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1.
Small ; 20(12): e2307685, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37946630

RESUMO

The rational design of metal-organic framework (MOF)-based electrocatalysts plays a key role in achieving high-efficiency oxygen evolution reaction (OER). Herein, a synergetic morphology and electronic structure engineering strategy are proposed to design a Co-MOF nanoflower grown on carbon paper via rare-earth cerium doping (CoCe-MOF/CP). Compared with Co-MOF/CP, the developed CoCe-MOF/CP exhibited superior OER performance with a low overpotential of 267 mV at 10 mA cm-2 and outstanding long-term stability over 100 h. Theoretical calculations show that the unique 4f valence electron structure of Ce induced charge redistribution of the Co-MOF surface through the strong Co 3d-O 2p-Ce 4f orbital electronic coupling below the Fermi level. Ce-doped plays a key role in the engineering of the electronic states of the Co sites to endow them with the optimal free energy landscape for enhanced OER catalytic activity. This work provides new insights into comprehending the RE-enhanced mechanism of electrocatalysis and provides an effective strategy for the design of MOF-based electrocatalysts.

2.
J Antimicrob Chemother ; 79(9): 2298-2305, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-38990679

RESUMO

BACKGROUND: Bacterial RNA polymerase (RNAP) is a promising target for antimicrobial chemotherapy due to its indispensable role in bacterial growth and survival. Among its components, only the rpoB gene encoding the ß-subunit is known for its association with rifampicin resistance. We recently identified a variant of the RNAP α-subunit (RpoA) in Pseudomonas aeruginosa, conferring heightened bacterial susceptibility to antimicrobials. This susceptibility was attributed to the specific down-regulation of the MexEF-OprN efflux pump. OBJECTIVES: We asked how to distinguish antimicrobial-susceptible variant strains from clinical isolates. METHODS: In this study, we identified various P. aeruginosa RpoA variants from clinical sources. Using the sequence alignment of different bacterial RpoA species, we computed the positional conservation of substitutions in RpoA variants using Shannon Entropy. RESULTS: Our findings revealed that selective RpoA variant strains exhibited distinct profiles of antimicrobial susceptibility. Notably, RpoA variant strains, containing single-substitutions in the C-terminal domain (α-CTD) but not the N-terminal domain (α-NTD), showed attenuated MexEF-OprN expression and increased susceptibility to MexEF-OprN-specific antibiotics. Furthermore, we observed a close correlation between the susceptibility of these α-CTD RpoA variant strains to antibiotics and the conservation degrees of positional substitutions. CONCLUSIONS: Our findings demonstrate the prevalence of antimicrobial-susceptible RpoA variant strains among P. aeruginosa clinical isolates. The identified positional conservation pattern in our study facilitates the rapid classification of RpoA variant strains with distinct drug resistances. Given the high conservation of RNAP across bacterial species, our findings open a new therapeutic perspective for precisely and efficiently combating pathogenic RpoA variant strains with specific antimicrobials.


Assuntos
Antibacterianos , RNA Polimerases Dirigidas por DNA , Testes de Sensibilidade Microbiana , Infecções por Pseudomonas , Pseudomonas aeruginosa , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/genética , RNA Polimerases Dirigidas por DNA/genética , Humanos , Antibacterianos/farmacologia , Infecções por Pseudomonas/microbiologia , Variação Genética , Proteínas de Bactérias/genética
3.
Biotechnol Bioeng ; 121(10): 3059-3067, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38923503

RESUMO

Spinal muscular atrophy (SMA) is a devastating neuromuscular disease caused by mutations in the survival motor neuron 1 (SMN1) gene. Gene editing technology repairs the conversion of the 6th base T to C in exon 7 of the paralogous SMN2 gene, compensating for the SMN protein expression and promoting the survival and function of motor neurons. However, low editing efficiency and unintended off-target effects limit the application of this technology. Here, we optimized a TaC9-adenine base editor (ABE) system by combining Cas9 nickase with the transcription activator-like effector (TALE)-adenosine deaminase fusion protein to effectively and precisely edit SMN2 without detectable Cas9 dependent off-target effects in human cell lines. We also generated human SMA-induced pluripotent stem cells (SMA-iPSCs) through the mutation of the splice acceptor or deletion of the exon 7 of SMN1. TaC9-R10 induced 45% SMN2 T6 > C conversion in the SMA-iPSCs. The SMN2 T6 > C splice-corrected SMA-iPSCs were directionally differentiated into motor neurons, exhibiting SMN protein recovery and antiapoptosis ability. Therefore, the TaC9-ABE system with dual guides from the combination of Cas9 with TALE could be a potential therapeutic strategy for SMA with high efficacy and safety.


