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1.
J Alzheimers Dis ; 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34602491

RESUMO

BACKGROUND: 40 Hz light flicker is a well-known non-invasive treatment that is thought to be effective in treating Alzheimer's disease. However, the effects of 40 Hz visual stimulation on neural networks, synaptic plasticity, and learning and memory in wild-type animals remain unclear. OBJECTIVE: We aimed to explore the impact of 40 Hz visual stimulation on synaptic plasticity, place cell, and learning and memory in wild-type mice. METHODS: c-Fos+ cell distribution and in vivo electrophysiology was used to explore the effects of 40 Hz chronic visual stimulation on neural networks and neuroplasticity in wild-type mice. The character of c-Fos+ distribution in the brain and the changes of corticosterone levels in the blood were used to investigate the state of animal. Place cell analysis and novel location test were utilized to examine the effects of 40 Hz chronic visual stimulation on learning and memory in wild-type mice. RESULTS: We found that 40 Hz light flicker significantly affected many brain regions that are related to stress. Also, 40 Hz induced gamma enrichment within 15 min after light flickers and impaired the expression of long-term potentiation (LTP), while facilitated the expression of long-term depression (LTD) in the hippocampal CA1. Furthermore, 40 Hz light flicker enhanced the expression of corticosterone, rendered well-formed place cells unstable and improved animal's learning and memory in novel local recognition test, which could be blocked by pre-treatment with the LTD specific blocker Glu2A-3Y. CONCLUSION: These finding suggested that 40 Hz chronic light flicker contains stress effects, promoting learning and memory in wild-type mice via LTD.

2.
Plant Dis ; 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34645301

RESUMO

Angelica sinensis (Oliv) Diels (Umbelliferae) is a popular Chinese herb that is mainly distributed in Gansu Province, China, accounting for more than 90% of the national output and sales. A survey for diseases of A. sinensis in Gansu Province in August 2019 found foliar disease with an incidence of 60 to100%, and severities ranging from 5 to 15%. The disease mainly occurred in late July and August. The initial symptoms included many light brown, small lesions, round or irregular in shape, which gradually increased in size. White mycelia was visible in the lesions. Severely affected leaves became chlorotic, withered and died. In the Angelica planting area in Weiyuan County (33°26'N, 104°02'E) diseased leaves from 20 plants were collected by the five-point sampling method (Zheng et al. 2018), and small samples (4 × 4 mm2) wee cut from the border between diseased and healthy tissue, successively sterilized with 75% ethanol for 30 sec, washed three times with sterilized water and dried on sterilized filter paper, and placed on potato dextrose agar plates. After 5 days at 25°C, five morphologically similar colonies were obtained. Colonies were somewhat round with pink overall and formed abundant fluffy white mycelium in the center. Conidia were solitary, macrospores slender, straight to slightly falcate with 2 to 6 septa, and ranged from 20.0 to 77.6 µm × 2.5 to 3.6 µm (n=50). The microspores were elliptical and ranged from 3.0 to 8.0 µm × 2.5 to 3.0 µm (n=5). The strong pink pigment was observed on the reverse side of the PDA culture. The morphological characteristics were consistent with the description of Fusarium avenaceum (Parikh et al. 2018; Jahedi et al. 2019). To further identify the strains, the internal transcribed spacer (ITS), ß-tubulin, translation elongation factor 1α (EF1-α), and RNA polymerase second largest subunit (RPB2) gene regions were amplified with ITS1/ITS4, Bt2a/Bt2b, EF1/EF2, and 5f2/7cr (Glass and Donaldson 1995; O'Donnell et al. 2010; White et al. 1990), respectively. The sequences of the five strains were identical, and that of representative strain K0721 were deposited in GenBank (ITS, MZ389899; TUB2, MZ398139; EF1-α, MZ388462; RPB2, MZ394004). BLAST analysis revealed that the ITS, ß-tubulin, EF1-α, and RPB2 sequences were 100% (563/563), 100% (423/423), 99% (643/649), and 99% (930/935) homology, with those of F. avenaceum (KP295511.1, KY475586.1, KU999088.1, and MH582082.1), respectively. A multigene phylogenetic tree was inferred by Maximum likelihood phylogenetic analyses based on the combined data set with ITS, EF1-α and RPB2. The strain K0721 was clustered with F. avenaceum. Pathogenicity tests were performed on five 1-month-old healthy plants in plastic pots (20 cm. diam.) with sterilized soil. Each was sprayed with 50 µl of a conidial suspension (1×104 conidia/mL), and 5 healthy plants were sprayed with sterile water as controls. Small lesions were observed after 5 days at 25℃ in a greenhouse. Symptoms were similar to those observed under field conditions. Control plants remained symptomless. Six isolates were reisolated from infected leaves and all confirmed to be F. avenaceum based on morphological observations and molecular identification. To our knowledge, only Septoria anthrisci has been previously reported as a pathogen of A. sinensis leaf spot (Wang et al. 2018), and this is the first report of F. avenaceum causing this disease. This discovery needs to be considered in developing and implementing disease management programs in A. sinensis production.

