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1.
Neuroreport ; 33(9): 399-407, 2022 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-35594431

RESUMO

BACKGROUND: Increasing data show that structural changes of spastic muscle and hyperexcitability of reticulospinal tract (RST) are involved in the pathogenesis of spasticity after stroke (SAS). Our previous study has indicated that the anti-spastic effect of acupuncture, especially waggle needling (WN, a multiple directional needling method with joint movement), on SAS rats was related to the KCC2-GABAA pathway in cerebral cortex. Furthermore, as a peripheral stimulation to treat upper motor neuron injury-related spasticity, acupuncture's effect on peripheral spastic muscles and inhibitory neurotransmitters in the brainstem, the origin of the RST, should be further clarified. This study aimed to examine the effect of acupuncture on the structure of spastic muscle and on the KCC2-GABAA pathway in the brainstem of SAS rats. METHODS: Middle cerebral artery occlusion (MCAO) or a sham operation were conducted in SD rats to establish SAS and control models. Behavioral assays, muscle myosin ATPase staining, and molecular biology technologies were used to compare different groups. RESULTS: In SAS models, hindlimb motor ability was decreased, neurologic deficits and spasticity were induced, the proportion of type I muscle fibers in spastic muscle was increased, and the expressions of γ-aminobutyric acid (GABA), KCC2, and the GABAAγ2 subunit of the pentameric GABAA receptor in the brainstem were decreased. Acupuncture including WN and perpendicular needling (PN) reversed these effects of MCAO. Furthermore, the therapeutic effect of WN was better than that of PN. CONCLUSIONS: Acupuncture after MCAO improves the structure of spastic muscle and decreases spasticity probably at least partly by enhancing GABA, KCC2, and GABAAγ2 in the brainstem in SAS rats.


Assuntos
Terapia por Acupuntura , AVC Isquêmico , Acidente Vascular Cerebral , Simportadores , Terapia por Acupuntura/métodos , Animais , Tronco Encefálico/metabolismo , Infarto da Artéria Cerebral Média , Espasticidade Muscular/etiologia , Espasticidade Muscular/metabolismo , Espasticidade Muscular/terapia , Músculos/metabolismo , Ratos , Ratos Sprague-Dawley , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia , Simportadores/metabolismo , Ácido gama-Aminobutírico/metabolismo
2.
Zhen Ci Yan Jiu ; 47(4): 283-9, 2022 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-35486007

RESUMO

OBJECTIVE: To observe the effect of acupuncture at "Yanglingquan" (GB34) and "Baihui" (GV20) on Na+/K+-ATPase, excitatory amino acid transporters (EAATs) and glutamate (Glu) in hippocampus of post-stroke spasticity rats, so as to explore the central mechanism in anti-spasticity. METHODS: In a total of 48 healthy SD rats, 12 rats were randomly selected to be included into sham operation group, and the remaining rats were used to make a middle cerebral artery occlusion (MCAO) model using a suture method. On the 3rd day after modeling, MCAO limb spasticity rats were screened by neurological deficit symptoms and muscle tension scores, and randomly divided into the model, GB34 (Hui-puncture at GB34) and GB34+GV20 (Hui-puncture at GB34 and horizontal insertion at GV20) groups (n=12 rats in each group), and the treatment was lasted for 7 conse-cutive days. The neurological symptoms and muscle tension score were observed with the Zea Longa score and modified Ashworth scale (MAS). The levels of Glu, EAAT1 (GLAST) and EAAT2 (GLT-1) in the ischemic area of cerebral hippocampus were detected by ELISA, the expression of Na+/K+-ATPase α1 (ATP1α1) was detected by Western blot, the expression of ATP1α1 mRNA was detected by real-time PCR, and the expression of GLAST, GLT-1 and ATP1α1 was detected by immunofluorescence. RESULTS: After modeling, Zea Longa score and MAS score were increased (P<0.01), the level of Glu in the ischemic area of cerebral hippocampus was increased (P<0.01), while the expression levels of GLAST, GLT-1, ATP1α1 protein and mRNA were all decreased (P<0.01) in the model group relevant to the sham operation group. After 7 days' treatment, all the increased and decreased levels of the indexes mentioned above were reversed in the two acupuncture groups relevant to the model group (P<0.01, P<0.05), and the effects of acupuncture at GB34+GV20 were obviously superior to that of acupuncture at GB34 (P<0.05, P<0.01). CONCLUSION: Acupuncture can alleviate post-stroke spasticity effectively, which may be related to its effect in up-regulating the expressions of Na+/K+-ATPase and EAATs in hippocampus. The anti-spastic effect of acupuncture at GB34+GV20 is superior to GB34 alone.


