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1.
Plant Commun ; : 100934, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38689493

RESUMO

In angiosperms, the pollen tube enters the receptive synergid cell, where they rupture to release its cytoplasm along with two sperm cells. Although this interaction is complex, the exact signal transducers that trigger the bursting of pollen tubes are not well understood. In this study, we identify three homologous Receptor-Like Cytoplasmic Kinase (RLCK) expressed in pollen tubes, named Delayed Burst 1/2/3 (DEB1/2/3) in Arabidopsis, which play a crucial role in this process. These genes produce proteins localized on the plasma membrane, and knockout of them causes delayed pollen tube burst and the entrance of additional pollen tubes into the embryo sac due to fertilization recovery. We show that DEBs interact with the Ca2+ pump ACA9, influencing the dynamics of cytoplasmic Ca2+ in pollen tubes through phosphorylation. These results highlight the importance of DEBs as key signal transducers and the critical function of the DEB-ACA9 axis in the timely pollen tube burst in synergids.

2.
Cell ; 186(17): 3593-3605.e12, 2023 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-37516107

RESUMO

Animal fertilization relies on hundreds of sperm racing toward the egg, whereas, in angiosperms, only two sperm cells are delivered by a pollen tube to the female gametes (egg cell and central cell) for double fertilization. However, unsuccessful fertilization under this one-pollen-tube design can be detrimental to seed production and plant survival. To mitigate this risk, unfertilized-gamete-controlled extra pollen tube entry has been evolved to bring more sperm cells and salvage fertilization. Despite its importance, the underlying molecular mechanism of this phenomenon remains unclear. In this study, we report that, in Arabidopsis, the central cell secretes peptides SALVAGER1 and SALVAGER2 in a directional manner to attract pollen tubes when the synergid-dependent attraction fails or is terminated by pollen tubes carrying infertile sperm cells. Moreover, loss of SALs impairs the fertilization recovery capacity of the ovules. Therefore, this research uncovers a female gamete-attraction system that salvages seed production for reproductive assurance.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Animais , Arabidopsis/fisiologia , Fertilização , Tubo Polínico , Sementes , Células Germinativas Vegetais
3.
ACS Omega ; 8(22): 19692-19704, 2023 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-37305289

RESUMO

Extracellular signal-regulated kinase 1 and 2 (Erk1/2) signaling has been shown to be involved in brain injury after subarachnoid hemorrhage (SAH). A first-in-human phase I study reported that ravoxertinib hydrochloride (RAH), a novel Erk1/2 inhibitor, has an acceptable safety profile and pharmacodynamic effects. Here, we showed that the level of Erk1/2 phosphorylation (p-Erk1/2) was significantly increased in the cerebrospinal fluid (CSF) of aneurysmal subarachnoid hemorrhage (aSAH) patients who developed poor outcomes. In a rat SAH model that was produced by the intracranial endovascular perforation method, western blot observed that the level of p-Erk1/2 was also increased in the CSF and basal cortex, showing a similar trend with aSAH patients. Immunofluorescence and western blot indicated that RAH treatment (i.c.v injection, 30 min post-SAH) attenuates the SAH-induced increase of p-Erk1/2 at 24 h in rats. RAH treatment can improve experimental SAH-induced long-term sensorimotor and spatial learning deficits that are evaluated by the Morris water maze, rotarod test, foot-fault test, and forelimb placing test. Moreover, RAH treatment attenuates neurobehavioral deficits, the blood-brain barrier damage, and cerebral edema at 72 h after SAH in rats. Furthermore, RAH treatment decreases the SAH-elevated apoptosis-related factor active caspase-3 and the necroptosis-related factor RIPK1 expression at 72 h in rats. Immunofluorescence analysis showed that RAH attenuated neuronal apoptosis but not neuronal necroptosis in the basal cortex at 72 h after SAH in rats. Altogether, our results suggest that RAH improves long-term neurologic deficits through early inhibition of Erk1/2 in experimental SAH.

