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1.
BMC Med ; 22(1): 55, 2024 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-38317152

RESUMO

BACKGROUND: Implementation of high-risk human papillomavirus (hrHPV) screening has greatly reduced the incidence and mortality of cervical cancer. However, a triage strategy that is effective, noninvasive, and independent from the subjective interpretation of pathologists is urgently required to decrease unnecessary colposcopy referrals in hrHPV-positive women. METHODS: A total of 3251 hrHPV-positive women aged 30-82 years (median = 41 years) from International Peace Maternity and Child Health Hospital were included in the training set (n = 2116) and the validation set (n = 1135) to establish Cervical cancer Methylation (CerMe) detection. The performance of CerMe as a triage for hrHPV-positive women was evaluated. RESULTS: CerMe detection efficiently distinguished cervical intraepithelial neoplasia grade 2 or worse (CIN2 +) from cervical intraepithelial neoplasia grade 1 or normal (CIN1 -) women with excellent sensitivity of 82.4% (95% CI = 72.6 ~ 89.8%) and specificity of 91.1% (95% CI = 89.2 ~ 92.7%). Importantly, CerMe showed improved specificity (92.1% vs. 74.9%) in other 12 hrHPV type-positive women as well as superior sensitivity (80.8% vs. 61.5%) and specificity (88.9% vs. 75.3%) in HPV16/18 type-positive women compared with cytology testing. CerMe performed well in the triage of hrHPV-positive women with ASC-US (sensitivity = 74.4%, specificity = 87.5%) or LSIL cytology (sensitivity = 84.4%, specificity = 83.9%). CONCLUSIONS: PCDHGB7 hypermethylation-based CerMe detection can be used as a triage strategy for hrHPV-positive women to reduce unnecessary over-referrals. TRIAL REGISTRATION: ChiCTR2100048972. Registered on 19 July 2021.


Assuntos
Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Feminino , Humanos , Metilação de DNA , Detecção Precoce de Câncer , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Papillomaviridae , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Estudos Prospectivos , Sensibilidade e Especificidade , Triagem , Displasia do Colo do Útero/diagnóstico , Displasia do Colo do Útero/epidemiologia , Displasia do Colo do Útero/genética , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/genética , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais
2.
Molecules ; 29(5)2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38474506

RESUMO

Natural products obtained from marine organisms continue to be a rich source of novel structural architecture and of importance in drug discovery, medicine, and health. However, the success of such endeavors depends on the exact structural elucidation and access to sufficient material, often by stereoselective total synthesis, of the isolated natural product of interest. (-)-Mucosin (1), a fatty acid derivative, previously presumed to contain a rare cis-bicyclo[4.3.0]non-3-ene moiety, has since been shown to be the trans-congener. Analytically, the fused bicyclic ring system in (-)-1 constitutes a particular challenge in order to establish its relative and absolute stereochemistry. Herein, data from biological evaluations, NMR and molecular modeling studies of (-)-1 are presented. An overview of the synthetic strategies enabling the exact structural elucidation of (-)-mucosin (1) is also presented.


Assuntos
Produtos Biológicos , Compostos Bicíclicos Heterocíclicos com Pontes , Produtos Biológicos/química , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Estereoisomerismo
3.
Small ; 19(37): e2301043, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37154208

RESUMO

Heterogeneity and drug resistance of tumor cells are the leading causes of incurability and poor survival for patients with recurrent breast cancer. In order to accurately deliver the biological anticancer drugs to different subtypes of malignant tumor cells for omnidirectional targeted treatment of recurrent breast cancer, a distinct design is demonstrated by embedding liposome-based nanocomplexes containing pro-apoptotic peptide and survivin siRNA drugs (LPR) into Herceptin/hyaluronic acid cross-linked nanohydrogels (Herceptin-HA) to fabricate a HER2/CD44-targeted hydrogel nanobot (named as ALPR). ALPR delivered cargoes to the cells overexpressing CD44 and HER2, followed by Herceptin-HA biodegradation, subsequently, the exposed lipid component containing DOPE fused with the endosomal membrane and released peptide and siRNA into the cytoplasm. These experiments indicated that ALPR can specifically deliver Herceptin, peptide, and siRNA drugs to HER2-positive SKBR-3, triple-negative MDA-MB-231, and HER2-negative drug-resistant MCF-7 human breast cancer cells. ALPR completely inhibited the growth of heterogeneous breast tumors via multichannel synergistic effects: disrupting mitochondria, downregulating the survivin gene, and blocking HER2 receptors on the surface of HER2-positive cells. The present design overcomes the chemical drug resistance and opens a feasible route for the combinative treatment of recurrent breast cancer, even other solid tumors, utilizing different kinds of biological drugs.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/metabolismo , Survivina , Hidrogéis , Trastuzumab/farmacologia , Trastuzumab/uso terapêutico , RNA Interferente Pequeno , Linhagem Celular Tumoral , Receptor ErbB-2/genética , Receptores de Hialuronatos/metabolismo
4.
Cancer Cell Int ; 23(1): 92, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-37183243

