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1.
Asian J Androl ; 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35439874

RESUMO

Body mass index (BMI) has been increasing globally in recent decades. Previous studies reported that BMI was associated with sex hormone levels, but the results were generated via linear regression or logistic regression, which would lose part of information. Quantile regression analysis can maximize the use of variable information. Our study compared the associations among different regression models. The participants were recruited from the Center of Reproductive Medicine, The First Hospital of Jilin University (Changchun, China) between June 2018 and June 2019. We used linear, logistic, and quantile regression models to calculate the associations between sex hormone levels and BMI. In total, 448 men were included in this study. The average BMI was 25.7 (standard deviation [s.d.]: 3.7) kg m-2; 29.7% (n = 133) of the participants were normal weight, 45.3% (n = 203) of the participants were overweight, and 23.4% (n = 105) of the participants were obese. The levels of testosterone and estradiol significantly differed among BMI groups (all P < 0.05). In linear regression and logistic regression, BMI was associated with testosterone and estradiol levels (both P < 0.05). In quantile regression, BMI was negatively associated with testosterone levels in all quantiles after adjustment for age (all P < 0.05). BMI was positively associated with estradiol levels in most quantiles (≤80th) after adjustment for age (all P < 0.05). Our study suggested that BMI was one of the influencing factors of testosterone and estradiol. Of note, the quantile regression showed that BMI was associated with estradiol only up to the 80th percentile of estradiol.

2.
J Neuroimmunol ; 367: 577858, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35487122

RESUMO

Myelin oligodendrocyte glycoprotein (MOG) antibody disease is a rare inflammatory disease of the central nervous system. There are a variety of clinical and imaging manifestations of MOG antibody disease (MOG-AD). At present, there is no report on related cases of MOG antibody positivity complicated with teratoma in China, and one case admitted to our hospital is reported. By reviewing relevant literature to increase the study of MOG-AD.

3.
Front Cardiovasc Med ; 9: 795903, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35282353

RESUMO

Objective: Cardiac arrhythmia remains a major public health problem worldwide. Combinations of traditional medicine (TM) and conventional medicine (CM) have been used for arrhythmia treatment, yet the effectiveness and safety of many TM preparations can be controversial. We analyzed the safety and effectiveness of Zhigancao decoction (ZGCD) combined with metoprolol for arrhythmia treatment. Methods: Systematic searches for randomized clinical trials (RCTs) were conducted in eight databases (January 2010-September 2020) without language restrictions. According to the Cochrane system evaluation method, the overall effectiveness and safety were evaluated by meta-analysis using Review Manager software (version 5.3), and publication bias was qualitatively analyzed using STATA 12.0. Results: A total of 39 RCTs were incorporated, including 4,260 patients with arrhythmia, with 2,133 patients in the experimental group (ZGCD + metoprolol, ZGCD + BB) and 2,127 patients in the control group (metoprolol only, BB). Meta-analysis revealed that compared with BB, ZGCD + BB could significantly increase the total efficacy (OR = 4.74, 95% CI: 3.78-5.94, P < 0.01) and lower the incidences of arrhythmia (MD = -3.39, 95% CI: -4.09 to -2.68, P < 0.01). Moreover, mean HR reductions were reported in patients receiving ZGCD + BB the ZGCD + BB group (MD = -8.48, 95% CI: -10.98 to -5.97, P < 0.01) and a decrease in TCM symptoms were reported also (MD = -2.92, 95% CI: -3.08 to -2.76, P < 0.01). The incidence of adverse events was lower in patients treated with ZGCD + BB (RR = 0.36, 95% CI: 0.26-0.51, P < 0.01). These results appeared consistent across common arrhythmias. Nevertheless, the majority of included studies were unable to be formally assessed for bias, and funnel-plot analysis implied a moderate risk of publication bias. Conclusion: ZGCD + BB appeared to demonstrate good efficacy and fewer adverse reactions compared to BB in the treatment of arrhythmia, and this may represent a useful complementary therapy. However, our findings must be cautiously evaluated because of the small sample size and low quality of the clinic trials cited in the review. Rigorous and large-scale RCTs are warranted in the future to confirm these results. Systematic Review Registration: https://inplasy.com/inplasy-2021-10-0045/.