Assuntos
Terapia por Acupuntura , Acidente Vascular Cerebral , Pontos de Acupuntura , Terapia por Acupuntura/métodos , Adenosina Trifosfatases , Animais , Ácido Glutâmico , Infarto da Artéria Cerebral Média , Espasticidade Muscular/genética , Espasticidade Muscular/terapia , RNA Mensageiro , Ratos , Ratos Sprague-Dawley , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/genética , Acidente Vascular Cerebral/terapia
3.
Zhen Ci Yan Jiu ; 47(3): 196-202, 2022 Mar 25.
Artigo em Chinês | MEDLINE | ID: mdl-35319835

RESUMO

OBJECTIVE: To observe and compare the effects of different acupuncture and moxibustionmethods at "San-yinjiao" (SP6) on uterine contraction and microcirculation in cold congealing dysmenorrhea rats, so as to explore its mechanism underlying treatment of dysmenorrhea. METHODS: A total of 140 female SD rats were randomly divided into normal control, mo-del, perpendicular needling, transverse needling and moxibustion groups, with 28 rats in each group. The cold congealing dysme-norrhea rat model was prepared by exposure in a freezer (25 ℃) for 4 h, once daily for 5 days, and subcutaneous injection of estradiol benzoate (once daily for 10 days) and intra-abdominal injection of oxytocin (once). For rats in three intervention groups, acupuncture needles were inserted into bilateral SP6 perpendicularly or transversely to a depth of 4~5 mm and retained for 20 min, or moxibustion was applied to SP6 for 20 min. The uterine contraction degree and the uterine microcirculation were recorded. The expression levels of transient receptor potential vanilloid 1 (TRPV1) and heat shock protein 70 (HSP70) in local tissues of SP6 area were detected by immunohistochemistry. The expression levels of µopioid receptor and endothelin 1 (ET1) mRNA in the uterus were assessed by quantitative real time-PCR. RESULTS: After modeling and compared with the normal control group, the number and peak-to-peak values of uterine contraction waves, and uterine motility were significantly increased (P<0.01,P<0.05), while the speed of blood flow in the microvessels was slowed down (P<0.01), diameters of the uterine microvessels and capillaries (cap) shrank obviously (P<0.01) in the model group. After the intervention, all indexes of uterine contraction and microcirculation were improved in three intervention groups (P<0.01, P<0.05), while transverse needling and moxibustion showed better effects compared to perpendicular needling (P<0.05, P<0.01). The expression of TRPV1 and HSP70 in SP 6 area had no significant changes (P>0.05), while the uterine µopioid receptor mRNA expression decreased (P<0.01), and ET1 mRNA expression increased (P<0.01) in the model group relevant to the normal control group. Following the intervention, the expression levels of TRPV1 and HSP70 in SP6 area were increased (P<0.05, P<0.01), and expression levels of uterine µopioid receptor mRNA increased (P<0.05, P<0.01) and uterine ET1 mRNA decreased (P<0.05, P<0.01) in the three intervention groups. The effect of moxibustion was considerably better than those of two acupuncture groups in up-regulating TRPV1 expression (P<0.05). Both transverse needling and moxibustion showed better effects of down-regulating uterine ET1 mRNA expression than perpendicular needling (P<0.01). CONCLUSION: Transverse needling and moxibustion at SP6 have a better effect of relieving ute-rine contraction and improving uterine microcirculation than perpendicular needling, which may be related to their effects in up-re-gulating the expression of TRPV1 and HSP70 in SP6 area, thereby modulating the mRNA expression of µ opioid receptor and ET1 in uterine tissue.


Assuntos
Terapia por Acupuntura , Moxibustão , Animais , Dismenorreia/genética , Dismenorreia/terapia , Feminino , Humanos , Microcirculação , Gravidez , Ratos , Ratos Sprague-Dawley , Contração Uterina
4.
Artigo em Inglês | MEDLINE | ID: mdl-35083705

RESUMO

Liquid submerged fermentation is an effective strategy to achieve large-scale production of active ingredients by macrofungi, and controlling mycelium morphology is a key factor restricting the development of this technology. Mining for superior morphological regulatory factors and elucidation of their regulatory mechanisms are vital for the further development of macrofungal fermentation technology. In this study, microparticles were used to control the morphology of Paraisaria dubia (P. dubia) in submerged fermentation, and the underlying regulatory mechanisms were revealed by transcriptomic. The relative frequency of S-type pellet diameter increased significantly from 7.14 to 88.31%, and biomass increased 1.54 times when 15 g/L talc was added. Transcriptome analysis showed that the morphological regulation of filamentous fungi was a complex biological process, which involved signal transduction, mycelium polar growth, cell wall synthesis and cell division, etc. It also showed a positive impact on the basic and secondary metabolism of P. dubia. We provided a theoretical basis for controlling the mycelium morphology of P. dubia in submerged fermentation, which will promote the development of macrofungal fermentation technology.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34899943