Assuntos
Edição de Genes , Células-Tronco Pluripotentes Induzidas , Proteína 2 de Sobrevivência do Neurônio Motor , Humanos , Proteína 2 de Sobrevivência do Neurônio Motor/genética , Edição de Genes/métodos , Células-Tronco Pluripotentes Induzidas/metabolismo , Atrofia Muscular Espinal/genética , Atrofia Muscular Espinal/terapia , Adenina/metabolismo , Adenina/análogos & derivados , Linhagem Celular
4.
BMC Infect Dis ; 24(1): 1029, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39333926

RESUMO

BACKGROUND: Although Toxoplasma gondii (T. gondii) infection has been linked to cardiac injury, the extent to which it increases the risk of cardiovascular disease (CVD) mortality remains unclear. We aimed to assess the association between T. gondii infection and CVD mortality in the United States population. METHODS: This study used data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2009 and 2014 to investigate the association between T. gondii infection and CVD mortality. The T. gondii infection status was determined by measuring serum T. gondii IgG antibody levels. CVD mortality outcomes were ascertained through linkage with the national mortality index records. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) of T. gondii infection on CVD mortality. RESULTS: A total of 10,237 (Male, n = 5010; Female, n = 5227) individuals aged ≥ 20 years were included in the analysis, of which 1,632 were positive for T. gondii serum IgG antibodies. After a median follow-up of eight years, there were 312 deaths due to CVD. In multivariable-adjusted analyses, the risk of death from CVD was 40% higher in T. gondii-seropositive men compared with seronegative men (HR: 1.40; 95%CI: 1.02-1.93), but not in women (HR: 0.87; 95% CI: 0.57-1.34). These results remained consistent in further stratified and sensitivity analyses. CONCLUSION: In this large population-based cohort study, T. gondii infection was associated with an increased risk of CVD mortality in men, but not in women. Further studies are required to elucidate the underlying mechanisms and potential sex-specific differences in the effects of T. gondii infection on CVD mortality. Future investigations should focus on validating these results and exploring the potential implications for cardiovascular risk assessment and management.


Assuntos
Anticorpos Antiprotozoários , Doenças Cardiovasculares , Imunoglobulina G , Toxoplasma , Toxoplasmose , Humanos , Masculino , Feminino , Toxoplasmose/mortalidade , Toxoplasmose/epidemiologia , Doenças Cardiovasculares/mortalidade , Estados Unidos/epidemiologia , Pessoa de Meia-Idade , Adulto , Toxoplasma/imunologia , Estudos de Coortes , Anticorpos Antiprotozoários/sangue , Imunoglobulina G/sangue , Fatores Sexuais , Idoso , Inquéritos Nutricionais , Adulto Jovem , Fatores de Risco , Modelos de Riscos Proporcionais
5.
Cell Mol Biol (Noisy-le-grand) ; 70(1): 94-98, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38372106

RESUMO

The purpose was to analyze the clinical significance of miR-200a in children with initially diagnosed SLE and renal damage. Children with initially diagnosed SLE (n=100) and healthy children (n=50) undergoing physical examinations during the same period were recruited. Disease activity of SLE children was determined based on SLEDAI (systemic lupus erythematosus disease activity index), and they were divided to SLEDAI≤9 group and SLEDAI>9 group, respectively. Moreover, SLE children were divided to LN group and non-LN group based on the occurrence of lupus nephritis. Differential level of miR-200a between groups was detected by qRT-PCR. Spearman correlation test was conducted to analyze the influence of miR-200a on SLEDAI and other laboratory indexes of SLE children. Its diagnostic potential in SLE and LN was assessed through depicting ROC curves. MiR-200a level was remarkably lower in SLE children than that of healthy children. Lower level of miR-200a was detected in SLE children with high SLEDAI or accompanied LN. MiR-200a level was negatively correlated to SLEDAI (r=-0.425), ESR (r=-0.284), CRP (r=-0.338), BUN (r=-0.263) and Scr (r=-0.345), while it was positively correlated to C3 (r=0.631), C4 (r=0.524) and ALB (r=0.394) in SLE children. The AUC of miR-200a in diagnosing SLE was 0.8379 (cut-off value=2.225, sensitivity=70%, specificity=70%). Besides, the AUC of miR-200a in diagnosing LN was 0.7619 (cut-off value=2.005, sensitivity=80%, specificity=76%). MiR-200a level has a certain correlation to the disease activity of children with initially diagnosed SLE, which can be utilized as an adjuvant indicator in evaluating SLE severity. Meanwhile, miR-200a has predictive value for SLE-induced renal damage.