RESUMO

BACKGROUND: Rather low vaccination rates for Human papillomavirus (HPV) and pre-existing cervical cancer patients with limited therapeutic strategies ask for more precise prognostic model development. On the other side, the clinical significance of circadian clock signatures in cervical cancer lacks investigation. METHODS: Subtypes classification based upon eight circadian clock core genes were implemented in TCGA-CESC through k-means clustering methods. Afterwards, KEGG, GO and GSEA analysis were conducted upon differentially expressed genes (DEGs) between high and low-risk groups, and tumor microenvironment (TME) investigation by CIBERSORT and ESTIMATE. Furthermore, a prognostic model was developed by cox and lasso regression methods, and verified in GSE44001 by time-dependent receiver-operating characteristic curve (ROC) analysis. Lastly, FISH and IHC were used for validation of CCL20 expression in patients' specimens and U14 subcutaneous tumor models were built for TME composition. RESULTS: We successfully classified cervical patients into high-risk and low-risk groups based upon circadian-oscillation-signatures. Afterwards, we built a prognostic risk model composed of GJB2, CCL20 and KRT24 with excellent predictive value on patients' overall survival (OS). We then proposed metabolism unbalance, especially for glycolysis, and immune related pathways to be major enriched signatures between the high-risk and low-risk groups. Then, we proposed an 'immune-desert'-like suppressive myeloid cells infiltration pattern in high-risk group TME and verified its resistance to immunotherapies. Finally, CCL20 was proved positively correlated with real-world patients' stages and induced significant less CD8+ T cells and more M2 macrophages infiltration in mouse model. CONCLUSIONS: We unraveled a prognostic risk model based upon circadian oscillation and verified its solidity. Specifically, we unveiled distinct TME immune signatures in high-risk groups.

5.
BMC Womens Health ; 23(1): 154, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-37005604

RESUMO

BACKGROUND: Benign metastasizing leiomyoma (BML) is a rare disease usually observed in women of reproductive or premenopausal age with a history of uterine myomectomy or hysterectomy. The most common sites of metastases are the pulmonary, and other sites include heart, bones, liver, lymph nodes, bladder, skeletal muscles, and central nervous system. Here, we report a case of a 50 year-old woman with a history of hysterectomy who was initially suspected of uterine sarcoma but was finally confirmed to have BML with lung and lymph node metastases, and discuss the treatment and prognosis of BML. CASE PRESENTATION: A 50 year-old woman with a history of total abdominal hysterectomy presented with mild but persistent abdominal pain for more than 3 months. She was suspected of having uterine sarcoma before surgery and laparoscopic extensive debulking surgery including bilateral oophorectomy, pelvic and para-aortic lymph node dissection to the level of the left renal vein, and transcutaneous dissection of the right inguinal lymph nodes. Pathology confirmed a benign leiomyoma, and the patient was diagnosed with BML. No medication was administered after the surgery, and the follow-up was of no significance. CONCLUSION: Benign metastasizing leiomyoma (BML) is a rare disorder in which histologically benign smooth muscle tumors metastasize to extrauterine sites. Metastases are commonly observed in the lung, liver, lymph nodes, skin, bladder, esophagus, and skeletal muscles. BML is usually misdiagnosed as a malignant tumor before surgery until the pathology confirms its benign nature. However, this treatment remains controversial and undetermined. The prognosis is usually favorable owing to its benign nature.


