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1.
Ann Neurol ; 2024 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-39096048

RESUMEN

OBJECTIVE: Glymphatic system is a recently discovered macroscopic waste clearance system associated with numerous neurological diseases. However, little is known about glymphatic system development in neonates. We sought to evaluate diffusion along the perivascular space (ALPS) index, a proxy for glymphatic system function, in neonates and investigate its potential associations with maturation, sex, and preterm birth. METHODS: Diffusion magnetic resonance imaging (MRI) data in 418 neonates, including 92 preterm neonates (57 males) and 326 term neonates (175 males), from the Developing Human Connectome Project were used for evaluating ALPS index. Linear regression modeling was performed to assess group differences in the ALPS index according to preterm birth and sex. Pearson's and partial correlation analysis were performed to assess the association between the ALPS index and gestational age (GA) as well as postmenstrual age (PMA) at MRI. Moderation analysis was performed to assess the moderation effect of preterm birth on the relationship between the ALPS index and PMA. RESULTS: Compared to term neonates, preterm neonates exhibited lower ALPS indices (p < 0.001). The ALPS index positively correlated with PMA (p = 0.004) and GA (p < 0.001). Preterm birth (p = 0.013) had a significant moderation effect on the relationship between the ALPS index and PMA. Sex had no significant direct effect (p = 0.639) or moderation effect (p = 0.333) on ALPS index. INTERPRETATION: Glymphatic system development is a dynamic process in neonates, which can be moderated by preterm birth, the ALPS index could serve as a sensitive biomarker for monitoring this process. ANN NEUROL 2024.

2.
Cereb Cortex ; 34(9)2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39285718

RESUMEN

Individuals engage in upward or downward comparisons with superiors or inferiors, respectively. Social comparison is associated with social anxiety. Utilizing event-related potentials, we investigated how individuals with high social anxiety (HSA) and low social anxiety (LSA) evaluate self- versus other-outcomes in upward and downward comparison contexts. We found significant valence effects of self- or other-outcomes on feedback-related negativity (FRN) and P300 for both groups, with loss inducing larger FRN and smaller P300 than gain. In the early stage, the valence effect of other-outcomes was significant when LSA participants gained money, but not when they lost money, revealing a social comparison effect on FRN. Conversely, this valence effect was significant whether HSA participants gained or lost money. At the late stage, the valence effect of other-outcomes was significant when HSA or LSA participants gained money but not when they lost, revealing social comparison effects on the P300. Notably, only the social comparison effect in the LSA group was further moderated by comparison direction. These findings suggest that LSA participants engaged in social comparison throughout all evaluation stages, whereas HSA participants started at the late stage. Moreover, LSA participants were more sensitive to different comparison directions in the late stage.


Asunto(s)
Ansiedad , Electroencefalografía , Potenciales Evocados , Humanos , Masculino , Femenino , Adulto Joven , Potenciales Evocados/fisiología , Ansiedad/fisiopatología , Ansiedad/psicología , Adulto , Comparación Social , Adolescente , Encéfalo/fisiología
3.
Neuroimage ; 290: 120565, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38453102

RESUMEN

People tend to perceive the same information differently depending on whether it is expressed in an individual or a group frame. It has also been found that the individual (vs. group) frame of expression tends to lead to more charitable giving and greater tolerance of wealth inequality. However, little is known about whether the same resource allocation in social interactions elicits distinct responses depending on proposer type. Using the second-party punishment task, this study examined whether the same allocation from different proposers (individual vs. group) leads to differences in recipient behavior and the neural mechanisms. Behavioral results showed that reaction times were longer in the unfair (vs. fair) condition, and this difference was more pronounced when the proposer was the individual (vs. group). Neural results showed that proposer type (individual vs. group) influenced early automatic processing (indicated by AN1, P2, and central alpha band), middle processing (indicated by MFN and right frontal theta band), and late elaborative processing (indicated by P3 and parietal alpha band) of fairness in resource allocation. These results revealed more attentional resources were captured by the group proposer in the early stage of fairness processing, and more cognitive resources were consumed by processing group-proposed unfair allocations in the late stage, possibly because group proposers are less identifiable than individual proposers. The findings provide behavioral and neural evidence for the effects of "individual/group" framing leading to cognitive differences. They also deliver insights into social governance issues, such as punishing individual and/or group violations.


