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1.
Integr Cancer Ther ; 22: 15347354221144310, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36624619

RESUMO

Holothurian glycosaminoglycan (hGAG) is extracted from the body wall of the sea cucumber, and previous studies have shown many unique bioactivities of hGAG, including antitumor, anti-angiogenesis, anti coagulation, anti thrombosis, anti-inflammation, antidiabetic effect, antivirus, and immune regulation. The effects of 3W and 5W molecular weights hGAG with hematoporphyrin derivative-photodynamic therapy (HPD-PDT) on lung cancer were investigated. Human lung adenocarcinoma A549 cells were divided into 6 groups: control group, 3W molecular weight hGAG group, 5W molecular weight hGAG group, HPD-PDT group, 3W molecular weight hGAG + HPD-PDT group, and 5W molecular weight hGAG + HPD-PDT group. Cell morphology was observed under inverted phase contrast microscope. Cell proliferative activity was detected by CCK8 and cell apoptosis was assayed by Hoechst33258 staining and flow cytometry. The results showed that two different molecular weights hGAG could inhibit proliferation, promote apoptosis rates of A549 cells, and enhance the sensitivity of A549 cells to HPD-PDT. The combined use of hGAG and HPD-PDT has synergistic inhibitory effects on A549 cells, and the effects of 3W molecular weight hGAG are better than that of 5W molecular weight hGAG.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Fotoquimioterapia , Humanos , Peso Molecular , Adenocarcinoma de Pulmão/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Apoptose , Glicosaminoglicanos , Derivado da Hematoporfirina , Proliferação de Células
2.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-970618

RESUMO

Dolomiaea plants are perennial herbs in the Asteraceae family with a long medicinal history. They are rich in chemical constituents, mainly including sesquiterpenes, phenylpropanoids, triterpenes, and steroids. The extracts and chemical constituents of Dolomiaea plants have various pharmacological effects, such as anti-inflammatory, antibacterial, antitumor, anti-gastric ulcer, hepatoprotective and choleretic effects. However, there are few reports on Dolomiaea plants. This study systematically reviewed the research progress on the chemical constituents and pharmacological effects of Dolomiaea plants to provide references for the further development and research of Dolomiaea plants.


Assuntos
Extratos Vegetais/farmacologia , Asteraceae , Triterpenos , Sesquiterpenos/farmacologia , Anti-Inflamatórios , Compostos Fitoquímicos/farmacologia
3.
Bioorg Med Chem Lett ; 73: 128884, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35835377

RESUMO

11ß-hydroxysteroid dehydrogenase 1 (11ß-HSD1) has been identified as the primary enzyme responsible for the activation of hepatic cortisone to cortisol in specific peripheral tissues, resulting in the concomitant antagonism of insulin action within these tissues. Dysregulation of 11ß-HSD1, particularly in adipose tissues, has been associated with a variety of ailments including metabolic syndrome and type 2 diabetes mellitus. Therefore, inhibition of 11ß-HSD1 with a small nonsteroidal molecule is therapeutically desirable. Implementation of a scaffold-hopping approach revealed a 3-point pharmacophore for 11ß-HSD1 that was utilized to design a 2-spiroproline derivative as a steroid mimetic scaffold. Reiterative optimization provided valuable insight into the bioactive conformation of our novel scaffold and led to the discovery of several leads, such as compounds 39 and 51. Importantly, deleterious hERG inhibition and pregnane X receptor induction were mitigated by the introduction of a 4-hydroxyl group to the proline ring system.


Assuntos
Diabetes Mellitus Tipo 2 , Síndrome Metabólica , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/metabolismo , Inibidores Enzimáticos/farmacologia , Humanos , Hidrocortisona/metabolismo
4.
Bioorg Med Chem Lett ; 69: 128782, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35537608

RESUMO

11ß-hydroxysteroid dehydrogenase 1 (11ß-HSD1) has been identified as the primary enzyme responsible for the activation of hepatic cortisone to cortisol in specific peripheral tissues resulting in the concomitant antagonism of insulin action within these tissues. Dysregulation of 11ß-HSD1, particularly in adipose tissues, has been associated with metabolic syndrome and type 2 diabetes mellitus. Therefore, inhibition of 11ß-HSD1 with a small nonsteroidal molecule is therapeutically desirable. Implementation of a scaffold-hopping approach revealed a three-point pharmacophore for 11ß-HSD1 that was utilized to design a steroid mimetic scaffold. Reiterative optimization provided valuable insight into the bioactive conformation of our novel scaffold and led to the discovery of INCB13739. Clinical evaluation of INCB13739 confirmed for the first time that tissue-specific inhibition of 11ß-HSD1 in patients with type 2 diabetes mellitus was efficacious in controlling glucose levels and reducing cardiovascular risk factors.