4.
Huan Jing Ke Xue ; 44(2): 954-964, 2023 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-36775618

RESUMO

The soil ecological stoichiometric characteristics of different agricultural land use types have a certain indicator function for characterizing the level of soil nutrient supply and are of great significance to the management of nutrient resources in farmland ecosystems. In order to reveal the soil carbon (C), nitrogen (N), and phosphorus (P) contents and their ecological stoichiometric characteristics in different vegetable fields and orchard agricultural land use types, this study took vegetable fields (taro field and jicama field) and orchards (citrus tree orchard, watermelon field, and pear tree orchard) as the research objects in the coastal area of Fuzhou City. The contents of soil C, N, and P and their ecological stoichiometric characteristics in different vegetable fields and orchard agricultural land uses were measured and analyzed. The soil C and N contents were in the order of orchard>vegetable field (P<0.05). The C content in the citrus tree orchard was the highest (4.44 g·kg-1), and the N content in the watermelon field was the highest (1.46 g·kg-1). The soil P content was vegetable field>orchard (P<0.05), and the jicama field had the highest P content (0.19 g·kg-1). The soil carbon and nitrogen ratio (C/N), carbon and phosphorus ratio (C/P), and nitrogen and phosphorus ratio (N/P) were orchard>vegetable field (P<0.05). Among them, the citrus tree orchard had the highest C/N (7.40) and C/P (61.43), and the watermelon field had the highest N/P (10.27). Soil N content was significantly and negatively correlated with bulk density and conductivity (r=-0.49, r=-0.28, P<0.05), and there was a significant and positive correlation with soil water content (r=0.61, P<0.05). C/P and C/N were significantly and positively correlated with SOM (r=0.71, r=0.64, P<0.01). In the process of crop planting and management in the coastal area of Fuzhou City, it is necessary to reasonably add nitrogen fertilizer to compensate for the N limitation, and slow-release nitrogen fertilizer is better for promoting the sustainable supply of nitrogen nutrients in the growth and development of crops.


Assuntos
Solo , Verduras , Ecossistema , Nitrogênio/análise , Fósforo/análise , Carbono/análise , Fertilizantes , Árvores , China
5.
Ann Transl Med ; 10(10): 593, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35722363

RESUMO

Background: Non-small cell lung cancer (NSCLC) is the most common subtype of all lung cancers, and KRAS is the most common mutation in this population. Unfortunately, this subgroup remains "undruggable" with the lack of an approved targeted therapy. Selumetinib has been investigated as a secondary therapy in several trials and compared to various drug regimens. Therefore, we conducted this systematic review and network meta-analysis to determine the comparative effectiveness of this drug as compared to others in patients with late-stage and malignant NSCLC. Methods: Up to July 1, 2020, 9 databases (PubMed, Scopus, Web of Science, mRCT, ICTRP, clinicaltrials.gov, VHL, SIGLE, and Google Scholar) were searched for studies following the PICOS framework: randomized trials reporting the efficacy (rate of disease progression/lack of response) of selumetinib compared to other therapies in patients with late-stage/metastatic NSCLC. The quality of retrieved studies were assessed with the revised Cochrane risk-of-bias tool. Frequentist network meta-analysis was conducted to estimate the efficacy of selumetinib as compared to other therapies and/or placebo. Results: Out of the 163 articles yielded from the primary search, 9 studies (1,195 patients) were finally included in our systematic review. The majority of clinical cases had a performance status (PS) of 0-2, and the mean age was 62 years. The overall efficacy of selumetinib was 71.77% (95% CI: 63.24-81.45%), with selumetinib administered alone having better efficacy compared to combined therapy (65.20% vs. 74.08%). In the network analysis, selumetinib had higher efficacy compared to chemo- or immune therapy, but not significantly so. The overall SAE rate of selumetinib was 42.96% (95% CI: 34.74-53.13%), with selumetinib having a significantly better safety profile compared to combined therapy (10.49% vs. 47.38%). In the network analysis, the placebo had the best safety profile followed by selumetinib and chemo- and immune therapy. Five studies had high risk of bias, 2 had some concerns, and 2 had low risk of bias. Discussion: The efficacy of selumetinib is not superior compared to combined therapy for treating NSCLC but does have a better safety profile. Current evidence is still limited, and more robust trials are still required.

