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1.
BMC Plant Biol ; 21(1): 340, 2021 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-34273968

RESUMO

BACKGROUND: TLPs (Tubby-like proteins) are widespread in eukaryotes and highly conserved in plants and animals. TLP is involved in many biological processes, such as growth, development, biotic and abiotic stress responses, while the underlying molecular mechanism remains largely unknown. In this paper we characterized the biological function of cucumber (Cucumis sativus L.) Tubby-like protein 8 (CsTLP8) in Arabidopsis. RESULTS: In cucumber, the expression of the tubby-like protein CsTLP8 was induced by NaCl treatment, but reduced by PEG (Polyethylene Glycol) and ABA (Abscisic Acid) treatment. Subcellular localization and transcriptional activation activity analysis revealed that CsTLP8 possessed two characteristics of classical transcription factors: nuclear localization and trans-activation activity. Yeast two-hybrid assay revealed interactions of CsTLP8 with CsSKP1a and CsSKP1c, suggesting that CsTLP8 might function as a subunit of E3 ubiquitin ligase. The growth activity of yeast with ectopically expressed CsTLP8 was lower than the control under NaCl and mannitol treatments. Under osmotic and salt stresses, overexpression of CsTLP8 inhibited seed germination and the growth of Arabidopsis seedlings, increased the content of MDA (Malondialdehyde), and decreased the activities of SOD (Superoxide Dismutase), POD (Peroxidase) and CAT (Catalase) in Arabidopsis seedlings. Overexpression of CsTLP8 also increased the sensitivity to ABA during seed germination and ABA-mediated stomatal closure. CONCLUSION: Under osmotic stress, CsTLP8 might inhibit seed germination and seedling growth by affecting antioxidant enzymes activities. CsTLP8 acts as a negative regulator in osmotic stress and its effects may be related to ABA.


Assuntos
Ácido Abscísico/metabolismo , Cucumis sativus/metabolismo , Germinação , Pressão Osmótica , Proteínas de Plantas/metabolismo , Sementes , Transdução de Sinais , Antioxidantes/metabolismo , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , Cucumis sativus/efeitos dos fármacos , Cucumis sativus/crescimento & desenvolvimento , Plântula/metabolismo , Sementes/embriologia , Cloreto de Sódio , Fatores de Transcrição/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
2.
Nanotechnology ; 32(39)2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34161927

RESUMO

Ferroptosis as an iron-dependent lipid peroxidation process causes sevely oxidative damage of cell, but lack of highly efficient and recycable antioxidant agents. To this end, cerium doped carbon dots (Ce-doped CDs) with radical scavenging activity were synthesized using a simple microwave-assisted hydrothermal carbonization. The resultant Ce-doped CDs exhibited an ultra-small size of only approximately 2.6 nm, excellent dispersion in water as well as optical performance. Taking advantage of inherent ultra-small size, Ce-doped CDs were endowed with high Ce3+/Ce4+ratio, which significantly enhanced their radical scavenging activity. Meanwhile, the Ce-doped CDs with superior biocompatibility could enter cells quickly and then localized in the cytoplasm. As we expected, the Ce-doped CDs strongly protected cells from oxidative damage of erastin-mediated ferroptosis. These findings suggest that the as-prepared Ce-doped CDs have the potential to be antioxidant drugs against for ferroptosis-induced oxidative damage.

3.
J Agric Food Chem ; 69(7): 2087-2098, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33560120

RESUMO

In this study, volatile organic compounds (VOCs) were generated by Pseudomonas fluorescens ZX with incubation in nutrient broth (NB), on NA (NB with agar), and on healthy orange fruits, and pure individual components of VOCs were used to manage citrus green mold infected by Penicillium digitatum. At a concentration of 1 × 1010 cfu/mL, the VOCs from antagonist-containing NA plates inhibited P. digitatum conidial germination and mycelial growth by about 60%, while the VOCs from bacterial fluid exhibited approximately 75% inhibitory effect. Biofumigation by VOCs significantly reduced the disease index, with a higher biocontrol efficacy by VOCs from bacterial fluid (about 51%) than from antagonist-containing NA plates (around 40%) or from antagonist-infested fruit (approximately 24%). Exposure to VOCs led to morphological abnormalities of P. digitatum conidia and hyphae. However, VOCs exhibited poor preventative and curative action against P. digitatum. The storage test showed that biofumigation had no negative effects on fruit quality. Antifungal assays suggested that dimethyl disulfide and dimethyl trisulfide exhibited the highest inhibitory effects, which afforded complete inhibition at the lowest concentrations. In addition, organic acids were also promising in controlling green mold, but only at suitable low concentrations to avoid eliciting fruit's physiological diseases.