Assuntos
Leiomioma , Neoplasias Pulmonares , Sarcoma , Neoplasias Uterinas , Feminino , Humanos , Pessoa de Meia-Idade , Leiomioma/cirurgia , Leiomioma/patologia , Neoplasias Uterinas/patologia , Histerectomia
6.
Ecotoxicol Environ Saf ; 268: 115698, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37976927

RESUMO

Humic acids (HA) are a popular soil additive to reduce metal availability, but they have the drawbacks of reduced effectiveness over time and a significant reduction in soil pH. An alkaline humic acid fertilizer (AHAF) combining alkaline additives with HA was developed to overcome such drawbacks. A field experiment was conducted to investigate the effects of different AHAF application rates on the physicochemical properties, bioavailability, accumulation, and translocation of Cd and Zn heavy metals in Sauropus androgynus grown in acidic soil. Based on our results, the 100AF (100% AHAF) treatment significantly increased soil pH, cation exchange capacity (CEC), and organic matter content (OM) after one year of application. Compared with the control treatment (CK), the application of different rates of AHAF resulted in a 37.1-40.3% decrease in soil exchangeable Cd fractions (Exc-Cd) and an increase in the humic acid-bound Cd fractions (HA-Cd) Fe- and Mn-oxide-bound Cd fractions (OX-Cd), and organic matter-bound Cd fractions (OM-Cd) by 9.5-64.6%, 24.8-45.1%, and 158.8-191.2%, respectively (P < 0.05). The different AHAF treatments decreased the Res-Zn, Exc-Zn, and OM-Zn fractions by 69.6-73.0%, 7.4-23.9%, and 18.1-23.2%, respectively (P < 0.05), and increased the HA-Zn fraction by 8.4-28.1%. In the control treatment, the bioconcentration factors (BCFs) for Cd and Zn in different S. androgynus plant organs were in the following order: (Cd) Leaves > Stems > Branches > Roots > Edible branches; (Zn) Roots > Stems > Leaves > Branches > Edible branches. The transfer factors (TFs) of Cd and Zn in S. androgynus were classified as follows: TF2 > TF1 > TF3 > TF4. Thus, S. androgynus stems, and roots had a strong ability to transport Cd and Zn to the leaves. Compared with CK, the 100AF treatment significantly increased the BCFs for Zn in all plant parts (except BCFedible branches). In contrast, it significantly decreased all BCFs and TFs for Cd and the TF4 for Zn, effectively reducing Cd and Zn accumulation in the edible branches of S. androgynus. Soil pH, CEC, OM, and HA-M fraction were highly and significantly negatively correlated with Cd and Zn content in edible branches (P < 0.001). Stepwise multiple linear regression analysis revealed that the soil HA-M fraction was the key contributing factor for Zn accumulation and translocation in S. androgynus. Moreover, based on our findings, the absorption, uptake, and translocation of Cd and Zn were mainly determined by metal speciation and the pH in the soil. Moreover, the competitive antagonistic mechanisms between Zn and Cd absorption also affected their accumulation in S. androgynus. Thus, AHAF can be used as a soil amendment to sustainably improve acidic soils and effectively reduce Cd and Zn accumulation in edible branches of S. androgynus.


Assuntos
Metais Pesados , Poluentes do Solo , Cádmio/análise , Zinco/análise , Solo/química , Substâncias Húmicas/análise , Fertilizantes/análise , Poluentes do Solo/análise , Metais Pesados/análise
7.
Acta Chir Belg ; 123(4): 448-453, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35135434

RESUMO

BACKGROUND: Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant disorder characterized by a predisposition to the development of multiple neoplasms. Gastric-type mucinous adenocarcinoma (GAS), a new variant of carcinoma of the cervix according to 2014 WHO classification, is less common compared with squamous cell carcinoma, is more aggressive and has a lower 5-year survival rate compared with the usual-type endocervical adenocarcinoma, and is also unrelated to human papillomavirus (HPV) infection. CASE SUMMARY: We herein present the case of a 32-year-old patient with PJS who was diagnosed with GAS of the cervix. The patient was not sexually active and had been diagnosed with PJS at 2 years of age. A tumor ∼6 cm was found on the cervix and was diagnosed as GAS of the cervix of clinical-stage IB3. The patient was treated with intra-arterial chemotherapy for one course, followed by radical surgery and then systematic chemotherapy. CONCLUSION: The present case highlights the need for more thorough cancer screening for patients with PJS, as this disorder is rare and is associated with a high risk of malignancies. Young patients with PJS, including those who are not sexually active, who present with watery vaginal discharge or bleeding should be screened for cervical carcinoma, even if the cytological results or HPV tests are negative.