Assuntos
Lúpus Eritematoso Sistêmico , Nefrite Lúpica , MicroRNAs , Criança , Humanos , Biomarcadores , Relevância Clínica , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/genética , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/genética , MicroRNAs/genética
6.
Dig Dis Sci ; 69(9): 3249-3260, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38987443

RESUMO

OBJECTIVE: To investigate the role and function of eIF6 in gastric cancer (GC). METHODS: The expression level of eIF6 in GC tissues and normal tissues was detected in different high-throughput sequencing cohorts. Survival analysis, gene differential analysis, and enrichment analysis were performed in the TCGA cohort. Biological networks centered on eIF6 were constructed through two different databases. Immunohistochemistry (IHC) and Western blot were used to detect protein expression of eIF6, and qRT-PCR was used to detect eIF6 mRNA expression. The correlation between the expression of eIF6 in GC tissues and clinicopathological parameters of GC was analyzed. siRNA knockout of eIF6 was used to study the proliferation, migration, and invasion. The effects of eIF6 on cell cycle and Cyclin B1 were detected by flow cytometry and Western blot. RESULTS: eIF6 was significantly overexpressed in GC tissues and predicted poor prognosis. In addition, 113 differentially expressed genes were detected in cancer-related biological pathways and functions by differential analysis. Biological networks revealed interactions of genes and proteins with eIF6. The expression intensity of eIF6 in cancer tissues was higher than that in adjacent tissues (P = 0.0001), confirming the up-regulation of eIF6 expression in GC tissues. The expression level of eIF6 was statistically significant with pTNM stage (P = 0.006). siRNA knockout of eIF6 significantly reduced the proliferation, colony formation, migration, and invasion ability of GC cells. Silencing of eIF6 also inhibited the cell cycle of GC cells in G2/M phase and decreased the expression level of CyclinB1. CONCLUSION: Our study suggests that eIF6 is up-regulated in GC and may promote the proliferation, migration, and invasion of GC by regulating cell cycle.


Assuntos
Movimento Celular , Proliferação de Células , Invasividade Neoplásica , Neoplasias Gástricas , Neoplasias Gástricas/patologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Linhagem Celular Tumoral , Fatores de Iniciação de Peptídeos/genética , Fatores de Iniciação de Peptídeos/metabolismo , Regulação Neoplásica da Expressão Gênica , Ciclo Celular/genética , Ciclina B1/metabolismo , Ciclina B1/genética , Regulação para Cima , Fatores de Iniciação em Eucariotos
7.
Sensors (Basel) ; 24(20)2024 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-39460237

RESUMO

Spatial resolution enhancement in remote sensing data aims to augment the level of detail and accuracy in images captured by satellite sensors. We proposed a novel spatial resolution enhancement framework using the convolutional attention-based token mixer method. This approach leveraged spatial context and semantic information to improve the spatial resolution of images. This method used the multi-head convolutional attention block and sub-pixel convolution to extract spatial and spectral information and fused them using the same technique. The multi-head convolutional attention block can effectively utilize the local information of spatial and spectral dimensions. The method was tested on two kinds of data types, which were the visual-thermal dataset and the visual-hyperspectral dataset. Our method was also compared with the state-of-the-art methods, including traditional methods and deep learning methods. The experiment results showed that the method was effective and outperformed state-of-the-art methods in overall, spatial, and spectral accuracies.

