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1.
ChemSusChem ; : e202401486, 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39324248

RESUMO

Cathode prelithium agent is regarded as the most applicable approach to compensate the initial capacity loss in lithium ion batteries (LIBs). Li2NiO2 (LNO) has attracted numerous attention due to its superior environmental stability and reliable synthesis approach. To promote the commercial application of LNO, the understanding of the degradation mechanism induced by air-exposure and finding reliable strategies to improve the air stability are necessary. Herein, by preserving the LNO in different environments (relative humidity of 70% and 40%), the surface chemistry evolution of LNO is subtly investigated, which shows Li2CO3 and LiOH cover the surface of the LNO, which decline the Li+ diffusion kinetics as well as the charge capacity. What's more, the slurry turns gel when the LNO exposed to the environment of 70% relative humidity for 2 days and 40% relative humidity for 5 days. Facile approaches, including washing the deteriorative LNO with ethanol, reacting the alkali components with H3BO3, and coating the LNO with Al2O3 are conducted to recover the disabled LNO, which retains 84.2% of initial capacity. In addition, a coating approach is proposed for the fresh LNO to effectively improve the air stability. This work provides guideline to the commercial application of the LNO.

2.
Life Sci ; 353: 122912, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39004272

RESUMO

DNA damage causes genomic instability. To maintain genome integrity, cells have evolved DNA damage response, which is involved in replication fork disassembly and DNA replication termination. However, the mechanism underlying the regulation of replication fork disassembly and its connection with DNA damage repair remain elusive. The CMG-MCM7 subunit ubiquitination functions on the eukaryotic replication fork disassembly at replication termination. Until now, only ubiquitin ligases CUL2LRR1 have been reported catalyzing MCM7 ubiquitination in human cells. This study discovered that in human cells, the ubiquitin ligase RNF8 catalyzes K63-linked multi-ubiquitination of MCM7 at K145 both in vivo and in vitro. The multi-ubiquitination of MCM7 is dynamically regulated during the cell cycle, primarily presenting on chromatin during the late S phase. Additionally, MCM7 polyubiquitylation is promoted by RNF168 and BRCA1 during DNA replication termination. Upon DNA damage, the RNF8-mediated polyubiquitination of MCM7 decreased significantly during the late S phase. This study highlights the novel role of RNF8-catalyzed polyubiquitination of MCM7 in the regulation of replication fork disassembly in human cells and linking it to DNA damage response.


Assuntos
Dano ao DNA , Replicação do DNA , Proteínas de Ligação a DNA , Componente 7 do Complexo de Manutenção de Minicromossomo , Ubiquitina-Proteína Ligases , Ubiquitinação , Humanos , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Componente 7 do Complexo de Manutenção de Minicromossomo/metabolismo , Componente 7 do Complexo de Manutenção de Minicromossomo/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Proteína BRCA1/metabolismo , Proteína BRCA1/genética , Células HEK293 , Reparo do DNA , Células HeLa
3.
Small ; 20(30): e2309890, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38420897

RESUMO

Lithium-sulfur (Li-S) battery is of great potential for the next generation energy storage device due to the high specific capacity energy density. However, the sluggish kinetics of S redox and the dendrite Li growth are the main challenges to hinder its commercial application. Herein, an organic electrolyte additive, i.e., benzyl chloride (BzCl), is applied as the remedy to address the two issues. In detail, BzCl can split into Bz· radical to react with the polysulfides, forming a Bz-S-Bz intermediate, which changes the conversion path of S and improves the kinetics by accelerating the S splitting. Meanwhile, a tight and robust solid electrolyte interphase (SEI) rich in inorganic ingredients namely LiCl, LiF, and Li2O, is formed on the surface of Li metal, accelerating the ion conductivity and blocking the decomposition of the solvent and lithium polysulfides. Therefore, the Li-S battery with BzCl as the additive remains high capacity of 693.2 mAh g-1 after 220 cycles at 0.5 C with a low decay rate of 0.11%. This work provides a novel strategy to boost the electrochemical performances in both cathode and anode and gives a guide on the electrolyte design toward high-performance Li-S batteries.