Assuntos
Citrus , Penicillium , Pseudomonas fluorescens , Compostos Orgânicos Voláteis , Frutas , Doenças das Plantas
4.
Nanoscale ; 13(6): 3594-3601, 2021 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-33564813

RESUMO

Cytomembrane cancer nanovaccines are considered a promising approach to induce tumor-specific immunity. Most of the currently developed nanovaccines, unfortunately, fail to study the underlying mechanism for cancer prevention and therapy, as well as immune memory establishment, with their long-term anti-tumor immunity remaining unknown. Here, we present a strategy to prepare biomimetic cytomembrane nanovaccines (named CCMP@R837) consisting of antigenic cancer cell membrane (CCM)-capped poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with imiquimod (R@837) as an adjuvant to activate the immune system. We found that our CCMP@R837 system enhanced bone-marrow-derived dendritic cell uptake and maturation, as well as increased anti-tumor response against breast cancer 4T1 cells in vitro. Moreover, an immune memory was established after three-time immunization with CCMP@R837 in BALB/c mice. The CCMP@R837-immunized BALB/c mice exhibited suppressed tumor growth and a long survival period (75% of mice lived longer than 50 days after tumor formation). This long-term anti-tumor immunity was achieved by increasing CD8+ T cells and decreasing regulatory T cells in the tumor while increasing effector memory T cells in the spleen. Overall, our platform demonstrates that CCMP@R837 can be a potential candidate for preventive cancer vaccines in the clinic.


Assuntos
Vacinas Anticâncer , Nanopartículas , Neoplasias , Animais , Biomimética , Linfócitos T CD8-Positivos , Células Dendríticas , Camundongos , Camundongos Endogâmicos BALB C , Copolímero de Ácido Poliláctico e Ácido Poliglicólico
5.
Food Chem ; 347: 129085, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33493837

RESUMO

Zanthoxylum Bungeanum Maxim. is an important seasoning in Chinese cooking, but its bitter taste limits its use by some consumers. In this study, metabolomic analysis based on ultra-high-performance liquid chromatograph-tandem mass spectrometry (UPLC-MS) was used to screen out a vast number of potential non-volatile bitter compounds in Z. bungeanum. Results showed that there were 37 potential bitter compounds in Z. bungeanum, and possible mechanisms underlying its bitter taste were provided. Further, instrumental analyses combined with sensory evaluation were used to identify the key bitter compounds in Gou jiao, a wild variant of Z. Bungeanum with a strong bitter taste. Totally 15 key bitter compounds were identified, most of which have a low bitterness recognition threshold. This study is the first comprehensive identification of non-volatile bitter compounds in Z. bungeanum and provides a basis for future investigations into mitigating bitterness and uncovering how the interaction between different bitter compounds affects taste.


Assuntos
Agentes Aversivos/análise , Metabolômica/métodos , Paladar/fisiologia , Zanthoxylum/química , Adulto , Agentes Aversivos/química , Cromatografia Líquida de Alta Pressão , Feminino , Frutas/química , Frutas/metabolismo , Humanos , Masculino , Espectrometria de Massas em Tandem , Limiar Gustativo , Adulto Jovem , Zanthoxylum/metabolismo
6.
Stroke ; 52(3): 1074-1078, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33504191

RESUMO

BACKGROUND AND PURPOSE: Complete P wave disappearance (CPWD) in patients without atrial fibrillation is an uncommon clinical phenomenon. We aimed to study the relationship between CPWD and thromboembolism. METHODS: Between July 2007 and December 2018, consecutive patients with CPWD on surface ECG and 24-hour Holter recording were recruited into the study from 4 centers in China. All recruited patients underwent transesophageal echocardiography or cardiac computed tomography to screen for atrial thrombus. Atrial electrical activity and scar were assessed by electrophysiological study (EPS) and 3-dimensional electroanatomic mapping. Cardiac structure and function were assessed by multimodality cardiac imaging. RESULTS: Twenty-three consecutive patients (8 male; mean age 48.5±14.7 years) with CPWD were included. Only 3 patients demonstrated complete atrial electrical silence with atrial noncapture. Thirteen patients who had invasive atrial endocardial mapping demonstrated extensive scar. Pulse-wave mitral inflow Doppler demonstrated absent and dampened A waves in 18 and 5 patients, respectively. Pulse-wave tricuspid inflow Doppler showed absent and dampened A waves in 19 and 4 patients, respectively. Upon recruitment, 8 patients had previous stroke and 3 patients had atrial thrombus. Warfarin was prescribed to all patients. During median follow-up of 42.0 months, 2 patients developed massive ischemic stroke due to warfarin discontinuation. CONCLUSIONS: Our study suggested that CPWD reflects extensive atrial electrical silence and significantly impaired atrial mechanical function. It was strongly associated with thromboembolism and the clinical triad of CPWD-atrial paralysis-stroke was proposed. Anticoagulation should be recommended in such patients.