6.
Sci Total Environ ; 838(Pt 3): 156534, 2022 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-35679939

RESUMO

Nitrite-dependent anaerobic methane oxidation (n-damo), catalyzed by bacteria closely related to Candidatus Methylomirabilis oxyfera, links the global carbon and nitrogen cycles. Currently, the contribution of n-damo in controlling methane emissions and nitrogen removal, and the key regulatory factors of this process in Chinese paddy fields are poorly known. Here, soil samples from 20 paddy fields located in different climate zones across China were collected to examine the n-damo activity and bacterial communities. The n-damo activity and bacterial abundance varied from 1.05 to 5.97 nmol CH4 g-1 (dry soil) d-1 and 2.59 × 105 to 2.50 × 107 copies g-1 dry soil, respectively. Based on the n-damo activity, it was estimated that approximately 0.91 Tg CH4 and 2.17 Tg N could be consumed annually via n-damo in Chinese paddy soils. The spatial variations in n-damo activity and community structure of n-damo bacteria were significantly (p < 0.05) affected by the soil ammonium content, labile organic carbon content and pH. Furthermore, significant differences in n-damo activity, bacterial abundance and community composition were observed among different climate zones. The n-damo activity was found to be positively correlated with the mean annual air temperature. Taken together, our results demonstrated the potential importance of n-damo in both methane consumption and nitrogen removal in Chinese paddy soils, and this process was regulated by local soil and climatic factors.


Assuntos
Metano , Nitritos , Anaerobiose , Bactérias/genética , Carbono , Desnitrificação , Nitrogênio , Oxirredução , Filogenia , RNA Ribossômico 16S , Solo
7.
Front Cell Neurosci ; 16: 878673, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35573833

RESUMO

Cell apoptosis plays an important role in early brain injury (EBI) after subarachnoid hemorrhage (SAH). Heat shock protein 27 (HSP27), a member of the small heat shock protein (HSP) family, is induced by various stress factors and exerts protective role on cells. However, the role of HSP27 in brain injury after SAH needs to be further clarified. Here, we reported that HSP27 level of cerebrospinal fluid (CSF) is increased obviously at day 1 in patients with aneurysmal SAH (aSAH) and related to the grades of Hunt and Hess (HH), World Federation of Neurological Surgeons (WFNS), and Fisher score. In rat SAH model, HSP27 of CSF is first increased and then obviously declined; overexpression of HSP27, not knockdown of HSP27, attenuates SAH-induced neurological deficit and cell apoptosis in the basal cortex; and overexpression of HSP27 effectively suppresses SAH-elevated activation of mitogen-activated protein Kinase Kinase 4 (MKK4), the c-Jun N-terminal kinase (JNK), c-Jun, and caspase-3. In an in vitro hemolysate-damaged cortical neuron model, HSP2765-90 peptide effectively inhibits hemolysate-induced neuron death. Furthermore, TAT-HSP2765-90 peptide, a fusion peptide consisting of trans-activating regulatory protein (TAT) of HIV and HSP2765-90 peptide, effectively attenuates SAH-induced neurological deficit and cell apoptosis in the basal cortex of rats. Altogether, our results suggest that TAT-HSP27 peptide improves neurologic deficits via reducing apoptosis.

8.
Microbiol Spectr ; 9(1): e0082021, 2021 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-34406837

RESUMO

Karst caves have recently been demonstrated to act as a sink for atmospheric methane, due in part to consumption by microbes residing in caves that can oxidize methane at atmospheric levels. However, our knowledge about the responsible atmospheric methane-oxidizing bacteria (atmMOB) in this vast habitat remains limited to date. To address this issue, weathered rock samples from three karst caves were collected in Guilin City and subjected to high-throughput sequencing of pmoA and 16S rRNA genes. The results showed that members of the high-affinity upland soil cluster (USC), especially upland soil cluster gamma (USCγ), with absolute abundances of 104 to 109 copies · g-1 dry sample, dominated the atmMOB communities, while Proteobacteria and Actinobacteria dominated the overall bacterial communities. Moreover, USCγ was a keystone taxon in cooccurrence networks of both the atmMOB and the total bacterial community, whereas keystone taxa in the bacterial network also included Gaiella and Aciditerrimonas. Positive links overwhelmingly dominated the cooccurrence networks of both atmMOB and the total bacterial community, indicating a consistent response to environmental disturbances. Our study shed new insights on the diversity and abundances underlining atmMOB and total bacterial communities and on microbial interactions in subterranean karst caves, which increased our understanding about USC and supported karst caves as a methane sink. IMPORTANCE Karst caves have recently been demonstrated to be a potential atmospheric methane sink, presumably due to consumption by methane-oxidizing bacteria. However, the sparse knowledge about the diversity, distribution, and community interactions of methanotrophs requires us to seek further understanding of the ecological significance of methane oxidation in these ecosystems. Our pmoA high-throughput results from weathered rock samples from three karst caves in Guilin City confirm the wide occurrence of atmospheric methane-oxidizing bacteria in this habitat, especially those affiliated with the upland soil cluster, with a gene copy number of 104 to 109 copies per gram dry sample. Methanotrophs and the total bacterial communities had more positive than negative interactions with each other as indicated by the cooccurrence network, suggesting their consistent response to environmental disturbance. Our results solidly support caves as an atmospheric methane sink, and they contribute to a comprehensive understanding of the diversity, distribution, and interactions of microbial communities in subsurface karst caves.