RESUMO

The low adverse effects of acupuncture for primary dysmenorrhea (PD), known as one of the most commonly reported gynecological debilitating conditions affecting women's overall health, have been thus far confirmed. Moreover, it has been increasingly recognized that inflammation is involved in such menstrual cramps, and recent studies have further shown that the anti-inflammatory effects of acupuncture are helpful in its control. This review portrays the role of inflammation in PD pathophysiology, provides evidence from clinical and animal studies on acupuncture for inflammation-induced visceral pain, and reflects on acupuncture-related therapies for dysmenorrhea with regard to their anti-inflammatory characteristics. Further research accordingly needs to be carried out to clarify the effects of acupuncture on proinflammatory factors in PD, particularly chemokines and leukocytes. Future studies on this condition from an anti-inflammatory perspective should be also performed in line with the notion of emphasizing stimulation modes to optimize the clinical modalities of acupuncture. Additionally, the effects and mechanism of more convenient self-healing approaches such as TENS/TEAS for PD should be investigated.

7.
Gland Surg ; 10(6): 1989-2001, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34268083

RESUMO

BACKGROUND: To investigate the performance of a radiomics model based on gray-scale ultrasonography (US) for the preoperative non-invasive prediction of ipsilateral axillary lymph node (ALN) metastasis in patients with breast cancer (BC). METHODS: A total of 192 pathologically confirmed BC patients were included in this study. The training set was comprised of 132 patients from hospital 1 and the test set was comprised of 60 patients from hospital 2. All patients underwent US before percutaneous core biopsy and the results of ALN status reported by a radiologist with 12 years of experience were recorded. Radiomic features were extracted from the gray-scale US images. Max-relevance and min-redundancy (MRMR) and least absolute shrinkage and selection operator (LASSO) were used for data dimension reduction and feature selection. A radiomics model was constructed using LASSO and was validated using the leave group out cross-validation (LGOCV) method. The performance of the model was validated with receiver operating characteristic (ROC), calibration curve, and decision curve analysis. RESULTS: A total of 860 features were extracted from the gray-scale US images of each breast lesion, and 9 radiomic features were selected for model construction. The area under the curve (AUC), sensitivity, and specificity of the model for predicting ALN metastasis were 0.85, 78.9%, and 77.3% in the training set and 0.65, 68.0%, and 79.4% in the test set, respectively. The prediction performance of the model was significantly higher than that of the radiologist (AUC: 0.85 vs. 0.59, P<0.01) in the training set and was slightly higher than that of the radiologist (AUC: 0.65 vs. 0.63, P>0.05) in the test set. CONCLUSIONS: The non-invasive radiomics model has the ability to predict ALN metastasis for patients with breast cancer and may outperform US-reported ALN status performed by the radiologist.

8.
J Med Ultrason (2001) ; 48(1): 53-61, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33439373

RESUMO

PURPOSE: To evaluate tissue stiffness values around breast lesions and stiff rim sign for the differentiation of benign and malignant lesions. METHODS: A total of 192 patients (mean age, 44.6 ± 13.6 years) with 199 breast lesions were included in this retrospective study. All lesions were pathologically proven by US-guided core needle biopsy (CNB), Mammotome biopsy, or surgery. We first observed the presence or absence of a stiff rim sign, which was defined as a red or orange halo around the breast lesion. The shell around the breast lesion on SWE was then automatically drawn by machine, with a width of 1 mm, 2 mm, and 3 mm. The elasticity moduli of the lesion and surrounding tissue were recorded, including maximum elasticity (Emax), mean elasticity (Emean), minimum elasticity (Emin), and elasticity ratio (shell/lesion ratio). The optimal thresholds of elasticity moduli were calculated according to the receiver operating characteristic (ROC) curve. RESULTS: There were 75 malignant lesions and 124 benign ones. The average Emax and Emean of lesions and shell were significantly higher in the malignant group than in the benign group (P < 0.05). The optimal cut-off value of Emax for diagnosing malignant lesions was 101.7 kPa, with a sensitivity of 66.3% and specificity of 87.9%. The optimal cut-off value of Emean was 29.1 kPa, with a sensitivity of 65.3% and specificity of 79.8%. The stiff rim sign had the highest diagnostic performance for malignancy as compared with other elastic parameters, with an accuracy of 88.4%. However, measuring peritumoral tissue stiffness can achieve relatively high sensitivity, whereas specificity was not improved significantly. CONCLUSIONS: The stiffness of tissue surrounding breast malignancies was significantly higher than the surrounding benign lesions. Stiff rim sign has the potential to improve the diagnostic performance of breast lesions.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Técnicas de Imagem por Elasticidade/métodos , Ultrassonografia Mamária/métodos , Adolescente , Adulto , Idoso , Biópsia com Agulha de Grande Calibre , Mama/diagnóstico por imagem , Mama/patologia , Neoplasias da Mama/patologia , Diagnóstico Diferencial , Módulo de Elasticidade , Feminino , Humanos , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto Jovem
9.
J Microbiol Immunol Infect ; 54(2): 206-212, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31204209