7.
Br J Ophthalmol ; 105(7): 995-1001, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32788330

RESUMO

BACKGROUND/AIMS: To describe some novel vitreoretinal microstructural findings in patients with mild familial exudative vitreoretinopathy (FEVR) on ultra-wide-field scanning laser ophthalmoscopy (UWF-SLO) and UWF optical coherence tomography (UWF-OCT) and to evaluate their clinical significance. METHODS: A total of 32 patients and 32 healthy controls were studied. An additional independent 40 FEVR patients, 44 patients with non-FEVR retinopathies and 40 healthy controls participated in a diagnostic test to validate the abilities of novel findings in FEVR screening. RESULTS: A novel anatomic change, named Temporal Mid-Peripheral Vitreoretinal Interface Abnormality (TEMPVIA), was found on UWF-SLO in 88.3% of FEVR patients and in none of the healthy controls. The clinical significance of TEMPVIA was further validated by a diagnostic test in new independent cases, with satisfying sensitivity (91.5%) and specificity (98.8%) and Youden Index 0.90. In addition to foveal hypoplasia, some previously unrecognised, novel clinical changes in FEVR, for instance, retinoschisis, focal retinal thickening, sudden thinning of the retina and retinal ridge, were identified using UWF-OCT. CONCLUSION: The results of this study have led to an update of the clinical spectrum of FEVR and have improved our understanding of its pathogenesis. TEMPVIA is therefore suggested to be a useful biomarker in the screening strategy for mild FEVR.

8.
J Sci Food Agric ; 101(5): 2014-2026, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32949169

RESUMO

BACKGROUND: There are abundant resources of Carapax Trionycis from soft-shelled turtle processing wastes each year in China. Our preliminary work showed that Carapax Trionycis ultrafine powder (CTUP) obtained using ball-milling with a particle size of 2.24 µm (D0.025) contained more active ingredients. The CTUP D0.025 has a good bioaccessibility, but there has been no report about the immunomodulatory function of CTUP. Therefore, using a cyclophosphamide-induced immunosuppression mice model, we investigated the immunomodulatory effects of CTUP D0.025. RESULTS: The results indicated that CTUP D0.025 administration significantly improved the immune organ (bone marrow, thymus and spleen) indices, ameliorated spleen tissue morphology and increased the capacity of splenocyte proliferation and the activity of macrophage phagocytosis. CTUP D0.025 also significantly promoted the secretion of cytokines (IL-2, IL-4, IL-10, IFN-γ and TNF-α), improved the related mRNA expression levels of IL2, IFN-γ, T-bet and GATA3 in immunosuppressed mice and increased the production of serum hemolysin and the levels of IgG, IgM as well as complement C3 . Moreover, CTUP D0.025 administration enhanced the antioxidant capacity of mice, exhibited a moderating effect on the damage of bone and skeletal muscle and improved the recovery of bone mineral density and calcium metabolism. CONCLUSIONS: These findings demonstrated that CTUP D0.025 had an effective immune-enhancing function in immunosuppressive Balb/c mice and also exhibited anti-osteoporosis properties. © 2020 Society of Chemical Industry.


Assuntos
Fatores Imunológicos/administração & dosagem , Inflamação/tratamento farmacológico , Inflamação/imunologia , Meliaceae/química , Extratos Vegetais/administração & dosagem , Animais , Medula Óssea/efeitos dos fármacos , Medula Óssea/imunologia , Ciclofosfamida/efeitos adversos , Citocinas/genética , Citocinas/imunologia , Feminino , Humanos , Fatores Imunológicos/química , Imunomodulação/efeitos dos fármacos , Imunossupressão , Inflamação/genética , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Fagocitose/efeitos dos fármacos , Extratos Vegetais/química , Pós/química , Baço/efeitos dos fármacos , Baço/imunologia , Timo/efeitos dos fármacos , Timo/imunologia
9.
Br J Ophthalmol ; 105(1): 103-108, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32161005

