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There has been a huge interest in studying human brain connectomes inferred from different imaging modalities and exploring their relationships with human traits, such as cognition. Brain connectomes are usually represented as networks, with nodes corresponding to different regions of interest (ROIs) and edges to connection strengths between ROIs. Due to the high-dimensionality and non-Euclidean nature of networks, it is challenging to depict their population distribution and relate them to human traits. Current approaches focus on summarizing the network using either pre-specified topological features or principal components analysis (PCA). In this paper, building on recent advances in deep learning, we develop a nonlinear latent factor model to characterize the population distribution of brain graphs and infer their relationships to human traits. We refer to our method as Graph AuTo-Encoding (GATE). We applied GATE to two large-scale brain imaging datasets, the Adolescent Brain Cognitive Development (ABCD) study and the Human Connectome Project (HCP) for adults, to study the structural brain connectome and its relationship with cognition. Numerical results demonstrate huge advantages of GATE over competitors in terms of prediction accuracy, statistical inference, and computing efficiency. We found that the structural connectome has a stronger association with a wide range of human cognitive traits than was apparent using previous approaches.
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Encéfalo/crescimento & desenvolvimento , Encéfalo/fisiologia , Cognição/fisiologia , Conectoma/métodos , Imageamento por Ressonância Magnética , Adolescente , Algoritmos , Criança , Simulação por Computador , Conjuntos de Dados como Assunto , Feminino , Humanos , Imageamento Tridimensional , Masculino , Modelos Neurológicos , Dinâmica não Linear , Fenótipo , Leitura , Adulto JovemRESUMO
It is increasingly recognized that the cellular microenvironment plays critical roles in regulating the fate and physiology of cells. Despite recent advancements in single-cell analysis technologies, engineering and integration of the microenvironment for single-cell analysis platforms remain limited. Here, we report a single-cell cytokine secretion analysis platform that integrated both the three-dimensional cell culture and the primary oral squamous cell carcinoma tumor cell co-culture to provide both physical and physiological cues for single cells to be analyzed. We apply the platform to investigate the immune responses of human macrophages stimulated with the ligand of toll-like receptor 4 lipopolysaccharide. Notably, we observe the differential modulation effect in cytokine secretions by the tumor microenvironment, in which antitumor cytokine TNF-a secretion was attenuated, and protumor cytokine IL-6 would increase. The differential modulation effect is conserved from cell line-derived macrophages to primary macrophages derived from healthy donors. Immunofluorescence staining further reveals that â¼50% of macrophage cells could be polarized from M1 to the M2 phenotype within 12 h in the engineered tumor microenvironment. This work demonstrates the significance of the cell microenvironment toward single-cell analysis, which could help to evaluate how immune cells will respond in the complex microenvironment more accurately.
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Carcinoma de Células Escamosas , Neoplasias Bucais , Humanos , Imunidade , Macrófagos , Análise de Célula Única , Microambiente TumoralRESUMO
OBJECTIVE: Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disease in reproductive women, and the endocrine levels are also affected by diseases. The aim of this study was to determine the effect of thrombospondin-1 (TSP-1) on PCOS rat model. METHODS: We established the PCOS rat model, the serum hormones including TSP-1 expression were determined and morphological characteristics were investigated to evaluate the model. These above endocrine and morphological features were investigated again to evaluate the effect of TSP-1 treatment. RESULTS: In the PCOS model group, the serum hormones change (higher luteinizing hormone, testosterone and estrogen) and decreased TSP-1 expression levels were found compared with the control group. Besides, the morphological characteristics of PCOS were also observed in the model group. After TSP-1 treatment, the higher TSP-1, ANGPT2, PDGFB and PDGFD expression levels, the lower LH and T levels, decreased vessel density as well as VEGFA and ANGPT1 expression levels were found compared with the control group, and the ovary morphological changes were also observed in the TSP-1 experimental group. CONCLUSIONS: TSP-1 delivery system might be an alternative therapy for PCOS treatment.