RESUMO

BACKGROUND: Interleukin 6 (IL-6) induce the inflammatory response directly related with the morbidity and mortality of neonatal. Here we aimed to explore the mechanism of IL-6 in neonatal inflammatory response by studying the IL-6/STAT3 signaling pathway. METHODS: Cord blood samples from health term neonatal and peripheral venous blood from health volunteers were collected. The monocytes of adults and cord blood were isolated and induced into macrophages. Then the macrophages were pretreated with or without MG132 before IL-6 stimulation. Proteins were analyzed by Western blot, mRNA by real time PCR and membrane molecule by flow cytometry. RESULTS: The acute phase protein gene expression in neonatal macrophages after stimulated with IL-6 were higher than that in adult. Significantly enhanced phosphorylation of STAT3 was seen in neonatal macrophages. Both mRNA and protein expression of SOCS3 in neonatal macrophages were lower than that in adult. After pretreated with MG132, the expression of SOCS3 protein was increased which lead to attenuate the STAT3 phosphorylation and APP gene expression. CONCLUSION: Neonatal exhibit an enhanced expression of downstream target genes and IL-6/STAT3 signal pathway which is related with the diminished SOCS3. This provides a new sight into inflammatory responses in neonatal.


Assuntos
Proteínas de Fase Aguda/genética , Proteínas de Fase Aguda/metabolismo , Interleucina-6/metabolismo , Proteína 3 Supressora da Sinalização de Citocinas/genética , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo , Adulto , Regulação da Expressão Gênica , Humanos , Macrófagos/metabolismo , Monócitos/metabolismo , RNA Mensageiro/genética , Fator de Transcrição STAT3 , Transdução de Sinais/genética , Adulto Jovem
10.
Eur J Pharmacol ; 887: 173474, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32783960

RESUMO

Propofol is generally used for the induction and maintenance of anesthesia in clinical procedures via activation of γ -aminobutyric acid A (GABAA) receptors. When administered at the clinical dose, propofol use is associated with movement disorders, including dystonia and ataxia, suggesting that propofol administration impacts the function of cerebellar neuronal circuitry. In this study, we investigated the effect of propofol on climbing fiber (CF)-Purkinje cell (PC) synaptic transmission in mouse cerebellar slices in the absence of GABAergic inhibition using a whole-cell recording technique and pharmacological methods. Our results showed that bath application of propofol enhanced CF-PC synaptic transmission, which was demonstrated by an increased amplitude and area under the curve (AUC) of the excitatory postsynaptic currents (EPSCs) accompanied by a decrease in the paired-pulse ratio (PPR). The propofol-induced increase in the amplitude of P1 was concentration-dependent with a half effective concentration (EC50) of 20.9 µM. The propofol-induced increases in the amplitude and AUC of CF-PC EPSCs were abolished by an N-Methyl-D-aspartate (NMDA) receptor blocker. Furthermore, the application of NMDA enhanced CF-PC EPSCs and overwhelmed the effect of propofol on CF-PC EPSCs. Moreover, intracellular blockade of NMDA receptors attenuated the propofol-induced enhancement of CF-PC synaptic transmission but strengthened the propofol-induced change in the PPR. These results indicate that propofol enhances CF-PC synaptic transmission by activation of NMDA receptors in the mouse cerebellar cortex, suggesting that propofol administration might be involved in propofol-induced dysfunction of the cerebellum via NMDA receptors.