RESUMO

PURPOSE: To assess the incidence, clinical features and predictive risk factors of subretinal fibrosis after treatment of active myopic choroidal neovascularisation (mCNV) with anti-vascular endothelial growth factor (VEGF). METHODS: This post-hoc analysis of a randomised controlled trial included a total of 54 patients with active mCNV. The clinical data at baseline, month 3 and month 12 were used. Fundus photography and optical coherence tomography at month 3 were used to determine the presence of subretinal fibrosis after anti-VEGF therapy, and its incidence was calculated. Best-corrected visual acuity (BCVA), Visual Function Questionnaire-25 score, macular integrity index (MI) and their changes were compared between eyes with and without subretinal fibrosis. A logistic regression model was used to evaluate the risk factors of subretinal fibrosis. RESULTS: Subretinal fibrosis occurred in 22 of 54 eyes with mCNV. Patients with subretinal fibrosis achieved similar BCVA improvement in comparison with those without fibrosis at 3 and 12 months after the treatment; however, they had lower visual acuity, more subfoveal CNV (p=0.002), higher CNV thickness at baseline (p=0.016), larger CNV size (p=0.030), larger leakage area (p=0.021) and higher presence of advanced myopic maculopathy (p=0.035). Age <45 years, BCVA <60 ETDRS letters, and MI index <20 at baseline were the predictors for subretinal fibrosis occurrence in a logistic regression model. CONCLUSIONS: The incidence of subretinal fibrosis after anti-VEGF therapy was 40.7% in eyes with mCNV. Age, baseline BCVA and MI index could serve as predictive risk factors of subretinal fibrosis after anti-VEGF treatment in patients with mCNV.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Neovascularização de Coroide/tratamento farmacológico , Miopia Degenerativa/tratamento farmacológico , Retina/patologia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Adulto , Idoso , Feminino , Fibrose/epidemiologia , Humanos , Incidência , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Fotografação , Estudos Prospectivos , Ranibizumab/uso terapêutico , Fatores de Risco , Tomografia de Coerência Óptica , Acuidade Visual/fisiologia
10.
J Interv Card Electrophysiol ; 60(3): 365-373, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32318962

RESUMO

PURPOSE: Sinus node inability or conduction disorders of its surrounding atrial myocardium cause sinus node dysfunction (SND). This study aimed to characterize right atrium (RA) substrates and long-term atrial lead performance after pacemaker implantation in non-senile SND patients. METHODS: Eighteen SND patients (53.3 ± 9.6 years) controlled by 18 age-matched supraventricular tachycardia patients were consecutively enrolled. The P-wave amplitude (PWA) and P-wave duration (PWD) were measured on surface electrocardiography. Electroanatomic mapping was conducted to assess the bipolar voltage, complex signals, volume, and activation time of RA. Pacemaker implantation was performed in SND patients after mapping. RESULTS: Compared with controls, SND patients showed significant PWA reduction (0.13 ± 0.02 vs. 0.16 ± 0.04 mV, p = 0.017) and PWD prolongation (120.8 ± 15.2 vs. 105.2 ± 8.6 ms, p = 0.001). The RA endocardial voltage was lower (1.56 ± 0.78 vs. 2.57 ± 0.55 mV, p < 0.001) and activation time was longer (112.1 ± 14.9 vs. 90.8 ± 12.4 ms, p < 0.001) in the study group. Atrial lead was anchored at the lower atrial septum in one patient and failed in another due to extensive atrial scarring. During a median follow-up of 86 (57-88) months, one patient lost atrial capturing, and overall atrial sensing was significantly decreased (2.44 ± 1.16 vs. 1.87 ± 1.01 mV, p = 0.003). CONCLUSIONS: Atrial involvement was proved and the process was progressive in non-senile SND patients, as demonstrated by diffused RA lower voltage, slower conduction, and the decrease of the atrial lead sensing.