4.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 44(1): 118-122, 2022 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-35300773

RESUMO

BR55 is an ultrasound contrast agent targeting vascular endothelial growth factor receptor 2,which can be used to detect tumor neovascularization and improve the diagnostic accuracy.Overseas researchers have used BR55 for human ultrasound molecular imaging,which showed good safety and tolerance.We reviewed the research progress on BR55 applied in the evaluation of tumor neovascularization from the composition,characteristics,animal experiments,and clinical studies of BR55.


Assuntos
Meios de Contraste , Imagem Molecular , Neovascularização Patológica , Receptor 2 de Fatores de Crescimento do Endotélio Vascular , Animais , Humanos , Microbolhas , Imagem Molecular/métodos , Neovascularização Patológica/diagnóstico por imagem , Ultrassonografia/métodos , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/análise
5.
Chemosphere ; 295: 133935, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35149011

RESUMO

The co-existence of volatile chlorinated hydrocarbons (VCHs) and nitrate pollution in groundwater is prominent, but how nitrate exposure affects weak-electrical stimulated bio-dechlorination activity of VCH is largely unknown. Here, by establishing weak-electrical stimulated trichloroethylene (TCE) dechlorination systems, the influence on TCE dechlorination by exposure to the different concentrations (25-100 mg L-1) of nitrate was investigated. The existence of nitrate in general decreased TCE dechlorination efficiency to varying degrees, and the higher nitrate concentration, the stronger the inhibitory effects, verified by the gradually decreased transcription levels of tceA. Although the TCE dechlorination kinetic rate constant decreased by 36% the most, under all nitrate concentration ranges, TCE could be completely removed within 32 h and no difference in generated metabolites was found, revealing the well-maintained dechlorination activity. This was due to the quickly enriched bio-denitrification activity, which removed nitrate completely within 9 h, and thus relieved the inhibition on TCE dechlorination. The obvious bacterial community structure succession was also observed, from dominating with dechlorination genera (e.g., Acetobacterium, Eubacterium) to dominating with both dechlorination and denitrification genera (e.g., Acidovorax and Brachymonas). The study proposed the great potential for the in situ simultaneous denitrification and dehalogenation in groundwater contaminated with both nitrate and VCHs.


Assuntos
Água Subterrânea , Hidrocarbonetos Clorados , Tricloroetileno , Biodegradação Ambiental , Estimulação Elétrica , Água Subterrânea/química , Nitratos , Tricloroetileno/química
6.
Taiwan J Obstet Gynecol ; 61(1): 163-169, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35181032

RESUMO

OBJECTIVE: We report a prenatal case of male fetus with a 2q13 deletion and an Xq27.3q28 duplication, presenting nasal bone dysplasia by ultrasound examination. And we compare the similarities of clinical features of cases consisting of similar 2q deletion and Xq duplication. CASE REPORT: A 30-year-old woman was referred for prenatal diagnosis and genetic counseling at 24 weeks of gestation. Prenatal ultrasound showed nasal bone dysplasia of the fetus. Amniocentesis revealed the karyotype of the fetus as 46, XY and the results of chromosomal microarray analysis was arr[GRCh37] 2q13(110467258-111370025)x1, arr[GRCh37]Xq27.3q28(144050780-149748782)x2. The parents both have normal karyotypes. The couple chose to continue the pregnancy and finally delivered a male infant at 39 weeks of gestation. His weight was 2850 g and length was 50 cm. Physical examination of the newborn revealed no apparent anomalies. Until the boy was one year old, there was no abnormalities in his growth and development. The long-term follow-up till adulthood for the healthy infant is necessary. CONCLUSION: The development of CMA plays a critical role in prenatal diagnosis and genetic counseling for unidentified chromosomal anomalies. More clinical information and further studies of patients with these anomalies will identify the pathogenicity of the involving genes and improve the understanding of the phenotype-genotype correlation.