Assuntos
Diabetes Mellitus Tipo 2 , Síndrome Metabólica , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Inibidores Enzimáticos/farmacologia , Humanos , Hidrocortisona/metabolismo , Síndrome Metabólica/metabolismo
5.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-940639

RESUMO

Smallanthus sonchifolius, a plant resource with both medicinal and edible values, has been taken as fruit for a long history. Studies have proved that phenolic acids, flavonoids, sesquiterpene lactones, and fructooligosaccharides are the major compounds in S. sonchifolius. The extract of S. sonchifolius demonstrates noticeable antioxidant, anti-inflammatory, antimicrobial, and anti-cancer effects, as well as the activities of lowering blood glucose level, regulating intestinal function and so on. The rhizomes and leaves of S. sonchifolius contain abundant phenolic acids, mainly caffeic acid and its derivatives, which endow S. sonchifolius with remarkable antioxidant effect. Moreover, these substances can reduce blood glucose by improving insulin sensitivity. Fructooligosaccharides are abundant in the tuber of this plant, which can improve intestinal function by regulating intestinal flora. The sesquiterpene lactones in glandular trichomes on the leaf surface can inhibit the proliferation of cancer cells, among which uvedafolin and enhydrofolin have particularly strong activities. Furthermore, the sesquiterpene lactones have obvious inhibitory effect on Gram-positive bacteria. In terms of structure, the number of epoxy groups is linked to the strength of anticancer and antimicrobial effects. In addition, S. sonchifolius contains other compounds such as volatile oils, fatty acids, sterols, diterpenes, p-hydroxyacetophenone derivatives, and octulosonic acid derivatives, thereby exhibiting the pharmacological effects of treating Alzheimer's disease, protecting kidney, and lowering blood lipids. However, the isolation and identification of the main compounds in S. sonchifolius need further exploration, and the mechanism of action remains to be studied. Here we summarized the principal chemical components and pharmacological activities of S. sonchifolius, aiming to give a clue for the comprehensive development and utilization of this plant.

6.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-936109

RESUMO

OBJECTIVE@#To investigate the effect of porous surface morphology of zirconia on the proliferation and differentiation of osteoblasts.@*METHODS@#According to different manufacturing and pore-forming methods, the zirconia specimens were divided into 4 groups, including milled sintering group (M-Ctrl), milled porous group (M-Porous), 3D printed sintering group (3D-Ctrl) and 3D printed porous group (3D-Porous). The surface micromorphology, surface roughness, contact angle and surface elements of specimens in each group were detected by scanning electron microscope (SEM), 3D laser microscope, contact angle measuring device and energy-dispersion X-ray analysis, respectively. MC3T3-E1 cells were cultured on 4 groups of zirconia discs. The cell morphology of MC3T3-E1 cells on zirconia discs was eva-luated on 1 and 7 days by SEM. The cell proliferation was detected on 1, 3 and 5 days by cell counting kit-8 (CCK-8). After osteogenic induction for 14 days, the relative mRNA expression of alkaline phosphatase (ALP), type Ⅰ collagen (Colla1), Runt-related transcription factor-2 (Runx2) and osteocalcin (OCN) in MC3T3-E1 cells were detected by real-time quantitative polymerase chain reaction.@*RESULTS@#The pore size [(419.72±6.99) μm] and pore depth [(560.38±8.55) μm] of 3D-Porous group were significantly larger than the pore size [(300.55±155.65) μm] and pore depth [(69.97±31.38) μm] of M-Porous group (P < 0.05). The surface of 3D-Porous group appeared with more regular round pores than that of M-Porous group. The contact angles of all the groups were less than 90°. The contact angles of 3D-Ctrl (73.83°±5.34°) and M-Porous group (72.7°±2.72°) were the largest, with no significant difference between them (P>0.05). Cells adhered inside the pores in M-Porous and 3D-Porous groups, and the proliferation activities of them were significantly higher than those of M-Ctrl and 3D-Ctrl groups after 3 and 5 days' culture (P < 0.05). After 14 days' incubation, ALP, Colla1, Runx2 and OCN mRNA expression in 3D-Porous groups were significantly lower than those of M-Ctrl and 3D-Ctrl groups (P < 0.05). Colla1, Runx2 and OCN mRNA expressions in M-Porous group were higher than those of 3D-Porous group (P < 0.05).@*CONCLUSION@#The porous surface morphology of zirconia can promote the proliferation and adhesion but inhibit the differentiation of MC3T3-E1 cells.