Assuntos
Adenocarcinoma Mucinoso , Infecções por Papillomavirus , Síndrome de Peutz-Jeghers , Neoplasias Gástricas , Neoplasias do Colo do Útero , Feminino , Humanos , Adulto , Colo do Útero/patologia , Síndrome de Peutz-Jeghers/complicações , Síndrome de Peutz-Jeghers/diagnóstico , Síndrome de Peutz-Jeghers/cirurgia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/patologia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/terapia , Adenocarcinoma Mucinoso/complicações , Adenocarcinoma Mucinoso/diagnóstico , Adenocarcinoma Mucinoso/cirurgia , Neoplasias Gástricas/patologia
8.
J Obstet Gynaecol Res ; 48(12): 3128-3136, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36056536

RESUMO

AIM: The aim of this study is to investigate the role of human chorionic gonadotropin (hCG) daily variations and levels prior to methotrexate treatment as predictors for treatment outcome. METHODS: This retrospective study included patients who had a sonographically confirmed ectopic pregnancy at the International Peace Maternity and Child Health Hospital between November 2015 and June 2020. The associations of hCG levels and daily variations with the treatment success were evaluated by multivariable logistic regression and receiver operator characteristic (ROC) curve. Establish a nomogram that predicts how methotrexate (MTX) therapy will turn out. The performance of the model was assessed utilizing concordance index, receiver operating characteristic curves, and calibration plots. RESULTS: The median serum hCG levels before treatment and hCG daily variation in the failure group were higher than those in the success group (487.8 vs. 270.7 IU/L, -1.86% vs. 7.29%, both p < 0.01). According to the ROC curve analysis, the cutoff values of serum hCG level before treatment and daily variations were 617.35 IU/L and 1.76%/day. By multivariable logistic regression analysis, serum hCG levels before treatment (odds ratio [OR]: 1.001, 95% confidence interval [CI]: 1.000 ~ 1.001) and hCG daily variations were independently associated with the treatment success (OR: 1.033, 95% CI: 1.015 ~ 1.052). The nomogram was effective at predicting the outcome of MTX treatment with a receiver operating characteristic area under the curve of 0.717 (p < 0.001). The nomogram's calibration curve was almost parallel to the ideal diagonal line. CONCLUSION: We successfully created a nomogram based on serum hCG levels before treatment and hCG daily changes to anticipate the result of MTX therapy, which could assist medical professionals in selecting therapeutic schedule for patients with tubal pregnancies.


Assuntos
Abortivos não Esteroides , Metotrexato , Criança , Humanos , Gravidez , Feminino , Metotrexato/uso terapêutico , Gonadotropina Coriônica Humana Subunidade beta , Estudos Retrospectivos , Gonadotropina Coriônica , Resultado do Tratamento
9.
Mol Carcinog ; 60(5): 313-330, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33631046

RESUMO

Oncogenic high-risk human papillomavirus (HR-HPV) infection causes a majority of cases of cervical cancer and pre-cancerous cervical lesions. However, the mechanisms underlying the direct evolution from HPV-16/18-infected epithelium to cervical intraepithelial neoplasia (CIN) III, which can progress to cervical cancer, remain poorly identified. Here, we performed RNA-seq after laser capture microdissection, and found that APOBEC3B was highly expressed in cervical cancer specimens compared with CIN III with HPV-16/18 infection. Furthermore, immunohistochemical analysis confirmed that high levels of APOBEC3B were correlated with lymph node metastasis in cervical cancer. Subsequent experiments revealed that HPV-16 E6 could upregulate APOBEC3B through direct binding to the promoter of APOBEC3B in cervical cancer cells. Silencing of APOBEC3B by stable short hairpin RNA-mediated knockdown reduced the proliferative capacity of Caski and HeLa cells in vitro and in vivo, but had only a small effect on the migration and invasion of two cervical cancer cell lines. Finally, we identified the changes in gene expression following APOBEC3B silencing in Caski cells by microarray, demonstrating a biological link between APOBEC3B and CCND1 in cervical cancer cells. Importantly, through methyl-capture sequencing and pyrosequencing, APOBEC3B was found to affect the levels of the downstream protein Cyclin D1 (which is encoded by the CCND1 gene) through hypomethylation of the CCND1 promoter. In conclusion, our study supports HPV-16 E6-induced APOBEC3B expression associates with proliferation of cervical cancer cells and hypomethylation of Cyclin D1. Thus, APOBEC3B may be a potential therapeutic target in human cervical cancer.