Assuntos
Amniocentese , Doenças do Desenvolvimento Ósseo/diagnóstico por imagem , Deleção Cromossômica , Duplicação Cromossômica , Diagnóstico Pré-Natal/métodos , Adulto , Hibridização Genômica Comparativa , Análise Citogenética , Feminino , Humanos , Lactente , Cariótipo , Cariotipagem , Masculino , Gravidez , Ultrassonografia Pré-Natal
7.
Adv Healthc Mater ; 11(1): e2101698, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34549554

RESUMO

Bacterial infections have become major threats to public health all over the world. With the emergence of antibiotic resistance, it is urgent to develop novel antimicrobial materials to efficiently overcome drug resistance with high bactericidal activity. In this work, UiO-66-NH-CO-MoS2 nanocomposites (UNMS NCs) are constructed through the amidation reaction. The UNMS NCs are positively charged which is beneficial for capturing and restricting bacteria. Significantly, UNMS NCs possess a synergistic bactericidal efficiency based on near-infrared irradiation (808 nm) regulated combination of photothermal, photodynamic, and peroxidase-like enzymatic activities. Both the photodynamic property and nanozymatic activity of UNMS NCs can lead to the generation of reactive oxygen species. The UNMS NCs show high catalytic activity in a wide pH range and exhibit excellent antibacterial ability against ampicillin-resistant Escherichia coli and methicillin-resistant Staphylococcus aureus with negligible cytotoxicity. Interestingly, due to the 808 nm irradiation-induced hyperthermia in the presence of UNMS NCs, the glutathione oxidation process can be accelerated, resulting in bacterial death more easily. Mice wound models are established to further manifest that UNMS NCs can promote wound healing with good biosafety in living systems.


Assuntos
Antibacterianos , Infecções Bacterianas , Farmacorresistência Bacteriana , Estruturas Metalorgânicas , Staphylococcus aureus Resistente à Meticilina , Animais , Antibacterianos/farmacologia , Infecções Bacterianas/tratamento farmacológico , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Camundongos , Molibdênio , Peroxidase , Peroxidases , Ácidos Ftálicos
8.
Biomater Sci ; 10(2): 499-513, 2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-34904598

RESUMO

Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial joint hyperplasia, joint inflammation, cartilage erosion and bone destruction. Macrophages play an essential role in the pathogenesis of RA, and folate receptor ß (FR-ß) is highly expressed on the surface of activated synovial macrophages in RA patients. Triptolide (TP) has anti-inflammatory properties, and it can protect the cartilage matrix, but its clinical application has been limited due to poor solubility, low bioavailability and systemic toxicity. Therefore, we constructed folate-modified triptolide liposomes (FA-TP-Lips) to target macrophages, thereby treating RA in a safe and effective way. The experiments indicated that FA-TP-Lips had properties of small particle size, uniform particle size distribution, high drug encapsulation and long circulation. Furthermore, FA-TP-Lips showed reduced cytotoxicity, increased cellular uptake and significant anti-inflammatory effects in vitro. It also inhibited osteoclastogenesis. In vivo experiments revealed that liposomes could prolong the circulation of TP in the body, as well as exhibit significant cartilage-protective and anti-inflammatory effects with lower toxicity compared with the free TP group, thereby providing a promising new approach for the treatment of RA.


Assuntos
Artrite Reumatoide , Lipossomos , Artrite Reumatoide/tratamento farmacológico , Diterpenos , Compostos de Epóxi , Ácido Fólico , Humanos , Macrófagos , Fenantrenos
9.
Bioresour Technol ; 344(Pt A): 126117, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34653631

RESUMO

Fucoxanthin (Fx) has gained a growing attention due to the remarkable biological activities. The limited biomass of was the restrictive factor for Fx production in Phaeodactylum tricornutum. In this study, Laminaria japonica hydrolysate (LPH) with a low addition proportion of 1.5 ml/L, was proved to promote fucoxanthin accumulation and cell growth simultaneously. Fx topped at 27.9 mg/L after 10-d cultivation in the LPH group, with a biomass of 1.59 g/L and a Fx content of 17.55 mg/g. Three key plant hormones in LPH were screened responsible for promoting fucoxanthin accumulation. Transcriptomic analysis and qRT-PCR results showed that genes related to Fx formation were generally up- regulated. The study demonstrated that LPH addition was a feasible and efficient strategy to enhance production of fucoxanthin, facilitating the scale-up production of Fx in autotrophic culture.


