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1.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(3): 348-353, 2024 Jun.
Artigo em Zh | MEDLINE | ID: mdl-38864299

RESUMO

Objective To investigate the relationship between cerebrovascular reactivity (CVR) and emotional disorders in the patients undergoing continuous hemodialysis for end-stage renal disease (ESRD).Methods The clinical data of the ESRD patients undergoing continuous hemodialysis were collected.Anxiety and depression of the patients were assessed by the Hamilton anxiety scale (HAMA) and Beck depression inventory,respectively.The cerebral hemodynamic changes during the breath holding test were monitored by transcranial Doppler sonography,and the breath-holding index (BHI) was calculated.The BHI≥0.69 and BHI<0.69 indicate normal CVR and abnormal CVR,respectively.Binary Logistic regression was employed to analyze the factors affecting the depressive state of ESRD patients.Results The group with abnormal CVR exhibited higher total cholesterol level (P=0.010),low density lipoprotein level (P=0.006),and incidence of depression (P=0.012) than the group with normal CVR.Compared with the non-depression group,the depression group displayed prolonged disease course (P=0.039),reduced body mass index (P=0.048),elevated HAMA score (P=0.001),increased incidence of anxiety (P<0.001),decreased BHI (P=0.015),and increased incidence of abnormal CVR (P=0.012).Binary Logistic regression analysis indicated anxiety as a contributing factor (OR=22.915,95%CI=2.653-197.956,P=0.004) and abnormal CVR as a risk factor (OR=0.074,95%CI=0.008-0.730,P=0.026) for depression.Conclusion Impaired CVR could pose a risk for depression in the patients with ESRD.


Assuntos
Depressão , Falência Renal Crônica , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Falência Renal Crônica/fisiopatologia , Falência Renal Crônica/complicações , Depressão/fisiopatologia , Adulto , Diálise Renal , Circulação Cerebrovascular/fisiologia , Idoso
2.
Artigo em Inglês | MEDLINE | ID: mdl-36549658

RESUMO

BACKGROUND: Congenital anomalies of the kidney and urinary tracts (CAKUT) are the leading cause of kidney failure in children with phenotypic and genotypic heterogeneity. Our objective was to describe the genetic spectrum and identify the risk factors for kidney failure in children with CAKUT. METHODS: Clinical and genetic data were derived from a multicenter network (Chinese Children Genetic Kidney Disease Database, CCGKDD) and the Chigene database. A total of 925 children with CAKUT who underwent genetic testing from 2014 to 2020 across China were studied. Data for a total of 584 children wereobtained from the CCGKDD, including longitudinal data regarding kidney function. The risk factors for kidney failure were determined by the Kaplan-Meier method and Cox proportional hazards models. RESULTS: A genetic diagnosis was established in 96 out of 925 (10.3%) children, including 72 (8%) with monogenic variants, 20 (2%) with copy number variants (CNVs), and 4 (0.4%)with major chromosomal anomalies. Patients with skeletal abnormalities were more likely to have large CNVs or abnormal karyotypes than monogenic variants. Eighty-two patients from the CCGKDD progressed to kidney failure at a median age of 13.0 (95% confidence interval, 12.4-13.6) years, and twenty-four were genetically diagnosed with variants of PAX2, TNXB, EYA1, HNF1B and GATA3 or the 48, XXYY karyotype. The multivariate analysis indicated that solitary kidney, posterior urethral valves, bilateral hypodysplasia, the presence of certain variants and premature birth were independent prognostic factors. CONCLUSIONS: The genetic spectrum of CAKUT varies among different subphenotypes. The identified factors indicate areas that require special attention.

3.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 51(2): 178-184, 2020 Mar.
Artigo em Zh | MEDLINE | ID: mdl-32220185