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Síndrome do Ovário Policístico/tratamento farmacológico , Trombospondina 1/uso terapêutico , Proteínas Angiogênicas/metabolismo , Animais , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Feminino , Ovário/efeitos dos fármacos , Síndrome do Ovário Policístico/metabolismo , Ratos Sprague-Dawley , Trombospondina 1/metabolismo , Trombospondina 1/farmacologiaRESUMO
Multiplexed single-cell protein secretion analysis provides an in-depth understanding of cellular heterogeneity in intercellular communications mediated by secreted proteins in both fundamental and clinical research. However, it has been challenging to increase the proteomic parameters co-profiled from every single cell in a facile way. Herein, a simple method to improve the multiplexed proteomic parameters of PDMS microwell based single-cell secretion analysis platform by sandwiching PDMS stencil in between two antibody-coated glass slides is introduced. Two different antibody panels can be immobilized easily by static coating, without using sophisticated fluid handling or bulky equipment. 5-plexed, 3-fluorescence color single-cell secretion assay is demonstrated with this platform to investigate human monocytic U937 cells in response to lipopolysaccharide and phorbol myristate acetate stimulation, which identified the existence of functional subsets dictated by different cytokine profiles. The technology introduced here is simple, easy to operate, which holds great potential to become a powerful tool for profiling multiplexed single-cell cytokine secretion at high throughput to dissect cellular heterogeneity in secretome signatures.
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Proteômica , Análise de Célula Única , Comunicação Celular , Humanos , Lipopolissacarídeos , Células U937RESUMO
Carotenoids are known to be involved in the regulation of the antioxidative capability, immune response and stress resistance in crustacean species; however, very limited information is available on their underlying molecular mechanisms. This study performed transcriptome sequencing of hemolymph and hepatopancreas of juvenile Chinese mitten crabs (Eriocheir sinensis) that fed with three diets, i.e. diet A containing 90 mg kg-1 dry weight of astaxanthin, diet B containing 200 mg kg-1 dry weight of ß-carotene and control diet without supplementation of dietary carotenoids. The results showed that there were 2955 and 497 differentially expressed genes (DEGs) in the hemolymph between the astaxanthin treatment and control groups, and between the ß-carotene treatment and control groups, respectively. Moreover, compared with the control group, 833 and 1886 DEGs were obtained in the hepatopancreas of the astaxanthin treatment and the ß-carotene treatment groups, respectively. The DEGs in the three groups were enriched in 255 specific KEGG metabolic pathways according to KEGG enrichment analysis. Through this study, a series of key genes involved in Nrf2 signalling, ROS production, intracellular antioxidant enzymes and chaperones were significantly affected by dietary carotenoids. Dietary carotenoids also significantly altered the expression levels of immune-related molecules associated with signal transduction, prophenoloxidase cascade, apoptosis, pattern recognition proteins/receptors and antimicrobial peptides. In conclusion, this transcriptomic study provides valuable information for understanding the molecular mechanism and potential pathway of dietary carotenoids improved the antioxidative capability and immunity of juvenile E. sinensis.
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Braquiúros/genética , Dieta/veterinária , Hemolinfa/efeitos dos fármacos , Hepatopâncreas/efeitos dos fármacos , beta Caroteno/administração & dosagem , Animais , Braquiúros/imunologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Hemolinfa/metabolismo , Hepatopâncreas/metabolismo , Xantofilas/administração & dosagemRESUMO
OBJECTIVE: The extensive breeding of commercial chickens has led to a sharp decrease in the resources of many indigenous chickens, especially the indigenous chickens in the southeastern coastal region, which are on the verge of extinction, and the indigenous chickens in the northwestern region of China, which are also at risk. However, there are few reports on the evaluation of genetic diversity and conservation of genetic resources of indigenous chickens in remote areas in the Northwest of China. METHODS: In the present study, the genetic diversity and phylogenetic relationship of six indigenous chickens from different regions were studied based on variation in mitochondrial DNA control region (D-loop), and the degree of introgression from commercial breeds into these chickens was determined by the amount of haplotype sharing between indigenous and commercial breeds. RESULTS: Twenty-five polymorphic sites and 25 haplotypes were detected in 206 individuals. Principal component analysis showed that the Jingning chicken had the highest genetic diversity among the six indigenous chickens. According to the degree of introgression, the six indigenous breeds may be involved in haplotype sharing with commercial breeds, and the introgression from commercial chickens into the Haidong chicken is the most serious. CONCLUSION: The genetic uniqueness of indigenous chickens has been eroded, so it is necessary to consider the protection of their genetic resources. Phylogenetic analysis suggests that the six indigenous chickens have two major matrilineal origins: one from Yunnan or its surrounding areas in China and the other from the Indian subcontinent.