Assuntos
Propofol/farmacologia , Células de Purkinje/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/agonistas , Transmissão Sináptica/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Antagonistas de Aminoácidos Excitatórios/farmacologia , Hipnóticos e Sedativos/farmacologia , Camundongos , Camundongos Endogâmicos ICR , Células de Purkinje/fisiologia , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Receptores de N-Metil-D-Aspartato/fisiologia , Transmissão Sináptica/fisiologia
11.
BMC Ophthalmol ; 20(1): 318, 2020 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-32753041

RESUMO

BACKGROUND: To report refractive outcomes, describe types of strabismus and evaluate the outcomes of surgical intervention for unilateral coronal synostosis (UCS) in paediatric patients. METHODS: This study retrospectively included 30 UCS cases. Patients aged from 3 months to 6 years (median: 1.8 years) were enrolled from January 2018 to December 2019 at Shanghai Children's Hospital. Sixteen patients had all types of strabismus; 15 of these patients underwent surgery. RESULTS: Refractive errors of 30 cases were included. In 60% of patients, astigmatism of 1.00D or more existed in not less than one eye at last record. Twenty (66.7%) patients had the larger amount of astigmatism in the contralateral eye. Fifteen patients received strabismus surgery, of whom 6 patients with monocular elevation deficiency (MED) underwent the standard Knapp procedure, with or without a horizontal deviation procedure. Fifteen cases were horizontally aligned within 5 prism dioptres (Δ). Six patients with MED (100%) had attained ≥25% elevation improvement after surgery, and the vertical deviation decreased from 25.83 Δ ± 4.92 Δ (range, 20 Δ-30 Δ) to 0.83 Δ ± 4.92 Δ after surgery (range, 0 Δ-10 Δ), for an improvement of 26.67 Δ ± 4.08 Δ (t = 16 P < 0.05). In 1 patient with esotropia, the horizontal deviation decreased from + 80 Δ to + 5 Δ after surgery. One patient was diagnosed with trichiasis and one with contralateral lacrimal duct obstruction. CONCLUSIONS: Contralateral MED was also the main type of strabismus in UCS. Superior oblique muscle palsy was still the most common, as previously reported. There is a risk of developing a higher astigmatism and anisometropia in the contralateral eye to synostosis. Other ophthalmic disorders should be treated in a timely manner. TRIAL REGISTRATION: The study was approved by the Institutional Review Board of Shanghai Children's Hospital (approval No. 2020R023-E01) and adhered to the tenets of the Declaration of Helsinki. Ethics approval was procured on March 30, 2020. This was a retrospective study. Written informed consent was sought from the patients' parents or legal guardians. Clinical Trials Registry number: ChiCTR2000034910 . Registration URL: http://www.chictr.org.cn/showproj.aspx?proj=56726 .


Assuntos
Craniossinostoses , Estrabismo , Criança , Pré-Escolar , China/epidemiologia , Craniossinostoses/cirurgia , Humanos , Músculos Oculomotores , Procedimentos Cirúrgicos Oftalmológicos , Estudos Retrospectivos , Estrabismo/cirurgia
12.
Zhongguo Zhong Yao Za Zhi ; 44(19): 4249-4256, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31872706

RESUMO

In this study,liquiritigenin sulfonation was characterized using recombinant human sulfotransferases( SULTs). The chemical structure of liquiritigenin sulfate was determined by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry( UPLC-Q-TOF-MS/MS). Then model fitting and parameter estimation were performed using the Graphpad Prism V5 software. Various SULT enzymes( SULT1 A1,1 A2,1 A3,1 B1,1 C2,1 C4,1 E1 and 2 A1) were able to catalyze the formation of liquiritigenin-7-O-sulfate. Sulfonation of liquiritigenin-7-hydroxy( 7-OH) by these eight SULT enzymes consistently displayed the classical Michaelis-Menten profile. According to the intrinsic clearance( CLint) value,the sulfonation rates of liquiritigenin-7-OH by expressed SULT enzymes followed the following rank order: SULT1 C4 > SULT1 A3 > SULT1 E1 > SULT1 A1 > SULT1 A2 > SULT1 B1 >SULT1 C2>SULT2 A1. Further,liquiritigenin-7-O-sulfonation was significantly correlated with the SULT1 A3 protein levels( P<0. 05).Then,human embryonic kidney( HEK) 293 cells over expressing SULT1 A3( named as HEK-SULT1 A3 cells) were conducted. As a result,liquiritigenin-7-O-sulfate( L-7-S) was rapidly generated upon incubation of the cells with liquiritigenin. Consistent with SULT1 A3,sulfonation of liquiritigenin-7-OH in HEK-SULT1 A3 cells also followed the Michaelis-Menten kinetics. The derived Vmaxvalues was( 0. 315±0. 009) µmol·min-1·g-1,Kmwas( 7. 04±0. 680) µmol·L-1,and CLintwas( 0. 045±0. 005) L·min-1·g-1. Moreover,the sulfonation characters of liquiritigenin( 7-OH) in SULT1 A3 were strongly correlated with that in HEK-SULT1 A3 cells( P<0. 001).The results indicated that HEK-SULT1 A3 cells have shown the catalytic function of SULT1 A3 enzymes. In conclusion,liquiritigenin was subjected to efficient sulfonation,and SULT1 A3 enzyme plays an important role in the sulfonation of liquiritigenin-7-OH. Significant sulfonation should be the main reason for the low bioavailability of liquiritigenin. In addition,HEK-SULT1 A3 cells were conducted and successfully used to evaluate liquiritigenin sulfonation,which will provide an appropriate tool to accurately depict the sulfonation disposition of liquiritigenin in vivo.