RESUMO

OBJECTIVE: To investigate the effect of miR-503-5p on the proliferation, invasion, migration and epithelialization of cervical cancer HeLa cells via targeting E2 F3. METHODS: Four ccervical cancer HeLa cells groups were set up including control group, mimic-NC group, miR-503-5p mimic group, E2 F3 group, miR-503-5p mimic+ E2 F3 group (mimic+ E2 F3 group). The plasmids were separately or jointly transinfected into cervical cancer Hela cells of each group by Lipofectamine 2000, After transinfection, the target gene was predicted by gene prediction software, the targeting relationship was verified by fluorescein experiment, the expression of miR-503-5p and E2 F3 was detected by RT-PCR, cell proliferation was detected by MTT assay, expression of Ki67, proliferating cell nuclear antigen (PCNA), E-cadherin and N-cadherin were detected by Western blot, cell invasion was detected by Transwell, and cell migration was detected by scratch test. Nude mice were divided into control group and miR-503-5p mimic group, and 0.2 mL of cervical cancer HeLa cell suspension transfected with mimic-NC or miR-503-5p mimic was injected subcutaneously into the ventral side of the right hind limb of nude mice. Thirty days post injection, the nude mice were sacrificed by cervical dislocation. The tumor weight was weighed by an electronic balance, and the expression of KI67 and Vimentin in the tumor tissue was detected by immunohistochemistry. RESULTS: The expression level of miR-503-5p in cervical cancer HeLa cells was down-regulated, miR-503-5p directly targeted E2 F3 by binding with E2 F3 at binding sites in the 3'UTR region. Over-expressing of miR-503-5p inhibited the expression of E2 F3, significantly decreased cell growth rate and the expression level of Ki67 and PCNA, decreased the number of invasive cells, widened the scratches, reduced the healing rate, up-regulated the expression of E-cadherin and also down-regulated the expression of N-cadherin ( P<0.01). Over-expressing of miR-503-5p significantly reduced the volume and weight of transplanted tumors, and decreased the proportion of positive Ki67 and Vimentin ( P<0.01). CONCLUSION: miR-503-5p inhibits the proliferation, invasion, migration and epithelialization of cervical cancer HeLa cells by targeting E2 F3.


Assuntos
Proliferação de Células , Fator de Transcrição E2F3/fisiologia , MicroRNAs/fisiologia , Neoplasias do Colo do Útero , Animais , Linhagem Celular Tumoral , Movimento Celular , Feminino , Células HeLa , Humanos , Camundongos , Camundongos Nus , Invasividade Neoplásica , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia
4.
Molecules ; 23(9)2018 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-30213112

RESUMO

Zhi zhu xiang (ZZX for short) is the root and rhizome of Valeriana jatamansi Jones, which is a Traditional Chinese Medicine (TCM) used to treat various mood disorders for more than 2000 years, especially anxiety. The aim of the present work was to identify the bioactive chemical markers in Zhi zhu xiang improving anxiety in rats by a fingerprint-efficacy study. More specifically, the chemical fingerprint of ZZX samples collected from 10 different regions was determined by High Performance Liquid Chromatography (HPLC) and the similarity analyses were calculated based on 10 common characteristic peaks. The anti-anxiety effect of ZZX on empty bottle stimulated rats was examined through the Open Field Test (OFT) and the Elevated Plus Maze Test (EPM). Then we measured the concentration of CRF, ACTH, and CORT in rat's plasma by the enzyme-linked immune sorbent assay (ELISA) kit, while the concentration of monoamine and metabolites (NE, DA, DOPAC, HVA, 5-HT, 5-HIAA) in the rat's cerebral cortex and hippocampus was analysed by HPLC coupled with an Electrochemical Detector. At last, the fingerprint-efficacy study between chemical fingerprint and anti-anxiety effect of ZZX was accomplished by partial least squares regression (PLSR). As a result, we screened out four compounds (hesperidin, isochlorogenic acid A, isochlorogenic acid B and isochlorogenic acid C) as the bioactive chemical markers for the anti-anxiety effect of ZZX. The fingerprint-efficacy study we established might provide a feasible way and some elicitation for the identification of the bioactive chemical markers for TCM.


Assuntos
Ansiedade/tratamento farmacológico , Ácido Clorogênico/administração & dosagem , Medicamentos de Ervas Chinesas/administração & dosagem , Hesperidina/administração & dosagem , Valeriana/química , Hormônio Adrenocorticotrópico/sangue , Animais , Ansiedade/sangue , Ansiedade/etiologia , Ácido Clorogênico/análogos & derivados , Ácido Clorogênico/química , Ácido Clorogênico/farmacologia , Cromatografia Líquida de Alta Pressão , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Hesperidina/química , Hesperidina/farmacologia , Análise dos Mínimos Quadrados , Masculino , Neuropeptídeos/sangue , Raízes de Plantas/química , Ratos , Receptores de Hormônio Liberador da Corticotropina/sangue , Rizoma/química
5.
Croat Med J ; 58(5): 349-357, 2017 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-29094813

RESUMO

AIM: To investigate the role of valproic acid (VPA), a class I selective histone deacetylase inhibitor, on Michigan Cancer Foundation (MCF)-7 breast cancer cells, named and explore its possible molecular mechanism. METHODS: MCF-7 cells were cultured with sodium valproate (0. 5-4.0 mmol/L) for 24 h, 48 h, and 72 h in vitro, respectively. The cell viability, apoptosis, and cell cycle were examined. The activities and protein expressions of caspase-3, caspase-8, and caspase-9 were subsequently assayed. Finally, mRNA and protein expressions of cyclin A, cyclin D1, cyclin E, and p21 were analyzed. RESULTS: Sodium valproate suppressed MCF-7 cell growth, induced cell apoptosis, and arrested G1 phase in a time- and concentration- dependent manner, with the relative cell viabilities decreased, cell apoptosis ratios increased, and percentage of G1 phase enhanced (P<0.05). Increased activity of caspase-3 and caspase-9, but not caspase-8, and increased protein levels were found under sodium valproate (2.0 mmol/L, 48h). P21 was up-regulated and cyclin D1 was down-regulated at both mRNA and protein levels under sodium valproate (2.0 mmol/L, 48h)(P<0.05), although cyclin E and cyclin A remained changed. CONCLUSION: These results indicate that VPA can suppress the growth of breast cancer MCF-7 cells by inducing apoptosis and arresting G1 phase. Intrinsic apoptotic pathway is dominant for VPA-induced apoptosis. For G1 phase arrest, p21 up-regulation and down-regulation of cyclin D1 may be the main molecular mechanism.