3.
IEEE Trans Image Process ; 30: 7914-7925, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34495831

RESUMO

Graph Convolution Network (GCN) has been successfully used for 3D human pose estimation in videos. However, it is often built on the fixed human-joint affinity, according to human skeleton. This may reduce adaptation capacity of GCN to tackle complex spatio-temporal pose variations in videos. To alleviate this problem, we propose a novel Dynamical Graph Network (DG-Net), which can dynamically identify human-joint affinity, and estimate 3D pose by adaptively learning spatial/temporal joint relations from videos. Different from traditional graph convolution, we introduce Dynamical Spatial/Temporal Graph convolution (DSG/DTG) to discover spatial/temporal human-joint affinity for each video exemplar, depending on spatial distance/temporal movement similarity between human joints in this video. Hence, they can effectively understand which joints are spatially closer and/or have consistent motion, for reducing depth ambiguity and/or motion uncertainty when lifting 2D pose to 3D pose. We conduct extensive experiments on three popular benchmarks, e.g., Human3.6M, HumanEva-I, and MPI-INF-3DHP, where DG-Net outperforms a number of recent SOTA approaches with fewer input frames and model size.

4.
Clin Ther ; 2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34548175

RESUMO

PURPOSE: Delirium is a common neurologic complication after cardiac surgery and is associated with a poor prognosis. Several studies have explored the effects of glucocorticoids on postoperative delirium (POD). However, conclusion have been inconsistent. The purpose of this systematic review and meta-analysis is to evaluate the effects of glucocorticoids on POD in adult patients undergoing cardiac surgery. METHODS: A systematic literature search was conducted using PubMed/MEDLINE, Embase, Cochrane Library/Central, and Web of Science from inception to January 28, 2021. Randomized controlled trials evaluating the effects of perioperative glucocorticoids administration on the incidence of POD in adults (≥18 years of age) undergoing cardiac surgery were included. The primary outcome of incidence of POD was assessed using the risk ratio (RR) with a fixed-effects model. Secondary analyses included the severity or duration of delirium, mortality at 30 days, length of hospital and intensive care unit (ICU) stay, duration of mechanical ventilatory support, the incidence of myocardial injury, new atrial fibrillation, renal and respiratory failure, postoperative infection and stroke, and the level of glucose and inflammatory factors. FINDINGS: A total 4 trials (n = 8448 patients) were included. Glucocorticoids did not significantly reduce the incidence of POD (RR = 0.99; 95% CI, 0.86-1.14) but increased the risk of myocardial injury (RR = 1.22; 95% CI, 1.08-1.38), decreased the duration of mechanical ventilatory support (mean difference, -0.83; 95% CI, -1.32 to -0.34), and led to a tendency toward short length of ICU stay (mean difference, -0.22; 95% CI, -0.47 to -0.03). No significant differences were observed in other secondary outcomes. IMPLICATIONS: The perioperative administration of glucocorticoids did not reduce the incidence of POD in adult patients undergoing cardiac surgery but might be associated with shorter duration of mechanical ventilatory support and a tendency toward a shorter length of ICU stay. Furthermore, we found that glucocorticoids may increase the rate of myocardial injury but have no effects on other clinical outcomes. International Prospective Register of Systematic Reviews identifier: CRD42021233458.