Assuntos
Flavanonas/metabolismo , Espectrometria de Massas em Tandem , Arilsulfotransferase , Humanos
13.
Cancer Cell Int ; 19: 168, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31285694

RESUMO

Background: DKK1 has been reported to act as a tumor suppressor in breast cancer. However, the mechanism of DKK1 inhibits breast cancer migration and invasion was still unclear. Methods: Western blot and real time PCR was used to detect the expression of DKK1, ß-catenin and MMP7 in breast cancer cells. Wound scratch assay and transwell assay was employed to examine migration and invasion of breast cancer cell. Results: DKK1 overexpression dramatically inhibits breast cancer cell migration and invasion. Knockdown of DKK1 promotes migration and invasion of breast cancer cells. DKK1 suppressed breast cancer cell migration and invasion through suppression of ß-catenin and MMP7 expression. XAV-939, an inhibitor of ß-catenin accumulation could reverse DKK1 silencing-induced MMP7 expression in breast cancer cells. Meanwhile, XAV-939 also could reverse the increase in the cell number invaded through Matrigel when DKK1 was knockdown. Furthermore, depletion of MMP7 also could reverse DKK1 knockdown-induced increase in the cell number invaded through Matrigel. Conclusions: DKK1 inhibits migration and invasion of breast cancer cell through suppression of ß-catenin/MMP7 pathway, our findings offered a potential alternative for breast cancer prevention and treatment.

14.
Cell Biol Int ; 43(8): 931-939, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31124219

RESUMO

Phosphoinositide 3-kinase (PI3K) signaling is frequently deregulated in breast cancer and plays a critical role in tumor progression. However, resistance to PI3K inhibitors in breast cancer has emerged, which is due to the enhanced ß-catenin nuclear accumulation. Until now, the mechanisms underlying PI3K inhibition-induced ß-catenin nuclear accumulation remains largely unknown. In the present study, we found inhibition of PI3K with LY294002 promoted ß-catenin nuclear accumulation in MCF-7 and MDA-MB-231 breast cancer cells. Combining PI3K inhibitor LY294002 with XAV-939, an inhibitor against ß-catenin nuclear accumulation, produced an additive anti-proliferation effect against breast cancer cells. Subsequent experiments suggested ß-catenin nuclear accumulation induced by PI3K inhibition depended on the feedback activation of epidermal growth factor receptor (EGFR) signaling pathway in breast cancer cells. Inhibition of EGFR phosphorylation with Gefitinib enhanced anti-proliferation effect of PI3K inhibitor LY294002 in MCF-7 and MDA-MB-231 cells. Taken together, our findings may elucidate a possible mechanism explaining the poor outcome of PI3K inhibitors in breast cancer treatment.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Cromonas/farmacologia , Gefitinibe/farmacologia , Compostos Heterocíclicos com 3 Anéis/farmacologia , Morfolinas/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB/antagonistas & inibidores , Feminino , Humanos , Células MCF-7 , Inibidores de Fosfoinositídeo-3 Quinase , beta Catenina/antagonistas & inibidores
15.
Pediatr Neonatol ; 59(3): 288-295, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29054363

RESUMO

BACKGROUND: The uncontrolled inflammatory response following infection is closely related to the morbidity and mortality of neonates. Interleukin 6 (IL-6) plays an important role in the pathogenesis and prognosis of this process. To better elucidate the secretion of IL-6 following infection in neonates, we investigated the IL-6 level and mechanism of IL-6/TLR4 signaling pathways. METHODS: We compared the IL-6, procalcitonin (PCT), and CRP levels between septic neonates and toddlers. In vitro cord blood samples from healthy term neonates and peripheral venous blood from healthy adult volunteers were collected. Protein expression was analyzed by Western blotting, mRNA expression by real-time PCR and membrane molecule expression by flow cytometry. RESULTS: The IL-6 concentrations were significantly higher in the neonate group than in the toddler group (p < 0.05). In the toddler group, the IL-6 concentrations were correlated positively with both PCT and CRP (PCT: r = 0.451, p = 0.001; CRP: r = 0.243, p = 0.023). In vitro, the secretion of IL-6 increased with the rising concentrations of LPS; at 1000 ng/ml LPS, IL-6 secretion from the monocytes of neonates was significantly higher than that of adults. There was a marked decreased level of MyD88 in neonate monocytes compared with that in adult monocytes. Additionally, the mRNA levels of Zc3h12a in neonate monocytes were significantly lower than those in adult monocytes following LPS stimulation. CONCLUSION: Neonates displayed enhanced IL-6 production after infection. Our study, for the first time, reported a significant decrease in the expression of Zc3h12a in neonates. Thus, Zc3h12a may be a key factor for the aberrant increase in IL-6 after neonate infection.