4.
Toxicol Res (Camb) ; 12(6): 1126-1134, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38145100

RESUMO

Background: Per- and polyfluoroalkyl substances (PFASs) are a class of environmental contaminants that pose significant health risks to both animals and humans. Although the hippocampal neurotoxic effects of numerous PFASs have been reported, the underlying mechanisms of combined exposure to PFASs-induced hippocampal neurotoxicity remain unclear. Methods: In this study, network pharmacology analysis was performed to identify the intersectional targets of PFASs for possible associations with hippocampal neurotoxicity. The evaluation of the influence of PFASs on intersectional targets was assessed using a weighted method. Additionally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the screened targets were performed, the intersected hub targets calculated by various algorithms were screened in the network and molecular docking was also used to analyze binding activities. Results: Our results indicated that eight PFASs, which acted on key targets (MYC, ESR1, STAT3, RELA, MAPK3) impacted the NF-κB signaling pathway, STAT3 signaling pathway, and MAPK signaling pathways to exert neurotoxicity in the hippocampus. The molecular docking results revealed that PFASs have strong binding potential to the hub targets. Conclusions: Our findings provided a basis for future studies to investigate the detailed mechanisms of PFASs-induced hippocampal neurotoxicity and to develop preventative and control strategies.

5.
Front Immunol ; 14: 1136290, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37275899

RESUMO

The mortality rate associated with acute lung injury (ALI) and its severe form, acute respiratory distress syndrome, is high. Induced pluripotent stem cell (iPSC) therapy is a potential treatment method for ALI, but its therapeutic efficacy is limited in injured lungs. Nitric oxide (NO) has various physiological actions. The current study investigated the effect of iPSCs pretreated with NO donors in paraquat (PQ)-induced ALI mouse model. Male C57BL/6 mice were intraperitoneally injected with PQ, followed by infusion of phosphate-buffered saline, iPSCs, L-arginine pretreated iPSCs, or Nitro-L-arginine methylester (L-NAME) pretreated iPSCs through the tail veins. Histopathological changes, pulmonary microvascular permeability, and inflammatory cytokine levels were analyzed after 3 or 28 d. The effects on iPSC proliferation, migration, and adhesion were evaluated in vitro. More L-arginine-pretreated iPSCs were selectively trafficked into the injured pulmonary tissue of mice with LPS-induced ALI, drastically diminishing the histopathologic changes and inflammatory cytokine levels (IL-1ß and IL-6). There was also markedly improved pulmonary microvascular permeability and pulmonary function. The NO inhibitor abolished the protective effects of iPSCs. In addition, the ability of L-arginine to promote the proliferation and migration of iPSCs was decreased by L-NAME pretreatment, suggesting that NO might mediate the therapeutic benefits of iPSC. The improvement of the iPSC physiological changes by the endogenous gaseous molecule NO reduces lung injury severity. L-Arginine represents a pharmacologically important strategy for enhancing the therapeutic potential of iPSCs.


Assuntos
Lesão Pulmonar Aguda , Células-Tronco Pluripotentes Induzidas , Óxido Nítrico/metabolismo , Paraquat/toxicidade , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Camundongos Endogâmicos C57BL , Masculino , Animais , Camundongos , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/metabolismo , Arginina/uso terapêutico
6.
J Clin Lab Anal ; 36(12): e24792, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36447406

RESUMO

BACKGROUND: We described a patient who exhibited a gradual increase in carbohydrate antigen 19-9 (CA19-9) concentrations for 4 years at three hospitals, with no associated clinical manifestations; however, we were unable to define the cause of this increase, forcing us to consider whether it was a false-positive result. METHODS: Given the potential for interference, this study used multiple system detection, gradient dilution, Polyethylene glycol (PEG) precipitation and heterophilic antibody blocking assay to evaluate the reliability of CA19-9 concentration increase. RESULTS: Analysis of the patient sample using multiple systems indicated that CA19-9 concentrations showed an obvious increase (154.0, and 889.2 IU/ml, respectively) using the Cobas E602 and Advia Centaur XP systems, and were within the reference ranges (<10 IU/ml) on other modules. PEG precipitation on the Cobas E602 and Advia Centaur XP systems reduced the CA19-9 concentration, as did heterophilic blocking tube (HBT-6, HBT-1) blockade. CONCLUSION: CA19-9 was incorrectly identified to increase due to the presence of heterophilic antibodies. We recommend that heterophilic antibodies should be evaluated in cases with elevated CA19-9 level but no associated clinical manifestations to prevent false positives.