Assuntos
Antineoplásicos/farmacologia , Inibidores de Histona Desacetilases/farmacologia , Ácido Valproico/farmacologia , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Caspase 9/metabolismo , Proliferação de Células/efeitos dos fármacos , Ciclina D1/metabolismo , Ciclina E/metabolismo , Feminino , Pontos de Checagem da Fase G1 do Ciclo Celular , Humanos , Células MCF-7 , Proteínas Oncogênicas/metabolismo , Transdução de Sinais
6.
Molecules ; 22(8)2017 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-28800105

RESUMO

Albizzia julibrissin Durazz, a Chinese Medicine, is commonly used for its anti-anxiety effects. (-)-syringaresnol-4-O-ß-d-apiofuranosyl-(1→2)-ß-d-glucopyranoside (SAG) is the main ingredient of Albizzia julibrissin Durazz. The present study investigated the anxiolytic effect and potential mechanisms on the HPA axis and monoaminergic systems of SAG on acute restraint-stressed rats. The anxiolytic effect of SAG was examined through an open field test and an elevated plus maze test. The concentration of CRF, ACTH, and CORT in plasma was examined by an enzyme-linked immune sorbent assay (ELISA) kit while neurotransmitters in the cerebral cortex and hippocampus of the brain were examined by High Performance Liquid Chromatography (HPLC). We show that repeated treatment with SAG (3.6 mg/kg, p.o.) significantly increased the number and time spent on the central entries in the open-field test when compared to the vehicle/stressed group. In the elevated plus maze test, 3.6 mg/kg SAG could increase the percentage of entries into and time spent on the open arms of the elevated plus maze. In addition, the concentration of CRF, ACTH, and CORT in plasma and neurotransmitters (NE, 5-HT, DA and their metabolites 5-HIAA, DOPAC, and HVA) in the cerebral cortex and hippocampus of the brain were decreased after SAG treatment, as compared to the repeated acute restraint-stressed rats. These results suggest that SAG is a potential anti-anxiety drug candidate.


Assuntos
Albizzia/química , Ansiolíticos/farmacologia , Glicosídeos/farmacologia , Lignanas/farmacologia , Estresse Psicológico/tratamento farmacológico , Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Hormônio Adrenocorticotrópico/sangue , Animais , Monoaminas Biogênicas/metabolismo , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Corticosterona/sangue , Hormônio Liberador da Corticotropina/sangue , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Ácido Homovanílico/metabolismo , Ácido Hidroxi-Indolacético/metabolismo , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Ratos Sprague-Dawley , Estresse Psicológico/metabolismo , Estresse Psicológico/psicologia
7.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 36(4): 460-5, 2016 Apr.
Artigo em Zh | MEDLINE | ID: mdl-27323620

RESUMO

OBJECTIVE: To observe the effect of Compound Zhajin Granule (CZG) on Toll-like re-ceptor 4 (TLR4) signaling pathway in high-fructose corn syrup induced NASH mice. METHODS: Thirty 6-week-old male C3H mice were divided into the high fat and high fructose (HFHFr) group (n = 20) and the control group (n = 10) according to body weight. Mice in the HFHFr group ate high fat diet and drank 20% fructose water, while those in the control group ate common diet and drank common water. After 8 weeks mice in the HFHFr group were divided into two group according to body weight, the HFHFr group and the CZG group, 10 in each group. Mice in the CZG group were fed with high fat forage and 20% fructose water, and administered with 50 mL/kg 12. 8% CZG (prepared by hawthorn, Radix Curcumae, Alisma Orientale, Fritillaria Thunbergii, Silybum Marianum, peach seed in the ratio of 3:1.5:1.5:2:1.5:2:1) by gastrogavage. Mice in the HFHFr group were fed in the same way and daily administered with equal volume of distilled water by gastrogavage. Sixteen weeks later all mice were sacrificed. Body weight, liver wet weight, liver function, and lipid metabolism were detected. Pathological changes of liver tissues were assessed by HE staining, oil red O staining, and Masson staining. Expressions of TLR4, myeloid differentiation factor 88 (MyD88), tumor necrosis factor-alpha (TNF-α) were detected using immunohistochemical staining and real-time fluorescent quantitative PCR. RESULTS: Body weight, alanine aminotransferase (ALT), aspartate aminotransferase (AST) were obviously lower in the CZG group than in the HFHFr group (P < 0.05); oil red O stained area and density were decreased more in the CZG group than in the control group. HE staining showed ballooning inflammation was reduced more in the CZG group than in the HFHFr group. Masson staining was negative. Positive rates of TLR4 and MyD88 and mRNA expressions were significantly lower in the CZG group than in the HFHFr group (all P < 0.05). CONCLUSION: CZG could significantly inhibit TLR4 signaling pathway of liver in NASH mice.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Dieta Hiperlipídica , Frutose/administração & dosagem , Frutose/efeitos adversos , Inflamação , Metabolismo dos Lipídeos , Masculino , Camundongos , Camundongos Endogâmicos C3H , Fator 88 de Diferenciação Mieloide/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
8.
Clin Exp Pharmacol Physiol ; 41(9): 643-9, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24837195