11.
Cell Biol Toxicol ; 37(1): 85-96, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33099657

RESUMO

Synovial mesenchymal stem cells (SMSCs) have the potential to attenuate osteoarthritis (OA)-induced injury. The role and mechanism of SMSC-derived exosomes (SMSC-Exos), pivotal paracrine factors of stem cells, in OA-associated injury remain unclear. We aimed to confirm the effect of SMSC-Exos with specific modifications on OA-induced damage and to investigate the potential molecular mechanisms. Exosomes derived from miR-155-5p-overexpressing SMSCs (SMSC-155-5p-Exos) and SMSCs (SMSC-Exos) were isolated and characterized. CCK-8, Transwell, and Western blot analyses were used to detect proliferation, migration, extracellular matrix (ECM) secretion, and apoptosis of osteoarthritic chondrocytes. The therapeutic effect of exosomes in a mouse model of OA was examined using immunohistochemical staining and OARSI scores. SPSS 17.0 and GraphPad software were used for all statistical analyses in this study. The SMSC-Exos enhanced the proliferation and migration and inhibited the apoptosis of osteoarthritic chondrocytes but had no effect on ECM secretion. The miR-155-5p-overexpressing exosomes showed common characteristics of exosomes in vitro and further promoted ECM secretion by targeting Runx2. Thus, the SMSC-155-5p-Exos promoted proliferation and migration, suppressed apoptosis and enhanced ECM secretion of osteoarthritic chondrocytes, and effectively prevented OA in a mouse model. In addition, overexpression of Runx2 partially reversed the effect of the SMSC-155-5p-Exos on osteoarthritic chondrocytes. Given the insufficient effect of the SMSC-Exos on the ECM secretion of osteoarthritic chondrocytes, we modified the SMSM-Exos and demonstrated that the SMSC-155-5p-Exos could prevent OA. Exosomes derived from modified SMSCs may be a new treatment strategy to prevent OA. Graphical abstract.

12.
J Neurosci ; 41(4): 594-612, 2021 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-33303678

RESUMO

Spontaneous bursts of electrical activity in the developing auditory system arise within the cochlea before hearing onset and propagate through future sound-processing circuits of the brain to promote maturation of auditory neurons. Studies in isolated cochleae revealed that this intrinsically generated activity is initiated by ATP release from inner supporting cells (ISCs), resulting in activation of purinergic autoreceptors, K+ efflux, and subsequent depolarization of inner hair cells. However, it is unknown when this activity emerges or whether different mechanisms induce activity during distinct stages of development. Here we show that spontaneous electrical activity in mouse cochlea from both sexes emerges within ISCs during the late embryonic period, preceding the onset of spontaneous correlated activity in inner hair cells and spiral ganglion neurons, which begins at birth and follows a base to apex developmental gradient. At all developmental ages, pharmacological inhibition of P2Y1 purinergic receptors dramatically reduced spontaneous activity in these three cell types. Moreover, in vivo imaging within the inferior colliculus revealed that auditory neurons within future isofrequency zones exhibit coordinated neural activity at birth. The frequency of these discrete bursts increased progressively during the postnatal prehearing period yet remained dependent on P2RY1. Analysis of mice with disrupted cholinergic signaling in the cochlea indicate that this efferent input modulates, rather than initiates, spontaneous activity before hearing onset. Thus, the auditory system uses a consistent mechanism involving ATP release from ISCs and activation of P2RY1 autoreceptors to elicit coordinated excitation of neurons that will process similar frequencies of sound.SIGNIFICANCE STATEMENT In developing sensory systems, groups of neurons that will process information from similar sensory space exhibit highly correlated electrical activity that is critical for proper maturation and circuit refinement. Defining the period when this activity is present, the mechanisms responsible and the features of this activity are crucial for understanding how spontaneous activity influences circuit development. We show that, from birth to hearing onset, the auditory system relies on a consistent mechanism to elicit correlate firing of neurons that will process similar frequencies of sound. Targeted disruption of this activity will increase our understanding of how these early circuits mature and may provide insight into processes responsible for developmental disorders of the auditory system.


Assuntos
Vias Auditivas/crescimento & desenvolvimento , Vias Auditivas/fisiologia , Receptores Purinérgicos/fisiologia , Trifosfato de Adenosina/metabolismo , Animais , Sinalização do Cálcio/fisiologia , Cóclea/crescimento & desenvolvimento , Cóclea/fisiologia , Feminino , Células Ciliadas Auditivas/fisiologia , Células Ciliadas Auditivas Internas/fisiologia , Colículos Inferiores/fisiologia , Células Labirínticas de Suporte/fisiologia , Masculino , Camundongos , Sistema Nervoso Parassimpático/efeitos dos fármacos , Sistema Nervoso Parassimpático/fisiologia , Antagonistas do Receptor Purinérgico P2Y/farmacologia , Receptores Purinérgicos P2Y1/fisiologia , Retina/fisiologia , Gânglio Espiral da Cóclea/fisiologia
13.
Eye (Lond) ; 2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33273717

