sci Rep ; 12(1): 7396, 2022 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-35513463

RESUMO

Pachypleurosaurs (Pachypleurosauroidea) are a group of small to medium-sized, lizard-like marine reptiles in the Early to Middle Triassic, including Pachypleurosauridae, Keichousauridae and closely related taxa. The group is generally considered as a sauropterygian radiation, but its phylogenetic interrelationships remain highly debated. Here, we present a new pachypleurosaurid, Honghesaurus longicaudalis gen. et sp. nov., from the early Middle Triassic (Anisian, ~ 244 Ma) marine deposits in Luxi, Yunnan, China. The discovery documents the first really long-tailed pachypleurosaur with totally 121 (69 caudal) vertebrae, providing new evidence for the vertebral multiplication and ecological adaption of this group. The long trunk associated with an incredibly long tail could provide Honghesaurus the advantage of maneuverability and energy efficiency for lateral undulatory swimming. Honghesaurus, although possessing a series of autapomorphies, fills the morphological gap between Qianxisaurus from the Ladinian Xingyi Biota and Wumengosaurus from the Anisian Panxian Biota. Phylogenetic studies unite these three pachypleurosaurids as a monophyletic clade above European pachypleurosaurid clades and provide new insights into the interrelationships of this group. Our scenario of pachypleurosaurian phylogeny combined with the stratigraphic data imply that the Tethys Ocean was a west-east corridor for dispersal of pachypleurosaurids from Europe into South China.


Assuntos
Fósseis , Répteis , Adaptação Fisiológica , Animais , Evolução Biológica , China , Filogenia , Répteis/anatomia & histologia
13.
Ther Apher Dial ; 26(3): 632-639, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34550646

RESUMO

AIM: To evaluate the cognitive function in dialysis patients over 60 years old and identify the contributing factors. METHODS: A group of elderly dialysis patients in the Department of Nephrology, Pan'an People's Hospital between March 2015 and June 2018 were chosen as the subjects for this study. Patients were divided into two groups, those with cognitive impairment and those with normal cognitive function. Results of their Montreal Cognitive Assessment (MoCA) scores, Controlled Oral Word Association Test (COWAT), Wechsler Adult Intelligence Scale Digit Span subtest (WDMS), and Stanford Diagnostic Math Test (SDMT) were reviewed and analyzed. RESULTS: Among the 110 elderly dialysis patients, 75 patients (68.18%) showed different levels of damage to their cognitive function. Their assessment scores on MoCA (total), MoCA subtests: visuospatial/executive, naming, attention, language, delayed recall, abstraction and orientation, COWAT (total), COWAT1, COWAT2, COWAT3, WMDS-Backward, and SDMT are significantly lower than patients with normal cognitive abilities (p < 0.05). Further analysis showed that the highest percentage (72.00%) of patients had impairment with visuospatial/executive function; and, of the 75 cognitive impaired patients, 37.33% showed cognitive damage in two MoCA subtests simultaneously. Patients with and without cognitive impairment showed a significant (p < 0.05) difference on factors including age, education level, employment status, financial situation, dialysis vintage, serum albumin, and hemoglobin. CONCLUSION: Elderly patients on dialysis have a higher risk of becoming cognitive impaired. The cognitive impairment in elderly dialysis patients was significantly associated with age, dialysis vintage, and levels of serum albumin and hemoglobin.


Assuntos
Disfunção Cognitiva , Diálise Renal , Adulto , Idoso , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , Função Executiva , Humanos , Pessoa de Meia-Idade , Testes Neuropsicológicos , Albumina Sérica
14.
Zhongguo Zhong Yao Za Zhi ; 46(21): 5693-5700, 2021 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-34951223

RESUMO

To investigate the potential molecular markers and drug-compound-target mechanism of Mahuang Shengma Decoction(MHSM) in the intervention of acute lung injury(ALI) by network pharmacology and experimental verification. Databases such as TCMSP, TCMIO, and STITCH were used to predict the possible targets of MHSM components and OMIM and Gene Cards were employed to obtain ALI targets. The common differentially expressed genes(DEGs) were therefore obtained. The network diagram of DEGs of MHSM intervention in ALI was constructed by Cytoscape 3. 8. 0, followed by Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses of target genes. The ALI model was induced by abdominal injection of lipopolysaccharide(LPS) in mice. Bronchoalveolar lavage fluid(BALF) was collected for the detection of inflammatory factors. Pathological sectioning and RT-PCR experiments were performed to verify the therapeutic efficacy of MHSM on ALI. A total of 494 common targets of MHSM and ALI were obtained. Among the top 20 key active compounds of MHSM, 14 from Ephedrae Herba were found to be reacted with pivotal genes of ALI [such as tumor necrosis factor(TNF), tumor protein 53(TP53), interleukin 6(IL6), Toll-like receptor 4(TLR4), and nuclear factor-κB(NF-κB)/p65(RELA)], causing an uncontrolled inflammatory response with activated cascade amplification. Pathway analysis revealed that the mechanism of MHSM in the treatment of ALI mainly involved AGE-RAGE, cancer pathways, PI3 K-AKT signaling pathway, and NF-κB signaling pathway. The findings demonstrated that MHSM could dwindle the content of s RAGE, IL-6, and TNF-α in the BALF of ALI mice, relieve the infiltration of inflammatory cells in the lungs, inhibit alveolar wall thickening, reduce the acute inflammation-induced pulmonary congestion and hemorrhage, and counteract transcriptional activities of Ager-RAGE and NF-κB p65. MHSM could also synergically act on the target DEGs of ALI and alleviate pulmonary pathological injury and inflammatory response, which might be achieved by inhibiting the expression of the key gene Ager-RAGE in RAGE/NF-κB signaling pathway and downstream signal NF-κB p65.