RESUMO

The non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS) has emerged as a useful predictor of long-term outcome in NAFLD patients. We evaluated the predictive performance of the NFS for overall mortality in a Chinese population with NAFLD. All NAFLD patients diagnosed ultrasonographically at Xixi Hospital of Hangzhou between 1996 and 2011 were retrospectively recruited to the study. Outcome was determined by interview and causes of death were confirmed by medical records. The area under the receiver operating characteristic curve (AUCROC ) was used to determine the predictive accuracy of the NFS, BARD (body mass index, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, diabetes) score, FIB-4 index and the AST/platelet ratio index (APRI) for mortality. Data from a total of 180 eligible patients (median age 39 years; 96 men) were analysed, with 12 deaths over a median follow-up period of 6.6 years (range 0.5-14.8 years). Using Cox model analysis, the NFS as a continuous variable was identified as the only predictor for all-cause mortality (hazard ratio 2.743, 95% confidence interval (CI) 1.670-4.504). The NFS yielded the highest AUCROC of 0.828 (95% CI 0.728-0.928, P < 0.05), followed by the FIB-4 index, APRI and BARD score (AUCROC 0.806 (P < 0.05), 0.732 (P < 0.05) and 0.632, respectively). The data indicated that the NFS is a useful predictor of 6.6-year all-cause mortality for Chinese patients with NAFLD.


Assuntos
Causas de Morte , Cirrose Hepática/patologia , Hepatopatia Gordurosa não Alcoólica/patologia , Valor Preditivo dos Testes , Adulto , Povo Asiático/estatística & dados numéricos , China/epidemiologia , Feminino , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/mortalidade , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/mortalidade , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Ultrassonografia , Adulto Jovem
9.
Clin Exp Pharmacol Physiol ; 41(7): 482-8, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24739055

RESUMO

The aim of the present study was to investigate Toll-like receptor-4 (TLR4) signalling at different stages of non-alcoholic fatty liver disease (NAFLD) induced by a high-fat, high-fructose (HFHFr) diet in mice. Both TLR4 wild-type (WT) and mutant (TLR4(mut) ) mice were fed either standard chow (SC) or the HFHFr diet for different periods of time from 4 to 16 weeks. Pathological characteristics and function of the liver were assessed. Simple steatosis, steatohepatitis and hepatic fibrosis occurred sequentially in Week 4, 8 and 16 in WT mice fed with the HFHFr. Expression of TLR4, myeloid differentiation factor 88 (MyD88), interferon regulatory factor (IRF) 3 and IRF7 started to increase at Week 4, peaked at Week 8 and then declined to basal levels at Week 16. This pattern was consistent with changes in inflammation in the liver revealed by haematoxylin and eosin staining. However, lipid accumulation, inflammation and fibrosis in livers of TLR4(mut) mice fed the HFHFr diet were significantly alleviated. In addition, the expression of activin A in WT mice fed the HFHFr diet increased at Week 16. The data suggest that TLR4 signalling mediates non-alcoholic steatohepatitis before fibrosis and that activin A is subsequently involved in NAFLD.