Assuntos
Ciclina D1/genética , Citidina Desaminase/genética , Papillomavirus Humano 16/metabolismo , Antígenos de Histocompatibilidade Menor/genética , Proteínas Oncogênicas Virais/metabolismo , Proteínas Repressoras/metabolismo , Neoplasias do Colo do Útero/patologia , Animais , Linhagem Celular Tumoral , Proliferação de Células , Ilhas de CpG , Ciclina D1/metabolismo , Citidina Desaminase/metabolismo , Metilação de DNA , Proteínas de Ligação a DNA/metabolismo , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Células HeLa , Papillomavirus Humano 18/metabolismo , Humanos , Camundongos , Antígenos de Histocompatibilidade Menor/metabolismo , Transplante de Neoplasias , Regiões Promotoras Genéticas , Análise de Sequência de DNA , Análise de Sequência de RNA , Regulação para Cima , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/virologia
10.
Sensors (Basel) ; 21(11)2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34205008

RESUMO

With the rapid development of wearable electronics, novel power solutions are required to adapt to flexible surfaces for widespread applications, thus flexible energy harvesters have been extensively studied for their flexibility and stretchability. However, poor power output and insufficient sensitivity to environmental changes limit its widespread application in engineering practice. A doubly clamped flexible piezoelectric energy harvester (FPEH) with axial excitation is therefore proposed for higher power output in a low-frequency vibration environment. Combining the Euler-Bernoulli beam theory and the D'Alembert principle, the differential dynamic equation of the doubly clamped energy harvester is derived, in which the excitation mode of axial load with pre-deformation is considered. A numerical solution of voltage amplitude and average power is obtained using the Rayleigh-Ritz method. Output power of 22.5 µW at 27.1 Hz, with the optimal load resistance being 1 MΩ, is determined by the frequency sweeping analysis. In order to power electronic devices, the converted alternating electric energy should be rectified into direct current energy. By connecting to the MDA2500 standard rectified electric bridge, a rectified DC output voltage across the 1 MΩ load resistor is characterized to be 2.39 V. For further validation of the mechanical-electrical dynamical model of the doubly clamped flexible piezoelectric energy harvester, its output performances, including both its frequency response and resistance load matching performances, are experimentally characterized. From the experimental results, the maximum output power is 1.38 µW, with a load resistance of 5.7 MΩ at 27 Hz, and the rectified DC output voltage reaches 1.84 V, which shows coincidence with simulation results and is proved to be sufficient for powering LED electronics.

11.
Cryobiology ; 96: 130-136, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32707123

RESUMO

Cryoablation, as a well-characterized technology, has multifarious clinical applications. But few are reported on ureteral endometriosis. Thus, we examined the feasibility and safety of cryotherapy with a novel balloon cryoprobe on ureter in a live porcine model. During the freezing and thawing cycle, temperature was recorded in different parts of the ureter in real-time. Two-minute cryoablation could induce necrosis within range in 1 cm diameter on serosa layer. The temperature respectively dropped to -136.5 °C, -96.1 °C and -17.5 °C at the cryotherapy center, 1 cm and 1.5 cm from center on serosal side. The ureters were harvested immediately, 2 weeks or 3 months after cryotherapy. No perforation, stricture, adhesions, or hydronephrosis was observed. Histopathologic representations of ureters after cryoablation indicated that full thickness necroses of ureters were seen in all samples. The results demonstrated ureteral cryoablation using a novel balloon probe was feasible, safe, and effective. These findings provided us reference before cryoablation could be applied in clinical practice in treating ureteral endometriosis.