Assuntos
Bactérias/isolamento & purificação , Cavernas/microbiologia , Microbiologia do Solo , Bactérias/classificação , Bactérias/genética , Bactérias/metabolismo , DNA Bacteriano/genética , Metano/análise , Metano/metabolismo , Microbiota , Filogenia , RNA Ribossômico 16S/genética
9.
Acta Pharmacol Sin ; 42(12): 2016-2032, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34226664

RESUMO

Macrophage-mediated inflammation plays an important role in hypertensive cardiac remodeling, whereas effective pharmacological treatments targeting cardiac inflammation remain unclear. Lipoprotein-associated phospholipase A2 (Lp-PLA2) contributes to vascular inflammation-related diseases by mediating macrophage migration and activation. Darapladib, the most advanced Lp-PLA2 inhibitor, has been evaluated in phase III trials in atherosclerosis patients. However, the role of darapladib in inhibiting hypertensive cardiac fibrosis remains unknown. Using a murine angiotensin II (Ang II) infusion-induced hypertension model, we found that Pla2g7 (the gene of Lp-PLA2) was the only upregulated PLA2 gene detected in hypertensive cardiac tissue, and it was primarily localized in heart-infiltrating macrophages. As expected, darapladib significantly prevented Ang II-induced cardiac fibrosis, ventricular hypertrophy, and cardiac dysfunction, with potent abatement of macrophage infiltration and inflammatory response. RNA sequencing revealed that darapladib strongly downregulated the expression of genes and signaling pathways related to inflammation, extracellular matrix, and proliferation. Moreover, darapladib substantially reduced the Ang II infusion-induced expression of nucleotide-binding oligomerization domain-like receptor with pyrin domain 3 (NLRP3) and interleukin (IL)-1ß and markedly attenuated caspase-1 activation in cardiac tissues. Furthermore, darapladib ameliorated Ang II-stimulated macrophage migration and IL-1ß secretion in macrophages by blocking NLRP3 inflammasome activation. Darapladib also effectively blocked macrophage-mediated transformation of fibroblasts into myofibroblasts by inhibiting the activation of the NLRP3 inflammasome in macrophages. Overall, our study identifies a novel anti-inflammatory and anti-cardiac fibrosis role of darapladib in Lp-PLA2 inhibition, elucidating the protective effects of suppressing NLRP3 inflammasome activation. Lp-PLA2 inhibition by darapladib represents a novel therapeutic strategy for hypertensive cardiac damage treatment.


Assuntos
1-Alquil-2-acetilglicerofosfocolina Esterase/antagonistas & inibidores , Benzaldeídos/uso terapêutico , Cardiotônicos/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Fibrose/prevenção & controle , Inflamação/prevenção & controle , Oximas/uso terapêutico , Angiotensina II , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Benzaldeídos/farmacologia , Cardiomegalia/induzido quimicamente , Cardiomegalia/metabolismo , Cardiomegalia/prevenção & controle , Cardiotônicos/farmacologia , Inibidores Enzimáticos/farmacologia , Fibrose/induzido quimicamente , Fibrose/metabolismo , Coração/efeitos dos fármacos , Inflamassomos/metabolismo , Inflamação/induzido quimicamente , Inflamação/metabolismo , Macrófagos/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Oximas/farmacologia
10.
Clin Cosmet Investig Dermatol ; 14: 285-290, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33790610