RESUMO
Binary spinel-type metal oxides (AB2O4) related materials, including ferrites (AFe2O4), are attractive photocatalysts thanks to their excellent visible light response for the photodegradation of organic pollutants. Currently, these materials are synthesized via conventional chemical routes suffering from long preparation duration and multistep. Moreover, the photocatalysts are obtained as nano-powders from conventional chemical routes would introduce another drawback for their recycling and reuse. From an industrial perspective, it is desirable to develop an efficient and facile synthesis process to produce photocatalysts in a non-dispersible form. Herein, we demonstrate that the solution precursor plasma spray (SPPS) process is a single-step method for depositing photocatalytically active zinc ferrite-based films within several minutes. The influence of the precursor ratio on the microstructures and phase compositions of the ZnFe2O4 films was investigated by XRD and Raman analyses. In addition, two optimized ZnFe2O4 films were prepared by increasing the ZnO loading and tailoring injection pattern of the precursor solution. The surface morphologies and optical bandgap were also determined by SEM and UV-visible spectroscopy. The photocatalytic activities of the ZnFe2O4 films were evaluated through the degradation of the Orange II dye and of tetracycline hydrochloride under UV or visible light irradiation. The results show that compositional ratios and composition distribution of the ZnFe2O4 films prepared via SPPS played a key role on the photocatalytic activity. The SPPS route was demonstrated to be a promising method for the synthesis and the deposition of metal oxide (i.e. perovskite type and spinel type) films within a single-step for functional applications.
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Estradiol is an important sex steroid hormone that involved in regulation of animal lipid metabolism. However, the effect of estradiol on lipid metabolism in swimming crab (Portunus trituberculatus) is unclear. The present study investigated the effect of four concentrations of exogenous estradiol (0, 0.01, 0.1 and 1⯵gâ¯g-1 crab weight) on the expression levels of lipid metabolism-related genes, lipid composition and histology of hepatopancreas in the P. trituberculatus. The results showed that the mRNA levels of carnitine palmitoyltransferase I and II (CPT-I and CPT-II) increased significantly at the low concentrations (0.01⯵gâ¯g-1 and 0.1⯵gâ¯g-1), while decreased significantly in the highest concentration (1⯵gâ¯g-1). The mRNA levels of acyl-CoA oxidase (ACOX), fatty acid transport protein (FATP), fatty acid-binding protein (FABP), diacylglycerol acyltransferase 1 (DGAT1) and acetyl-CoA carboxylase (ACC) were significantly down-regulated. The transcripts of fatty acid synthase (FAS) and fatty acyl desaturase (FAD) decreased significantly only in 1⯵gâ¯g-1 treatment. All estradiol treatments (0.01, 0.1 and 1⯵gâ¯g-1) had significantly higher percentages of 20:4n6, 20:5n3 and 22:6n3, but lower percentages of total monounsaturated fatty acids and polar lipids than the control treatment (0⯵gâ¯g-1). Histological observations indicated the size of B cell became larger under estradiol treatment. The results indicated that estradiol promoted lipid catabolism in the hepatopancreas of P. trituberculatus.