Assuntos
Diatomáceas , Laminaria , Biomassa , Diatomáceas/genética , Xantofilas
10.
Onco Targets Ther ; 14: 5197-5204, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34744437

RESUMO

EP300-ZNF384-positive B cell acute lymphoblastic leukemia (B-ALL) patients are reported to have a unique immunophenotype with high expression of CD19 and CD22, weak expression of CD20 and aberrant expression of CD13 and/or CD33, sensitivity to chemotherapy and a favorable outcome. To date, the cases of only 53 patients have been reported, albeit few reports on salvage therapy when conventional chemotherapies failed. Here, we describe two relapsed and refractory adult B-ALL patients with EP300-ZNF384 who achieved second remission through tandem CD19/CD22 CAR T-cell therapy. Grade 3 and 2 cytokine release syndrome were observed in cases 1 and 2, respectively. No immune effector cell-associated neurotoxicity syndrome was detected. Both patients underwent consolidate haploidentical hematopoietic stem cell transplantation (HSCT), and each maintained measurable residual disease-negative remission for 14 and 13 months, respectively. Our study suggests that CD19/CD22 CAR T-cell therapy bridging to allogeneic HSCT may be a viable option for EP300-ZNF384-positive B-ALL.

11.
Biotechnol Biofuels ; 14(1): 181, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34526122

RESUMO

BACKGROUND: Raw materials composed of easily assimilated monosaccharides have been employed as carbon source for production of microbial lipids. Nevertheless, agro-industrial wastes rich in galactose-based carbohydrates have not been introduced as feedstocks for oleaginous yeasts. RESULTS: In this study, Aureobasidium namibiae A12 was found to efficiently accumulate lipid from soy molasses and whey powder containing galactose-based carbohydrates, with lipid productions of 5.30 g/L and 5.23 g/L, respectively. Over 80% of the fatty acids was C16:0, C18:0, C18:1, and C18:2. All kinds of single sugar components in the two byproducts were readily converted into lipids, with yields ranging between 0.116 g/g and 0.138 g/g. Three α-galactosidases and five ß-galactosidases in the strain were cloned and analyzed. Changes of transcriptional levels indicated GalB and GalC were key α-galactosidases, and GalG was key ß-galactosidase. In 10 L fermentor, lipid production from SM and WP achieved 6.45 g/L and 6.13 g/L, respectively. ß-galactosidase was responsible for lactose hydrolysis; sucrase and α-galactosidase both contributed to the efficient hydrolysis of raffinose and stachyose in a cooperation manner. CONCLUSIONS: This is a new way to produce lipids from raw materials containing galactose-based carbohydrates. This finding revealed the significance of sucrase in the direct hydrolysis of galactose-based carbohydrates in raw materials for the first time and facilitated the understanding of the efficient utilization of galactose-based carbohydrates to manufacture lipid or other chemicals in bioprocess.

12.
Food Chem Toxicol ; 156: 112516, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34411643

RESUMO

Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by dementia. Inhibition of soluble epoxide hydrolase (sEH) regulates inflammation involving in central nervous system (CNS) diseases. However, the exactly mechanism of sEH in AD is still unclear. In this study, we evaluated the vital role of sEH in amyloid beta (Aß)-induced AD mice, and revealed a possible molecular mechanism for inhibition of sEH in the treatment of AD. The results showed that the sEH expression and activity were remarkably increased in the hippocampus of Aß-induced AD mice. Chemical inhibition of sEH by TPPU, a selective sEH inhibitor, alleviated spatial learning and memory deficits, and elevated levels of neurotransmitters in Aß-induced AD mice. Furthermore, inhibition of sEH could ameliorate neuroinflammation, neuronal death, and oxidative stress via stabilizing the in vivo level of epoxyeicosatrienoic acids (EETs), especially 8,9-EET and 14,15-EET, further resulting in the anti-AD effect through the regulation of GSK3ß-mediated NF-κB, p53, and Nrf2 signaling pathways. These findings revealed the underlying mechanism of sEH as a potential therapeutic target in treatment of AD.