Assuntos
Anticorpos Heterófilos , Antígeno CA-19-9 , Humanos , Reprodutibilidade dos Testes , Seguimentos , Carboidratos
7.
Stem Cell Res Ther ; 13(1): 389, 2022 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-35908001

RESUMO

BACKGROUND: Induced pluripotent stem cells (iPSCs) have the potential to promote wound healing; however, their adhesion to the extracellular matrix (ECM) might decrease iPSC migration, thereby limiting their therapeutic potential. Integrin ß1 (Itgb1) is the major integrin subunit that mediates iPSC-ECM adhesion, suggesting that knocking out Itgb1 might be an effective method for enhancing the therapeutic efficacy of iPSCs. METHODS: We knocked out Itgb1 in mouse iPSCs and evaluated its effects on the therapeutic potential of topically applied iPSCs, as well as their underlying in vivo and in vitro mechanisms. RESULTS: The Itgb1-knockout (Itgb1-KO) did not change iPSC pluripotency, function, or survival in the absence of embedding in an ECM gel but did accelerate wound healing, angiogenesis, blood perfusion, and survival in skin-wound lesions. However, embedding in an ECM gel inhibited the in vivo effects of wild-type iPSCs but not those of Itgb1-knockout iPSCs. Additionally, in vitro results showed that Itgb1-knockout decreased iPSC-ECM adhesion while increasing ECM-crossing migration. Moreover, ECM coating on the culture surface did not change cell survival, regardless of Itgb1 status; however, the in vivo and in vitro functions of both Itgb1-knockout and wild-type iPSCs were not affected by the presence of agarose gel, which does not contain integrin-binding sites. Knockout of Integrin α4 (Itga4) did not change the above-mentioned cellular and therapeutic functions of iPSCs. CONCLUSIONS: Itgb1-knockout increased iPSCs migration and the wound-healing-promoting effect of topically applied iPSCs. These findings suggest the inhibition of Itgb1 expression is a possible strategy for increasing the efficacy of iPSC therapies.


Assuntos
Células-Tronco Pluripotentes Induzidas , Integrina beta1/metabolismo , Animais , Movimento Celular , Matriz Extracelular/fisiologia , Integrina beta1/genética , Integrinas , Camundongos , Camundongos Knockout , Cicatrização/genética
8.
ACS Omega ; 7(18): 15267-15274, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35571832

RESUMO

The fluorescent probe has become an important method for accurate detection of H2O2, with advantages of simple operation, high sensitivity, good selectivity, and real-time dynamic monitoring. This paper reviews the research progress in organic small-molecule fluorescent probe H2O2 detection methods that are based on different recognition reactions. In addition, the application prospect of fluorescent probes in the detection of trace H2O2 is anticipated.

9.
Risk Manag Healthc Policy ; 15: 845-864, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35519502

RESUMO

Purpose: The emergence of the mutant virus has exacerbated the COVID-19 epidemic, and vaccines remain an effective and viable means of resistance. As a socially influential young group, university students' awareness and acceptance of the COVID-19 vaccine are crucial to achieving herd immunity. This study aimed to assess the awareness and acceptance of the COVID-19 vaccine among Chinese university students and identify possible factors associated with their awareness level and vaccine hesitancy. Patients and Methods: An anonymous cross-sectional survey was conducted among Chinese university students between 10 and 28 June 2021. We collected information on the demographic characteristics, awareness and acceptance of the COVID-19 vaccine, and influencing factors. Sleep disturbances and anxiety disorders were also evaluated. Multinomial logistic regression analyses were performed. Results: Among the 721 participants (aged 18 to 23 years) with a female predominance (68.9%), 40.4% of cases exhibited moderate awareness the COVID-19 vaccine, and 87.4% of cases expressed high acceptance of the vaccine. Participants' awareness of the COVID-19 vaccine was associated with gender, ethnicity, region of residence, grade level, satisfaction with current state of pandemic control, the perceived likelihood of a COVID-19 pandemic rebound, the source number of COVID-19 information, concerns about differences in vaccine manufacturers, acceptance of current state-approved vaccines and insomnia level. Furthermore, age, preferred channels for vaccination and the acceptance of current state-approved vaccines were significantly associated with their acceptance of the vaccine. Conclusion: This study reflected Chinese university students' high acceptance, but insufficient awareness of the COVID-19 vaccine, some students have insomnia and anxiety problems. These require the government to take measures such as individualized publicity and education, adding professional psychological counseling courses to improve the university students' awareness of vaccines and public health events, and comprehensively promote vaccination to cope with the ever-changing situation of the COVID-19 epidemic.