Assuntos
Braquiúros/metabolismo , Estradiol/farmacologia , Hepatopâncreas/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Natação , Animais , Peso Corporal/efeitos dos fármacos , Braquiúros/efeitos dos fármacos , Braquiúros/genética , Ácidos Graxos/metabolismo , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Hepatopâncreas/citologia , Hepatopâncreas/efeitos dos fármacos , Metabolismo dos Lipídeos/genética , Oxirredução , RNA Mensageiro/genéticaRESUMO
Relative humidity (RH) at the body-seat interface is considered an important factor in both sitting comfort and generation of health concerns such as skin lesions. Technical difficulties appear to have limited research aimed at the detailed and simultaneous exploration of RH and temperature changes at the body-seat interface; using RH sensors without the capability to record temperature where RH is recorded. To explore the causes of a spike in RH consistently produced on first contact between body and seat surface, we report data from the first use of dual temperature and RH (HTU21D) sensors in this interface. Following evaluation of sensor performance, the effect of local thermal changes on RH was investigated. The expected strong negative correlation between temperature and RH (R² = -0.94) supported the importance of considering both parameters when studying impact of sitting on skin health. The influence of sensor movement speed (higher velocity approach: 0.32 cm/s ± 0.01 cm/s; lower velocity approach: 0.17 cm/s ± 0.01 cm/s) into a static RH region associated with a higher local temperature were compared with data gathered by altering the rate of a person sitting. In all cases, the faster sitting down (or equivalent) generated larger RH outcomes: e.g., in human sitting 53.7% ± 3.3% RH (left mid-thigh), 56.4% ± 5.1% RH (right mid-thigh) and 53.2% ± 2.7% RH (Coccyx). Differences in size of RH change were seen across the measurement locations used to study the body-seat interface. The initial sitting contact induces a transient RH response (duration ≤ 40 s) that does not accurately reflect the microenvironment at the body-seat interface. It is likely that any movement during sitting would result in similar artefact formation. As a result, caution should be taken when investigating RH performance at any enclosed interface when the surfaces may have different temperatures and movement may occur.
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Umidade , Cóccix , Humanos , Masculino , Movimento , Temperatura , Adulto JovemRESUMO
Despite rapid progresses in single-cell analysis technologies, efforts to control the three-dimensional microenvironment for single cell measurements have been lacking. Here, we report a simple method to incorporate three-dimensional scaffolds, including polyvinylidene fluoride (PVDF) membranes and PVDF membrane replicated analog polydimethylsiloxane, into multiplexed single cell secretomic analysis platforms (including a microwell array and a single cell barcode microchip) to mimic the extracellular physical matrix and mechanical support for single cells. Applying this platform to brain tumor cell line U87 to investigate single cell protein secretion behavior on different substrates, we revealed that single cell protein secretions were regulated differently in three-dimensional (3D) microenvironments. This finding was further verified with intracellular cytokine staining, highlighting the significance of 3D single cell microenvironments. This new single cell biomimetic platform can be easily adaptable to other three-dimensional cell culture scaffolds or other single cell assays and may become a broadly applicable three-dimensional single cell analysis system to study the effect of microenvironment conditions on cellular functional heterogeneity in vitro.
Assuntos
Papel , Polivinil/química , Impressão Tridimensional , Análise de Célula Única , Microambiente Celular , Humanos , Células Tumorais CultivadasRESUMO
17beta-estradiol (E2) is important for crustacean ovarian development. This study aims to investigate the distribution and change pattern of E2 in the ovary, hepatopancreas, thoracic ganglion and brain ganglion as well as Vg-mRNA expression level during ovarian development of Chinese mitten crab Eriocheir sinensis. Results showed that strongly positive signals of E2 were mainly distributed in follicle cells of ovaries for all developmental stages as well as oocyte cytoplasm of stages III to V ovaries. In hepatopancreas, the E2-positive signal was mainly detected in the cytoplasm and nucleus of fibrillar cells and the nucleus of resorptive cells, while the maximum fluorescence intensity was observed in stage III hepatopancreas. On the contrary, the E2 immunoreactivities in nervous tissues were relatively stable during ovarian development. Moreover, the changing pattern of E2 concentration was similar within hemolymph, ovary and hepatopancreas during the ovarian development. From stages I to III, the E2 content in three tissues increased significantly, then decreased gradually until stage V. As for the Vg-mRNA expression level in hepatopancreas and ovaries, an increasing trend was found in ovaries but no significant difference was detected during the period of ovarian stages III to V. Hepatopancreatic Vg-mRNA expression level increased significantly during stages I to IV and dramatically decreased at stage V. In conclusion, our study suggests that ovary, hepatopancreas, hemolymph and nervous tissues are the target organs of E2 in E. sinensis and E2 concentrations in different tissues are closely related to vitellogenesis in ovary and hepatopancreas during ovarian development.