RESUMO

PURPOSE: The purpose of this study is to compare the lesion detection rates of ocular toxocariasis (OT) between ultra-wide-field scanning laser ophthalmoscopy (UWF-SLO) and conventional fundus photography (CFP), and to evaluate the potential diagnostic ability of UWF-SLO in OT. METHODS: A total of 56 patients with serological/immunological confirmed unilateral OT were enrolled. The presence of OT characteristic features included the posterior granuloma (postG), peripheral granuloma (periG), tractional retinal detachment (TRD), retinal folds (RF), and vitreous strands (VS) and was analyzed in 36 patients with UWF-SLO and 56 patients with CFP. Diagnostic tests were employed using the clinical examination as gold standard. RESULTS: In total of the 56 OT eyes, granulomas were identified in 91.1% (51/56) of eyes, including postG in 46.4% (26/56) of eyes, periG in 41.1% (23/56) of eyes, and combined granulomas in 3.6% (2/56) of eyes. TRD, RF, and VS were found in 28.6% (16/56), 51.8% (29/56), and 83.9% (47/56) of patients, respectively. Although the specificities of the diagnosis in clinical features were similar by the diagnostic tests, the sensitivities of postG, periG, TRD, RF, and VS using UWF-SLO were 100%, 100%, 66.7%, 95%, and 81.8%, respectively, which were significantly higher those of CFP (72.2%, 31.3%, 11.1%, 55%, and 48.5%). Additionally, the extent of vitreous haze was milder graded by UWF-SLO compared to CFP (p = 0.0099). CONCLUSIONS: The diagnostic ability of UWF-SLO was superior to CFP using clinical examination as gold standard for the ascertainment of the characteristic manifestations of OT, especially for granulomas and RF.

14.
Aging (Albany NY) ; 12(21): 21706-21729, 2020 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-33176281

RESUMO

In this study, we investigated the mechanisms by which puerarin alleviates osteoclast-related loss of bone mass in ovariectomy (OVX)-induced osteoporosis model mice. Puerarin-treated OVX mice exhibited higher bone density, fewer tartrate-resistant acid phosphatase (TRAcP)-positive osteoclasts, and levels of lower reactive oxygen species (ROS) within bone tissues than vehicle-treated OVX mice. Puerarin suppressed in vitro osteoclast differentiation, hydroxyapatite resorption activity, and expression of osteoclastogenesis-related genes, such as NFATc1, MMP9, CTSK, Acp5 and c-Fos, in RANKL-induced bone marrow macrophages (BMMs) and RAW264.7 cells. It also reduced intracellular ROS levels by suppressing expression of TRAF6 and NADPH oxidase 1 (NOX1) and increasing expression of antioxidant enzymes such as heme oxygenase-1 (HO-1). Puerarin inhibited TRAF6/ROS-dependent activation of the MAPK and NF-κB signaling pathways in RANKL-induced RAW264.7 cells, and these effects were partially reversed by HO-1 silencing or TRAF6 overexpression. These findings suggest puerarin alleviates loss of bone mass in the OVX-model mice by suppressing osteoclastogenesis via inhibition of the TRAF6/ROS-dependent MAPK/NF-κB signaling pathway.


Assuntos
Isoflavonas/farmacologia , Osteogênese/efeitos dos fármacos , Osteoporose Pós-Menopausa/patologia , Transdução de Sinais/efeitos dos fármacos , Animais , Feminino , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Osteoporose Pós-Menopausa/metabolismo , Ovariectomia , Células RAW 264.7 , Espécies Reativas de Oxigênio , Fator 6 Associado a Receptor de TNF/metabolismo
15.
Plant Sci ; 301: 110683, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33218644

RESUMO

The LATERAL ORGAN BOUNDARIES DOMAIN (LBD)-containing genes are plant-specific genes that play important roles in lateral organ development. In this study, we identified LBD40 (Solyc02g085910), which belongs to subfamily II of the LBD family of genes in tomato. LBD40 was highly expressed in roots and fruit. LBD40 expression was significantly induced by PEG and salt. Moreover, SlLBD40 expression was induced by methyl jasmonate treatment, while SlLBD40 expression could not be induced in the jasmonic acid-insensitive1 (jai1) mutant or MYC2-silenced plants, in which jasmonic acid (JA) signaling was disrupted. These findings demonstrate that SlLBD40 expression was dependent on JA signaling and that it might be downstream of SlMYC2, which is the master transcription factor in the JA signal transduction pathway. Overexpressing and CRISPR/Cas9 mediated knockout transgenic tomato plants were generated to explore SlLBD40 function. The drought tolerance test showed that two SlLBD40 knockout lines wilted slightly, while SlLBD40 overexpressing plants suffered severe wilting. The statistical water loss rate and midday leaf water potential also confirmed that knockout of SlLBD40 improved the water-holding ability of tomato under drought conditions. Taken together, our study demonstrates that SlLBD40, involved in JA signaling, was a negative regulator of drought tolerance and that knockout of SlLBD40 enhanced drought tolerance in tomato. This study also provides a novel function of SlLBD40, which belongs to subfamily II of LBD genes.