Assuntos
Criocirurgia , Ureter , Animais , Criopreservação/métodos , Estudos de Viabilidade , Feminino , Congelamento , Suínos , Ureter/cirurgia
12.
Cryobiology ; 94: 89-94, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32305255

RESUMO

Young patients with early endometrial cancer have a strong desire to retain reproductive function, which require us to develop a therapeutic method that can not only assure the complete resection of tumor but also retain the uterine integrity. In the present study, we proposed a fertility-sparing surgery option that combined hysteroscopic resection with cryoablation to achieve this goal. To verify the safety and effectiveness of cryoablation for local uterine wall, we designed the experiment in pig model using a novel cryoablation balloon probe. In the process of freezing and thawing, the temperature of different parts of the uterus was measured in real time. The uterus was harvested immediately, three weeks after cryotherapy for histological evaluation. The results demonstrated cryoablation using the new cryoprobe is safe and effective. The effective freezing range can cover a range of 2 cm in diameter at least. This study provided us evidence before cryoablation could be applied in clinical practice of fertility-sparing treatment for young women with early endometrial cancer.


Assuntos
Criocirurgia , Neoplasias do Endométrio/cirurgia , Preservação da Fertilidade/métodos , Animais , Neoplasias do Endométrio/patologia , Feminino , Suínos , Útero/patologia
13.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(8): 815-820, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-32800026

RESUMO

Cornelia de Lange syndrome (CdLS) is a genetic syndrome with severe neurodevelopmental disorders as the main manifestation. Its clinical manifestations included mental retardation, typical facial features, intrauterine and postnatal developmental delay, and deformity in multiple organs and systems, with an incidence rate of about 1/10000 to 1/30000. International CdLS Consensus Group was established in 2017 and issued the first international consensus on CdLS, i.e., "Diagnosis and management of Cornelia de Lange syndrome: first international consensus statement", in July 2018. Being developed through a modified Delphi consensus process, this consensus provides guidance on the diagnosis and management of children with CdLS. This article gives an interpretation of this consensus, aiming to help clinicians with early identification, diagnosis, standard follow-up, and management of this disease.


Assuntos
Síndrome de Cornélia de Lange , Consenso , Humanos
14.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(6): 567-572, 2020 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-32571453

RESUMO

OBJECTIVE: To study the effect of functional chewing training (FuCT) on masticatory function, the severity of tongue thrust, and the severity and frequency of drooling in children with cerebral palsy. METHODS: A prospective study was performed for 48 children who were diagnosed with oral motor dysfunction from January 2019 to January 2020, and they were randomly divided into an FuCT group and an oral motor training group, with 24 children in each group. Both groups received FuCT or oral motor training for 12 weeks, and then they were evaluated in terms of the changes in the masticatory function, the severity of tongue thrust, and the severity and frequency of drooling. RESULTS: There were no significant differences between the two groups in the masticatory function, the severity of tongue thrust, and the severity and frequency of drooling before treatment (P>0.05). After the 12-week training, the FuCT group showed significant improvements in the masticatory function and the severity of tongue thrust and drooling (P<0.05), but with no improvement in the frequency of drooling (P>0.05), while the oral motor training group had no improvements in the masticatory function, the severity of tongue thrust, and the severity and frequency of drooling (P>0.05). After the 12-week training, the FuCT group had more significantly improvements in the severity of tongue thrust and the severity and frequency of drooling than the oral motor training group (P<0.05). CONCLUSIONS: FuCT can effectively improve the masticatory function, the severity of tongue thrust, and the severity and frequency of drooling in children with cerebral palsy.


Assuntos
Paralisia Cerebral , Sialorreia , Criança , Humanos , Mastigação , Estudos Prospectivos
15.
Biochem Biophys Res Commun ; 499(2): 354-360, 2018 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-29577901

RESUMO

The Liver X Receptor α (LXRα) belongs to the nuclear receptor superfamily and plays an essential role in regulating cholesterol, lipid and glucose metabolism and inflammatory responses. We have previously shown that LXRα is post-translationally modified by O-linked ß-N-acetyl-glucosamine (O-GlcNAc) with increased transcriptional activity. Moreover, we showed that LXRα associates with O-GlcNAc transferase (OGT) in vitro and in vivo in mouse liver. In this study, we report that human LXRα is O-GlcNAc modified in its N-terminal domain (NTD) by identifying a specific O-GlcNAc site S49 and a novel O-GlcNAc modified peptide 20LWKPGAQDASSQAQGGSSCILRE42. However, O-GlcNAc site-mutations did not modulate LXRα transactivation of selected target gene promoters in vitro. Peptide array and co-immunoprecipitation assays demonstrate that LXRα interacts with OGT in its NTD and ligand-binding domain (LBD) in a ligand-independent fashion. Moreover, we map two new O-GlcNAc sites in the longest OGT isoform (ncOGT): S437 in the tetratricopeptide repeat (TPR) 13 domain and T1043 in the far C-terminus, and a new O-GlcNAc modified peptide (amino acids 826-832) in the intervening region (Int-D) within the catalytic domain. We also map four new O-GlcNAc sites in the short isoform sOGT: S391, T393, S399 and S437 in the TPRs 11-13 domain. Future studies will reveal the biological role of identified O-GlcNAc sites in LXRα and OGT.