5.
Technol Cancer Res Treat ; 20: 15330338211039940, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34520285

RESUMO

Esophageal squamous cell carcinoma (ESCC) is a common cancer in East Asia and in other parts of the world and exhibits a poor prognosis. Growth inhibitor 5 (ING5) is a new member of the growth inhibitor (ING) protein family and is involved in many important cellular functions, such as the cell cycle, apoptosis, and chromatin remodeling. As a newly discovered tumor suppressor, ING5 has been shown to inhibit lung cancer proliferation and distant metastasis through the AKT pathway. In lung cancer tumors, ING5 can attenuate the ability of cancer cells to invade normal tumor-adjacent tissues. However, ING5 has rarely been studied in ESCC. Here, we found that in ESCC EC-109 cancer cells, ING5 overexpression inhibited cell proliferation and tumor invasion, whereas, in ESCC TE-1 cancer cells, ING5 knockdown promoted cell invasion. In a nude mouse xenograft model, ING5 overexpression inhibited tumor growth and the invasion ability of ESCC cells. Further studies revealed that ING5 overexpression inhibited IL-6/CXCL12 expression at both the mRNA and protein levels as well as morphological changes. We found for the first time that ING5 inhibits ESCC cell migration and invasion by downregulating the IL-6/CXCL12 signaling pathway.

6.
Cancer Lett ; 521: 268-280, 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34481935

RESUMO

Diffuse large B-cell lymphoma (DLBCL) exhibits frequent inactivating mutations of the histone acetyltransferase CREBBP, highlighting the attractiveness of targeting CREBBP deficiency as a therapeutic strategy. In this study, we demonstrate that chidamide, a novel histone deacetylase (HDAC) inhibitor, is effective in treating a subgroup of relapsed/refractory DLBCL patients, achieving an overall response rate (ORR) of 25.0% and a complete response (CR) rate of 15.0%. However, the clinical response to chidamide remains poor, as most patients exhibit resistance, hampering the clinical utility of the drug. Functional in vitro and in vivo studies have shown that CREBBP loss of function is correlated with chidamide sensitivity, which is associated with modulation of the cell cycle machinery. A combinatorial drug screening of 130 kinase inhibitors targeting cell cycle regulators identified AURKA inhibitors, which inhibit the G2/M transition during the cell cycle, as top candidates that synergistically enhanced the antitumor effects of chidamide in CREBBP-proficient DLBCL cells. Our study demonstrates that CREBBP inactivation can serve as a potential biomarker to predict chidamide sensitivity, while combination of an AURKA inhibitor and chidamide is a novel therapeutic strategy for the treatment of relapsed/refractory DLBCL.

7.
Neurochem Int ; 150: 105187, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34534609

RESUMO

Hydrogen sulfide (H2S) serves as a neuromodulator and regulator of neuroinflammation. It is reported to be therapeutic for Parkinson's disease (PD) animal and cellular models. However, whether it affects α-synuclein accumulation in dopaminergic cells, the key pathological feature in PD, is poorly understood. In this study we reported that exogenous H2S donors NaHS and GYY4137 (GYY) enhanced the autophagy activity, as indicated by the increases of autophagy marker LC3-II expression and LC3 dots formation even during lysosome inhibition in dopaminergic cell lines and HEK293 cells. The enhancement of H2S donors on autophagic flux was mediated by adenosine 5'-monophosphate-activated protein kinase (AMPK)-dependent mammalian target of rapamycin (mTOR) inhibition, as H2S donors activated AMPK but reduced the mTOR activity and H2S donors-induced LC3-II increase was diminished by mTOR activator. Moreover, point mutation of Cys302 into alanine (C302A) in AMPKα2 subunit abolished the AMPK activation and mTOR inhibition, as well as autophagic flux increase elicited by NaHS. Interestingly, NaHS triggered AMPK S-sulfuration, which was not observed in AMPK C302A-transfected cells. Further, NaHS was able to attenuate α-synuclein accumulation in a cellular model induced by dopamine oxidized metabolite 3, 4-dihydroxyphenylacetaldehyde (DOPAL), and this effect was interfered by autophagy inhibitor wortmannin and also eliminated in AMPK Cys302A-transfected cells. In sum, the findings identified a role of Cys302 S-sulfuration in AMPK activation induced by exogenous H2S and demonstrated that H2S donors could enhance the autophagic flux via AMPK-mTOR signaling and thus reduce α-synuclein accumulation in vitro.