Assuntos
Diferenciação Celular , Proliferação de Células , Cerâmica , Osteoblastos , Osteogênese , Porosidade , Zircônio
7.
Environ Sci Technol ; 55(24): 16636-16645, 2021 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-34860015

RESUMO

Uronic acid in extracellular polymeric substances is a primary but often ignored factor related to the difficult hydrolysis of waste-activated sludge (WAS), with alginate as a typical polymer. Previously, we enriched alginate-degrading consortia (ADC) in batch reactors that can enhance methane production from WAS, but the enzymes and metabolic pathway are not well documented. In this work, two chemostats in series were operated to enrich ADC, in which 10 g/L alginate was wholly consumed. Based on it, the extracellular alginate lyase (∼130 kD, EC 4.2.2.3) in the cultures was identified by metaproteomic analysis. This enzyme offers a high specificity to convert alginate to disaccharides over other mentioned hydrolases. Genus Bacteroides (>60%) was revealed as the key bacterium for alginate conversion. A new Entner-Doudoroff pathway of alginate via 5-dehydro-4-deoxy-d-glucuronate (DDG) and 3-deoxy-d-glycerol-2,5-hexdiulosonate (DGH) as the intermediates to 2-keto-3-deoxy-gluconate (KDG) was constructed based on the metagenomic and metaproteomic analysis. In summary, this work documented the core enzymes and metabolic pathway for alginate degradation, which provides a good paradigm when analyzing the degrading mechanism of unacquainted substrates. The outcome will further contribute to the application of Bacteroides-dominated ADC on WAS methanogenesis in the future.


Assuntos
Alginatos , Redes e Vias Metabólicas , Bactérias , Ácido Glucurônico , Esgotos
8.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1011646

RESUMO

【Objective】 To explore the establishment of individualized prediction model of recurrence after percutaneous endoscopic lumbar discectomy (PELD) in patients with lumbar disc herniation (LDH). 【Methods】 We selected 124 LDH patients treated with PELD in Department of Orthopedics, The First Affiliated Hospital of Xi’an Jiaotong University, from January 2017 to January 2020 as the research subjects. Their clinical data were retrospectively analyzed, and the independent risk factors affecting PELD recurrence in the LDH patients were screened by univariate analysis and Logistic regression analysis, respectively; the correlation histogram prediction model was established. 【Results】 Age, history of diabetes, course of disease, work intensity and IDDG were the risk factors for the recurrence of PELD in LDH patients (P<0.05). Based on the risk factors screened out, the prediction model of the histogram was established, and the model was verified. The results showed that the C-index of the modeling set and the validation set was 0.944 (95% CI: 0.902-0.963) and 0.969 (95% CI: 0.911-0.978), respectively. The correction curves of both groups were well fitted with the standard curves. The areas under the ROC curve (AUC) in the two groups were 0.944 and 0.969, respectively, which proved that the model had good prediction accuracy. 【Conclusion】 LDH patients have many independent risk factors for recurrence after PELD, and the model based on risk factors with good predictive ability can be useful in preoperative evaluation, appropriate patient selection, and decrease of recurrence rate after PELD.