10.
Front Endocrinol (Lausanne) ; 13: 1041027, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36636478

RESUMO

Introduction: Obesity is a metabolic disease accompanied by abnormalities in lipid metabolism that can cause hyperlipidemia, non-alcoholic fatty liver disease, and artery atherosclerosis. Sleeve gastrectomy (SG) is a type of bariatric surgery that can effectively treat obesity and improve lipid metabolism. However, its specific underlying mechanism remains elusive. Methods: We performed SG, and sham surgery on two groups of diet-induced obese mice. Histology and lipid analysis were used to evaluate operation effect. Immunohistochemistry, immunoblotting, real-time quantitative PCR, immunoprecipitation, immunofluorescence and mass spectrometry were used to reveal the potential mechanisms of SG. Results: Compared to the sham group, the SG group displayed a downregulation of deubiquitinase ubiquitin-specific peptidase 20 (USP20). Moreover, USP20 could promote lipid accumulation in vitro. Co-immunoprecipitation and mass spectrometry analyses showed that heat-shock protein family A member 2 (HSPA2) potentially acts as a substrate of USP20. HSPA2 was also downregulated in the SG group and could promote lipid accumulation in vitro. Further research showed that USP20 targeted and stabilized HSPA2 via the ubiquitin-proteasome pathway. Conclusion: The downregulation of the USP20-HSPA2 axis in diet-induced obese mice following SG improved lipid dysmetabolism, indicating that USP20-HSPA2 axis was a noninvasive therapeutic target to be investigated in the future.


Assuntos
Dieta Hiperlipídica , Proteínas de Choque Térmico HSP70 , Obesidade , Ubiquitina Tiolesterase , Animais , Camundongos , Gastrectomia/métodos , Lipídeos , Camundongos Obesos , Obesidade/cirurgia , Obesidade/complicações
11.
Front Chem ; 10: 1113546, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36700071

RESUMO

Bioluminescence imaging is a non-invasive technology used to visualize physiological processes in animals and is useful for studying the dynamics of metabolic syndrome. Metabolic syndrome is a broad spectrum of diseases which are rapidly increasing in prevalence, and is closely associated with obesity, type 2 diabetes, nonalcoholic fatty liver disease, and circadian rhythm disorder. To better serve metabolic syndrome research, researchers have established a variety of animal models expressing luciferase, while also committing to finding more suitable luciferase promoters and developing more efficient luciferase-luciferin systems. In this review, we systematically summarize the applications of different models for bioluminescence imaging in the study of metabolic syndrome.

12.
J Int Med Res ; 49(11): 3000605211055618, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34772308

RESUMO

OBJECTIVE: This study aimed to analyze the changes in serum inflammatory cytokines and anti-inflammatory cytokines in patients with gouty arthritis (GA). METHODS: The clinical data and serum samples in patients with gouty arthritis and those in healthy volunteers were collected in China-Japan Friendship Hospital from July 2018 to January 2019. Serum cytokine concentrations in patients with GA and volunteers (controls) were determined by a chemiluminescence method. The differences in cytokine concentrations were compared between the two groups. RESULTS: Concentrations of serum interleukin-1 beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), IL-6, IL-8, and IL-4 were significantly higher in patients with acute GA than in controls. Serum concentrations of IL-1ß, TNF-α, IL-6, IL-8, and immunoglobulin E in patients with remission of GA were significantly lower, whereas concentrations of IL-10 and interferon-γ were significantly higher, compared with those in patients with acute GA. CONCLUSION: This study shows that serum concentrations of IL-1ß, TNF-α, IL-6, IL-8, and IL-4 are significantly elevated in patients with GA, and may be involved in the pathogenesis of GA.