RESUMO

OBJECTIVE: This study aims to measure and analyze the lip and tooth dynamic esthetic characteristics at rest and during speech in order to provide a reference for its esthetic design and restoration among the Hani and Han populations in Yunnan Province, China. METHODS: Subjects of Hani and Han ethnicity in Yunnan were selected using multistage stratified sampling and inclusive criteria. The lip and tooth dynamic esthetic characteristics of the subjects at rest and during the pinyin pronunciation of "me", "yi", "fu", and "si" were recorded using digital photography and analyzed with computer software. RESULTS: No statistical difference was detected between the Hani and Han groups in the upper central-incisor display, when pronouncing the pinyin "yi". Furthermore, there were no statistical differences in lip dynamic esthetic parameters between the Hani and Han groups, except for the distance between the upper and lower lips when pronouncing "si". There were three kinds of correlation between the upper central-incisor edge and lower lip: separation, contact, and overlap. CONCLUSION: The display of upper central incisors and the mouth width of Hani people are larger than those of Han people when at rest. When the pinyin "si" is pronounced, the display of upper central incisors and the upper-lower lip distance of Hani people is less than that of Han people due to labial muscle movement.

11.
Dent Mater J ; 40(2): 348-355, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33087633

RESUMO

The purpose of this study was to investigate the effect of amylase activity on the mechanical properties of three dental composite resin (Filtek Z350; Filtek Z250 and Polofil Supra). The specimens were immersed in amylase solution at four different activities (25, 50, 100 and 200 KIU/L) with an artificial saliva solution (AS) as a control. The flexural strength (FS) and elastic modulus (EM) were determined in a three-point bending test after immersion for periods up to 12 months. In addition, surface roughness and surface morphology also determined. The FS of Filtek Z350 reaching the lowest level of 67.86 MPa after AS immersion for one year. There was a general trend for FS to decrease following immersion in AS for all the tested materials. However, the amylase groups did not undergo a significant decrease in FS and EM, and there was a slight increase in FS and EM for Polofil Supra.


Assuntos
Resinas Compostas , Resistência à Flexão , Amilases , Materiais Dentários , Teste de Materiais , Propriedades de Superfície
12.
Materials (Basel) ; 13(22)2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33187157

RESUMO

The aim of this study was to investigate the dynamic viscoelasticity of dental soft polymer material containing citrate ester-based plasticizers. Three kinds of citrate ester-based plasticizer (Citroflex® C-2: TEC, Citroflex® A-2: ATEC, and Citroflex® A-4: ATBC), with the combination of 5 wt% ethyl alcohol, were used as the liquid phase. The dynamic viscoelastic properties of nine ethyl methacrylate polymers: (A, B, C, D, E, F, G, H, and I) were immersed in 37 °C distilled water for 0, 1, 3, 7, 14 and 30 days, respectively. The dynamic viscoelastic properties were measured at 37 °C with an automatic dynamic mechanical analyzer. The shear storage modulus (G'), shear loss modulus (G″), and loss tangent (tan δ) were determined at 1 Hz. These parameters were statistically analyzed by two-way and one-way ANOVA and Tukey's multiple comparison test at a predetermined significance level of 0.05. A significant difference was found among the materials in terms of the dynamic viscoelasticity. The materials containing citrate ester-based plasticizer ATBC showed the most stable dynamic viscoelasticity. Considering the limitations of this study, the results suggest that the inclusion of citrate ester-based plasticizer can improve the durability of dental soft polymer materials.

13.
ACS Chem Neurosci ; 11(18): 2869-2880, 2020 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-32786302

RESUMO

Aneurysmal subarachnoid hemorrhage (SAH) causes permanent neurological sequelae, but the underlying mechanism needs to be further clarified. Here, we show that inhibition of metabotropic glutamate receptor 1 (mGluR1) with negative allosteric modulator JNJ16259685 improves long-term neurobehavioral outcomes in an endovascular perforation model of SAH. JNJ16259685 improves cerebrovascular dysfunction through attenuation of cerebral blood flow (CBF) reduction, cerebral vasoconstrictio, and microthrombosis formation in a rat SAH model. Moreover, JNJ16259685 reduces experimental SAH-induced long-term neuronal damage through alleviation of neuronal death and degeneration. Mechanically, JNJ16259685 maintains phosphorylation of endothelial NO synthase (eNOS) and vasodilator-stimulated phosphoprotein (VASP) and decreases apoptosis-related factors Bax, active caspase-9, and active caspase-3 following experimental SAH. Altogether, our results suggest JNJ16259685 improves long-term functional impairment through neurovascular protection.