Asunto(s)
Electroencefalografía , Juegos Experimentales , Humanos , Potenciales Evocados/fisiología , Interacción Social , Castigo/psicología
4.
Clin Proteomics ; 21(1): 50, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39004717

RESUMEN

BACKGROUND: Estrogen receptor-positive (ER+) breast cancer accounts for two-thirds of all breast cancers, and its early and late recurrences still threaten patients' long-term survival and quality of life. Finding candidate tumor antigens and potential therapeutic targets is critical to addressing these unmet needs. METHOD: The isobaric tags for relative and absolute quantitation (iTRAQ) proteomic analysis was employed to identify the differentially expressed proteins (DEPs) between ER + breast cancer and corresponding adjacent normal tissue. Candidate DEPs were screened by bioinformatic analyses, and their expression was confirmed by immunohistochemical (IHC) staining and western blot. A series of in vitro experiments, including wound healing assay, colony formation, and cell cycle assay, were performed to reveal the functions of selected DEPs. Additionally, their clinical significances were further analyzed. RESULT: A total of 369 DEPs (fold change ≥ 2.0 or ≤ 0.66, P < 0.05) were discovered. Compared with normal tissue, 358 proteins were up-regulated and 11 proteins were down-regulated in ER + breast cancer. GO and KEGG enrichment analysis showed that DEPs were closely associated with RNA regulation and metabolic pathways. STRING analysis found ESF1 and MIPEP were the hub genes in breast cancer, whose increased expressions were verified by the IHC staining and western blot. Knocking down ESF1 and MIPEP inhibited colony formation and increased cell apoptosis. Besides, knocking down ESF1 inhibited wound healing but not MIPEP. In addition, ESF1 and MIPEP expression were negatively associated with patient prognosis. CONCLUSION: The upregulation of ESF1 and MIPEP promoted ER + breast cancer proliferation, which might provide novel targets for the development of new therapies.

5.
Aesthetic Plast Surg ; 48(15): 2879-2886, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38806829

RESUMEN

BACKGROUND: Fat grafting is widely used in breast reconstruction and aesthetic plastic surgery. However, the success rate and effects of fat grafting, especially in elderly female donors, are observed. This study aimed to explore the difference in the survival rate of donor fat from elderly women and young women in fat grafting. METHODS: We collected adipose tissue samples from two healthy Chinese women: a young woman and an elderly woman. In addition, adipose tissue samples were collected from female nude mice in four experimental groups-CON-Y, CON-O, OVX-Y, and OVX-O-after fat transplantation. Grafts were harvested, weighed, and subjected to assessment of histology and angiogenesis. RESULTS: An ovariectomy model was successfully established to validate the effect of low estrogen levels on fat grafting results. Due to the influence of low estrogen levels, the graft survival rate of donor site fat was significantly higher in elderly women than in young women, accompanied by a lesser degree of angiogenesis. Low estrogen levels led to adipocyte hypertrophy, which may be related to decreased AQP-7 expression. CONCLUSIONS: AQP-7 downregulation due to low estrogen levels induces adipocyte hypertrophy, and donor fat from elderly women exhibits a higher survival rate after fat transplantation. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Asunto(s)
Tejido Adiposo , Estrógenos , Supervivencia de Injerto , Humanos , Femenino , Tejido Adiposo/trasplante , Animales , Factores de Edad , Ratones , Anciano , Ratones Desnudos , Adulto , Mamoplastia/métodos , Ovariectomía , Persona de Mediana Edad
6.
Int J Med Sci ; 20(6): 810-817, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37213666