Assuntos
Gorduras na Dieta/toxicidade , Sacarose Alimentar/toxicidade , Frutose/toxicidade , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Receptor 4 Toll-Like/metabolismo , Ativinas/genética , Ativinas/metabolismo , Animais , Gorduras na Dieta/administração & dosagem , Sacarose Alimentar/administração & dosagem , Frutose/administração & dosagem , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/fisiologia , Fator Regulador 3 de Interferon/genética , Fator Regulador 3 de Interferon/metabolismo , Fator Regulador 7 de Interferon/genética , Fator Regulador 7 de Interferon/metabolismo , Camundongos , Camundongos Knockout , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Transdução de Sinais , Receptor 4 Toll-Like/genética , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
10.
Eur J Med Chem ; 264: 115997, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38056303

RESUMO

The suppression of ferroptosis is emerging as a promising therapeutic strategy for effectively treating a wide range of diseases, including neurodegenerative disorders, organ ischemia-reperfusion injury, and inflammatory conditions. However, the clinical utility of ferroptosis inhibitors is significantly impeded by the limited availability of rational drug designs. In our previous study, we successfully unraveled the efficacy of ferrostatin-1 (Fer-1) attributed to the synergistic effect of its ortho-diamine (-NH) moiety. In this study, we present the discovery of the ortho-hydroxyl-amino moiety as a novel scaffold for ferroptosis inhibitors, employing quantum chemistry as well as in vitro and in vivo assays. 2-amino-6-methylphenol derivatives demonstrated remarkable inhibition of RSL3-induced ferroptosis, exhibiting EC50 values ranging from 25 nM to 207 nM. These compounds do not appear to modulate iron homeostasis or lipid reactive oxygen species (ROS) generation pathways. Nevertheless, they effectively prevent the accumulation of lipid peroxides in living cells. Furthermore, compound 13 exhibits good in vivo activities as it effectively protect mice from kidney ischemia-reperfusion injury. In summary, compound 13 has been identified as a potent ferroptosis inhibitor, warranting further investigation as a promising lead compound.


Assuntos
Peróxidos Lipídicos , Traumatismo por Reperfusão , Animais , Camundongos , Peroxidação de Lipídeos , Peróxidos Lipídicos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Fenóis/farmacologia
11.
Food Chem ; 439: 138059, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38039608

RESUMO

Lipids are widespread in nature and play a pivotal role as a source of energy and nutrition for the human body. Vegetable oils (VOs) constitute a significant category in the food industry, containing various lipid components that have garnered attention for being natural, environmentally friendly and health-promoting. The review presented the classification of raw materials (RMs) from oil crops and quality analysis techniques of VOs, with the aim of improving comprehension and facilitating in-depth research of VOs. Brief descriptions were provided for four categories of VOs, and quality analysis techniques for both RMs and VOs were generalized. Furthermore, this study discussed the applications of lipidomics technology in component analysis, processing and utilization, quality determination, as well as nutritional function assessment of VOs. Through reviewing RMs and quality analysis techniques of VOs, this study aims to encourage further refinement and development in the processing and utilization of VOs, offering valuable references for theoretical and applied research in food chemistry and food science.


Assuntos
Lipidômica , Óleos de Plantas , Humanos , Valor Nutritivo , Alimentos
12.
Int J Mol Sci ; 14(3): 4385-99, 2013 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-23439548

RESUMO

Selenoprotein M (SelM), one of the executants of selenium in vivo, is highly expressed in human brain and most probably involved in antioxidation, neuroprotection, and intracellular calcium regulation, which are the key factors for preventing the onset and progression of Alzheimer's disease (AD). In this paper, human SelM was successfully overexpressed in human embryonic kidney cells HEK293T. Sodium selenite (Na(2)SeO(3) 0.5 µmol/L) increased the expression of full-length SelM and inhibited the expression of truncated SelM. The full-length SelM exhibited higher antioxidant activity than its selenocysteine-to-cysteine mutation form SelM', whereas the truncated SelM had an adverse effect that increased the oxidative stress level of cells. When ß-amyloid (Aß(42), an AD relevant peptide) was cotransfected with the empty expression vector, SelM, or SelM' under the induction of 0.5 µmol/L Na(2)SeO(3), the intracellular Aß(42) aggregation rates were detected to be 57.9% ± 5.5%, or 22.3% ± 2.6%, or 26.3% ± 2.1%, respectively, showing the inhibitory effects on Aß aggregation by the full-length SelM and SelM'. Meanwhile, the intumescentia of mitochondria caused by Aß(42) transfection was significantly mitigated by the cotransfection of SelM or SelM' with Aß(42) under the induction of 0.5 µmol/L Na(2)SeO(3). On the contrary, cotransfection of SelM and Aß(42) without the induction of Na(2)SeO(3) increased Aß(42) aggregation rate to 65.1% ± 3.2%, and it could not inhibit the Aß-induced intumescent mitochondria. In conclusion, full-length SelM and SelM¢ might prevent Aß aggregation by resisting oxidative stress generated during the formation of Aß oligomers in cells.