8.
Cell Signal ; 87: 110140, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34478827

RESUMO

Hypoxia-inducible factor-1α (HIF-1α) and heme oxygenase-1 (HO-1) are important transcription regulators in hypoxic cells and for maintaining cellular homeostasis, but it is unclear whether they participate in hypoxia-induced excessive proliferation of yak pulmonary artery smooth muscle cells (PASMCs). In this study, we identified distribution of HIF-1α and HO-1 in yak lungs. Immunohistochemistry and immunofluorescence results revealed that both HIF-1α and HO-1 were mainly concentrated in the medial layer of small pulmonary arteries. Furthermore, under induced-hypoxic conditions, we investigated HIF-1α and HO-1 protein expression and studied their potential involvement in yak PASMCs proliferation and apoptosis. Western blot results also showed that both factors significantly increased in age-dependent manner and upregulated in hypoxic PASMCs (which exhibited obvious proliferation and anti-apoptosis phenomena). HIF-1α up-regulation by DMOG increased the proliferation and anti-apoptosis of PASMCs, while HIF-1α down-regulation by LW6 decreased proliferation and promoted apoptosis. More so, treatment with ZnPP under hypoxic conditions down-regulated HO-1 expression, stimulated proliferation, and resisted apoptosis in yak PASMCs. Taken together, our study demonstrated that both HIF-1α and HO-1 participated in PASMCs proliferation and apoptosis, suggesting that HO-1 is important for inhibition of yak PASMCs proliferation while HIF-1α promoted hypoxia-induced yak PASMCs proliferation.

9.
Ecotoxicol Environ Saf ; 225: 112786, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34555717

RESUMO

The occurrence of immuno-compromised status in animals with zearalenone (ZEA) exposure may be a critical contributor to associated mucosal (gastrointestinal tract) diseases. However, it is difficult to assess the associated risks with limited reference data. This study comprehensively discussed the effects of ZEA on intestinal immune components, cytokines and molecular mechanism of juvenile grass carp infected with Aeromonas hydrophila. Specifically, the fish were fed six graded levels of dietary ZEA (0-2507 µg kg-1 diet) for 70 d. The results pointed out that the average residual amount of ZEA in the intestines increased with dose level after ZEA feeding. We further performed an infection assay using A. hydrophila. After 14 d, ZEA groups increased enteritis morbidity rate compared with controls. The acid phosphatase (ACP), lysozyme (LZ) activities and immunoglobulin M (IgM) content were significantly decreased in three intestinal segments. Furthermore, ZEA could reduce the transcription of ß-defensin-1, Hepcidin, liver expressed antimicrobial peptide 2A/2B (LEAP-2A/2B) and Mucin-2. We next confirmed the loss of these immune components accompanied by the invasion of the intestinal barrier by bacteria, as indicated by activation of the nuclear factor κB (NF-κB) and the expression of downstream cytokines. Notably, the phosphorylated target of rapamycin (TOR) plays an important role in regulating these genes, thus indicating a possible target caused by ZEA. In summary, the extensive inhibition of immune components by ZEA promotes the spread of pathogens, which may increase the possibility of intestinal mucosa exposure and the risk of transforming disease.


Assuntos
Carpas , Zearalenona , Aeromonas hydrophila , Animais , NF-kappa B/genética , Sirolimo , Zearalenona/toxicidade
10.
Front Endocrinol (Lausanne) ; 12: 693977, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34484115

RESUMO

Since the potential roles of extracellular vesicles secreted by adipose-derived mesenchymal stem cells (ADSCs) are not well understood in collagen metabolism, the purpose of this research was to evaluate the effects of ADSCs-extracellular vesicles in stress urinary incontinence and the regulatory mechanism of delivered microRNA-93 (miR-93). ADSCs were isolated and cultured, and ADSCs-extracellular vesicles were extracted and identified. Stress urinary incontinence primary fibroblasts or satellite cells were treated with ADSCs-extracellular vesicles to detect the expression of Elastin, Collagen I, and Collagen III in fibroblasts and Pax7 and MyoD in satellite cells. After transfecting ADSCs with miR-93 mimics or inhibitors, extracellular vesicles were isolated and treated with stress urinary incontinence primary fibroblasts or satellite cells to observe cell function changes. The online prediction and luciferase activity assay confirmed the targeting relationship between miR-93 and coagulation factor III (F3). The rescue experiment verified the role of ADSCs-extracellular vesicles carrying miR-93 in stress urinary incontinence primary fibroblasts and satellite cells by targeting F3. ADSCs-extracellular vesicles treatment upregulated expression of Elastin, Collagen I, and Collagen III in stress urinary incontinence primary fibroblasts and expression of Pax7 and MyoD in stress urinary incontinence primary satellite cells. miR-93 expression was increased in stress urinary incontinence primary fibroblasts or satellite cells treated with ADSCs-extracellular vesicles. Extracellular vesicles secreted by ADSCs could deliver miR-93 to fibroblasts and then negatively regulate F3 expression; ADSCs-extracellular vesicles could reverse the effect of F3 on extracellular matrix remodeling in stress urinary incontinence fibroblasts. miR-93 expression was also increased in stress urinary incontinence primary satellite cells treated by ADSCs-extracellular vesicles. Extracellular vesicles secreted by ADSCs were delivered to satellite cells through miR-93, which directly targets F3 expression and upregulates Pax7 and MyoD expression in satellite cells. Our study indicates that miR-93 delivered by ADSCs-extracellular vesicles could regulate extracellular matrix remodeling of stress urinary incontinence fibroblasts and promote activation of stress urinary incontinence satellite cells through targeting F3.