Assuntos
Receptores de Glutamato Metabotrópico , Hemorragia Subaracnóidea , Vasoespasmo Intracraniano , Animais , Modelos Animais de Doenças , Ratos , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/tratamento farmacológico
14.
Shanghai Kou Qiang Yi Xue ; 29(2): 133-137, 2020 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-32626874

RESUMO

PURPOSE: To analyze the effect of porcelain layer thicknesses and substrates on color properties and translucency of IPS e.max LT porcelain laminate veneers used to restore tetracycline stained teeth. METHODS: Porcelain specimens with different core and veneer thickness (veneer/core thickness: 0.25 mm/0.25 mm, 0.50 mm/0.25 mm, 0.25 mm/0.50 mm, 0.50 mm/0.50 mm, and 0.25 mm/0.75 mm) were fabricated by heat-press layering technique. CIE L*a*b* parameters were measured under simulated tetracycline backgrounds and black and white backgrounds by a spectrophotometer, color differences ΔE001 between specimens on simulated tetracycline backgrounds and backgrounds themselves and ΔE002 between specimens on simulated tetracycline backgrounds and white background were calculated. The translucent parameter(TP) was also calculated. The data were submitted to statistical analysis with SPSS 17.0 software package. RESULTS: ΔE001 increased with increase of thickness of the core and veneer layer, but there was no significant difference between 0.25 mm and 0.50 mm core thickness groups with 0.50 mm veneer in thickness (P>0.01). Except for light grey, ΔE002 decreased over other substrates with increase of thickness of the core and veneer layer, but there was no significant difference between 0.50 mm and 0.75 mm core thickness groups with 0.25 mm veneer in thickness (P>0.01). Both ΔE001 and ΔE002 were significantly different over different substrates(P<0.01). TP decreased as the increase of core and veneer thickness and TP was significantly different with different core and veneer thickness(P<0.01). CONCLUSIONS: Both the core/veneer thickness and the substrate have significant influence on color matching and masking ability of IPS e.max LT porcelain laminate veneers used to restore tetracycline stained teeth. As for IPS e.max LT porcelain veneers, the color property was the best when yellowish tetracycline stained teeth were restored, while the light grey was worst. The thickness of core and veneer has significant influence on the translucency of porcelain laminate veneers.


Assuntos
Porcelana Dentária , Facetas Dentárias , Cerâmica , Cor , Teste de Materiais , Tetraciclina
15.
Acta Pharmacol Sin ; 41(7): 986-994, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32317755

RESUMO

Current cancer immunotherapy has limited response rates in a large variety of solid tumors partly due to the low immunogenicity of the tumor cells and the immunosuppressive tumor microenvironment (ITM). A number of clinical cancer treatment modalities, including radiotherapy, chemotherapy, photothermal and photodynamic therapy, have been shown to elicit immunogenicity by inducing immunogenic cell death (ICD). However, ICD-based immunotherapy is restricted by the ITM limiting its efficacy in eliciting a long-term antitumor immune response, and by severe systemic toxicity. To address these challenges, nanomedicine-based drug delivery strategies have been exploited for improving cancer immunotherapy by boosting ICD of the tumor cells. Nanosized drug delivery systems are promising for increasing drug accumulation at the tumor site and codelivering ICD inducers and immune inhibitors to simultaneously elicit the immune response and relieve the ITM. This review highlights the recent advances in nanomedicine-based immunotherapy utilizing ICD-based approaches. A perspective on the clinical translation of nanomedicine-based cancer immunotherapy is also provided.