Assuntos
Braquiúros/fisiologia , Estradiol/metabolismo , Ovário/metabolismo , Vitelogênese/fisiologia , Animais , DNA Complementar/genética , DNA Complementar/metabolismo , Estradiol/análogos & derivados , Feminino , Gânglios dos Invertebrados/metabolismo , Hemolinfa/metabolismo , Hepatopâncreas/metabolismo , Oócitos/metabolismo , Folículo Ovariano/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
The published online version contains mistake in Title and in Acknowledgement section. Please find below for the needed corrections.
RESUMO
BACKGROUND The aim of this study was to compare the effects of liraglutide, a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist, and insulin glargine, a long-acting insulin analog, on glycemic control and pancreatic ß-cell function in db/db mice. MATERIAL AND METHODS Eight-week-old male db/db mice (n=40) were divided into five groups: the vehicle-treated group (VG) (n=8); the insulin glargine-treated group (GG) (dose, 450 mg/kg) (n=8), the low-dose liraglutide-treated group (LLG) (dose, 75 µg/kg) (n=8), the mid-dose liraglutide-treated group (MLG) (150 µg/kg) (n=8), and the high-dose liraglutide-treated group (HLG) (300 µg/kg) (n=8), treated with subcutaneous injection once daily, from 8-14 weeks-of-age. Body weight, pancreatic weight, levels of blood glucose, triacylglycerol, C-peptide, and the intraperitoneal glucose tolerance test (IPGTT) were used. Expression levels of the INS1 gene were measured using reverse transcription polymerase chain reaction (RT-PCR), and pancreatic and duodenal homeobox 1 (Pdx1), paired box 4 (Pax4), and paired box 6 (Pax6) mRNA expression were measured. RESULTS Both insulin glargine and liraglutide improved glycemic control of db/db mice when compared with vehicle. The following were significantly increased in the HLG compared with the GG: the receiver operating characteristic (ROC) area under the curve (AUC) for the IPGTT; C-peptide levels; the pancreas to body weight coefficient; expression levels of the INS1 gene and pancreatic transcription factors Pdx1, Pax4 and Pax6. Liraglutide treatment was without hypoglycemic effects. CONCLUSIONS Liraglutide acted in a dose-dependent manner on glycemic control of db/db mice, and was more effective than insulin glargine, when administered at a high dose.
Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/patologia , Hipoglicemiantes/farmacologia , Insulina Glargina/uso terapêutico , Células Secretoras de Insulina/metabolismo , Liraglutida/uso terapêutico , Animais , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Peptídeo C/sangue , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/genética , Relação Dose-Resposta a Droga , Teste de Tolerância a Glucose , Insulina Glargina/farmacologia , Células Secretoras de Insulina/efeitos dos fármacos , Liraglutida/farmacologia , Masculino , Camundongos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Triglicerídeos/sangue , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genéticaRESUMO
Piperlongumine (PL) is a very promising natural agent with a high potential for cancer treatment. To overcome the poor water solubility of PL, there is a need to develop a novel water-soluble formulation in which PL is non-covalently bound to human serum albumin (HSA). PL binding to HSA was studied by various spectroscopic techniques under simulated physiological conditions. Spectroscopic evidence showed that the interaction of PL with HSA could form a PL-HSA complex. The binding constant (Ka ) values increased with increasing temperature, and a similar dependence was observed for the number of binding sites (n) values. The number of PL molecules bound to HSA reached 8.1 when the temperature was raised to 308 K. Thermodynamic calculation results suggested that the binding reaction occurred spontaneously but was an entropy-driven process, and hydrophobic forces played a major role in stabilizing the complex. Furthermore, PL binding induced conformational and microenvironmental changes in HSA. Displacement studies indicated that PL and warfarin had separate binding regions in site I. Therefore, it would be possible to develop a novel water-soluble formulation involving PL and HSA. This study may provide some valuable information in terms of improving the poor water solubility of PL.