9.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-942251

RESUMO

OBJECTIVE@#To evaluate the effects of femtosecond laser treated microgrooved surface on microscopic topography, phase transformation, and three-points flexural strength of zirconia, and to provide reference for surface microstructure optimization of zirconia implant.@*METHODS@#According to different surface treatment methods, 57 computer aided design/computer aided manufacture (CAD/CAM) zirconia bars (20.0 mm×4.0 mm×1.4 mm) were evenly divided into three groups: sintered group, no treatment after sintering, taken as control; sandblasted group, sandblasted with 110 μm aluminium oxide (Al2O3) after sintering; microgrooved group, femtosecond laser fabricated microgrooves with 50 μm width, 30 μm depth, and 100 μm pitch. Surface microscopic topography was observed with scanning electron microscope (SEM) and 3D laser microscope. Further, surface roughness in each group and microgroove size were measured. Crystal phase was analyzed with X-ray diffraction. Specimens were subjected to three- points flexural strength test, and Weibull distribution was used to analyze their strength characteristics.@*RESULTS@#SEM showed that sintered surface was flat with clear grain structure; sandblasted surface exihibited bumps and holes with sharp margins and irregular shape; microgrooves were regularly aligned without evident defect, and nano-scale particles were observed on the surface inside of the microgrooves. Ra value of microgrooved group [(9.42±0.28)] μm was significantly higher than that of sandblasted group [(1.04±0.03) μm] and sintered group [(0.60±0.04) μm], and there was statistical difference between sandblasted group and sintered group (P < 0.001). The microgroove size was precise with (49.75±1.24) μm width, (30.85±1.02) μm depth, and (100.58±1.94) μm pitch. Crystal phase analysis showed that monoclinic volume fraction of sandblasted group (18.17%) was much higher than that of sintered group (1.55%), while microgrooved group (2.21%) was similar with sintered group. The flexural strength of sandblasted group (986.22±163.25) MPa had no statistical difference with that of sintered group (946.46±134.15) MPa (P=0.847), but the strength in microgrooved group (547.92±30.89) MPa dropped significantly compared with the other two groups (P < 0.001). Weibull modulus of sintered, sandblasted, microgrooved groups were 7.89, 6.98, and 23.46, respectively.@*CONCLUSION@#Femtosecond laser was able to form micro/nanostructured microgrooves on zirconia surface, which deleteriously affected the flexural strength of zirconia.


Assuntos
Humanos , Cerâmica , Materiais Dentários , Resistência à Flexão , Lasers , Teste de Materiais , Microscopia Eletrônica de Varredura , Propriedades de Superfície , Ítrio , Zircônio
10.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-878538

RESUMO

Microbial fuel cell (MFC) is a bioelectrochemical device, that enables simultaneous wastewater treatment and energy generation. However, a few issues such as low output power, high ohmic internal resistance, and long start-up time greatly limit MFCs' applications. MFC anode is the carrier of microbial attachment, and plays a key role in the generation and transmission of electrons. High-quality bioelectrodes have developed into an effective way to improve MFC performance. Conjugated polymers have advantages of low cost, high conductivity, chemical stability and good biocompatibility. The use of conjugated polymers to modify bioelectrodes can achieve a large specific surface area and shorten the charge transfer path, thereby achieving efficient biological electrochemical performance. In addition, bacteria can be coated with nano-scale conjugated polymer and effectively transfer the electrons generated by cells to electrodes. This article reviews the recently reported applications of conjugated polymers in microbial fuel cells, focusing on the MFC anode materials modified by conjugated polymers. This review also systematically analyzes the advantages and limitations of conjugated polymers, and how these composite hybrid bioelectrodes solve practical issues such as low energy output, high inner resistance, and long starting time.


Assuntos
Bactérias , Fontes de Energia Bioelétrica , Eletricidade , Eletrodos , Polímeros , Purificação da Água
11.
12.
Bioresour Technol ; 313: 123680, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32562970

RESUMO

Psychrophilic microbial fuel cell (PMFC) offers an alternative method for low temperature wastewater treatment, but is seldom reported. In this study, the two-chamber PMFC was constructed at 10 °C using acetate as an electron donor. The maximum voltage under external resistance of 1000 Ω was around 550 mV. The columbic efficiency (CE) was 82.4% under external resistance of 100 Ω and the max power density was 582.4 mW/m2. After temperature decreasing to 4 °C, the maximum voltage also reached 530 mV and CE was 38.4%. The direct electron transfer was proposed in PMFC according to cyclic voltammetry curves. The short enriching time (~30 days) of biofilm in the anodic electrode may be due to the high activity of enriched novel exoelectrogens of M. fermentans (46.2%) and E. lemanii (15.4%). The development of PMFC involved biotechnologies in low temperature regions shall benefit for valuable chemicals production and energy generation in the future.