RESUMEN

Interferon gamma (IFNγ) is a cytokine implicated in the pathogenesis of autoimmune diseases. SAM and HD domain-containing protein 1 (SAMHD1) is an IFNγ-inducible protein that modulates cellular dNTP levels. Mutations in the human SAMHD1 gene cause Aicardi-Goutières (AG) syndrome, an autoimmune disease sharing similar clinical features with systemic lupus erythematosus (SLE). Klotho is an anti-inflammatory protein which suppresses aging through multiple mechanisms. Implication of Klotho in autoimmune response is identified in rheumatologic diseases such as SLE. Little information exists regarding the effect of Klotho in lupus nephritis, one of the prevalent symptoms of SLE. The present study verified the effect of IFNγ on SAMHD1 and Klotho expression in MES-13 glomerular mesangial cells, a special cell type in glomerulus that is critically involved in lupus nephritis. IFNγ upregulated SAMHD1 expression in MES-13 cells through the Janus kinase-signal transducer and activator of transcription 1 (JAK-STAT1) and the nuclear factor kappa B (NFκB) signaling pathways. IFNγ decreased Klotho protein expression in MES-13 cells. Treatment of MES-13 cells with recombinant Klotho protein inhibited SAMHD1 expression by blocking IFNγ-induced NFκB nuclear translocation, but showed no effect on JAK-STAT1 signaling. Collectively, our findings support the protective role of Klotho in attenuating lupus nephritis through the inhibition of IFNγ-induced SAMHD1 expression and IFNγ downstream signaling in MES-13 cells.


Asunto(s)
Nefritis Lúpica , FN-kappa B , Humanos , Células Cultivadas , Interferón gamma/metabolismo , Nefritis Lúpica/genética , Células Mesangiales/metabolismo , FN-kappa B/genética , FN-kappa B/metabolismo , Proteína 1 que Contiene Dominios SAM y HD/genética , Proteína 1 que Contiene Dominios SAM y HD/metabolismo , Proteína 1 que Contiene Dominios SAM y HD/farmacología , Receptor de Interferón gamma
7.
Neural Plast ; 2021: 9938566, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34367273

RESUMEN

Background: Parkinson's disease (PD) is a common neurological degenerative disease that cannot be completely cured, although drugs can improve or alleviate its symptoms. Optogenetic technology, which stimulates or inhibits neurons with excellent spatial and temporal resolution, provides a new idea and approach for the precise treatment of Parkinson's disease. However, the neural mechanism of photogenetic regulation remains unclear. Objective: In this paper, we want to study the nonlinear features of EEG signals in the striatum and globus pallidus through optogenetic stimulation of the substantia nigra compact part. Methods: Rotenone was injected stereotactically into the substantia nigra compact area and ventral tegmental area of SD rats to construct rotenone-treated rats. Then, for the optogenetic manipulation, we injected adeno-associated virus expressing channelrhodopsin to stimulate the globus pallidus and the striatum with a 1 mW blue light and collected LFP signals before, during, and after light stimulation. Finally, the collected LFP signals were analyzed by using nonlinear dynamic algorithms. Results: After observing the behavior and brain morphology, 16 models were finally determined to be successful. LFP results showed that approximate entropy and fractal dimension of rats in the control group were significantly greater than those in the experimental group after light treatment (p < 0.05). The LFP nonlinear features in the globus pallidus and striatum of rotenone-treated rats showed significant statistical differences before and after light stimulation (p < 0.05). Conclusion: Optogenetic technology can regulate the characteristic value of LFP signals in rotenone-treated rats to a certain extent. Approximate entropy and fractal dimension algorithm can be used as an effective index to study LFP changes in rotenone-treated rats.