Assuntos
Antineoplásicos/farmacologia , Morte Celular Imunogênica/efeitos dos fármacos , Imunoterapia , Nanomedicina , Neoplasias/terapia , Sistemas de Liberação de Medicamentos , Humanos , Morte Celular Imunogênica/imunologia , Neoplasias/imunologia , Fotoquimioterapia , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia
16.
Chin Med J (Engl) ; 133(1): 9-16, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31923099

RESUMO

BACKGROUND: The effects of keto acid (KA) supplements on Chinese patients receiving maintenance hemodialysis (MHD) are unclear. This study aimed to evaluate the effects of KA supplementation on nutritional status, inflammatory markers, and bioelectric impedance analysis (BIA) parameters in a cohort of Chinese patients with MHD without malnutrition. METHODS: This was a prospective, randomized, controlled, single-center clinical study conducted in 2011 till 2014. Twenty-nine patients with MHD were randomly assigned to a control (n = 14) or a KA (n = 15) group. The control group maintained a dietary protein intake of 0.9 g/kg/day. The KA group received additional KA supplement (0.1 g/kg/day). BIA was used to determine the lean tissue mass, adipose tissue mass, and body cell mass. The patients' nutritional status, dialysis adequacy, and biochemical parameters were assessed at the ends of the third and sixth months with t test or Wilcoxon rank-sum test. RESULTS: The daily total energy intake for both groups was about 28 kcal/kg/day. After 6 months, the Kt/V (where K is the dialyzer clearance of urea, t is the dialysis time, and V is the volume of the distribution of urea) was 1.33 ±â€Š0.25 in KA group, and 1.34 ±â€Š0.25 in the control group. The median triceps skin-fold thickness in KA group was 12.00 and 9.00 mm in the control group. In addition, the median hand-grip strength in KA group was 21.10 and 25.65 kg in the control group. There were no significant differences between the groups with respect to the anthropometry parameters, dialysis adequacy, serum calcium and phosphorus levels, inflammatory markers, and amino-acid profiles, or in relation to the parameters determined by BIA. Both groups achieved dialysis adequacy and maintained nutritional status during the study. CONCLUSIONS: In this cohort of Chinese patients with MHD, the patients in the control group whose dietary protein intake was 0.9 g/kg/day and total energy intake was 28 kcal/kg/day, maintained well nutritional status during study period. The KA supplement (0.1 g/kg/day) did not improve the essential amino acid/non-essential amino acid ratio, nor did it change the patients' mineral metabolism, inflammatory parameters, or body compositions.


Assuntos
Cetoácidos/uso terapêutico , Diálise Renal/métodos , Adolescente , Adulto , Idoso , Suplementos Nutricionais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Insuficiência Renal Crônica/terapia , Adulto Jovem
17.
Huan Jing Ke Xue ; 41(1): 489-498, 2020 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854952

RESUMO

We investigate whether slag and biochar applications have subsequent effects on greenhouse gas emissions from paddy fields by applying biochar (B), slag (S), and a biochar-slag mix (BS) to paddy fields in the Fuzhou Plain, China. Applications of the three treatments along with a control (CK) of no amendment were made in 2015 before early and late rice seedlings were transplanted. Two years later in 2017, the CO2, CH4, and N2O emissions in the different treatments and control were measured in the early and late rice growing seasons. The results showed that, in the rice growing season, the averaged CO2 emission in the control, biochar, slag, and mixed applications were (1723.66±194.56), (1245.52±155.05), (1140.29±79.68), and (1055.83±62.13) mg·(m2·h)-1, respectively. The CO2 emissions from the three treatments were significantly lower than the control group (P<0.05), and the reduction ratios of each treatment to the control were 27.74%, 33.84%, and 38.75%, respectively. The averaged CH4 emissions in the control, biochar, slag, and mixed applications were (0.45±0.03), (0.40±0.05), (0.36±0.10), and (0.25±0.04) mg·(m2·h)-1, respectively, which were lower, but not significantly so (P>0.05), than the control. The ratios of CH4 emissions from each treatment to the control were 11.11%, 20.00%, and 44.44%, respectively. The averaged N2O emissions from the control, biochar, slag, and mixed applications were (62.47±27.00), (115.09±30.94), (79.75±24.98), and (112.68±23.59) µg·(m2·h)-1, respectively. In comparison to the control, the biochar, slag, and mixed treatments increased the N2O emissions by 84.23%, 27.66%, and 80.37%, respectively. The global comprehensive warming potential indicated that the application treatments increased the comprehensive warming potential of the early and late rice paddy ecosystems; after 2 years of applying slag and biochar treatments, their effect on the emission reductions were not obvious.