11.
Gene Expr Patterns ; 42: 119203, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34481069

RESUMO

Despite comprising much of the genome, transposons were once thought of as junk. However, transposons play many roles in the eukaryotic genome, such as providing new proteins as domesticated genes, expressing during germline-soma differentiation, function in DNA rearrangement in the offspring, and so on. We sought to describe the distribution and structural organization of the two autonomous transposons (ZB and PS) in the zebrafish genome and examine their expression patterns in embryos and adult tissues. The intact copy of ZB and PS was queried by BLAST on NCBI and ENSEMBL using default parameters. Of the copies with coverage and identity, more than 90 % were downloaded to do structural analysis. Spatial and temporal expression patterns were detected by qRT-PCR and Whole-mount in situ hybridization (WISH). There are 19 intact copies of ZB, encoding 341 amino acid residues with DD34E catalytic domain and flanked by 201bp TIRs, and seven intact PS copies, containing 425 amino acid residues with DD35D catalytic domain flanked by 28bp TIRs, were detected in the genome of zebrafish respectively. Analysis of genomic insertions indicated that both ZB and PS transposons are prone to be retained in the intron and intergenic regions of the zebrafish genome. The sense and antisense transcripts of ZB and PS were detected during embryonic development stages and exhibited similar expression patterns. The difference is that the sense strand transcript of ZB was explicitly expressed in midbrain-hindbrain boundary (MHB) and otic vesicle (OV), and pharyngeal arches and pharyngeal pouches (PA&PP) at 48 hpf. In adult zebrafish, the expressions of ZB and PS in muscle and brain are much higher than in other tissues. Our study results indicate that ZB and PS transposons may be involved in the embryonic development and regulation of somatic cells of certain adult tissues, such as the brain and muscle.

12.
Brain Behav ; 11(8): e2295, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34337881

RESUMO

OBJECTIVE: This study aims to investigate the efficacy of modified Ginseng Yangrong decoction (GSYRD) promoting angiogenesis after ischemic stroke. METHODS: In an in vivo study, rats that survived surgery were allocated into four groups: the control group and model group were treated with normal saline, the GSYRD group was treated with 18.9 mg/kg of GSYRD daily, and the positive control group was treated with Tongxinluo (TXL) (1 g/kg/d). At the end of the seven-day treatment, the area of cerebral infarction, the expression changes of miRNA-210 and ephrin A3 were determined. In an in vitro study, HUVECs were divided into a normal control serum group (NC group), normal control serum OGD group (Oxygen Glucose Deprivation group) (OGD group), OGD + drug-containing serum group (OGD+GSYRD group), and OGD + drug-containing serum + ES group (Endostatin group) (OGD+GSYRD+ES group). The cells in all groups except the NC group were cultured in a sugar-free DMEM medium under hypoxia for 48 h. Cell proliferation, angiogenic structure formation ability, the expression changes of miRNA-210, ephrin A3, and the HIF/VEGF/Notch signaling pathway-related molecules were determined. RESULTS: In vivo, GSYRD significantly reduced infarct size (p < .01), the expression of miRNA-210 and ephrin A3 were decreased in the GSYRD group (p < .05). In vitro, the cell proliferation and tube formation ability were significantly increased in the GSYRD group (p < .05), and the expression of miRNA-210 and ephrin A3 was decreased (p < .05). In addition, in the GSYRD group, the expression of the HIF/VEGF/Notch signaling pathway-related molecules was significantly increased (p < .01 or p < .05). CONCLUSION: GSYRD promotes cerebral protection following angiogenesis and ischemic brain injury. The specific mechanism was activating the HIF/VEGF/Notch signaling pathway via miRNA-210.