Assuntos
Doença de Alzheimer/induzido quimicamente , Peptídeos beta-Amiloides/toxicidade , Eicosanoides/metabolismo , Epóxido Hidrolases/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Compostos de Fenilureia/farmacologia , Piperidinas/farmacologia , Animais , Epóxido Hidrolases/genética , Regulação da Expressão Gênica , Glicogênio Sintase Quinase 3 beta/genética , Transtornos da Memória , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais , Aprendizagem Espacial/efeitos dos fármacos
13.
Mol Cell Endocrinol ; 536: 111414, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34314740

RESUMO

Bone morphogenetic protein 6 (BMP6) and connective tissue growth factor (CTGF) are critical growth factors required for normal follicular development and luteal function. Cluster of Differentiation 68 (CD68) is an intraovarian marker of macrophages that plays an important role in modulating the physiological regression of the corpus luteum. The aim of this study was to investigate the effect of BMP6 on the expression of CTGF and the subsequent increase in CD68 expression as well as its underlying mechanisms. Primary and immortalized (SVOG) human granulosa cells obtained from infertile women undergoing in vitro fertilization treatment were used as cell models to conduct the in vitro experiments. Our results showed that BMP6 treatment significantly increased the expression levels of CTGF and CD68. Using BMP type I receptor inhibitors (dorsomorphin, DMH-1 and SB431542), we demonstrated that both activin receptor-like kinase (ALK)2 and ALK3 are involved in BMP6-induced stimulatory effects on the expression of CTGF and CD68. Additionally, SMAD4-knock down reversed the BMP6-induced up-regulation of CTGF and CD68, indicating that the canonical SMAD signaling pathway is required for these effects. Moreover, CTGF-knock down abolished the BMP6-induced up-regulation of CD68 expression. These findings indicate that intrafollicular CTGF mediates BMP6-induced increases in CD68 expression through the ALK2/ALK3-mediated SMAD-dependent signaling pathway.


Assuntos
Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Proteína Morfogenética Óssea 6/metabolismo , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Células da Granulosa/citologia , Células Lúteas/citologia , Linhagem Celular , Feminino , Fertilização In Vitro , Técnicas de Silenciamento de Genes , Células da Granulosa/metabolismo , Humanos , Infertilidade Feminina/metabolismo , Células Lúteas/metabolismo , Cultura Primária de Células , Transdução de Sinais , Proteína Smad4/genética , Regulação para Cima
14.
Nature ; 595(7868): 521-525, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34290425

RESUMO

Whereas ferromagnets have been known and used for millennia, antiferromagnets were only discovered in the 1930s1. At large scale, because of the absence of global magnetization, antiferromagnets may seem to behave like any non-magnetic material. At the microscopic level, however, the opposite alignment of spins forms a rich internal structure. In topological antiferromagnets, this internal structure leads to the possibility that the property known as the Berry phase can acquire distinct spatial textures2,3. Here we study this possibility in an antiferromagnetic axion insulator-even-layered, two-dimensional MnBi2Te4-in which spatial degrees of freedom correspond to different layers. We observe a type of Hall effect-the layer Hall effect-in which electrons from the top and bottom layers spontaneously deflect in opposite directions. Specifically, under zero electric field, even-layered MnBi2Te4 shows no anomalous Hall effect. However, applying an electric field leads to the emergence of a large, layer-polarized anomalous Hall effect of about 0.5e2/h (where e is the electron charge and h is Planck's constant). This layer Hall effect uncovers an unusual layer-locked Berry curvature, which serves to characterize the axion insulator state. Moreover, we find that the layer-locked Berry curvature can be manipulated by the axion field formed from the dot product of the electric and magnetic field vectors. Our results offer new pathways to detect and manipulate the internal spatial structure of fully compensated topological antiferromagnets4-9. The layer-locked Berry curvature represents a first step towards spatial engineering of the Berry phase through effects such as layer-specific moiré potential.

15.
Exp Ther Med ; 22(1): 684, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33986849

RESUMO

The complement system plays a vital role in myocardial ischemia/reperfusion (I/R) injury. microRNA (miR)-499 is involved in the cardioprotection of ischemic postconditioning (IPostC). The present study aimed to study the role of the complement system and miR-499 in IPostC. Rat hearts were subjected to coronary ligation for 30 min, followed by reperfusion for 2 h. IPostC was introduced at the onset of reperfusion with three cycles of reperfusion for 30 sec and coronary artery occlusion for 30 sec. To study the role of miR-499 in IPostC, adeno-associated virus (AAV) vectors of miR-499-5p (AAV-miR-499-5p) and miR-499-5p-sponge (AAV-miR-499-5p-sponge) were transfected via tail vein injection, followed by IPostC protocols. Cardiac injury as well as the status of local and systemic complement activation and inflammation were assessed. IPostC significantly attenuated I/R-induced rat cardiomyocyte apoptosis and the myocardial infarct size. These beneficial effects were accompanied by decreased local and circulating complement component (C)3a and C5a levels, decreased inflammatory marker expression, decreased NF-κB signaling and increased cardiac miR-499 expression. AAV-miR-499-5p prevented local and systemic complement activation and inflammation as well as enhanced the cardioprotection of IPostC, whereas AAV-miR-499-5p-sponge produced the opposite effects. In summary, IPostC protected the rat myocardium against I/R injury, by inhibiting local and systemic complement activation; inflammation; NF-κB signaling; and upregulation of miR-499. As such, miR-499 may have a critical role in IPostC-mediated cardioprotection against I/R injury.