18.
Transl Stroke Res ; 11(4): 799-811, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-31833035

RESUMO

The blood-brain barrier (BBB) disruption leads to the vasogenic brain edema and contributes to the early brain injury (EBI) after subarachnoid hemorrhage (SAH). However, the mechanisms underlying the BBB damage following SAH are poorly understood. Here we reported that the neurotransmitter glutamate of cerebrospinal fluid (CSF) was dramatically increased in SAH patients with symptoms of cerebral edema. Using the rat SAH model, we found that SAH caused the increase of CSF glutamate level and BBB permeability in EBI, intracerebroventricular injection of exogenous glutamate deteriorated BBB damage and cerebral edema, while intraperitoneally injection of metabotropic glutamate receptor 1(mGluR1) negative allosteric modulator JNJ16259685 significantly attenuated SAH-induced BBB damage and cerebral edema. In an in vitro BBB model, we showed that glutamate increased monolayer permeability of human brain microvascular endothelial cells (HBMEC), whereas JNJ16259685 preserved glutamate-damaged BBB integrity in HBMEC. Mechanically, glutamate downregulated the level and phosphorylation of vasodilator-stimulated phosphoprotein (VASP), decreased the tight junction protein occludin, and increased AQP4 expression at 72 h after SAH. However, JNJ16259685 significantly increased VASP, p-VASP, and occludin, and reduced AQP level at 72 h after SAH. Altogether, our results suggest an important role of glutamate in disruption of BBB function and inhibition of mGluR1 with JNJ16259685 reduced BBB damage and cerebral edema after SAH.


Assuntos
Regulação Alostérica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Edema Encefálico/metabolismo , Quinolinas/administração & dosagem , Receptores de Glutamato Metabotrópico/agonistas , Hemorragia Subaracnóidea/complicações , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Edema Encefálico/líquido cefalorraquidiano , Edema Encefálico/etiologia , Permeabilidade Capilar/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Ácido Glutâmico/líquido cefalorraquidiano , Humanos , Masculino , Pessoa de Meia-Idade , Ratos Sprague-Dawley , Hemorragia Subaracnóidea/líquido cefalorraquidiano
19.
Nanoscale ; 10(17): 8162-8169, 2018 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-29676415

RESUMO

Construction of multifunctional photoelectrochemical energy devices is of great importance to energy saving. In this study, we have successfully prepared a mesoporous WO3 film on FTO glass via a facile dip-coating sol-gel method; the designed mesoporous WO3 film exhibited advantages including high transparency, good adhesion and high porosity. Also, multifunctional integrated energy storage and optical modulation ability are simultaneously achieved by the mesoporous WO3 film. Impressively, the mesoporous WO3 film exhibits a noticeable electrochromic energy storage performance with a large optical modulation up to 75.6% at 633 nm, accompanied by energy storage with a specific capacity of 75.3 mA h g-1. Furthermore, a full electrochromic energy storage window assembled with the mesoporous WO3 anode and PANI nanoparticle cathode is demonstrated with large optical modulation and good long-term stability. Our research provides a new route to realize the coincident utilization of optical-electrochemical energy.

20.
Dent Mater J ; 36(6): 770-777, 2017 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-28747598

RESUMO

This study aimed to determine the effect of crude drugs on the dynamic viscoelasticity and angiogenic property of soft polymer materials, in vitro. Two kinds of polyethyl methacrylates, and crude drugs (Astragalus membranaceus Bunge [HQ] and Salvia miltiorrhiza Bunge [DS]) were used in their powdered forms. And, acetyl tributyl citrate and ethyl alcohol were used in the liquid form. The dynamic viscoelasticity of each specimen was measured after 0, 1, 3, 7, 14 and 28 days of immersion in distilled water. The CellPlayer angiogenesis PrimeKit assay was used to test angiogenesis. Significant differences in dynamic viscoelasticity were observed among the materials. Specimens containing 1 wt% HQ showed higher angiogenic activity than those containing 5 wt% and 10 wt% HQ, and DS. Our results suggest that the addition of low amounts of crude drugs to soft polymer materials may promote angiogenesis in human tissues.


Assuntos
Astrágalo , Fibroblastos/efeitos dos fármacos , Metilmetacrilatos/química , Neovascularização Fisiológica/efeitos dos fármacos , Extratos Vegetais/química , Salvia miltiorrhiza , Células Cultivadas , Citratos/química , Elasticidade , Etanol/química , Humanos , Técnicas In Vitro , Polímeros , Pós , Viscosidade
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