Assuntos
Artrite Gotosa , Citocinas/sangue , Artrite Gotosa/sangue , Humanos , Inflamação , Interferon gama , Fator de Necrose Tumoral alfa
13.
BMC Bioinformatics ; 20(1): 443, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31455212

RESUMO

BACKGROUND: Cryo-electron tomography (Cryo-ET) is an imaging technique used to generate three-dimensional structures of cellular macromolecule complexes in their native environment. Due to developing cryo-electron microscopy technology, the image quality of three-dimensional reconstruction of cryo-electron tomography has greatly improved. However, cryo-ET images are characterized by low resolution, partial data loss and low signal-to-noise ratio (SNR). In order to tackle these challenges and improve resolution, a large number of subtomograms containing the same structure needs to be aligned and averaged. Existing methods for refining and aligning subtomograms are still highly time-consuming, requiring many computationally intensive processing steps (i.e. the rotations and translations of subtomograms in three-dimensional space). RESULTS: In this article, we propose a Stochastic Average Gradient (SAG) fine-grained alignment method for optimizing the sum of dissimilarity measure in real space. We introduce a Message Passing Interface (MPI) parallel programming model in order to explore further speedup. CONCLUSIONS: We compare our stochastic average gradient fine-grained alignment algorithm with two baseline methods, high-precision alignment and fast alignment. Our SAG fine-grained alignment algorithm is much faster than the two baseline methods. Results on simulated data of GroEL from the Protein Data Bank (PDB ID:1KP8) showed that our parallel SAG-based fine-grained alignment method could achieve close-to-optimal rigid transformations with higher precision than both high-precision alignment and fast alignment at a low SNR (SNR=0.003) with tilt angle range ±60∘ or ±40∘. For the experimental subtomograms data structures of GroEL and GroEL/GroES complexes, our parallel SAG-based fine-grained alignment can achieve higher precision and fewer iterations to converge than the two baseline methods.


Assuntos
Algoritmos , Microscopia Crioeletrônica/métodos , Tomografia com Microscopia Eletrônica/métodos , Chaperonina 10/ultraestrutura , Chaperonina 60/ultraestrutura , Bases de Dados de Proteínas , Processamento de Imagem Assistida por Computador/métodos , Razão Sinal-Ruído , Fatores de Tempo
14.
Neurogastroenterol Motil ; 31(2): e13493, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30334342

RESUMO

BACKGROUND: Inflammatory bowel disease (IBD) is a functional disorder with chronic and relapsing clinical features. Vasopressin (VP) is a hormone responsible for water and stress homeostasis and also regulates gastrointestinal inflammation and motility. We explored whether VP was related to IBD pathogenesis and its possible pathway. METHODS: Colitis was induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS) in mice. The disease activity and colonic damage were evaluated through a scoring system. Locations of the V1a receptor were revealed by immunochemistry method in colon. Ussing chamber technique was performed for the electrophysiological characterization by using rat ileum. The (Arg8 )-Vasopressin (AVP)-evoked short-circuit current (Isc) was recorded in the presence of conivaptan (V1a and V2 receptor antagonist), tolvaptan (V1b receptor antagonist), tetrodotoxin (TTX), atropine, cyclooxygenase (COX) inhibitors (indomethacin, nonspecific COX antagonist; SC560, COX-1 antagonist; NS560, COX-2 antagonist), and a stabilizer of mast cell (cromolyn sodium), respectively. KEY RESULTS: TNBS resulted in the obvious loss of body weight and tissue damages in mice. AVP significantly aggravated the TNBS-induced colitis, which was attenuated by conivaptan but not tolvaptan. V1a receptors were found immunopositive in neurons among the enteric nervous system. AVP evoked a pulsatile response in Isc. Its amplitude, frequency, and cycle duration were around 8-15 µA/cm2 , 10-11 mHz, and 1.5 minutes, respectively. Notably, the AVP-evoked change in Isc was abolished by TTX, atropine, conivaptan, indomethacin, NS560, and cromolyn sodium, respectively. CONCLUSIONS AND INFERENCES: VP-V1a receptor played the proinflammatory role in TNBS-induced colitis by promoting COX-2-dependent prostaglandin release from mucosal mast cells, which was mediated by the cholinergic pathway.