Assuntos
Acetilglucosamina/metabolismo , Receptores X do Fígado/metabolismo , N-Acetilglucosaminiltransferases/metabolismo , Sequência de Aminoácidos , Linhagem Celular Tumoral , Humanos , Receptores X do Fígado/química , Mutação/genética , N-Acetilglucosaminiltransferases/química , Ligação Proteica , Domínios Proteicos , Transcrição Gênica
16.
J Neuroinflammation ; 15(1): 176, 2018 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-29879988

RESUMO

BACKGROUND: Diabetic neuropathic pain (DNP) is a common and distressing complication in patients with diabetes, and the underlying mechanism remains unclear. Tricyclic antidepressants (TCAs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) are recommended as first-line drugs for DNP. Ammoxetine is a novel and potent SNRI that exhibited a strong analgesic effect on models of neuropathic pain, fibromyalgia-related pain, and inflammatory pain in our primary study. The present study was undertaken to investigate the chronic treatment properties of ammoxetine on DNP and the underlying mechanisms for its effects. METHODS: The rat model of DNP was established by a single streptozocin (STZ) injection (60 mg/kg). Two weeks after STZ injection, the DNP rats were treated with ammoxetine (2.5, 5, and 10 mg/kg/day) for 4 weeks. The mechanical allodynia and locomotor activity were assayed to evaluate the therapeutic effect of ammoxetine. In mechanism study, the activation of microglia, astrocytes, the protein levels of pro-inflammatory cytokines, the mitogen-activated protein kinases (MAPK), and NF-κB were evaluated. Also, microglia culture was used to assess the direct effects of ammoxetine on microglial activation and the signal transduction mechanism. RESULTS: Treatment with ammoxetine for 4 weeks significantly relieved the mechanical allodynia and ameliorated depressive-like behavior in DNP rats. In addition, DNP rats displayed increased activation of microglia in the spinal cord, but not astrocytes. Ammoxetine reduced the microglial activation, accumulation of pro-inflammatory cytokines, and activation of p38 and c-Jun N-terminal kinase (JNK) in the spinal cord of DNP rats. Furthermore, ammoxetine displayed anti-inflammatory effects upon challenge with LPS in BV-2 microglia cells. CONCLUSION: Our results suggest that ammoxetine may be an effective treatment for relieving DNP symptoms. Moreover, a reduction in microglial activation and pro-inflammatory release by inhibiting the p-p38 and p-JNK pathways is involved in the mechanism.


Assuntos
Benzodioxóis/uso terapêutico , Neuropatias Diabéticas/complicações , Neuropatias Diabéticas/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Microglia/efeitos dos fármacos , Mielite , Propilaminas/uso terapêutico , Animais , Benzodioxóis/química , Proteínas de Ligação ao Cálcio/metabolismo , Linhagem Celular Transformada , Neuropatias Diabéticas/induzido quimicamente , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Cloridrato de Duloxetina/uso terapêutico , Comportamento Exploratório/efeitos dos fármacos , Hiperalgesia/tratamento farmacológico , Hiperalgesia/fisiopatologia , Hipoglicemiantes/química , Lipopolissacarídeos/farmacologia , Locomoção/efeitos dos fármacos , Proteínas dos Microfilamentos/metabolismo , Mielite/tratamento farmacológico , Mielite/etiologia , Mielite/patologia , Propilaminas/química , Ratos , Estreptozocina/toxicidade
19.
Surg Radiol Anat ; 39(4): 383-391, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27717980