Asunto(s)
Ganglios Basales/efectos de los fármacos , Potenciales de la Membrana/efectos de los fármacos , Neuronas/efectos de los fármacos , Optogenética/métodos , Rotenona/farmacología , Animales , Masculino , Ratas , Ratas Sprague-Dawley , Desacopladores/farmacología
8.
Biol Proced Online ; 22: 5, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32140080

RESUMEN

BACKGROUND: The toxicity and side effects caused by adjuvant chemotherapy (ACT) after radical surgery for lung adenocarcinoma (LAC) lead to early termination frequently. This study was conducted to provide an objective basis for the effect of Chinese herbal medicine formulas (CHMFs) combined with chemotherapy in reducing toxicity and enhancing efficacy of ACT. METHOD: From February 17th, 2012 to March 20th, 2015, 233 patients from 7 hospitals diagnosed with LAC in IB~IIIA stage were randomly assigned into ACT + CHMF group (116 patients) and ACT + placebo group (117 patients). CHMF was taken orally until the end of chemotherapy. Chemotherapy-related toxic, side effects were investigated as the primary outcome. Disease-free survival (DFS) and overall survival (OS) were used as the secondary outcome. RESULTS: At one week following chemotherapy, the incidence of dry mouth, diarrhea and thrombocytopenia significantly decreased in CHMF group (P = 0.017, P = 0.033, P = 0.019, respectively). At two weeks following chemotherapy, fatigue and diarrhea were more obvious in the placebo group (P = 0.028, P = 0.025, respectively). In addition, patients in the CHMF group showed an increase in median DFS from 37.1 to 51.5 months compared with placebo group although there was no statistical significance (P = 0.16). In the stage IB subgroup, the CHMF group had a significantly better DFS (HR (95% CI) = 0.53 (0.28-0.99), P = 0.046). There was no significant difference in OS between the groups (P = 0.72). CONCLUSION: For patients with LAC, ACT combined with CHMF after radical surgery can prolong the DFS time especially in the early stage, and reduces the chemotherapy-related toxic and side effects. TRIAL REGISTRATION: NCT01441752. Registered 14 July, 2011.

9.
Nat Mater ; 18(12): 1321-1326, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31591530

RESUMEN

Alternative technologies are required in order to meet a worldwide demand for clean non-polluting energy sources. Thermoelectric generators, which generate electricity from heat in a compact and reliable manner, are potential devices for waste heat recovery. However, thermoelectric performance, as encapsulated by the figure of merit ZT, has remained at around 1.0 at room temperature, which has limited practical applications. Here, we study the effects of pressure on ZT in Cr-doped PbSe, which has a maximum ZT of less than 1.0 at a temperature of about 700 K. By applying external pressure using a diamond anvil cell, we obtained a room-temperature ZT value of about 1.7. From thermoelectric, magnetoresistance and Raman measurements, as well as density functional theory calculations, a pressure-driven topological phase transition is found to enable this enhancement. Experiments also support the appearance of a topological crystalline insulator after the transition. These findings point to the possibility of using compression to increase not just ZT in existing thermoelectric materials, but also the possibility of realizing topological crystalline insulators.

10.
J Org Chem ; 85(5): 3954-3962, 2020 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-31994398

RESUMEN

A strategy for the synthesis of cis-hydrocarbazole with a C3 quaternary carbon center has been developed through nickel/Lewis acid dual-catalyzed arylcyanation. A wide array of cis-hydrocarbazoles was accessed with high diastereoselectivities and atom economies in a good yield. The rich chemistry of the installed nitrile group was demonstrated in the preparation of tryptamine- and tryptophol-derived cis-hydrocarbazoles.

11.
Angew Chem Int Ed Engl ; 59(10): 3966-3970, 2020 03 02.
Artículo en Inglés | MEDLINE | ID: mdl-31898399

RESUMEN

The first total synthesis of the Euphorbia diterpenoid pepluanol B in both racemic and enantioenriched form involves 20 steps from a known bicyclic diol. This synthesis features an unprecedented bromo-epoxidation to control the eight-membered-ring conformation. In addition, salient reactions for the construction of the tetracyclic backbone include a sterically challenging aldol reaction to establish the quaternary center, a ring closing metathesis (RCM) to forge the eight-membered ring, and a diastereoselective cyclopropanation to assemble the embedded cyclopropane motif.