Assuntos
Antineoplásicos/química , Dioxolanos/química , Albumina Sérica Humana/química , Alcaloides/química , Dicroísmo Circular , Sistemas de Liberação de Medicamentos , Humanos , Cinética , Ligação Proteica , TermodinâmicaRESUMO
BACKGROUND The aim of this study was to investigate the effects of sleep duration and bedtime on sperm health, and the possible mechanism involved. MATERIAL AND METHODS We randomly divided 981 healthy Chinese men into groups according to research-set bedtimes (A=8-10 PM, B=after 10 PM, and C=after midnight) and sleep durations: group 1=<6.0 h (short), group 2=7.0-8.0 h (average), and group 3=>9.0 h (long). Sperm morphology, count, survival, and motility were examined according to sleep patterns. Antisperm antibody (ASA) production in semen was determined. RESULTS Sperm counts and their survival rates were lower in the short sleepers as compared to others within each group (all P<0.01). The lower counts and survival rates were observed in different bedtimes, with significant differences found between measurements of C1 vs. A1 and C2 vs. A2 or B2 (all P<0.05 or 0.01). Semen motility was lower in the short sleepers as compared to the average and long sleepers (all P<0.01). There were differences in the bedtime-related results between measurements of C1 vs. A1 or B1 (P<0.05 or 0.01). Additionally, the population proportion for the ASA-positive participates and incidence of the ASA-expressed population obviously increased in the short sleepers as compared to others within each group (all P<0.05). CONCLUSIONS Short and long sleep durations and late bedtime were associated with impaired sperm health in the study cohort, partly through increasing ASA production in the semen.
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Sêmen/fisiologia , Privação do Sono/imunologia , Espermatozoides/imunologia , Adulto , Idoso , Formação de Anticorpos , Estudos de Casos e Controles , China , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sêmen/imunologia , Sono/imunologia , Privação do Sono/patologia , Motilidade dos Espermatozoides , Espermatozoides/citologiaRESUMO
p38 MAPK (mitogen-activated protein kinase) is a critical regulator in lung inflammation. It can be inactivated by DUSP1 (dual-specificity phosphatase 1) which was identified as a putative target of miR-429. miR-429 mimics directly targeted to the 3'-UTR of the gene encoding DUSP1 may result in the translational attenuation of DUSP1. Moreover, the phosphorylation of p38 MAPK was prolonged after miR-429 mimic treatment. Additionally, miR-429 expression was sensitive to LPS (lipopolysaccharide) stimulation and the miR-429 mimics increased the production of pro-inflammatory cytokines. However, anti-miR-429 reduced the LPS-induced production of pro-inflammatory cytokines. These results provide direct evidence that miR-429 is involved in the LPS-induced inflammatory response. In parallel with miR-429, miR-200b and miR-200c, but not miR-200a or miR-141, shared similar effects. In vivo, LPS induced the expression of miR-429, miR-200b and miR-200c in lung. At the same time, inhibiting these miRNAs by anti-miRNAs attenuated the LPS-induced pulmonary inflammatory response and injury. These findings reveal that miR-429 possesses pro-inflammatory activities and may be a potential therapy target for LPS-induced lung injury.