Assuntos
Lesão Pulmonar Aguda , Medicamentos de Ervas Chinesas/farmacologia , NF-kappa B , Receptor para Produtos Finais de Glicação Avançada , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/genética , Animais , Lipopolissacarídeos , Pulmão/metabolismo , Camundongos , NF-kappa B/genética , NF-kappa B/metabolismo , Farmacologia em Rede , Receptor para Produtos Finais de Glicação Avançada/genética , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Transdução de Sinais
15.
Int J Mol Med ; 47(5)2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33649781

RESUMO

Glioblastoma (GBM) is the most common aggressive brain tumor and is associated with an extremely poor prognosis, as the current standard of care treatments have limited efficacy. Natural compounds have attracted increasing attention as potential anticancer drugs. Alantolactone (ATL) is a natural small molecule inhibitor, that has antitumor properties. In the present study, U87MG and U251 cells were treated ATL and changes in actin/G­actin/F­actin/cofilin pathway were detected in whole cells, in the cytoplasm and mitochondria by western blot analysis. Immunofluorescence and immunoprecipitation analysis identified changes in the expression levels of target proteins and interactions, respectively. A LIMK enzyme inhibitor was also applied to assess the effects of ATL on the migration and invasion of GBM cells. Flow cytometry was used to detect the levels of apoptosis of GBM cells. The expression of matrix metalloproteinase (MMP)­2/MMP­9, caspase­3/caspase­9/poly(ADP­ribose) polymerase (PARP)/cytochrome c, were determined by western blot analysis to assess the effects of targeting LIMK. The in vitro findings were verified in vivo by characterizing changes in the expression of cofilin/LIMK in xenograft tumors in immunodeficient mice. It was found that ATL activated cofilin through the targeted inhibition of LIMK enzyme activity and it thus upregulated the ratio of G/F actin, and inhibited GBM cell migration and invasion. Conversely, the activation of cofilin and G­actin could be co­transferred to the mitochondria to initiate the mitochondrial­cytochrome c pathway to induce apoptosis. On the whole, the findings of the present study further illustrate the molecular mechanisms through which ATL inhibits the metastatic phenotype of GBM cells and induces apoptosis. Given previous findings, it can be deduced that ATL can function through multiple pathways and has multiple targets in GBM models, highlighting its potential for use in clinical applications.


Assuntos
Fatores de Despolimerização de Actina/metabolismo , Actinas/metabolismo , Apoptose/efeitos dos fármacos , Glioblastoma/metabolismo , Lactonas/farmacologia , Quinases Lim/metabolismo , Proteínas de Neoplasias/metabolismo , Sesquiterpenos de Eudesmano/farmacologia , Fatores de Despolimerização de Actina/genética , Actinas/genética , Linhagem Celular Tumoral , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Glioblastoma/patologia , Humanos , Quinases Lim/genética , Metástase Neoplásica , Proteínas de Neoplasias/genética
17.
Am J Transl Res ; 12(7): 3926-3939, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32774746

RESUMO

Transient Receptor Potential Melastatin 4 (TRPM4) is a nonselective channel conducting monovalent ions and indirectly regulates intracellular Ca2+. Aberrant expression has been reported in a number of cancers. However, the biological function of TRPM4 in endometrial carcinoma (EC) is still unknown. We find that decreased TRPM4 expression is significantly correlated with a poor prognosis, overall survival (OS, P<0.001) and recurrence-free survival (P=0.002) through The Cancer Genome Atlas (TCGA) datasets in mRNA level. Multivariate Cox regression analysis suggests that TRPM4 is an independent prognostic factor for OS in EC patients. In vitro assays show that TRPM4-deletion results in significant promotion of proliferation and migration in EC cells. We then conducted a gene set enrichment analysis (GSEA) and according to the results, the expression of TRPM4 is modulated by estrogen, which is inhibited by ER antagonist. Furthermore, the silencing of TRPM4 causes a decreased p53 and hyper-activation of EMT, PI3K/AKT/mTOR signaling pathway in EC, as demonstrated in vitro. Overall, these results indicate that TRPM4 is clinically useful in predicting EC prognosis and represent a potential candidate as a new therapeutic target.