Asunto(s)
Compuestos Bicíclicos con Puentes/química , Ciclopropanos/química , Diterpenos/síntesis química , Ciclización , Diterpenos/química , Conformación Molecular , Estereoisomerismo
13.
Bioorg Med Chem ; 27(21): 115092, 2019 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-31521460

RESUMEN

Phenylpyrazole insecticides are successful for crop protection and public hygiene by blocking gamma-aminobutyric acid (GABA)-gated chloride channels and glutamate-gated chloride (GluCl) channels. A series of novel phenylpyrazoles containing arylimine or 1-methoxyaryl groups were designed and synthesized. The addition reaction of methanol to the imines 1-11 was investigated and the cayno addition products 13-15 were obtained. The compounds 1-15 were confirmed by 1H NMR and elemental analysis. The results of bioassay indicated that some compounds exhibited comparable bioactivity to fipronil against a broad spectrum of insects such as bean aphid (Aphis craccivora), mosquito (Culex pipiens pallens), diamondback moth (Plutella xylostella) and Oriental armyworm (Mythimna separata). Especially, the foliar contact activity against bean aphid of compound 7 at 10 µg mL-1 was 68%, the larvacidal activity against mosquito of compounds 5, 13 and 15 at 0.0025 µg mL-1 was 100%, the larvacidal activity against diamondback moth of compounds 9 and 11 at 0.05 µg mL-1 was 100%, the larvacidal activity against Oriental armyworm of compound 9 at 1 µg mL-1 was 100%. The 3-cayno moiety on pyrazole ring was essential for the high insecticidal activities against bean aphid, diamondback moth and Oriental armyworm, while the 3-carbimidate moiety on pyrazole ring was crucial to the excellent high insecticidal activities against mosquito.


Asunto(s)
Iminas/toxicidad , Insecticidas/toxicidad , Pirazoles/toxicidad , Animales , Diseño de Fármacos , Iminas/síntesis química , Insectos/efectos de los fármacos , Insecticidas/síntesis química , Larva/efectos de los fármacos , Estructura Molecular , Pirazoles/síntesis química , Relación Estructura-Actividad
14.
Molecules ; 23(7)2018 06 24.
Artículo en Inglés | MEDLINE | ID: mdl-29937519

RESUMEN

Natural products are an important source of pesticide discovery. A series of N-amino-maleimide derivatives containing hydrazone group were designed and synthesized based on the structure of linderone and methyllinderone which were isolated from Lindera erythrocarpa Makino. According to the bioassay results, compounds 2 and 3 showed 60% inhibition against mosquito (Culex pipiens pallens) at 0.25 µg·mL−1. Furthermore, the results of antifungal tests indicated that most compounds exhibited much better antifungal activities against fourteen phytopathogenic fungi than linderone and methyllinderone and some compounds exhibited better antifungal activities than commercial fungicides (carbendazim and chlorothalonil) at 50 µg·mL−1. In particular, compound 12 exhibited broad-spectrum fungicidal activity (>50% inhibitory activities against 11 phytopathogenic fungi) and compounds 12 and 14 displayed 60.6% and 47.9% inhibitory activity against Rhizoctonia cerealis at 12.5 µg·mL−1 respectively. Furthermore, compound 17 was synthesized, which lacks N-substituent at maleimide and its poor antifungal activity against Sclerotinia sclerotiorum and Rhizoctonia cerealis at 50 µg·mL−1 showed that the backbone structure of N-amino-maleimide derivatives containing hydrazone group was important to the antifungal activity.