Assuntos
Interleucina-6/biossíntese , Lipopolissacarídeos/farmacologia , Monócitos/imunologia , Ribonucleases/fisiologia , Fatores de Transcrição/fisiologia , Adulto , Proteína C-Reativa/análise , Criança , Pré-Escolar , Humanos , Recém-Nascido , NF-kappa B/fisiologia , Pró-Calcitonina/sangue , Receptor 4 Toll-Like/fisiologia
16.
Zhongguo Zhong Yao Za Zhi ; 42(1): 170-174, 2017 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-28945044

RESUMO

Cor pulmonale rat models were induced by a single intraperitoneal injection of monocrotaline(MCT), and the sham group received a single intraperitioneal injection of normal saline. After the model rats received intragastric administration of Qishen Yiqi droplet(QS) for 6 weeks, the contents of adenylate(ATP, ADP and AMP) in right myocardial tissues were measured by HPLC, and then the metabolism changes in myocardium of cor pulmonale rats with QS were investigated. The results showed that ATP, ADP, and AMP were well separated, with a good linearity within a certain range of concentration; and the recovery rates were within the range of 90%-108%. As compared with model group, the level of ATP was significantly elevated in high-dose treatment group; ADP contents showed an increasing trend and AMP contents showed a decreasing trend, indicating that QS could significantly improve energy metabolism system in myocardium. By using the HPLC, a qualitative and quantitative analysis method was given for the determination of ATP, ADP and AMP contents in myocardium, providing a method for energy metabolism measurement in biological samples.


Assuntos
Monofosfato de Adenosina/química , Medicamentos de Ervas Chinesas/farmacologia , Miocárdio/química , Doença Cardiopulmonar/tratamento farmacológico , Animais , Ratos
17.
J Immunol Res ; 2017: 8745254, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28251166

RESUMO

Chronic Granulomatous Disease (CGD) is a rare inherited primary immunodeficiency, which is characterized by recurrent infections due to defective phagocyte NADPH oxidase enzyme. Nowadays, little is known about Chinese CGD patients. Here we report 48 CGD patients in our single center study, which is the largest cohort study from Mainland China. The ratio of male to female was 11 : 1. The mean onset age was 0.29 years old, and 52% patients had an onset within the 1st month of life. The mean diagnosis age was 2.24 years old. 11 patients (23%) had died with an average age of 2.91 years old. 13 patients (28%) had positive family histories. The most prevalent infectious sites were the lungs (77%), followed by gastrointestinal tract (54%), lymph nodes (50%), and skin (46%). In addition, septicopyemia, thrush, and hepatosplenomegaly were also commonly observed, accounting for 23%, 23%, and 40% of the cases. Lesions due to BCG vaccination occurred in more than half of the patients. X-linked CGD due to CYBB gene mutations accounted for 75% of the cases, and 11 of them were novel mutations. Autosomal recessive inheritance accounted for 6% patients, including 1 patient with CYBA, 1 with NCF1, and 1 with NCF2 gene mutations.


Assuntos
Doença Granulomatosa Crônica/genética , Doença Granulomatosa Crônica/fisiopatologia , Mutação , Adolescente , Adulto , Idoso , Vacina BCG/efeitos adversos , Criança , Pré-Escolar , China/epidemiologia , Estudos de Coortes , Feminino , Trato Gastrointestinal/microbiologia , Testes Genéticos , Doença Granulomatosa Crônica/congênito , Doença Granulomatosa Crônica/epidemiologia , Humanos , Síndromes de Imunodeficiência/genética , Lactente , Pulmão/microbiologia , Linfonodos/microbiologia , Masculino , Glicoproteínas de Membrana/genética , Pessoa de Meia-Idade , NADPH Oxidase 2 , NADPH Oxidases/genética , Pele/microbiologia , Adulto Jovem
18.
J Agric Food Chem ; 65(12): 2615-2627, 2017 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-28260382