8.
Int J Mol Sci ; 25(9)2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38731870

RESUMO

Transcranial magneto-acoustic stimulation (TMAS), which is characterized by high spatiotemporal resolution and high penetrability, is a non-invasive neuromodulation technology based on the magnetic-acoustic coupling effect. To reveal the effects of TMAS treatment on amyloid-beta (Aß) plaque and synaptic plasticity in Alzheimer's disease, we conducted a comparative analysis of TMAS and transcranial ultrasound stimulation (TUS) based on acoustic effects in 5xFAD mice and BV2 microglia cells. We found that the TMAS-TUS treatment effectively reduced amyloid plaque loads and plaque-associated neurotoxicity. Additionally, TMAS-TUS treatment ameliorated impairments in long-term memory formation and long-term potentiation. Moreover, TMAS-TUS treatment stimulated microglial proliferation and migration while enhancing the phagocytosis and clearance of Aß. In 5xFAD mice with induced microglial exhaustion, TMAS-TUS treatment-mediated Aß plaque reduction, synaptic rehabilitation improvement, and the increase in phospho-AKT levels were diminished. Overall, our study highlights that stimulation of hippocampal microglia by TMAS treatment can induce anti-cognitive impairment effects via PI3K-AKT signaling, providing hope for the development of new strategies for an adjuvant therapy for Alzheimer's disease.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Microglia , Placa Amiloide , Animais , Microglia/metabolismo , Camundongos , Placa Amiloide/metabolismo , Placa Amiloide/patologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/terapia , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Estimulação Magnética Transcraniana/métodos , Estimulação Acústica , Camundongos Transgênicos , Modelos Animais de Doenças , Sinapses/metabolismo , Hipocampo/metabolismo , Masculino , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Plasticidade Neuronal , Potenciação de Longa Duração , Transdução de Sinais
9.
Yi Chuan ; 46(5): 408-420, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38763775

RESUMO

Lesch-Nyhan syndrome (LNS) is a congenital defect disease that results in defective purine metabolism. It is caused by pathogenic variants of the HPRT gene. Its clinical symptoms mainly include high uric acid levels, gout, and kidney stones and damage. The mechanism of LNS has not been fully elucidated, and no cure exists. Animal models have always played an important role in exploring causative mechanisms and new therapies. This study combined CRISPR/Cas9 and microinjection to knock out the HPRT gene to create an LNS rabbit model. A sgRNA targeting exon 3 of HPRT gene was designed. Subsequently, Cas9 mRNA and sgRNA were injected into rabbit zygotes, and injected embryos were transferred to the uterus. The genotype and phenotype of rabbits were analyzed after birth. Four infant rabbits (named R1, R2, R3 and R4), which showed varying levels of gene modification, were born. The gene-editing efficiency was 100%. No wild-type sequences at the target HPRT gene were detected in R4 rabbit. Next, 6-thioguanine drug testing confirmed that HPRT enzymatic activity was deficient in R4 infant rabbit. HE staining revealed kidney abnormalities in all infant rabbits. Overall, an sgRNA capable of knocking out the HPRT gene in rabbits was successfully designed, and HPRT gene-modified rabbits were successfully constructed by using CRISPR/Cas9 technology and microinjection. This study provides a new nonrodent animal model for studying LNS syndrome.


Assuntos
Sistemas CRISPR-Cas , Modelos Animais de Doenças , Hipoxantina Fosforribosiltransferase , Síndrome de Lesch-Nyhan , Animais , Coelhos , Síndrome de Lesch-Nyhan/genética , Hipoxantina Fosforribosiltransferase/genética , Hipoxantina Fosforribosiltransferase/metabolismo , Feminino , Edição de Genes , RNA Guia de Sistemas CRISPR-Cas/genética , Masculino , Fenótipo
10.
Small ; 19(22): e2205833, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36876447