Asunto(s)
Productos Biológicos/química , Materiales Biomiméticos/síntesis química , Diseño de Fármacos , Lindera/química , Maleimidas/síntesis química , Plaguicidas/síntesis química , Alquenos/farmacología , Animales , Ascomicetos/efectos de los fármacos , Ascomicetos/crecimiento & desarrollo , Bencimidazoles/farmacología , Productos Biológicos/aislamiento & purificación , Productos Biológicos/farmacología , Materiales Biomiméticos/farmacología , Carbamatos/farmacología , Culex/efectos de los fármacos , Culex/fisiología , Ciclopentanos/farmacología , Descubrimiento de Drogas , Flavonoides/farmacología , Fungicidas Industriales/farmacología , Maleimidas/farmacología , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Nitrilos/farmacología , Plaguicidas/farmacología , Extractos Vegetales/química , Rhizoctonia/efectos de los fármacos , Rhizoctonia/crecimiento & desarrollo , Relación Estructura-Actividad
15.
Molecules ; 23(9)2018 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-30200298

RESUMEN

In order to find pesticides with insecticidal and antifungal activities, a series of novel benzoyl pyrimidinylurea derivatives were designed and synthesized. All target compounds were identified by ¹H-NMR spectroscopy and HRMS. Insecticidal and antifungal activity of these compounds were evaluated and the structure-activity relationships (SAR) were clearly and comprehensively illustrated. Compound 7, with low toxicity to zebrafish (LC50 = 378.387 µg mL-1) showed 100% inhibition against mosquito (Culex pipiens pallens) at 0.25 µg mL-1. Both compounds 19 and 25 exhibited broad-spectrum fungicidal activity (>50% inhibitory activities against 13 phytopathogenic fungi), which were better than those of the commercial pesticide pyrimethanil (>50% inhibitory activities against eight phytopathogenic fungi). Furthermore, compounds 19 and 25 exhibited protective activity against Sclerotinia sclerotiorum on leaves of Brassica oleracea L. during in vivo experiments.


Asunto(s)
Antifúngicos/química , Antifúngicos/farmacología , Diseño de Fármacos , Insecticidas/química , Insecticidas/farmacología , Plaguicidas/química , Plaguicidas/farmacología , Urea/farmacología , Animales , Antifúngicos/síntesis química , Bioensayo , Culex/efectos de los fármacos , Embrión no Mamífero/efectos de los fármacos , Hongos/efectos de los fármacos , Insecticidas/síntesis química , Larva/efectos de los fármacos , Plaguicidas/síntesis química , Sustancias Protectoras/farmacología , Pirimidinas/síntesis química , Pirimidinas/química , Pirimidinas/farmacología , Relación Estructura-Actividad , Pruebas de Toxicidad Aguda , Urea/síntesis química , Urea/química , Pez Cebra/embriología
16.
J Clin Lab Anal ; 30(5): 719-26, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27228385

RESUMEN

BACKGROUND: Because of the life-consuming treatment and severe consequences associated with thalassemia, it is more effective to prevent than cure thalassemia. Rapid and sensitive detection is critical for controlling thalassemia. In this study, we developed a rapid and accurate test to genotype nondeletional α- and ß-thalassemia mutations by an electrochemical DNA sensor. METHODS: Screen-printed electrodes were used as electrochemical transducers for the sensor, in which the capture probe DNA was attached to the golden surface of the working electrode via an S-Au covalent bond, which is highly suitable for immobilizing the biological element. In addition, two types of ferrocene with varying redox potentials for modified signal probe DNA were adopted. The hybridization signal is detected by alternating current voltammetry when the capture probe and signal probe hybridize with the target DNA. RESULTS: With this technique, 12 types of nondeletional α- and ß-thalassemia mutations were detected, which constitute more than 90% of all the nondeletional types of thalassemia mutation determinants found in China, including the CD142 (TAA>CAA) Constand spring, CD125 (CTG>CCG) Quonsze, CD122 (CAC>CAG) Weastmead, -28 (A>G), Cap+1 (A>C), initiation codon (ATG>AGG), CD17 (AAG>TAG), CD26 (GAG>AAG), CD31(-C), CD41-42 (-CTTT), CD71-72 (+A), and IVS-II-654 (C>T) mutations. Concordance levels were 100% within the 20 blood samples of homozygous wild-type individuals and 238 blood samples of heterozygous mutant individuals. CONCLUSIONS: The electrochemical DNA sensor developed here can be applied for rapid genotyping of thalassemia or other clinical genotyping applications and is useful for early screening of thalassemia in high-risk groups by minimizing the time and investment cost.