13.
BMC Complement Med Ther ; 23(1): 7, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36624423

RESUMO

BACKGROUND: Suanzaoren-Wuweizi herb-pair (SWHP), composed of Zizyphi Spinosi Semen (Suanzaoren in Chinese) and Schisandrae Chinensis Fructus (Wuweizi in Chinese), is a traditional herbal formula that has been extensively used for the treatment of insomnia. The study aimed to explore the targets and signal pathways of Suanzaoren-Wuweizi (S-W) in the treatment of anxiety by network pharmacology, and to verify the pharmacodynamics and key targets of SWHP in mice. METHODS: The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) as well as literature mining were used to obtain the main chemical ingredients of Suanzaoren and Wuweizi. The SwissTargetPrediction platform was used to predict drug-related targets. The GeneCards, TTD, DisGeNET and OMIM databases were used to obtain potential targets for the treatment of anxiety with the chemical components of S-W. Drug-disease intersection genes were selected, and a protein-protein interaction (PPI) network was constructed using STRING. The core targets of S-W in the treatment of anxiety were selected according to the topological parameters, and GO functional enrichment as well as KEGG pathways enrichment analyses were performed for potential targets. The relationship network of the "drug-active ingredient-disease-target-pathway" was constructed through Cytoscape 3.8.0. The pharmacodynamics of SWHP in the treatment of anxiety was evaluated by the elevated plus maze (EPM), the light/dark box test (LDB) and the open field test (OFT). The mechanisms were examined by measuring monoamine neurotransmitters in brain of mice. RESULTS: The results showed that there were 13 active ingredients for the treatment of anxiety in the network. This includes sanjoinenine, swertisin, daucosterol, schizandrer B, wuweizisu C and gomisin-A. Additionally, there were 148 targets, such as AKT1, TNF, SLC6A4, SLC6A3, EGFR, ESR1, HSP90AA1, CCND1, and DRD2, mainly involved in neuroactive ligand-receptor interactions, the Serotonergic synapse pathway and the cAMP signaling pathway. After 1 week of treatment, SWHP (2 and 3 g/kg) induced a significant increase on the percentage of entries into and time spent on the open arms of the EPM. In the LDB test, SWHP exerted anxiolytic-like effect at 2 g/kg. In the open-field test, SWHP (2 g/kg) increased the number of central entries and time spent in central areas. The levels of brain monoamines (5-HT and DA) and their metabolites (5-HIAA, DOPAC) were decreased after SWHP treatment. CONCLUSIONS: The anti-anxiety effect of SWHP may be mediated by regulating 5-HT, DA and other signaling pathways. These findings demonstrated that SWHP produced an anxiolytic-like effect and the mechanism of action involves the serotonergic and dopaminergic systems, although underlying mechanism remains to be further elucidated.


Assuntos
Ansiolíticos , Schisandra , Animais , Camundongos , Ansiolíticos/farmacologia , Farmacologia em Rede , Serotonina
14.
World J Oncol ; 14(6): 580-583, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38022399

RESUMO

Osteoblastic bone reaction, the occurrence of new osteoblastic lesions, is a paradoxical phenomenon during the treatment of cancers and can be defined as disease progression or bone metastases. Osteoblastic bone reactions usually occur in patients who receive treatments such as chemotherapy or hormonal or targeted therapy; however, it is difficult to differentiate them from disease progression or an increase in osteoblastic activity in response to therapy. Although osteoblastic bone reaction in lung cancer has been described in a few reports, it has never been reported in patients with KRASG12V-mutant lung adenocarcinoma treated with immunotherapy and antiangiogenesis. Here, we describe a case of a 77-year-old male with KRASG12V-mutant lung adenocarcinoma whose osteoblastic bone response was found during treatment with sintilimab and bevacizumab. We showed the course of the disease as well as systematic imaging manifestations of lung cancer with osteoblastic bone reaction and discussed their mechanisms.

15.
Genomics ; 96(6): 369-76, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20828606

RESUMO

Cotton fiber as a single-celled trichome is a biological model system for studying cell differentiation and elongation. However, the complexity of its gene expression and regulatory mechanism allows only marginal progress. Here, we report the high-throughput tag-sequencing (Tag-seq) analysis using Solexa Genome Analyzer platform on transcriptome of -2 to 1 (fiber initiation, stage I) and 2-8 (fiber elongation, stage II) days post anthesis (DPA) cotton (Gossypium hirsutum) ovules (wild type: WT; Xuzhou 142 and its mutant: fuzzless/lintless or flM, in the same background). To this end, we sequenced 3.5-3.8 million tags representing 0.7-1.0 million unique transcripts for each library (WT1, WT2, M1, and M2). After removal of low quality tags, we obtained a total of 2,973,104, 3,139,306, 2,943,654, and 3,392,103 clean sequences that corresponded to 357,852, 280,787, 372,952, and 382,503 distinct tags for WT1, WT2, M1, and M2, respectively. All clean tags were aligned to the publicly available cotton transcript database (TIGR, http://www.tigr.org). About 15% of the distinct tags were uniquely mapped to the reference genes, and 31.4% of existing genes were matched by tags. The tag mapping to the database sequences generated 23,854, 24,442, 23,497, and 19,957 annotated genes for WT1, WT2, M1, and M2 libraries, respectively. Analyses of differentially expressed genes revealed the substantial changes in gene type and abundance between the wild type and mutant libraries. Among the 20 most differentially expressed genes in WT1/M1 and WT2/M2 libraries were cellulose synthase, phosphatase, and dehydrogenase, all of which are involved in the fiber cell development. Overall, the deep-sequencing analyses demonstrate the high degree of transcriptional complexity in early developing fibers and represent a major improvement over the microarrays for analyzing transcriptional changes on a large scale.