RESUMO

A rapid, sensitive, and efficient ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) method has been developed to analyze polymethoxylated flavonoids (PMFs) in 14 Citrus peels, including 7 Citrus reticulata (C. reticulata) and 7 Citrus sinensis (C. sinensis). In this study, fast separation can be achieved within 12 min and 42 PMFs have been identified including 33 flavones and 9 flavanones. Most C. reticulata were shown to contain more than 20 PMFs, except Guangxihongpisuanju (GX) containing only 12 PMFs, while most C. sinensis contained fewer than 20 PMFs, except Edangan (EG) containing as many as 32 PMFs. To our knowledge, there are few reports about the quantitation of PMFs using the MS response. Here, a MS quantitative method was established and systematically validated in linearity, precision, and recovery. The linearity was from 1.25 ng/mL to 1.0 µg/mL with the limit of detection (LOD) as low as 75 pg/mL and the limit of quantitation (LOQ) as low as 0.25 ng/mL. Up to 13 PMFs, more types than ever before, were undoubtedly identified and quantitated according to the PMF standards. The results showed that the contents of PMFs in the C. reticulata were generally higher than those in the C. sinensis. This study is systematic for analyzing PMFs and is of great significance because it can provide guidance on utilization of both PMFs and citrus germplasm resources in the future.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Citrus/química , Flavonoides/química , Extratos Vegetais/química , Espectrometria de Massas em Tandem/métodos , Limite de Detecção , Estrutura Molecular , Espectrometria de Massas por Ionização por Electrospray/métodos
19.
Medicine (Baltimore) ; 95(32): e4544, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27512878

RESUMO

X-linked agammaglobulinemia (XLA) is a humoral primary immunodeficiency. XLA patients typically present with very low numbers of peripheral B cells and a profound deficiency of all immunoglobulin isotypes. Most XLA patients carry mutations in Bruton tyrosine kinase (BTK) gene.The genetic background and clinical features of 174 Chinese patients with XLA were investigated. The relationship between specific BTK gene mutations and severity of clinical manifestations was also examined. Mutations were graded from mild to severe based on structural and functional prediction through bioinformatics analysis.One hundred twenty-seven mutations were identified in 142 patients from 124 families, including 45 novel mutations and 82 recurrent mutations that were distributed over the entire BTK gene sequence. Variation in phenotypes was observed, and there was a tendency of association between genotype and age of disease onset.This report constitutes the largest group of patients with BTK mutations in China. A genotype-phenotype correlation was observed in this study. Early diagnosis of congenital agammaglobulinemia should be based on clinical symptoms, family history, and molecular analysis of the BTK gene.


Assuntos
Agamaglobulinemia/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Adolescente , Tirosina Quinase da Agamaglobulinemia , Agamaglobulinemia/patologia , Idade de Início , Antígenos CD19/imunologia , Criança , Pré-Escolar , China/epidemiologia , Estudos de Associação Genética , Doenças Genéticas Ligadas ao Cromossomo X/patologia , Humanos , Imunoglobulinas/sangue , Masculino , Mutação/genética , Proteínas Tirosina Quinases/genética , Estudos Retrospectivos
20.
Orthop Surg ; 8(2): 150-61, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27384723

RESUMO

OBJECTIVE: To introduce a new classification of Enneking type IV pelvic tumors involving the sacrum and a corresponding system of standardized surgical approaches and procedures for resection of such tumors, and to investigate the feasibility and therapeutic effect of the new system. METHODS: Data on 59 patients treated between February 2003 and February 2013 by standardized surgical approaches and procedures were retrospectively reviewed. The study subjects comprised 28 male and 31 female patients with a mean age at diagnosis of 36 years (range, 2-72 years). There are four subtypes in the new classification: (i) subtype IVa, neoplasms invading the ipsilateral sacral wing; (ii) subtype IVb, neoplasms invading the ipsilateral sacral foramina; (iii) subtype IVc, neoplasms invading the contralateral sacral foramina; and (iv) subtype IVd, neoplasms invading the whole of the sacrum. Standardized surgical approaches and procedures were devised for en-bloc resection for each subtype with adequate margins. RESULTS: Adequate margins were achieved in 43/59 patients (72.9%). The mean operation time was 5.0 h and the mean intraoperative blood loss 2157 mL. At the final follow-up, 27/53 patients (50.9%) who had been followed up were alive and in complete remission. The mean Musculoskeletal Tumor Society 93 score was 17.4 (58%) of a possible 30 points. The mean functional score for patients who had undergone a pelvic zone II resection was 15.2, compared with 19.0 for those with an intact pelvic zone II. CONCLUSIONS: The proposed standardized protocols should help orthopaedic surgeons to achieve adequate margins, manage risk, achieve better oncologic and functional outcomes, and minimize perioperative complications when treating massive pelvic tumors involving the sacrum.


Assuntos
Neoplasias Ósseas/classificação , Estadiamento de Neoplasias , Procedimentos Ortopédicos/métodos , Sacro , Adolescente , Adulto , Idoso , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/cirurgia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Reconstrutivos/métodos , Estudos Retrospectivos , Adulto Jovem
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