16.
J Clin Invest ; 131(12)2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-33945512

RESUMO

Down syndrome (DS), caused by trisomy of chromosome 21, occurs in 1 of every 800 live births. Early defects in cortical development likely account for the cognitive impairments in DS, although the underlying molecular mechanism remains elusive. Here, we performed histological assays and unbiased single-cell RNA-Seq (scRNA-Seq) analysis on cerebral organoids derived from 4 euploid cell lines and from induced pluripotent stem cells (iPSCs) from 3 individuals with trisomy 21 to explore cell-type-specific abnormalities associated with DS during early brain development. We found that neurogenesis was significantly affected, given the diminished proliferation and decreased expression of layer II and IV markers in cortical neurons in the subcortical regions; this may have been responsible for the reduced size of the organoids. Furthermore, suppression of the DSCAM/PAK1 pathway, which showed enhanced activity in DS, using CRISPR/Cas9, CRISPR interference (CRISPRi), or small-molecule inhibitor treatment reversed abnormal neurogenesis, thereby increasing the size of organoids derived from DS iPSCs. Our study demonstrates that 3D cortical organoids developed in vitro are a valuable model of DS and provide a direct link between dysregulation of the DSCAM/PAK1 pathway and developmental brain defects in DS.


Assuntos
Moléculas de Adesão Celular/metabolismo , Córtex Cerebral/metabolismo , Síndrome de Down/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Neurogênese , Organoides/metabolismo , Transdução de Sinais , Quinases Ativadas por p21/metabolismo , Moléculas de Adesão Celular/genética , Linhagem Celular , Síndrome de Down/genética , Humanos , Quinases Ativadas por p21/genética
17.
Int J Biol Macromol ; 183: 811-817, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-33957203

RESUMO

Inhibition of soluble epoxide hydrolase (sEH) is considered to be an effective treatment for inflammation-related diseases, and small molecules origin from natural products show promising activity against sEH. Two undescribed protostanes, 3ß-hydroxy-25-anhydro-alisol F (1) and 3ß-hydroxy-alisol G (2) were isolated from Alisma orientale and identified as new sEH inhibitors with IC50 values of 10.06 and 30.45 µM, respectively. Potential lead compound 1 was determined as an uncompetitive inhibitor against sEH, which had a Ki value of 5.13 µM. In-depth molecular docking and molecular dynamics simulations revealed that amino acid residue Ser374 plays an important role in the inhibition of 1, which also provides an idea for the development of sEH inhibitors based on protostane-type triterpenoids.


Assuntos
Alisma/química , Inibidores Enzimáticos/farmacologia , Epóxido Hidrolases/antagonistas & inibidores , Triterpenos/farmacologia , Inibidores Enzimáticos/química , Epóxido Hidrolases/química , Concentração Inibidora 50 , Modelos Moleculares , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Estrutura Molecular , Farmacocinética , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Conformação Proteica , Triterpenos/química
18.
Zhongguo Zhong Yao Za Zhi ; 46(7): 1743-1751, 2021 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-33982478

RESUMO

Alzheimer's disease(AD) is a chronic progressive neurodegenerative disease with recent memory impairment as the main clinical manifestation and senile plaques and neurofibrillary tangles as the main pathological changes. In recent years, the effect of microRNAs on AD has attracted widespread attention. Patients with AD have abnormal expression of miRNA, which is closed related to regulation of AD pathophysiology-related genes. Therefore, this paper first elaborated neuroprotective and toxic effects of microRNA in AD, and then explored relevant traditional Chinese medicines that can regulate miRNA in the treatment of AD, so as to provide basis for revealing the pathogenesis relationship between miRNA and AD and provide ideas for further development of anti-AD traditional Chinese medicine.