Assuntos
Fibra de Algodão , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Gossypium/crescimento & desenvolvimento , Mutação , Proteínas de Plantas/genética , Etiquetas de Sequências Expressas , Regulação da Expressão Gênica no Desenvolvimento , Biblioteca Gênica , Genoma de Planta , Gossypium/citologia , Gossypium/genética , Sequenciamento de Nucleotídeos em Larga Escala , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas de Plantas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNA
16.
Yi Chuan ; 33(12): 1393-7, 2011 Dec.
Artigo em Zh | MEDLINE | ID: mdl-22207386

RESUMO

A ultra-dwarf mutant was newly found in upland cotton (Gossypium hirsutum L.). This mutant was controlled by single recessive gene du. Seventy pairs of polymorphic primers were selected from 1350 primers, which covered all the identified chromosomes by screening in parents and near-isogenic lines. Gene du was mapped using an F2 population derived from intraspecific crosses between "Ultra-dwarf 1" and "Xinluzao 16". Thirty-six primers were distributed in eight linkage groups, and du was linked to LG01. Seven co-dominant markers linked to du were NAU2679, NAU2749, NAU905, NAU2838, NAU5373, NAU2238, and NAU4946. Based on the known genetic map of tetraploid cotton, the markers NAU4946, NAU2238, NAU905, NAU5373, and NAU2679 were located on chromosome 6, and the target gene du was located between NAU2238 and NAU4946 with the genetic distances of 3.3 cM and 1.4 cM, respectively. Hence, gene du was located on chromosome 6.


Assuntos
Mapeamento Cromossômico , Gossypium/genética , Mutação
17.
Histochem Cell Biol ; 132(6): 639-46, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19847458

RESUMO

Controlled invasion of the uterine wall by the trophoblast cells is pivotal for the successful pregnancy, and various kinds of protease are involved in this process. Serine protease prostasin has been shown to participate in the proteolytic activation of epithelial sodium channel as well as cleavage of epidermal growth factor receptor extracellular domain in human epithelial cells. Its physiological significance in human placentation has been suggested but not validated. In the present study, we found that prostasin was expressed at a relatively high level in human placenta trophoblasts in early pregnant weeks. In the in vitro cultured human choriocarcinomal JEG-3 cells, treatment with functional antibody against prostasin led to promotion in cell invasion capability, as well as increase in the production of MMP-2, MMP-26, TIMP-1, and TIMP-4. Our data indicated that this serine protease may function as an invasion suppressor in human trophoblast, participating in the invasion-restrictive regulation of trophoblasts to avoid their over-penetration into the uterine wall.


Assuntos
Coriocarcinoma/patologia , Invasividade Neoplásica , Serina Endopeptidases/fisiologia , Linhagem Celular Tumoral , Movimento Celular , Feminino , Humanos , Metaloproteinase 2 da Matriz/biossíntese , Metaloproteinases da Matriz Secretadas/biossíntese , Gravidez , Inibidor Tecidual de Metaloproteinase-1/biossíntese , Inibidores Teciduais de Metaloproteinases/biossíntese , Trofoblastos/citologia , Útero/citologia , Inibidor Tecidual 4 de Metaloproteinase
18.
Yi Chuan ; 31(8): 855-8, 2009 Aug.
Artigo em Zh | MEDLINE | ID: mdl-19689948

RESUMO

Analysis of linkage inheritance of sub-red plant, a natural mutant from upland cotton, was conducted by two-point test using parents Gossypium barbadense Hai7124 and G. hirsutum B026 both with petal spots and green leaves, and G. hirsutum E083 with normal white flowers and, sub-red plants. The average percentage of recombination was 1.35% when calculating test-cross combining populations derived from E083/B026//Su9701 and B026/E083//Su9701. The average percentage of recombination was 2.94% when calculating test-cross combining populations derived from E083/Hai7124// Su9701 and Hai7124/E083//Su9701. Meanwhile, the genetic stocks having genotype Rs, Lc1, r2, and rs, lc1, and R2 were used in the three-point test, which demonstrated that the mutant gene Rs was located between genes Lc and R2. The genetic distance between Rs and Lc1 was 42.21 cM, and 1.68 cM between Rs and R2. Coefficient of interference among R2, Lc1, and Rs was 0.79, indicating that the single cross between Rs and R2 has less impact on the other single cross between Rs and Lc1. Based on known genetic distance around gene Rs, the genetic linkage map was drawn. Rs is located between genes Lc1 and R2, molecular marker NAU2863, NAU3735 and NAU3735, NAU1048. The genetic distances between Rs and two markers NAU3735, NAU1048 are 0.1 and 0.2 cM, respectively.