Assuntos
Lycopersicon esculentum/genética , Reguladores de Crescimento de Plantas/metabolismo , Proteínas de Plantas/metabolismo , Acetatos/metabolismo , Sistemas CRISPR-Cas , Ciclopentanos/metabolismo , Secas , Frutas/genética , Frutas/fisiologia , Lycopersicon esculentum/fisiologia , Mutagênese , Oxilipinas/metabolismo , Folhas de Planta/genética , Folhas de Planta/fisiologia , Proteínas de Plantas/genética , Raízes de Plantas/genética , Raízes de Plantas/fisiologia , Plantas Geneticamente Modificadas , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
16.
Front Cell Dev Biol ; 8: 585619, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33195233

RESUMO

Cortactin, a member of the actin-binding protein family, plays an important role in cell movement involving the cytoskeleton, as cell movement mediated by cortactin may induce the epithelial-mesenchymal transition. Cortactin participates in tumor proliferation, migration, and invasion and other related disease processes by binding to different proteins and participating in different pathways and mechanisms that induce the occurrence of these disease processes. Therefore, this article reviews the correlations between cortactin, the actin cytoskeleton, and the epithelial-mesenchymal transition and discusses its clinical importance in tumor therapy.

17.
PLoS One ; 15(10): e0240125, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33035227

RESUMO

Public value is gaining prominence from both academics and politicians with regards to China's rural development. However, rural planning authorities and practitioners showed limited confidence on public, which manifests as few public perceptions were integrated into the planning documents. This study explores the potential role of residents' experiences in illustrating local economic development within the context of coastal villages in which economic and industries are rapidly transforming. Two case studies from within the locale of the Greater Hangzhou Bay Rim Area are used in this article to examine the gap between residents' experiences and the actual economic development that has occurred. The main findings suggest that rural residents can directly reflect upon both current and historic trends of local economic development. Moreover, household income satisfaction (HIS) is a comprehensive notion of residents' experiences, and indicates social and economic sustainability of industrial transformation, or "thriving business", that have been highlighted in coastal villages. Public experiences could therefore act as a valid and accessible evidence for planners in rural economic planning in China and other developing countries.


Assuntos
População Rural , Planejamento Social , Adolescente , Adulto , Baías , China , Economia , Características da Família , Feminino , Humanos , Renda , Masculino , Pessoa de Meia-Idade , Adulto Jovem
18.
Ann Palliat Med ; 9(5): 3453-3461, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33065796

RESUMO

BACKGROUND: One of the common adverse reactions to anthracyclines, a group of chemotherapeutics, is cardiotoxicity. Cancer patients receiving anthracycline-based chemotherapeutic regimens often discontinue treatment due to cardiotoxicity. How to prevent and reduce the cardiotoxicity of anthracyclines is one of the hot topics in the field of onco-cardiology. Traditional Chinese medicine can reduce the toxic side effects of chemotherapeutics. The present study aimed to investigate the protective effect of Qishen Huanwu capsule (QSHWC) on pirarubicin (THP)-induced myocardial injury in rats and the underlying mechanisms. METHODS: Forty-eight male Sprague-Dawley (SD) rats were randomly divided into six groups: control group, THP, low-dose QSHWC, moderate-dose QSHWC, high-dose QSHWC, and LY294002 [phosphatidylinositol 3-kinase (PI3K) inhibitor] (n=8 each). Echocardiographic examination was performed to examine heart structure and function. Hematoxylin and eosin (HE) staining was conducted to examine histopathological changes in myocardial tissue. Immunofluorescence staining was carried out to examine the expression of the autophagosome-specific marker protein microtubule-associated protein 1 light chain 3 (LC3). Western blot was performed to analyze the expression of LC3-I, LC3-II, PI3K, phosphorylated (p)-PI3K, protein kinase B (Akt), p-Akt, mammalian target of rapamycin (mTOR), and p-mTOR. RESULTS: Compared with the control group, the THP group had a higher left ventricular end-systolic diameter (LVESD), lower left ventricular ejection fraction (LVEF), lower left ventricular fractional shortening (LVFS), and inferior heart function. In addition, compared with the control group, the THP group had significantly higher LC3 protein expression, a significantly higher LC3-II/LC3-I ratio (P<0.05), and significantly lower p-PI3K, p-Akt, and p-mTOR (P<0.05). QSHWC attenuated the THP-induced decline in heart function, downregulated LC3 protein in rat myocardial tissue, decreased the LC3-II/LC3-I ratio, and increased p-PI3K, p-Akt, and p-mTOR. In the LY294002 group, the above effects of QSHWC were reversed. CONCLUSIONS: QSHWC alleviated THP-induced myocardial injury. The underlying mechanism was related to the activation of the PI3K/Akt/mTOR pathway and the mitigation of the excessive autophagy of cardiomyocytes caused by THP.