Assuntos
Lesão Pulmonar Aguda/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Macrófagos Alveolares/metabolismo , MicroRNAs/biossíntese , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/patologia , Animais , Citocinas/biossíntese , Macrófagos Alveolares/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
OBJECTIVE: The objective of this study was to determine the levels of thrombospondin-1 (TSP-1), transforming growth factor-ß1 (TGF-ß1) and nuclear factor kappaß (NF-κß) in polycystic ovarian syndrome (PCOS) patients with and without insulin resistance and after treatment with cyproterone acetate/ethinyloestradiol with or without concomitant metformin. DESIGN: Prospective. PATIENTS: Patients with PCOS and healthy women were recruited. Patients were subdivided into obese and nonobese based on body mass index. Patients with PCOS were also grouped according to homoeostasis model assessment-insulin resistance (HOMA-IR) ≥ 2·69 or <2·69, and by PCOS phenotype. Patients with PCOS-IR were treated with a 6-month course of cyproterone acetate/ethinyloestradiol with or without concomitant metformin. MEASUREMENTS: Inflammatory markers were examined at baseline, and after 6 months of treatment. RESULTS: A total of 445 women with PCOS (mean age 25·9 ± 2·7 years; 298 obese, 147 nonobese) and 213 normal controls (mean age 24·9 ± 3·0 years) were included. Regardless of obesity status, testosterone, free androgen index (FAI), luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratio, HOMA-IR, TSP-1 and NF-κB in the PCOS groups were significantly higher than in the control group, whereas TSP-1 was lower in the PCOS groups (all, P < 0·05). Patients with PCOS without IR had lower TSP-1 levels than control patients (P < 0·05). Treatment with cyproterone acetate/ethinyloestradiol with addition of metformin reduced the level of NF-κB, TGF-ß1 and HOMA-IR and increased the level of TSP-1. CONCLUSIONS: These results support the association between PCOS and chronic inflammation.
Assuntos
Inflamação/sangue , NF-kappa B/sangue , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/imunologia , Trombospondina 1/sangue , Fator de Crescimento Transformador beta1/sangue , Adulto , Feminino , Humanos , Inflamação/imunologia , Estudos Prospectivos , Adulto JovemRESUMO
Lonicera japonica Thunb. (LJT) is known for its valuable medicinal properties that highlight its potential application in the pharmaceutical and health food industry. We predict that LJT polyphenols by network pharmacology may be involved in immunomodulation, and the study of LJT polyphenols regulating immunity is still insufficient; therefore, we experimentally found that LJT enhances immunity by promoting the proliferation and phagocytic activity of RAW246.7 cells. A model of an immunosuppressed mouse was constructed using cyclophosphamide-induced, and LJT was extracted for the intervention. We found that LJT restored immune homeostasis in immune deficiency mice by inhibiting the abnormal apoptosis in lymphocytes, enhancing natural killer cell cytotoxicity, promoting T lymphocyte proliferation, and increasing the CD4+ and CD8+ T lymphocytes in quantity. Moreover, LJT treatment modulates immunity by significantly downregulating lipopolysaccharide-induced inflammation and oxidative stress levels. We verified the immunomodulatory function of LJT through both cell and animal experiments. The combination of potential-protein interactions and molecular docking later revealed that LJT polyphenols were associated with immunomodulatory effects on MAPK1; together, LJT intervention significantly modulates the immune, with the activation of MAPK1 as the underlying mechanism of action, which provided evidence for the utilization of LJT as a nutraceutical in immune function.
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Imunomodulação , Lonicera , Farmacologia em Rede , Extratos Vegetais , Lonicera/química , Animais , Camundongos , Extratos Vegetais/farmacologia , Farmacologia em Rede/métodos , Imunomodulação/efeitos dos fármacos , Células RAW 264.7 , Simulação de Acoplamento Molecular , Polifenóis/farmacologia , Proliferação de Células/efeitos dos fármacos , Masculino , Apoptose/efeitos dos fármacos , Camundongos Endogâmicos BALB CRESUMO
Many theories of motivation suggest that motivation and academic achievement reinforce each other over time, yet few longitudinal studies have examined behavioral pathways that may mediate interplay from motivation to achievement. Moreover, empirical studies so far have mostly focused on Western countries. In this study, we first examined whether students' value of education, as a measure of motivation, is reciprocally related to achievement (class rank and self-rated performance) in a sample of junior high schoolers in an East-Asian country (N = 3445, Korean Youth Panel Study). We tested this reciprocity using different statistical models. Second, we investigated whether the relation between motivation and achievement was mediated by time invested in learning. Reciprocal effects between value of education and academic achievement were found in classic cross-lagged panel models, but only unilateral effects (from achievement to value of education) were found when we used random-intercept and random-curve cross-lagged panel models. Adding the time investment variable, the reciprocal effect between value of education, time investment, and academic achievement was found with the random intercept model. In conclusion, the reciprocity between of motivation and achievement are more elusive than previous research suggested; further studies should be dedicated to scrutinizing its existence with various statistical models.