Assuntos
Isquemia Encefálica , AVC Isquêmico , MicroRNAs , Acidente Vascular Cerebral , Animais , Isquemia Encefálica/tratamento farmacológico , Medicamentos de Ervas Chinesas , MicroRNAs/genética , Ratos , Transdução de Sinais , Acidente Vascular Cerebral/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular
13.
J Cell Mol Med ; 25(17): 8115-8126, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34346538

RESUMO

Previous findings have highlighted the association between oxidized high-density lipoprotein (ox-HDL) and polycystic ovary syndrome (PCOS) development; however, the underlying mechanism remains unclear. Under such context, the present study aimed to investigate the mechanism underlying the involvement of ox-HDL in PCOS in relation to the p65/micro-RNA-34a (miR-34a)/FOS axis. PCOS rat models were established with the injection of dehydroepiandrosterone (6 mg/100 g body weight). Both PCOS-modelled rats and granulosa cells (GCs) were received treatment with ox-HDL in order to identify its role in PCOS. Next, apoptosis and viability of GCs were detected with the application of TdT-mediated dUTP Nick-End Labeling and flow cytometry and Cell counting kit-8, respectively. A series of assays were performed to determine the interaction among ox-HDL, p65, miR-34a, FOS and nuclear factor-κB (NF-κB). The results revealed high expression of ox-HDL in PCOS, and enhanced endocrine disorders and ovarian damage in rats. ox-HDL promoted apoptosis of GCs and decreased its viability. ox-HDL activated NF-κB pathway and induced p65 phosphorylation to promote miR-34a expression. miR-34a targeted and inhibited FOS expression. In conclusion, our findings suggested that ox-HDL promoted the activation of p65 and transcription of miR-34a, which stimulated apoptosis of GCs and inhibited expression of FOS, resulting in the overall acceleration of PCOS development.

14.
Bioorg Chem ; 115: 105255, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34435574

RESUMO

Alzheimer's disease (AD) has become a serious threat to the developed nations with burgeoning patients and annual costs on health care system in modern society. Neuroinflammation, as one of the specific biochemical factors in the progress of neurodegeneration diseases, performs a crucial role in the pathogenesis and development of AD. Therefore, it is of great significance to develop effective anti-neuroinflammatory strategies for the treatment of AD. N-salicyloyl tryptamine derivatives were previously reported and demonstrated that possessed great potential anti-neuroinflammatory effects and favorable blood-brain barrier (BBB) permeation. Herein, a series of novel N-salicyloyl tryptamine derivatives were synthesized and their anti-AD potential was evaluated both in vitro and in vivo. Among them, L7 performed well anti-neuroinflammatory effects and excellent neuroprotective effects, as well as little toxicity. To lucubrate its potential for the treatment of AD, behavior tests including morris water maze (MWM), eight-arm radial maze, open field test and novel object recognition (NOR) test were carried out and the results showed that L7 could remarkably improve Aß-induced cognitive impairment. Moreover, the mechanism of action of L7 on improving Aß-induced AD was preliminarily investigated, and the results uncovered that the neuroprotective effects of L7 was might exerte via intervening Aß-induced pyroptosis through NLRP3-caspase-1-GSDMD axis and ameliorating neuronal apoptosis by mitochondrial apoptosis pathway. Besides, the distribution of Aß plaques in brain tissues were detected by immunohistochemical (IHC) assay and the results indicated that L7 could significantly attenuate the deposition of Aß plaques in the brain.

15.
Neurosci Lett ; 762: 136166, 2021 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-34371125

RESUMO

Parkinson's disease (PD) is the second most common neurodegenerative disorder and affects dopaminergic neurons. Autophagy often shows a circadian rhythm pattern under physiological conditions across 24 h. Abnormal autophagy and circadian dysfunction are two characteristics of PD. Whether the rhythm of autophagy is altered in PD has not yet been reported. Therefore, in this study, we collected peripheral blood samples at 6:00 h and 18:00 h from PD patients and age-matched controls, and analyzed the mRNA expressions of ULK1, BECN1, LAMP2, AMPK, and SNCA using real-time quantitative PCR. Blood samples analysis found that BECN1 and LAMP2 levels were decreased in patients with PD. Simultaneously, the rhythm of autophagy in PD is not consistent with that in the Control group, which may be a manifestation of the abnormal biological rhythm of PD.