Assuntos
Colite/fisiopatologia , Mastócitos/metabolismo , Receptores de Vasopressinas/metabolismo , Vasopressinas/metabolismo , Animais , Colite/induzido quimicamente , Colite/metabolismo , Ciclo-Oxigenase 2/metabolismo , Sistema Nervoso Entérico/metabolismo , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/fisiopatologia , Camundongos , Camundongos Endogâmicos BALB C , Neurônios/metabolismo , Prostaglandinas/metabolismo , Ratos , Ratos Wistar , Ácido Trinitrobenzenossulfônico/toxicidade
15.
Angew Chem Int Ed Engl ; 57(43): 14070-14074, 2018 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-30184314

RESUMO

Dehydrogenative annulation under oxidizing reagent-free conditions is an ideal strategy to construct cyclic structures. Reported herein is an unprecedented synthesis of pyrrolidine and tetrahydropyridine derivatives through electrochemical dehydrogenative annulation of N-allyl amides with 1,3-dicarbonyl compounds. The electrolytic method employs an organic redox catalyst, which obviates the need for oxidizing reagents and transition-metal catalysts. In these reactions, the N-allyl amides serve as a four-atom donor to react with dimethyl malonate to give pyrrolidines by a (4+1) annulation, or with ß-ketoesters to afford tetrahydropyridine derivatives by a (4+2) annulation.

16.
PLoS One ; 13(6): e0198614, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29879176

RESUMO

OBJECTIVE: Metabolic disturbances induce endoplasmic reticulum stress (ERS) in pancreatic beta cells. This study aims to investigate whether a common pathway exists in the ERS induced by various chemicals, including high levels of glucose and palmitate in INS-1-3 cells. METHOD: ERS in INS-1-3 cells was induced by exposure cells to thapsigargin (TG), tunicamycin (TM) or palmitic acid (PA) +high glucose (HG). Digital gene expression (DGE) profiling technique was used to detect differentially expressed genes. The profile of gene expression was detected by gene oncology (GO) function and pathway enrichment analysis. Nkx6.1 over-expression was established in INS-1-3 cell lines by lentivirus infection to revert the inhibition of Nkx6.1 expression found in the situation of ERS. Real time reverse transcription polymerase chain reaction (RT-PCR) was used to verify the expression changes of key genes. Cell viability was measured by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. The apoptosis was determined by flow cytometry. INS-1-3 cell function was measured by glucose stimulated insulin secretion test(GSIS). RESULTS: As compared to control, DGE demonstrated that there were 135, 57 and 74 differentially expressed genes in TM, TG and HG+PA groups, respectively. Those differentially expressed genes were enriched to ERS, antigen processing and presentation, protein export pathways, and interestingly, the maturity onset diabetes of the young (MODY) pathway. Nkx6.1 is one of common down-regulated gene in MODY signaling pathway among TM, TG and HG+PA groups. Over-expression of Nkx6.1 ameliorated glucolipotoxicity induced apoptosis rate by 45.4%, and increased proliferation by 40.9%. At the same time, GSIS increased by 1.82 folds. CONCLUSIONS: MODY pathway genes expression was changed in the state of ERS. Over-expression of Nkx6.1 protected the INS-1-3 cells from glucolipotoxicity.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Estresse do Retículo Endoplasmático/fisiologia , Células Secretoras de Insulina/metabolismo , Redes e Vias Metabólicas/genética , Animais , Linhagem Celular , Diabetes Mellitus Tipo 2/genética , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Perfilação da Expressão Gênica , Proteínas de Homeodomínio/metabolismo , Insulina/metabolismo , Células Secretoras de Insulina/citologia , Células Secretoras de Insulina/efeitos dos fármacos , Ratos , Tapsigargina/farmacologia , Tunicamicina/farmacologia , Regulação para Cima
17.
Chem Commun (Camb) ; 54(36): 4601-4604, 2018 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-29670957

RESUMO

The intramolecular C(sp3)-H/C(sp2)-H cross-coupling of 1,3-dicarbonyl compounds has been achieved through Cp2Fe-catalyzed electrochemical oxidation. The key to the success of these dehydrogenative cyclization reactions is the selective activation of the acidic α-C-H bond of the 1,3-dicarbonyl moiety to generate a carbon-centered radical.