Assuntos
Fontes de Energia Bioelétrica , Microbiota , Eletricidade , Eletrodos , Águas Residuárias
13.
J Bone Miner Res ; 35(10): 2015-2031, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32460388

RESUMO

Despite the best treatment, approximately 10% of fractures still face undesirable repair. Recently, many studies have focused on the importance of macrophages in bone repair; however, the cellular mechanisms by which they work are not yet fully understood. In this study, we explored the functions of macrophage G-protein-coupled receptor interacting protein 1 (GIT1) in healing a tibial monocortical defect model. Using GIT1flox/flox Lyz2-Cre (GIT1 CKO) mice, we observed that a GIT1 deficiency in the macrophages led to an exacerbation of interleukin 1ß (IL1ß) production, more M1-like macrophage infiltration, and impaired intramembranous ossification in vivo. The results of in vitro assays further indicated that the macrophage GIT1 plays a critical role in several cellular processes in response to lipopolysaccharide (LPS), such as anti-oxidation, IL1ß production alleviation, and glycolysis control. Although GIT1 has been recognized as a scaffold protein, our data clarified that GIT1-mediated extracellular-signal-regulated kinase (ERK) phosphorylation could activate nuclear factor (erythroid-derived 2)-like 2 (NRF2) in macrophages after LPS treatment. Moreover, we demonstrated that macrophage GIT1-activated ERK/NRF2 negatively regulates the 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3 (PFKFB3), facilitating the decrease of glycolysis. Our findings uncovered a previously unrecognized role of GIT1 in regulating ERK/NRF2 in macrophages to control the inflammatory response, suggesting that macrophage GIT1 could be a potential target to improve bone regeneration. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research..


Assuntos
Regeneração Óssea , Proteínas de Ciclo Celular/fisiologia , MAP Quinases Reguladas por Sinal Extracelular , Proteínas Ativadoras de GTPase/fisiologia , Macrófagos , Fator 2 Relacionado a NF-E2 , Animais , Inflamação , Camundongos
14.
Bioresour Technol ; 308: 123318, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32278998

RESUMO

Caproate production by mixed culture fermentation (MCF) is economically attractive. Xylose is known as the second most abundant sugar in nature, however, producing caproate from xylose is never reported. In this study, caproate production from xylose by mesophilic MCF was firstly investigated. The results showed that as pH decreasing to 5.0, the caproate concentration was 2.06 g/L in a batch reactor and was between 0.45 and 1.07 g/L in a continuously stirred reactor. Microbial analysis illustrated that Caproiciproducens and Clostridium_sensu_stricto_12, as two main identified caproate producers, occupied over 50% and around 10% of mixed culture, respectively. Thus, caproate production from xylose was proposed via the fatty acid biosynthesis pathway, not the well-known reverse ß-oxidation pathway. These unexpected differences from literatures gains more understanding about caproate production from organic substrates via MCF.


Assuntos
Caproatos , Xilose , Clostridium , Fermentação , Glucose
15.
Sci Total Environ ; 723: 138080, 2020 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-32220738

RESUMO

Huge amounts of wastewater that contain aromatic compounds such as benzene and phenols are discharged worldwide. Benzoate is a typical intermediate in the anaerobic transformation of those aromatic compounds. In this study, electrically conductive carbon-based materials of granulated activated carbon (GAC), multiwalled carbon nanotubes (MwCNTs), and graphite were evaluated for the ability to promote the benzoate degradation. The results showed that 82-93% of the electrons were recovered in CH4 production from benzoate. The carbon materials stimulated benzoate degradation in the sequence of GAC (5 g/L) > MwCNTs (1 g/L) ~ Graphite (0.1 g/L) > Control. Acetate was the only detected intermediate in the process of benzoate degradation. Taxonomic analyses revealed that benzoate was degraded by Syntrophus to acetate and H2, which were subsequently converted to methane by Methanosarcina (both acetoclastic methanogens and hydrogenotrophic methanogens) and Methanoculleus (hydrogenotrophic methanogens), and direct interspecies electron transfer (DIET) of Desulfovibrio and Methanosarcina. Thus, these results suggest a method to effectively enhance the removal of aromatic compounds and methane recovery.