18.
Medicine (Baltimore) ; 99(31): e21494, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756182

RESUMO

To evaluate real dynamic assessment of tear film optical quality for monitoring and prevention of dry eye.Right eyes of 62 normal and 39 dry eye subjects were included. Dynamic measurement of objective scatter index (OSI) was performed by using the Optical Quality Analysis System II (OQAS II), correlation coefficient between OSI and time (CCOT) was calculated. According to whether the CCOT was significantly ascending, normal and dry eye groups were further subdivided for comparison. By using Scheimpflug-Placido topographer, non-invasive tear break-up time (NITBUT) was recorded, and a 2-dimensional precorneal tear film map was reconstructed and divided into central, middle, and peripheral corneal zones, distribution of tear break-up spots in the 3 corneal zones were analyzed.The numbers of tear break-up spots were higher in all the 3 corneal zones of the dry eye subjects (P < .01), when compared with the normal subjects. The Dry Eye subjects with ascending CCOT had the shortest NITBUT (P < .001-.034) and the most tear break-up spots over the whole cornea (P < .001-.044). Between the dry eye subjects with non-ascending CCOT and those with ascending CCOT, difference of tear break-up spots was found significant only in the peripheral corneal zone (P < .01).Non-ascending and ascending CCOT of dry eye patients reflect different stability of tear film. Real dynamic assessment of tear film optical quality is potential for monitoring and early prevention of dry eye.


Assuntos
Síndromes do Olho Seco/diagnóstico por imagem , Difusão Dinâmica da Luz/métodos , Lágrimas/diagnóstico por imagem , Adulto , Estudos de Casos e Controles , Córnea/diagnóstico por imagem , Síndromes do Olho Seco/prevenção & controle , Feminino , Humanos , Masculino , Adulto Jovem
19.
Front Med (Lausanne) ; 7: 70, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32258043

RESUMO

Introduction: Radiotherapy, combined regimens as platinum-paclitaxel chemotherapy and/or endocrine therapy is an important adjuvant treatment after surgery for endometrial cancer (EC). While, the resistance to them remain unclear. In our study, to separate the characteristics of side population (SP) cells from EC cell lines, study the mechanism of Taxol-resistance, progestin resistance and radioresistanc, and provide the basic for EC. Methods: SP cells from EC cell lines HEC-1A, Ishikawa and RL95-2 were separated by Hoechst 33342 staining and flow cytometry analysis. The expression of breast cancer resistance protein (BCRP) in SP cells and non-SP cells from HEC-1A was examined by immunocytochemistry, and the radiation-resistant and Taxol-resistant characteristics of SP cells and non-SP cells were compared by MTS. Ishikawa, Ishikawa-SP, and Ishikawa-non-SP cells incubated with MPA were selected for cell apoptosis assays by using flow cytometry. The expression of caspase-3 was examined by immunocytochemistry, and autophagy was detected by MDC staining. Results: Small proportions of SP cells, namely, 1.44 ± 0.93%, 2.86 ± 3.09%, and 2.87 ± 1.29%, were detected in HEC-1A, Ishikawa and RL95-2, respectively. There was a stronger clone formation efficiency for the SP cells than for non-SP cells in HEC-1A [(6.02 ± 1.17) vs. (0.53±0.20)%, P = 0.001], and there was a significant difference in the rate of tumourigenicity between the SP cells and non-SP cells in HEC-1A (87.5 vs. 12.5%). There were higher levels of BCRP expression (P = 0.001) and resistance to Taxol and radiation (P < 0.05) in the SP cells than in non-SP cells. After MPA treatment, the apoptosis rates were significantly different among the Ishikawa, Ishikawa-SP and Ishikawa-non-SP groups [(4.64 ± 0.18)%, (4.01 ± 0.43)%, and (9.3 ± 0.67)%; (P = 0.05)], and the expression of Caspase-3 in the Ishikawa group was higher than that in Ishikawa-SP group. The autophagic activity of the Ishikawa-SP cells was the strongest, while the autophagic activity of Ishikawa-non-SP was the weakest. Conclusions: There is a significant enrichment in SP cells among different EC cell lines, and these SP cells be more resistant to Taxol, MPA and radiation therapy. The overexpression of BCRP among SP cells may be the cause of resistance to Taxol, progestin and radiotherapy, which may be related to apoptosis and autophagic activity.

20.
Mitochondrial DNA B Resour ; 5(3): 2760-2762, 2020 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-33457939

RESUMO

The complete chloroplast genome of Catalpa 'Bairihua' a hybrid variety with multi season flowering obtained from hybrid progeny of C. bungei 'Luoqiu Sihao' (C. bungei '01' × C. bungei 'Changguo Qiu') and C. fargesii f. duclouxii was first sequenced with the Illumina HiSeq 2000 platform. Which was 158,210 bp in length with a typical quadruple structure and contained a large single copy (LSC: 84,928 bp) region and a small single copy (SSC: 12,664 bp) region that were separated by a pair of inverted repeats (IRa, b: 30,309 bp) region. The GC content of the whole chloroplast genome is 38.1%. A total of 130 genes was annotated in the complete chloroplast genome, including 85 protein-coding genes, 37 tRNA genes and 8rRNA genes. ML phylogenetic analysis by comparing with 39 chloroplast genomes of the Bignoniaceae indicated that Catalpa 'Bairihua' was close to Tecomaria capensis.

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