RESUMO

PURPOSE: To quantitatively measure the morphology parameters of the right auricle with 256-slice multidetector computed tomography angiography (MDCTA) in healthy people. MATERIALS AND METHODS: A retrospective analysis of 200 patients who had undergone coronary MDCTA with negative findings was performed. The raw imaging data were reconstructed and the right auricular volume, right atrial volume, right auricle height, base long and short axes, base perimeter and area, normal angle, and distance were quantitatively measured. RESULTS: Men had significantly (P < 0.05) greater values than women in the right auricular volume (13.3 ± 4.0 vs. 11.7 ± 3.7 mL) and height (33.0 ± 5.0 vs. 30.5 ± 5.2 mm), the base long axis (34.4 ± 4.1 vs. 33.2 ± 3.9 mm), area (787.6 ± 177.6 vs. 771.0 ± 143.2 mm2) and perimeter (119.2 ± 17.5 vs. 115.0 ± 13.0), and the normal distance (22.4 ± 6.6 vs. 20.2 ± 6.7 mm). The normal 95 % reference range for the right auricular parameters was put forward. The right auricular parameters had a good correlation with the right atrium volume, aortic diameter, the body weight, height, and body surface area but a bad correlation with the vertebral body height. Significantly (P < 0.05) greater values were found in the normal angle and distance in subjects below than over 40 years of age. No other significant (P > 0.05) difference existed in the other right auricular parameters. CONCLUSION: Quantitative measurements of the right auricle can help us get a good understanding of the right auricular morphology and its relationship with surrounding structures and are helpful for cardiac interventions of electrophysiology and radiofrequency ablation.


Assuntos
Apêndice Atrial/anatomia & histologia , Adulto , Idoso , Apêndice Atrial/diagnóstico por imagem , Angiografia por Tomografia Computadorizada/métodos , Angiografia Coronária/métodos , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores/métodos , Estudos Retrospectivos , Fatores Sexuais
20.
J Magn Reson Imaging ; 44(5): 1143-1150, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27015960

RESUMO

PURPOSE: To quantitatively investigate left ventricular volume and function in middle-aged healthy subjects. MATERIALS AND METHODS: Ninety healthy volunteers underwent cardiac 3 Tesla MRI. The left ventricular end-diastolic volume (EDV) and end-systolic volume (ESV), stroke volume (SV), ejection fraction (EF), cardiac output (CO), myocardial mass (MM), and their normalized indices (EDVI, ESVI, SVI, CI, and MI, respectively) after corrected with the body surface area (BSA) were analyzed and compared at different ages. RESULTS: All subjects had successfully completed the 3-Tesla cardiac MR. Females had significantly smaller EDV (110.5 ± 9.2 versus 125.7 ± 8.3 mL), ESV (36.1 ± 3.5 versus 41.5 ± 3.8 mL), SV (74.3 ± 6.3 versus 84.2 ± 6.7 mL), CO (5.4 ± 0.8 versus 5.8 ± 0.9 l/min) and MM (73.0 ± 10.5 versus 94.8 ± 10.6 g) than males (P < 0.05). The EF had no significant (P = 0.47) difference between genders (67.3 ± 1.7 percent in females versus 66.9 ± 2.4 percent in males). After normalization with BSA, no significant (P > 0.05) difference was detected between the genders in EDVI (71.2 ± 4.3 versus 71.1 ± 4.2 mL/m2 , P = 0.882), ESVI (23.3 ± 1.9 versus 23.5 ± 1.9 mL/m2 , P = 0.733) and SVI (47.9 ± 2.9 versus 47.7 ± 3.7 mL/m2 , P = 0.698) except for CI and MI. Females had significantly (P < 0.05) greater CI (3.5 ± 0.4 versus 3.3 ± 0.4) but smaller MI (46.9 ± 5.3 versus 53.6 ± 7.6) than males. EDV, EDVI, ESV, ESVI, SV, and SVI significantly (P < 0.05) decreased with age increase. BSA was positively correlated with EDV, ESV, SV, MM, and CO. No significance (P > 0.05) was detected in other parameters. CONCLUSION: The left ventricular volume and function differs in women compared with men in the middle-aged population, and these parameters have a tendency of decrease with ageing. J. Magn. Reson. Imaging 2016;44:1143-1150.


Assuntos
Envelhecimento/fisiologia , Ventrículos do Coração/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Volume Sistólico/fisiologia , Função Ventricular Esquerda/fisiologia , Adulto , Distribuição por Idade , Idoso , Envelhecimento/patologia , China/epidemiologia , Feminino , Ventrículos do Coração/anatomia & histologia , Humanos , Imageamento por Ressonância Magnética/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Distribuição por Sexo
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