Assuntos
Ligação Genética , Gossypium/genética , Mutação , Cruzamento , Mapeamento Cromossômico , Cromossomos de Plantas/genética , Recombinação Genética
19.
Zhonghua Xin Xue Guan Bing Za Zhi ; 37(6): 532-6, 2009 Jun.
Artigo em Zh | MEDLINE | ID: mdl-19927636

RESUMO

OBJECTIVE: To investigate chronic stress induced tissue action potential and pathological changes of thoracic spinal cord 1 - 5 nerves and heart in SD rats. METHODS: SD rats (weighing 180 - 250 g) were randomly divided into depressive group and control group (n = 10 each). Depressive model (unpredicted chronic mild stress) was established according to Gronli's protocol. The heart rhythm, tissue field action potential duration (FAPD) of thoracic spinal cord 1 - 5 nerves, atrium and ventricle were mapped by microelectrode arrays (MEA) technique. Heart was sectioned and stained with Massion and HE for pathological analysis. RESULTS: After 3 weeks chronic stress, P wave [(35.09 +/- 7.92) ms vs. (25.43 +/- 3.38) ms, P<0.05] and Q-T interval [(114.64 +/- 35.08) ms vs. (81.93 +/- 16.35) ms, P<0.01] were significantly increased, FAPD of thoracic spinal cord 1 - 5 nerves and heart was significantly prolonged, atrial field action potential duration dispersion (FAPDd) was significantly increased, atrial premature beats (n = 2) and ventricular premature beats ( n = 3) were also recorded in rats from depressive group. Moreover, increased collagen deposition was evidenced in Massion stained myocardium and increased inflammatory cell infiltration in the heart was found by both HE stain and electron microscope from depressive rats. CONCLUSION: Chronic mild stress could activate sympathetic nerves system, promote inflammatory cell myocardial infiltration and myocardial fibrosis, induce arrhythmias by prolonging FAPD and increasing FADPd in thoracic spinal cord 1 - 5 nerves and/or heart tissue.


Assuntos
Potenciais de Ação , Transtorno Depressivo/fisiopatologia , Coração/fisiopatologia , Microeletrodos , Medula Espinal/fisiopatologia , Animais , Transtorno Depressivo/diagnóstico , Modelos Animais de Doenças , Eletrocardiografia , Ratos , Ratos Sprague-Dawley , Estresse Fisiológico
20.
Int J Ophthalmol ; 12(10): 1598-1604, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31637196

RESUMO

AIM: To investigate the effect of albuminuria on diabetic macular edema (DME) and the possible association between baseline urinary albumin excretion (UAE) and intravitreal conbercept (IVC) treatment frequency in DME patients. METHODS: In this hospital-based retrospective study, a total of 350 in-patients with type 2 diabetes mellitus were recruited and their clinical records were reviewed. Thereafter, 52 patients identified with severe non-proliferative diabetic retinopathy (NPDR) combined with albuminuria were divided into the microalbuminuria (UAE 30-300 mg/24h) and macroalbuminuria (UAE>300 mg/24h) groups, which were compared and analyzed by both independent sample t-test and Chi-square test. Correlations between the systemic variables and the central foveal thickness (CFT) were evaluated using Spearman's correlation and linear regression analyses. Of the 52 patients with center-involved DME, 43 received an initial combined injection of conbercept (0.5 mg/0.05 mL) and triamcinolone acetonide (1 mg/0.05 mL), followed by an IVC injection, as needed. The relationship between baseline UAE and number of IVC injections during the first year of treatment was analyzed using Spearman's partial correlation. RESULTS: Of 350 patients, a higher incidence of DME was observed in severe non-proliferative retinopathy (NPDR) patients than that observed in other groups. By dividing the 52 patients with severe NPDR into the micro- and macro-albuminuria subgroups, significant differences in CFT, systolic blood pressure, total cholesterol and serum creatinine levels, and UAE were revealed. Furthermore, a positive liner correlation between the UAE and CFT was found. Finally, the partial correlation coefficient adjusted for either the CFT or UAE indicated that both parameters directly correlated with the number of IVC injections administered during the 12mo of follow-up. CONCLUSION: Generally, macular edema occurred in patients with severe NPDR, for whom the UAE is an independent risk predictor of DME. The baseline UAE and CFT predicted the treatment frequency of IVC injections administered in the first year for eyes with DME.

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