RESUMO

Thermochromic smart windows with rational modulation in indoor temperature and brightness draw considerable interest in reducing building energy consumption, which remains a huge challenge to meet the comfortable responsive temperature and the wide transmittance modulation range from visible to near-infrared (NIR) light for their practical application. Herein, a novel thermochromic Ni(II) organometallic of [(C2 H5 )2 NH2 ]2 NiCl4 for smart windows is rationally designed and synthesized via an inexpensive mechanochemistry method, which processes a low phase-transition temperature of 46.3 °C for the reversible color evolution from transparent to blue with a tunable visible transmittance from 90.5% to 72.1%. Furthermore, cesium tungsten bronze (CWO) and antimony tin oxide (ATO) with excellent NIR absorption in 750-1500 and 1500-2600 nm are introduced in the [(C2 H5 )2 NH2 ]2 NiCl4 -based smart windows, realizing a broadband sunlight modulation of a 27% visible light modulation and more than 90% of NIR shielding ability. Impressively, these smart windows demonstrate stable and reversible thermochromic cycles at room temperature. Compared with the conventional windows in the field tests, these smart windows can significantly reduce the indoor temperature by 16.1 °C, which is promising for next-generation energy-saving buildings.

11.
Clin Genet ; 104(6): 613-624, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37706265

RESUMO

Cancer, one of the leading causes of death, usually commences and progresses as a result of a series of gene mutations and dysregulation of expression. With the development of clustered regularly interspaced palindromic repeat (CRISPR)/Cas9 gene-editing technology, it is possible to edit and then decode the functions of cancer-related gene mutations, markedly advance the research of biological mechanisms and treatment of cancer. This review summarizes the mechanism and development of CRISPR/Cas9 gene-editing technology in recent years and describes its potential application in cancer-related research, such as the establishment of human tumor disease models, gene therapy and immunotherapy. The challenges and future development directions are highlighted to provide a reference for exploring pathological mechanisms and potential treatment protocols of cancer.


Assuntos
Sistemas CRISPR-Cas , Neoplasias , Humanos , Edição de Genes , Terapia Genética , Imunoterapia , Neoplasias/genética
12.
Opt Lett ; 48(13): 3523-3526, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37390171

RESUMO

We demonstrate for the first time that optical rogue waves (RWs) can be generated using a chaotic semiconductor laser with energy redistribution. Chaotic dynamics are numerically generated using the rate equation model of an optically injected laser. The chaotic emission is then sent to an energy redistribution module (ERM) that consists of a temporal phase modulation and a dispersive propagation. The process enables a temporal energy redistribution of the chaotic emission waveforms, where coherent summation of consecutive laser pulses leads to random generation of giant intensity pulses. Efficient generation of optical RWs are numerically demonstrated by varying the ERM operating parameters in the entire injection parameter space. The effects of the laser spontaneous emission noise on the generation of RWs are further investigated. The RW generation approach offers a relatively high flexibility and tolerance in the choice of ERM parameters according to the simulation results.


Assuntos
Lasers Semicondutores , Fenômenos Físicos , Simulação por Computador
13.
Tohoku J Exp Med ; 259(3): 209-219, 2023 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-36543245

RESUMO

The Holliday Junction-Recognition Protein (HJURP) was upregulated in several tumors, which was associated with poor outcome. This study investigated the effects of the HJURP-mediated c-Jun N-terminal kinase (JNK)/ signal transducer and activator of transcription 3 (STAT3) pathway on bladder urothelial carcinoma (BLUC). Online databases were used to analyze HJURP expression in BLUC and the correlation of HJURP to JNK1 [mitogen-activated protein kinase 8 (MAPK8)], JNK2 (MAPK9), STAT3, marker of proliferation Ki-67 (MKI67), proliferating cell nuclear antigen (PCNA), cyclin dependent kinase 2 (CDK2), CDK4 and CDK6. HJURP expression was detected in BLUC cells and human normal primary bladder epithelial cells (BdECs). BLUC cells were treated with HJURP lentivirus activation /shRNA lentivirus particles or JNK inhibitor SP600125. HJURP was upregulated in BLUC tissues and correlated with poor prognosis of patients (all P < 0.05). HJURP in tumor positively correlated with MAPK8 (R = 0.30), MAPK9 (R = 0.30), STAT3 (R = 0.15), MKI67 (R = 0.60), PCNA (R = 0.46), CDK2 (R = 0.39), CDK4 (R = 0.24) and CDK6 (R = 0.21). The JNK inhibitor SP600125 decreased p-JNK/JNK and p-STAT3/STAT3 in BLUC cells, which was reversed by HJURP overexpression (P < 0.05). The HJURP-mediated JNK/STAT3 pathway promoted BLUC cell proliferation and inhibited cell apoptosis (P < 0.05). HJURP reversed the arrested G0/G1 phase of BLUC cells by SP600125. HJURP acted as an oncogene to regulate BLUC cell proliferation, apoptosis and the cell cycle by mediating the JNK/STAT3 pathway. Therefore, HJURP targeting might be an attractive novel therapeutic target for early diagnosis and treatment in BLUC.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Antígeno Nuclear de Célula em Proliferação/metabolismo , Antígeno Nuclear de Célula em Proliferação/farmacologia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/farmacologia , DNA Cruciforme , Proteína C/metabolismo , Proteína C/farmacologia , Bexiga Urinária , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Ciclo Celular , Proliferação de Células , Apoptose
14.
Phytother Res ; 37(1): 89-100, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36161389