16.
Comput Math Methods Med ; 2021: 3195957, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34413896

RESUMO

A ligand-based and docking-based virtual screening was carried out to identify novel MDM2 inhibitors. A pharmacophore model with four features was used for virtual screening, followed by molecular docking. Seventeen compounds were selected for an in vitro MDM2 inhibition assay, and compounds AO-476/43250177, AG-690/37072075, AK-968/15254441, AO-022/43452814, and AF-399/25108021 showed promising MDM2 inhibition activities with K i values of 9.5, 8.5, 23.4, 3.2, and 23.1 µM, respectively. Four compounds also showed antiproliferative activity, and compound AO-022/43452814 was the most potent hit with IC50 values of 19.35, 26.73, 12.63, and 24.14 µM against MCF7 (p53 +/+), MCF7 (p53 -/-), HCT116 (p53 +/+), and HCT116 (p53 -/-) cell lines, respectively. Compound AO-022/43452814 could be used as a scaffold for the development of anticancer agents targeting MDM2.

17.
J Ethnopharmacol ; 281: 114563, 2021 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-34438033

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Amomum belonging to the family Zingiberaceae, is mainly distributed in tropical regions of Asia and Oceania. Their fruits and seeds are valuable traditional medicine and used extensively, particularly in South China, India, Malaysia, and Vietnam. The genus Amomum has long been used for treating gastric diseases, digestive disorder, cancer, hepatopathy, malaria, etc. AIMS OF THE REVIEW: The main purpose of this review is to provide the available information on the traditional medicinal uses, phytochemistry, and pharmacology aspects of the genus Amomum in order to explore the trends and perspectives for further studies on its non-volatile constituents. MATERIALS AND METHODS: The present review collected the literatures published prior to 2020 on the traditional medicinal uses, phytochemistry, and pharmacology of the genus Amomum. The available literatures were extracted from scientific databases, such as Sci-finder, PubMed, Web of Science, Google Scholar, Baidu Scholar, and CNKI, books, and others. RESULTS: Herein, we summarize all 166 naturally occurring non-volatile compounds from 16 plants of the genus Amomum reported in 171 references, including flavonoids, terpenoids, diarylheptanoids, coumarins, etc. Triterpenes and flavonoids are the main constituents among these compounds and maybe play an important role in the activities directly or indirectly. As traditional medicine, the plants from the genus Amomum have been usually used in some traditional herbal prescriptions, and pharmacological researches in vitro and in vivo revealed that the extracts possessed significant antioxidant, anti-inflammatory, anti-allergic activities, etc. CONCLUSION: The review systematically summarizes current studies on traditional medicinal uses, phytochemistry, pharmacological activity on the plants from the genus Amomum. To date, the majority of publications still focused on the research of volatile constituents. However, the promising preliminary data of non-volatile constituents indicated the research potential of this genus in phytochemical and pharmacological aspects. Furthermore, the further in-depth investigations on the safety, efficacy, as well as the stereo-chemistry and structure-activity relationships of pure compounds from this genus are essential in the future.

18.
Front Immunol ; 12: 650105, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34394072

RESUMO

Glioblastoma is considered to be the most malignant disease of the central nervous system, and it is often associated with poor survival. The immune microenvironment plays a key role in the development and treatment of glioblastoma. Among the different types of immune cells, tumor-associated microglia/macrophages (TAM/Ms) and CD8-positive (CD8+) T cells are the predominant immune cells, as well as the most active ones. Current studies have suggested that interaction between TAM/Ms and CD8+ T cells have numerous potential targets that will allow them to overcome malignancy in glioblastoma. In this review, we summarize the mechanism and function of TAM/Ms and CD8+ T cells involved in glioblastoma, as well as update on the relationship and crosstalk between these two cell types, to determine whether this association alters the immune status during glioblastoma development and affects optimal treatment. We focus on the molecular factors that are crucial to this interaction, and the role that this crosstalk plays in the biological processes underlying glioblastoma treatment, particularly with regard to immune therapy. We also discuss novel therapeutic targets that can aid in resolving reticular connections between TAM/Ms and CD8+ T cells, including depletion and reprogramming TAM/Ms and novel TAM/Ms-CD8+ T cell cofactors with potential translational usage. In addition, we highlight the challenges and discuss future perspectives of this crosstalk between TAM/Ms and CD8+ T cells.