18.
ACS Appl Bio Mater ; 1(2): 328-339, 2018 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-35016372

RESUMO

A reasonably intelligent response to glucose concentration fluctuations is crucial for developing a self-regulated insulin delivery system. Inspired by the relationship between the higher ordered structures of proteins and their versatile functions, the introduction of polypeptides capable of mimicking different secondary structures into the delivery system will be anticipated for adjusting glucose concentration sensitivity. Herein, this work presents the impact of different secondary structural architectures of polypeptide blocks on the stability of glucose-responsive complex nanoparticles (CNPs) in the normal physiological environment and their response to the stimuli of normoglycemic and hyperglycemic conditions in vitro. Results from the conformational investigations of the CNPs carried out using circular dichroism and insulin release under the different stimuli suggested that the stability and glucose sensitivity of the CNPs are closely related to the secondary structure composition of the polypeptide blocks. The CNPs with a dominant α-helix structure exhibit a promising potential to improve normal glycemic control and to reduce the incidences of hyperglycemia and hypoglycemia both in vitro and in vivo.

19.
Biosens Bioelectron ; 98: 325-329, 2017 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-28697445

RESUMO

Abnormal expression of γ-Glutamyltranspeptidase (GGT) in living organisms is closely implicated in the development of several human tumors. The GGT levels in tissue and serum have emerged as a potential criterion for tumor diagnosis. However, precise "light up" GGT activity in vivo is still challenging due to the signal interferes of background. Bioluminescence based on the firefly luciferase-catalyzed reaction for light production provides a feasible strategy for GGT detection in vivo. In this report, a bioluminogenic probe, Glu-Luc, was designed and synthesized by connecting D-luciferin with γ-glutamyl group. The cleavage of γ-glutamyl group is triggered by GGT, resulting in the release of D-luciferin, which generates a bright bioluminescence emission in the present of luciferase and ATP. The probe exhibits very high selectivity and sensitivity toward GGT activity from in vitro to in vivo and in clinical samples, which offers a promising tool for investigations of the GGT-overexpressing related biological process including tumor diagnosis and prognosis in living organisms.


Assuntos
Técnicas Biossensoriais/métodos , Neoplasias/sangue , gama-Glutamiltransferase/sangue , Benzotiazóis/química , Regulação Neoplásica da Expressão Gênica , Humanos , Luciferases de Vaga-Lume/química , Medições Luminescentes , Neoplasias/genética , Neoplasias/patologia , gama-Glutamiltransferase/genética
20.
Mediators Inflamm ; 2017: 1732638, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28167850

RESUMO

The recently discovered IL-33 as an IL-1 cytokine family member has been proved to be specifically released from osteonecrotic bones. We aimed to investigate the potential role of IL-33 in the development of osteonecrosis of femoral head (ONFH). Forty patients diagnosed with ONFH and forty age-, sex-, and body mass index- (BMI-) matched healthy subjects were included in this prospective study between March 2016 and September 2016. A commercially available ELISA kit was used to test the level of plasma IL-33. The IL-33 levels were compared among different ARCO stages, CJFH types, and etiology groups. Plasma IL-33 levels were significantly higher in the ONFH patients than that in the control subjects. The levels of IL-33 did not differ significantly among the ONFH patients with different ARCO stages. The IL-33 levels of patients with CJFH type L3 were significantly higher than that of patients with types L1 and L2. No significant differences were observed in IL-33 levels between steroid-induced, alcohol-induced, and idiopathic patients. Our findings seem to indicate that IL-33 effects may be detrimental during ONFH, which appeared to be associated with the prognosis of ONFH. The IL-33 deserves particular attention in the pathogenesis of ONFH.


Assuntos
Necrose da Cabeça do Fêmur/sangue , Necrose da Cabeça do Fêmur/patologia , Interleucina-33/sangue , Adulto , Índice de Massa Corporal , Feminino , Necrose da Cabeça do Fêmur/imunologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos
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