RESUMO

Inflammatory bowel disease is a disease that can invade the whole digestive tract and is accompanied by immune abnormalities. Immune dysfunction involving dendritic cells (DCs) and T cells is recognized as a key factor in diseases. Indirubin (IDRB) exerts antiinflammatory effects and can help in treating immune diseases. This study aimed to isolate bone marrow-derived dendritic cells (BMDCs) using lipopolysaccharide (LPS) to obtain mature DCs (mDCs). The expression of CD80, CD86, CD40, and MHC-II was detected using flow cytometry after treatment with IDRB. αVß8 siRNA was used to knock down αVß8 in mDCs, and the expression of CD80, CD86, CD40, and MHC-II was detected. Meanwhile, DCs were co-cultured with T cells. Then, T cell differentiation was detected using flow cytometry, and the cytokine levels were detected using enzyme-linked immunosorbent assay. The animal model of dextran sulfate sodium (DSS)-induced inflammatory bowel disease was established in mice. After intervention with IDRB and αVß8 shRNA, the intestinal tissues were evaluated using H&E staining, disease activity index (DAI) score, and histological damage index, and the corresponding factors and cytokines to regulatory T cells (Treg) and Th17 were measured. The results showed that αVß8 was expressed in immature DCs and mDCs. CD80, CD86, CD40, and MHC-II expression decreased after IDRB treatment in mDCs. Meanwhile, the expression of TNF-α and TGF-ß also decreased after IDRB treatment. The effect of IDRB on the expression of CD80, CD86, CD40, MHC-II, TNF-α, and TGF-ß in mDCs was reversed by αVß8 siRNA. The Treg differentiation increased after IDRB treatment, while the differentiation of Th17 cells was inhibited. This effect of IDRB was reversed by mDCs after treatment with αVß8 siRNA. In vivo experiments showed that IDRB alleviated the symptoms of inflammatory bowel disease in animals. Enteritis significantly reduced, and the effect of IDRB was reversed by αVß8 shRNA. The results suggested that IDRB regulated the differentiation of T cells by mediating the maturation of BMDCs through αVß8. This study confirmed the therapeutic effect of IDRB in inflammatory bowel disease and suggested that IDRB might serve as a potential drug.


Assuntos
Doenças Inflamatórias Intestinais , Fator de Necrose Tumoral alfa , Camundongos , Animais , Fator de Necrose Tumoral alfa/metabolismo , Medula Óssea/metabolismo , Diferenciação Celular , Citocinas/metabolismo , Fator de Crescimento Transformador beta/farmacologia , Células Cultivadas , Doenças Inflamatórias Intestinais/tratamento farmacológico , RNA Interferente Pequeno/metabolismo , RNA Interferente Pequeno/farmacologia , Células Dendríticas/metabolismo , Camundongos Endogâmicos C57BL
15.
Environ Toxicol ; 38(7): 1678-1689, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37087754