Asunto(s)
Técnicas Biosensibles/instrumentación , ADN/análisis , Electroquímica/instrumentación , Electroquímica/métodos , Talasemia alfa/diagnóstico , Talasemia beta/diagnóstico , China , Cartilla de ADN/metabolismo , Compuestos Ferrosos/química , Homocigoto , Humanos , Metalocenos , Sensibilidad y Especificidad
17.
Zhongguo Zhong Yao Za Zhi ; 40(22): 4482-90, 2015 Nov.
Artículo en Zh | MEDLINE | ID: mdl-27097428

RESUMEN

The study on the effective core formulae (CEF) not only summarized traditional chinese medicine (TCM) treatment experience, but also helped reveal the underlying knowledge in the formulation of TCM prescriptions. The aim of the present paper was to investigate the method of data mining for the discovery of core effective formulae for lung cancer. In the present study, a prescription fingerprint approach was used to characterize the staged prescription information of patients. The D index was used to screen potential beneficial herbs. Then, based on a herbal compatibility network, the maximal clique searching algorithm (BK algorithm) and survival analysis were applied to discover CEF for lung cancer, and a mining analysis was made for the 322 cases from Longhua hospital. The correlation between prescriptions and survival time was analyzed by prescription fingerprints. Forty-three potentially beneficial herbs were obtained, and two CEFs were significant for the survival time by a parametric survival model based on lognormal distribution, the results were verified by a multivariate survival model. The rules of combination of the two CEFs basically conform to TCM onco-therapeutic theory of strengthening the body resistance and the actual conditions in clinic. All results showed that the established approach was feasible for discovering the core effective formulae for lung cancer and mining survival data for complex TCM onco-therapy.


Asunto(s)
Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Algoritmos , Minería de Datos , Prescripciones de Medicamentos , Humanos , Neoplasias Pulmonares/mortalidad , Análisis de Supervivencia
18.
World J Diabetes ; 15(5): 958-976, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38766439

RESUMEN

BACKGROUND: Synaptotagmins (SYTs) are a family of 17 membrane transporters that function as calcium ion sensors during the release of Ca2+-dependent neurotransmitters and hormones. However, few studies have reported whether members of the SYT family play a role in glucose uptake in diabetic retinopathy (DR) through Ca2+/glucose transporter-1 (GLUT1) and the possible regulatory mechanism of SYTs. AIM: To elucidate the role of the SYT family in the regulation of glucose transport in retinal pigment epithelial cells and explore its potential as a therapeutic target for the clinical management of DR. METHODS: DR was induced by streptozotocin in C57BL/6J mice and by high glucose medium in human retinal pigment epithelial cells (ARPE-19). Bioinformatics analysis, reverse transcriptase-polymerase chain reaction, Western blot, flow cytometry, ELISA, HE staining, and TUNEL staining were used for analysis. RESULTS: Six differentially expressed proteins (SYT2, SYT3, SYT4, SYT7, SYT11, and SYT13) were found between the DR and control groups, and SYT4 was highly expressed. Hyperglycemia induces SYT4 overexpression, manipulates Ca2+ influx to induce GLUT1 fusion with the plasma membrane, promotes abnormal expression of the glucose transporter GLUT1 and excessive glucose uptake, induces ARPE-19 cell apoptosis, and promotes DR progression. Parkin deficiency inhibits the proteasomal degradation of SYT4 in DR, resulting in SYT4 accumulation and enhanced GLUT1 fusion with the plasma membrane, and these effects were blocked by oe-Parkin treatment. Moreover, dysregulation of the myelin transcription factor 1 (Myt1)-induced transcription of SYT4 in DR further activated the SYT4-mediated stimulus-secretion coupling process, and this process was inhibited in the oe-MYT1-treated group. CONCLUSION: Our study reveals the key role of SYT4 in regulating glucose transport in retinal pigment epithelial cells during the pathogenesis of DR and the underlying mechanism and suggests potential therapeutic targets for clinical DR.