Assuntos
Methanosarcina , Nanotubos de Carbono , Anaerobiose , Benzoatos , Transporte de Elétrons , Metano
16.
J Neuroinflammation ; 17(1): 62, 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32066456

RESUMO

BACKGROUND: A sustained inflammatory response following spinal cord injury (SCI) contributes to neuronal damage, inhibiting functional recovery. Macrophages, the major participants in the inflammatory response, transform into foamy macrophages after phagocytosing myelin debris, subsequently releasing inflammatory factors and amplifying the secondary injury. Here, we assessed the effect of macrophage scavenger receptor 1 (MSR1) in phagocytosis of myelin debris after SCI and explained its possible mechanism. METHODS: The SCI model was employed to determine the critical role of MSR1 in phagocytosis of myelin debris in vivo. The potential functions and mechanisms of MSR1 were explored using qPCR, western blotting, and immunofluorescence after treating macrophages and RAW264.7 with myelin debris in vitro. RESULTS: In this study, we found improved recovery from traumatic SCI in MSR1-knockout mice over that in MSR1 wild-type mice. Furthermore, MSR1 promoted the phagocytosis of myelin debris and the formation of foamy macrophage, leading to pro-inflammatory polarization in vitro and in vivo. Mechanistically, in the presence of myelin debris, MSR1-mediated NF-κB signaling pathway contributed to the release of inflammatory mediators and subsequently the apoptosis of neurons. CONCLUSIONS: Our study elucidates a previously unrecognized role of MSR1 in the pathophysiology of SCI and suggests that its inhibition may be a new treatment strategy for this traumatic condition.


Assuntos
Apoptose/fisiologia , Macrófagos/metabolismo , Neurônios/metabolismo , Receptores Depuradores Classe A/deficiência , Traumatismos da Medula Espinal/metabolismo , Animais , Células Cultivadas , Macrófagos/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neurônios/patologia , Células RAW 264.7 , Receptores Depuradores Classe A/genética , Traumatismos da Medula Espinal/patologia
17.
FASEB J ; 34(2): 2055-2074, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31908016

RESUMO

In spinal cord ischemia-reperfusion (I/R) injury, large amounts of reactive oxygen species can cause mitochondrial damage. Therefore, mitophagy acts as the main mechanism for removing damaged mitochondria and protects nerve cells. This study aimed to illustrate the important role of GPCR kinase 2-interacting protein-1 (GIT1) in mitophagy in vivo and in vitro. The level of mitophagy in the neurons of Git1 knockout mice was significantly reduced after ischemia-reperfusion. However, the overexpression of adeno-associated virus with Git1 promoted mitophagy and inhibited the apoptosis of neurons. GIT1 regulated the phosphorylation of Beclin-1 in Thr119, which could promote the translocation of Parkin to the mitochondrial outer membrane. This process was independent of PTEN-induced kinase 1 (PINK1), but it could not rescue the role in the absence of PINK1. Overall, GIT1 enhanced mitophagy and protected neurons against ischemia-reperfusion injury and, hence, might serve as a new research site for the protection of ischemia-reperfusion injury.


Assuntos
Proteína Beclina-1/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas Ativadoras de GTPase/metabolismo , Mitofagia , Traumatismo por Reperfusão , Doenças da Medula Espinal , Ubiquitina-Proteína Ligases/metabolismo , Animais , Proteína Beclina-1/genética , Proteínas de Ciclo Celular/genética , Proteínas Ativadoras de GTPase/genética , Camundongos , Camundongos Knockout , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/prevenção & controle , Doenças da Medula Espinal/genética , Doenças da Medula Espinal/metabolismo , Doenças da Medula Espinal/patologia , Doenças da Medula Espinal/prevenção & controle , Ubiquitina-Proteína Ligases/genética
18.
Bioresour Technol ; 295: 122266, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31669871

RESUMO

The production of value added chemicals from CO2 is of critical importance for the practical application of microbial electrosynthesis (MES). Here, a binary electron donor (ED) design (using electrode and ethanol) was introduced to provide an efficient caproate production with the bioconversion of both CO2 and ethanol. A maximum caproate production rate of 2.41 ±â€¯0.69 g L-1 d-1, and a final concentration of 7.66 ±â€¯1.38 g L-1 was achieved. Caproate production selectivity based on the substrate increased to 91.47 ±â€¯0.58% (Binary EDs) from 32.22 ±â€¯32.58% (open circuit Electrode ED). An observed amount of 23.43 ±â€¯0.69% of carbon within the final binary ED products originated from the CO2. This work proves for the first time the potential of caproate production from CO2 utilization and ethanol upgrading using solid electrodes to regulate the chain elongation process.