RESUMO

PURPOSE: This study identified the function of neural precursor cell expressed developmentally down-regulated 4-like (NEDD4L) on bladder cancer (BLCA). METHODS: NEDD4L expression in BLCA patients was scrutinized. The function of NEDD4L on the viability, apoptosis, migration and invasion of BLCA cells was evaluated by cell counting kit-8, flow cytometry and Transwell assays. The effect of NEDD4L on the cisplatin (DDP) resistance of the DDP-resistant BLCA cells was explored. The influence of NEDD4L on the p62/Keap1/Nrf2 pathway activity in BLCA cells was tested by Western blot. Rescue experiments were implemented to verify whether NEDD4L regulated BLCA cell malignant behavior by mediating the Keap1/Nrf2 pathway activity via p62. The effect of NEDD4L on the growth and the p62/Keap1/Nrf2 pathway activity in vivo was researched in xenograft tumor nude mice models. RESULTS: The down-regulated NEDD4L in BLCA patients was associated with unfavorable survival. NEDD4L suppressed the viability (inhibition rate 57.1%/49.0%), migration (inhibition rate 49.7%/77.1%), invasion (inhibition rate 50.6%/75.7%), promoted the apoptosis of T24/5637 cells (promotion rate 243.8%/201.9%), reduced IC 50 of DDP-resistant T24/5637 cells from 132.2/101.8 to 57.81/59.71 µM, respectively, and inactivated the p62/Keap1/Nrf2 pathway in T24/5637 cells. p62 up-regulation partially abrogated the inhibition of NEDD4L on the Keap1/Nrf2 pathway activity, the malignant behavior of BLCA cells, and the DDP resistance of DDP-resistant BLCA cells. NEDD4L overexpression inhibited the tumor growth and the p62/Keap1/Nrf2 pathway activity in vivo in BLCA. CONCLUSION: NEDD4L inhibits the progression of BLCA by inactivating the p62/Keap1/Nrf2 pathway. It may be an effective target for BLCA treatment.


Assuntos
Cisplatino , Neoplasias da Bexiga Urinária , Animais , Camundongos , Humanos , Cisplatino/farmacologia , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Camundongos Nus , Transdução de Sinais , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Apoptose , Linhagem Celular Tumoral
16.
Foodborne Pathog Dis ; 20(9): 398-404, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37486675

RESUMO

Cherry tomatoes are highly well-liked and have a lot of nutritional value. However, the edible value of cherry tomatoes rapidly declines as their storage duration is extended. Pleurotus citrinopileatus polysaccharide (PCP) is a kind of polysaccharide obtained from P. citrinopileatus by water extraction. The effects of PCP were investigated to identify a way to maximally postpone cherry tomato degradation. The results showed that PCP had inhibitory effects on all 10 tested strains, and the inhibitory effect on Pseudomonas aeruginosa was the strongest. PCP could effectively reduce the weight loss rate and malondialdehyde accumulation of cherry tomatoes during storage, weaken the activity of polyphenol oxidase, and delay the decline of hardness, titratable acid content, and VC content compared with untreated cherry tomatoes. PCP solution at a concentration of 2 g/L exerted the best preservation effects. Therefore, PCP can potentially contribute to the preservation of vegetables and fruits.


Assuntos
Pleurotus , Solanum lycopersicum , Polissacarídeos/farmacologia
17.
FASEB J ; 35(2): e21226, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33236397

RESUMO

The Wiskott-Aldrich syndrome (WAS) is a severe recessive X-linked immunodeficiency resulting from loss-of-function mutations in the WAS gene. Mouse is the only mammalian model used for investigation of WAS pathogenesis. However, the mouse model does not accurately recapitulate WAS clinical phenotypes, thus, limiting its application in WAS clinical research. Herein, we report the generation of WAS knockout (KO) rabbits via embryo co-injection of Cas9 mRNA and a pair of sgRNAs targeting exons 2 and 7. WAS KO rabbits exhibited many symptoms similar to those of WAS patients, including thrombocytopenia, bleeding tendency, infections, and reduced numbers of T cell in the spleen and peripheral blood. The WAS KO rabbit model provides a new valuable tool for preclinical trials of WAS treatment.


Assuntos
Modelos Animais de Doenças , Coelhos , Proteína da Síndrome de Wiskott-Aldrich/genética , Síndrome de Wiskott-Aldrich/genética , Animais , Sistemas CRISPR-Cas , Técnicas de Inativação de Genes/métodos , Fenótipo , Síndrome de Wiskott-Aldrich/patologia
18.
Cereb Cortex ; 31(7): 3363-3373, 2021 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-33690839