Assuntos
Neoplasias Encefálicas/imunologia , Comunicação Celular/imunologia , Glioblastoma/imunologia , Microambiente Tumoral/imunologia , Animais , Encéfalo/imunologia , Encéfalo/patologia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/terapia , Linfócitos T CD8-Positivos/imunologia , Comunicação Celular/efeitos dos fármacos , Ensaios Clínicos como Assunto , Modelos Animais de Doenças , Glioblastoma/patologia , Glioblastoma/terapia , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia Adotiva/métodos , Linfócitos do Interstício Tumoral/imunologia , Microglia/imunologia , Microglia/patologia , Receptores de Antígenos Quiméricos/imunologia , Resultado do Tratamento , Microambiente Tumoral/efeitos dos fármacos , Macrófagos Associados a Tumor/imunologia
19.
Food Chem ; 365: 130489, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34243120

RESUMO

The present study aimed to investigate the effect of initial vacuum package (VP), air package (AP) and salt-solution package (NP) on texture softening and package-swelling of Paocai by comparing the changes in physicochemical properties, pectinolysis, microstructure, microbial profile, as well as sugar and organic acid profiles during storage. Results showed that, when compared with AP and NP, with suppressive microbial invasion and less total pectinase activity, VP could retain more soluble pectin and induce more compact microstructure of Paocai, leading to higher hardness of Paocai during storage. As for package-swelling, VP mitigated gas-production in package by changing the microbial composition and metabolic patterns of sugar and organic acid in Paocai, especially targeted regulating the abundance of genus Kazachstania. This study provided a perspective for appropriate packaging technology to control the pectinase activity as well as cell-invading and gas-producing microorganisms for manufacturing fermented vegetable with better texture and non-package-swelling.


Assuntos
Ácidos , Açúcares , Parede Celular , Fermentação , Verduras
20.
Fish Shellfish Immunol ; 116: 140-149, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34256134

RESUMO

Most antibiotics, insecticides, and other chemicals used in agricultural and fishery production tend to persist in the environment. Fenvalerate, sulfide gatifloxacin, and ridomil are widely used in aquaculture as antibacterial, antifungal, and antiparasitic drugs; however, their toxicity mechanism remains unclear. Thus, we herein analyzed the effects of these three drugs on the hepatopancreas of Procambarus clarkii at the transcriptome level. Twelve normalized cDNA libraries were constructed using RNA extracted from P. clarkii after treatment with fenvalerate, sulfide gatifloxacin, or ridomil and from an untreated control group, followed by Kyoto Encyclopedia of Genes and Genomes pathway analysis. In the control vs fenvalerate and control vs sulfide gatifloxacin groups, 14 and seven pathways were significantly enriched, respectively. Further, the effects of fenvalerate and sulfide gatifloxacin were similar on the hepatopancreas of P. clarkii. We also found that the expression level of genes encoding senescence marker protein-30 and arylsulfatase A was downregulated in the sulfide gatifloxacin group, indicating that sulfide gatifloxacin accelerated the apoptosis of hepatopancreatocytes. The expression level of major facilitator superfamily domain containing 10 was downregulated, implying that it interferes with the ability of the hepatopancreas to metabolize drugs. Interestingly, we found that Niemann pick type C1 and glucosylceramidase-ß potentially interact with each other, consequently decreasing the antioxidant capacity of P. clarkii hepatopancreas. In the fenvalerate group, the downregulation of the expression level of xanthine dehydrogenase indicated that fenvalerate affected the immune system of P. clarkii; moreover, the upregulation of the expression level of pancreatitis-associated protein-2 and cathepsin C indicated that fenvalerate caused possible inflammatory pathological injury to P. clarkii hepatopancreas. In the ridomil group, no pathway was significantly enriched. In total, 21 genes showed significant differences in all three groups. To conclude, although there appears to be some overlap in the toxicity mechanisms of fenvalerate, sulfide gatifloxacin, and ridomil, further studies are warranted.


Assuntos
Alanina/análogos & derivados , Antibacterianos/toxicidade , Astacoidea/efeitos dos fármacos , Fungicidas Industriais/toxicidade , Gatifloxacina/toxicidade , Inseticidas/toxicidade , Nitrilas/toxicidade , Piretrinas/toxicidade , Poluentes Químicos da Água/toxicidade , Alanina/toxicidade , Animais , Astacoidea/genética , Perfilação da Expressão Gênica , Hepatopâncreas/efeitos dos fármacos , Hepatopâncreas/metabolismo , Transcriptoma/efeitos dos fármacos
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