Assuntos
Dióxido de Carbono , Etanol , Caproatos , Eletrodos
19.
Journal of Experimental Hematology ; (6): 1144-1151, 2020.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-827149

RESUMO

OBJECTIVE@#To explore the effect of regulating A20 expression on NF-κB and biological characteristics of Jurkat cells with glucocorticoid (GC) resistance.@*METHODS@#CCRF CEM and Jurkat cells were treated with dexamethasone (DEX) at concentrations of 100、10、1、0.1、0.01 and 0.001 μmol/L, and cultured for 24、48 and 72 h. The proliferation inhibition rate of Jurkat cell was detected by CCK-8. A20 plasmid was constructed, A20-siRNA was designed and synthesized, and transfected into Jurkat cells by liposome. CCK-8 was used to detect the proliferation rates of Jurkat cells in different concentrations of DEX group, DEX combined with A20 plasmid group and A20-siRNA group. The mRNA expression level of NF-κB was detected by RT-qPCR, the protein expression level of NF-κB was detected by Western blot, and the apoptosis of Jurkat cells was examined by flow cytometry.@*RESULTS@#The inhibitory effects of DEX at different concentrations on the growth of CCRF CEM cells were time-dependent (r=0.984, P<0.05) and concentration-dependent (r=0.966, P<0.05). At the point of 24 hour, the IC approached 1 μmol/L in CCRF CEM cells. Great large differences began to appear between 1 and 10 μmol/L, the proliferation rate of Jurkat cells treated with 1 μmol/L DEX did not show a significant change. Therefore, 1 μmol/L was selected as control group. The cell proliferation rate of A20 plasmid transfection combined with different concentrations of DEX group was lower than that of DEX group and A20-siRNA combined with DEX group. After transfection of A20 plasmid, the expression level of NF-κB was significantly lower than that of control group (P<0.05), and the apoptotic rate was significantly higher than that of control group (P<0.05). After transfection of Jurkat cells with A20-siRNA, the expression level of NF-κB was significantly higher than that of control group (P<0.05). The apoptotic rate of cells in A20-siRNA group was not significantly changed (P>0.05).@*CONCLUSION@#Jurkat cells are resistant to DEX. A20 overexpression combined with DEX can increase sensitivity of Jurkat cells with GC resistance and decrease the proliferation rate of Jurkat cells, down-regulate the expression level of NF-κB and promote the apoptosis of Jurkat cells.


Assuntos
Humanos , Apoptose , Proliferação de Células , Células Jurkat , NF-kappa B , RNA Interferente Pequeno , Transfecção , Proteína 3 Induzida por Fator de Necrose Tumoral alfa
20.
Sci Rep ; 9(1): 12291, 2019 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-31444364

RESUMO

Buprofezin, a chitin synthesis inhibitor that can be used for the control of hemipteran pests, especially melon aphid, Aphis gossypii. The impact of low lethal concentrations of buprofezin on the biological parameters and expression profile of CHS1 gene were estimated for two successive generations of A. gossypii. The present result shows that the LC15 and LC30 of buprofezin significantly decreased the fecundity and longevity of both generations. Exposure of F0 individuals to both concentrations delay the developmental period in F1. Furthermore, the survival rate, intrinsic rate of increase (r), finite rate of increase (λ), and net reproductive rate (R0) were reduced significantly in progeny generation at both concentrations. However, the reduction in gross reproductive rate (GRR) was observed only at LC30. Although, the mean generation time (T) prolonged substantially at LC30. Additionally, expression of the CHS1 gene was significantly increased in F0 adults. Significant increase in the relative abundance of CHS1 mRNA transcript was also observed at the juvenile and adult stages of F1 generation following exposure to LC15 and LC30. Therefore, our results show that buprofezin could affect the biological traits by diminishing the chitin contents owing to the inhibition of chitin synthase activity in the succeeding generation of melon aphid.


Assuntos
Afídeos/enzimologia , Quitina Sintase/genética , Cucurbitaceae/parasitologia , Tiadiazinas/toxicidade , Animais , Afídeos/efeitos dos fármacos , Afídeos/genética , Quitina Sintase/metabolismo , Cruzamentos Genéticos , Feminino , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Masculino , Reprodução , Análise de Sobrevida , Testes de Toxicidade
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