RESUMO

Identifying dynamic changes in biomarkers and clinical profiles is essential for understanding the progression of Alzheimer's disease (AD). The relevant studies have primarily relied on patients with autosomal dominant AD; however, relevant studies in sporadic AD are poorly understood. Here, we analyzed longitudinal data from 665 participants (mean follow-up 4.90 ± 2.83 years). By aligning normal cognition (CN) baseline with a clinical diagnosis of mild cognitive impairment (MCI) or AD, we studied the progression of AD using a linear mixed model to estimate the clinical and biomarker changes from stable CN to MCI to AD. The results showed that the trajectory of hippocampal volume and fluorodeoxyglucose (FDG) was consistent with the clinical measures in that they did not follow a hypothetical sigmoid curve but rather showed a slow change in the initial stage and accelerated changes in the later stage from MCI conversion to AD. Dramatic hippocampal atrophy and the ADAS13 increase were, respectively, 2.5 and 1 years earlier than the MCI onset. Besides, cognitively normal people with elevated and normal amyloid showed no significant differences in clinical measures, hippocampal volume, or FDG. These results reveal that pre-MCI to pre-AD may be a better time window for future clinical trial design.


Assuntos
Doença de Alzheimer/fisiopatologia , Encéfalo/diagnóstico por imagem , Disfunção Cognitiva/fisiopatologia , Hipocampo/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico por imagem , Peptídeos beta-Amiloides/metabolismo , Compostos de Anilina , Biomarcadores , Encéfalo/metabolismo , Encéfalo/patologia , Disfunção Cognitiva/diagnóstico por imagem , Progressão da Doença , Etilenoglicóis , Feminino , Fluordesoxiglucose F18 , Hipocampo/patologia , Humanos , Modelos Lineares , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Tamanho do Órgão , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos
19.
Build Environ ; 214: 108932, 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35221454

RESUMO

Wearing masks to study and work places has become a daily protective measure during the COVID-19 pandemic. In the summer of 2021, environmental parameters were monitored, and students in a university library in Guangzhou, China, were surveyed to analyze the possible symptoms of wearing masks for a long time, and to assess the sensitivity of various body parts to the environmental parameters. Concurrently, the preference of subjects wearing masks for various environmental parameters was also analyzed. Additionally, the relationship between thermal sensation and thermal index was analyzed to identify acceptable and comfortable temperature ranges. The expected duration of wearing masks was counted. Subjects wearing masks had greater requirements for environmental comfort, and reported increased thermal discomfort of the face and head, compared to those without masks. More than 70% of the subjects wearing masks reported that they experienced discomfort on their faces. Among the subjects who experienced discomfort, 62.7% reported that facial fever was the main symptom; while some reported symptoms of dyspnea (25.4%) and rapid heartbeat (9.1%). More than 75% of the subjects were expected to wear masks for 2.0 h or less. Evaluation of environmental thermal sensation, including overall, facial, and head thermal sensation, differed among subjects who wore and did not wear masks. The indexes of neutral Operative temperature/Standard Effective Temperature (T op /SET*) and preferred T op /SET* were lower among subjects with masks than among those without masks. The neutral T op /SET* deviation was 0.3 °C, and the preferred T op /SET* deviation was 0.5 °C. Additionally, the acceptable and comfortable temperature zones differed between the two cases. The subjects who wore masks preferred colder temperatures. These findings indicated that the environmental parameters should be adjusted to improve the thermal comfort of the human body while wearing masks in work or study places.

20.
Zhongguo Zhong Yao Za Zhi ; 47(5): 1184-1189, 2022 Mar.
Artigo em Zh | MEDLINE | ID: mdl-35343143

RESUMO

Since the pathogenesis of depression is complicated, the therapeutic effects of western medicine are poor accompanied by severe side effects. Chinese medicine has unique advantages in the treatment based on syndrome differentiation and contains many effective components against depression, including flavonoids, terpenes, phenylpropanoids, quinones, and alkaloids. These chemical components can delay the course of the disease, improve the curative effect, and reduce side effects of western medicine by regulating the biochemical abnormalities of monoamine neurotransmitters, brain tissue protein content, and internal environment as well as energy metabolism to make the treatment of Chinese medicine highlighted and recognized. This study systematically reviewed the effective components and mechanisms of anti-depressive Chinese medicine to inspire the rational development and utilization of new Chinese medicines against depression.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Medicamentos de Ervas Chinesas , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Medicina Tradicional Chinesa , Síndrome
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