19.
J Neurosci Methods ; 409: 110217, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38964477

RESUMEN

BACKGROUND: Parkinson's patients have significant autonomic dysfunction, early detect the disorder is a major challenge. To assess the autonomic function in the rat model of rotenone induced Parkinson's disease (PD), Blood pressure and ECG signal acquisition are very important. NEW METHOD: We used telemetry to record the electrocardiogram and blood pressure signals from awake rats, with linear and nonlinear analysis techniques calculate the heart rate variability (HRV) and blood pressure variability (BPV). we applied nonlinear analysis methods like sample entropy and detrended fluctuation analysis to analyze blood pressure signals. Particularly, this is the first attempt to apply nonlinear analysis to the blood pressure evaluate in rotenone induced PD model rat. RESULTS: HRV in the time and frequency domains indicated sympathetic-parasympathetic imbalance in PD model rats. Linear BPV analysis didn't reflect changes in vascular function and blood pressure regulation in PD model rats. Nonlinear analysis revealed differences in BPV, with lower sample entropy results and increased detrended fluctuation analysis results in the PD group rats. COMPARISON WITH EXISTING METHODS AND CONCLUSIONS: our experiments demonstrate the ability to evaluate autonomic dysfunction in models of Parkinson's disease by combining the analysis of BPV with HRV, consistent with autonomic impairment in PD patients. Nonlinear analysis by blood pressure signal may help in early detection of the PD. It indicates that the fluctuation of blood pressure in the rats in the rotenone model group tends to be regular and predictable, contributes to understand the PD pathophysiological mechanisms and to find strategies for early diagnosis.


Asunto(s)
Sistema Nervioso Autónomo , Presión Sanguínea , Modelos Animales de Enfermedad , Electrocardiografía , Frecuencia Cardíaca , Rotenona , Animales , Rotenona/toxicidad , Frecuencia Cardíaca/fisiología , Frecuencia Cardíaca/efectos de los fármacos , Presión Sanguínea/fisiología , Presión Sanguínea/efectos de los fármacos , Masculino , Sistema Nervioso Autónomo/fisiopatología , Sistema Nervioso Autónomo/efectos de los fármacos , Telemetría/métodos , Dinámicas no Lineales , Ratas , Trastornos Parkinsonianos/fisiopatología , Trastornos Parkinsonianos/inducido químicamente , Ratas Sprague-Dawley , Enfermedad de Parkinson/fisiopatología
20.
Front Neuroinform ; 18: 1392271, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39211912

RESUMEN

Background: The above studies indicate that the SCZ animal model has abnormal gamma oscillations and abnormal functional coupling ability of brain regions at the cortical level. However, few researchers have focused on the correlation between brain complexity and connectivity at the cortical level. In order to provide a more accurate representation of brain activity, we studied the complexity of electrocorticogram (ECoG) signals and the information interaction between brain regions in schizophrenic rats, and explored the correlation between brain complexity and connectivity. Methods: We collected ECoG signal from SCZ rats. The frequency domain and time domain functional connectivity of SCZ rats were evaluated by magnitude square coherence and mutual information (MI). Permutation entropy (PE) and permutation Lempel-Ziv complexity (PLZC) were used to analyze the complexity of ECoG, and the relationship between them was evaluated. In addition, in order to further understand the causal structure of directional information flow among brain regions, we used phase transfer entropy (PTE) to analyze the effective connectivity of the brain. Results: Firstly, in the high gamma band, the complexity of brain regions in SCZ rats is higher than that in normal rats, and the neuronal activity is irregularity. Secondly, the information integration ability of SCZ rats decreased and the communication of brain network information was hindered at the cortical level. Finally, compared with normal rats, the causal relationship between brain regions of SCZ rats was closer, but the information interaction center was not clear. Conclusion: The above findings suggest that at the cortical level, complexity and connectivity are valid biomarkers for identifying SCZ. This bridges the gap between peak potentials and EEG. This may help to understand the pathophysiological mechanisms at the cortical level in schizophrenics.

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