Assuntos
Fosfatidilinositol 3-Quinase , Proteínas Proto-Oncogênicas c-akt , Animais , Cardiotoxicidade/prevenção & controle , Doxorrubicina/análogos & derivados , Humanos , Masculino , Fosfatidilinositol 3-Quinase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Volume Sistólico , Serina-Treonina Quinases TOR/metabolismo , Função Ventricular Esquerda
19.
Cancer Cell Int ; 20: 460, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32973404

RESUMO

Background: LncRNAs act as functional regulators in tumor progression through interacting with various signaling pathways in multiple types of cancer. However, the effect of LINC02418 on colorectal cancer (CRC) progression and the underling mechanisms remain unclear. Methods: LncRNA expression profile in CRC tissues was investigated by the TCGA database. The expressional level of LINC02418 in CRC patients was determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Kaplan-Meier analyses was used to investigate the correlation between LINC02418 and overall survival (OS) of CRC patients. Cell proliferative, migratory and invasive abilities were detected by CCK-8 assays, colony formation assays and trans-well assays in HCT116 and LoVo cells which were stably transduced with sh-LINC02418 or sh-NC. The binding between LINC02418 and miR-34b-5p, and the interaction between miR-34b-5p and BCL2 were determined by dual-luciferase assays. Western blot experiments were conducted to further explore the effect of miR-34b-5p on BCL2 signaling pathway. Rescue experiments were performed to uncover the role of LINC02418/miR-34b-5p/BCL2 axis in CRC progression. Results: LINC02418 was upregulated in human colon cancer samples when compared with adjacent tissue, and its high expressional level correlated with poor prognosis of CRC patients. LINC02418 promoted cancer progression by enhancing tumor growth, cell mobility and invasiveness of colon cancer cells. Additionally, LINC02418 could physically bind to miR-34b-5p and subsequently affect BCL2 signaling pathway. Down-regulation of LINC02418 reduced cell proliferation, while transfection of miR-34b-5p inhibitor or BCL2 into LINC02418-silenced CRC cells significantly promoted CRC cells growth. Conclusions: LINC02418 was upregulated in human CRC samples and could be used as the indicator for prediction of prognosis. LINC02418 acted as a tumor driver by negatively regulating cell apoptosis through LINC02418/miR-34b-5p/BCL2 axis in CRC.

20.
Arch Med Sci ; 16(5): 1119-1129, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32864001

RESUMO

Introduction: MicroRNAs (miRNAs) are considered as crucial modulators in myocardial ischemia and reperfusion (I/R) injury. The present study aimed to investigate the expression and biological functions of miR-214-5p via targeting Fas ligand (FASLG) in I/R injury. Material and methods: Lactate dehydrogenase, casein kinase, malondialdehyde assay, reactive oxygen species (ROS) detection and cell apoptosis analysis measured cell damage and cell apoptosis in H9c2 cells under hypoxia/reperfusion (H/R) treatment. Bioinformatics and dual luciferase reporter assays demonstrated the molecular mechanism of miR-214-5p in cardiac cells. 2,3,5-Triphenyltetrazolium chloride (TTC) staining, hematoxylin-eosin (HE) staining and adenovirus injection were performed in I/R treated mice. Results: The expression of miR-214-5p was decreased in H/R injured H9c2 cells compared with control cells (p < 0.001). Overexpression of miR-214-5p reduced cell damage and apoptosis in H9c2 cells under H/R treatment (p < 0.001). Further study revealed that FASLG was a target of miR-214-5p. Enhanced expression of FASLG attenuated the protective function of miR-214-5p in H9c2 cells subjected to H/R injury (P < 0.001). Moreover, the elevated expression of miR-214-5p by adenovirus injection protected cardiac cells from I/R injury in mice (n = 6/per group). Conclusions: We found that miR-214-5p exerted a protective role in I/R injured cardiac cells by direct targeting FASLG in vitro and in vivo.

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