Assuntos
Doença de Alzheimer , MicroRNAs , Doenças Neurodegenerativas , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Humanos , Medicina Tradicional Chinesa , MicroRNAs/genética
19.
Sheng Li Xue Bao ; 73(2): 208-216, 2021 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-33903882

RESUMO

The transcription factor X-box binding protein-1 (XBP1) plays a key role in unfolded protein reaction. This study was aimed to investigate the expression pattern and regulation of XBP1 in the mouse uterus during early pregnancy. The methods of immunohistochemistry (IHC) and real time quantitative RT-PCR were used to test XBP1 expression in early pregnancy, artificial decidualization, oestrous cycle and hormone-regulated mouse models. The results showed that XBP1 was spatiotemporally expressed in mouse uterus during early pregnancy. The XBP1 protein was mainly detected in the luminal and glandular epithelia on days 1-4 of pregnancy, and was strongly detected in the decidual area on days 5-8 of pregnancy. Similarly, XBP1 expression was also mainly expressed in decidual cells following artificial decidualization. During the oestrous cycle, Xbp1, Xbp1u, and Xbp1s mRNA was predominantly present in proestrus. In the ovariectomized uterus, the expression of XBP1 in luminal and glandular epithelia was up-regulated after estrogen treatment. These results suggest that XBP1 is associated with embryo implantation and decidualization during early pregnancy in mice, and the expression of XBP1 in luminal and glandular epithelia may be regulated by estrogen.


Assuntos
Decídua , Implantação do Embrião , Animais , Estrogênios , Feminino , Camundongos , Gravidez , RNA Mensageiro/genética , Útero
20.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(3): 300-305, 2021 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-33691926

RESUMO

OBJECTIVE: To study the effect of different melatonin treatment regimens on long-term behavior and white matter damage in neonatal rats with hypoxic-ischemic brain damage (HIBD), and to seek an optimal melatonin treatment regimen. METHODS: Healthy Sprague-Dawley rats, aged 7 days, were randomly divided into four groups: sham-operation, HIBD, single-dose immediate treatment (SDIT), and 7-day continuous treatment (7DCT), with 8 rats in each group. A neonatal rat model of HIBD was prepared according to the classical Rice-Vannucci method. On day 21 after HIBD, the Morris water maze test was used to evaluate spatial learning and memory abilities. On day 70 after HIBD, immunofluorescence assay was used to measure the expression of neuronal nuclear antigen (NeuN) in the cerebral cortex and the hippocampal CA1 region of neonatal rats, and double-label immunofluorescence was used to measure the expression of myelin basic protein (MBP) and neurofilament 200 (NF200) in the corpus striatum and the corpus callosum. RESULTS: The results of the Morris water maze test showed that the SDIT and 7DCT groups had a significantly shorter mean escape latency than the HIBD group, and the 7DCT group had a significantly shorter mean escape latency than the SDIT group (P < 0.05). The results of immunofluorescence assay for NeuN showed that the SDIT and 7DCT groups had a significantly higher number of NeuN+ cells in the cerebral cortex and the hippocampal CA1 region than the HIBD group, and the 7DCT group had a significantly higher number than the SDIT group (P < 0.05). MBP/NF200 double-label immunofluorescence showed that compared with the HIBD group, the SDIT group and the 7DCT group had significantly higher fluorescence intensities of MBP and NF200 in the corpus striatum, and the 7DCT group had significantly higher fluorescence intensities than the SDIT group (P < 0.05); the 7DCT group had significantly higher fluorescence intensities of MBP and NF200 in the corpus callosum than the SDIT and HIBD groups (P < 0.05). CONCLUSIONS: Both SDIT and 7DCT can improve long-term behavior and reduce white matter damage in neonatal rats with HIBD, and 7DCT is more effective than SDIT.


Assuntos
Hipóxia-Isquemia Encefálica , Melatonina , Substância Branca , Animais , Animais Recém-Nascidos , Hipóxia-Isquemia Encefálica/tratamento farmacológico , Melatonina/farmacologia , Ratos , Ratos Sprague-Dawley
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