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1.
PLoS Pathog ; 19(2): e1011189, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36812247

RESUMO

Increasing evidence highlights the role of bacteria in promoting tumorigenesis. The underlying mechanisms may be diverse and remain poorly understood. Here, we report that Salmonella infection leads to extensive de/acetylation changes in host cell proteins. The acetylation of mammalian cell division cycle 42 (CDC42), a member of the Rho family of GTPases involved in many crucial signaling pathways in cancer cells, is drastically reduced after bacterial infection. CDC42 is deacetylated by SIRT2 and acetylated by p300/CBP. Non-acetylated CDC42 at lysine 153 shows an impaired binding of its downstream effector PAK4 and an attenuated phosphorylation of p38 and JNK, consequently reduces cell apoptosis. The reduction in K153 acetylation also enhances the migration and invasion ability of colon cancer cells. The low level of K153 acetylation in patients with colorectal cancer (CRC) predicts a poor prognosis. Taken together, our findings suggest a new mechanism of bacterial infection-induced promotion of colorectal tumorigenesis by modulation of the CDC42-PAK axis through manipulation of CDC42 acetylation.


Assuntos
Neoplasias Colorretais , Infecções por Salmonella , Proteína cdc42 de Ligação ao GTP , Humanos , Acetilação , Carcinogênese , Proteína cdc42 de Ligação ao GTP/metabolismo , Transformação Celular Neoplásica , Quinases Ativadas por p21/metabolismo , Transdução de Sinais
2.
Adv Sci (Weinh) ; 9(36): e2204849, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36354175

RESUMO

Centenarians, who show mild infections and low incidence of tumors, are the optimal model to investigate healthy aging. However, longevity related immune characteristics has not been fully revealed largely due to lack of appropriate controls. In this study, single-cell transcriptomic analysis of peripheral blood mononuclear cells (PBMCs) derived from seven centenarians (CEN), six centenarians' offspring (CO), and nine offspring spouses or neighbors (Control, age-matched to CO) are performed to investigate the shared immune features between CEN and CO. The results indicate that among all 12 T cell clusters, the cytotoxic-phenotype-clusters (CPC) and the naïve-phenotype-clusters (NPC) significantly change between CEN and ontrol. Compared to Control, both CEN and CO are characterized by depleted NPC and increased CPC, which is dominated by CD8+ T cells. Furthermore, CPC from CEN and CO share enhanced signaling pathways and transcriptional factors associated with immune response, and possesse similar T-cell-receptor features, such as high clonal expansion. Interestingly, rather than a significant increase in GZMK+ CD8 cells during aging, centenarians show accumulation of GZMB+ and CMC1+ CD8 T cells. Collectively, this study unveils an immune remodeling pattern reflected by both quantitative increase and functional reinforcement of cytotoxic T cells which are essential for healthy aging.


Assuntos
Centenários , Leucócitos Mononucleares , Humanos , Transcriptoma/genética , Linfócitos T CD8-Positivos , Longevidade/genética
3.
World J Clin Cases ; 10(31): 11638-11645, 2022 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-36387819

RESUMO

BACKGROUND: Primary pancreatic paraganglioma is exceedingly rare. Most patients with pancreatic paraganglioma lack a typical clinical presentation, and the tumor is difficult to accurately differentiate from other pancreatic neuroendocrine tumors, making the misdiagnosis rate extremely high. Surgical excision is the primary treatment modality but is considered high risk. Because of its rich vascularity, the tumor easily bleeds during surgery, especially malignant paragangliomas invading large blood vessels. Thus, a thorough preoperative evaluation of the tumor is necessary. Here, we report a primary malignant pancreatic paraganglioma, the second such case in a young patient that was successfully resected surgically. CASE SUMMARY: A 26-year-old female patient was admitted to the hospital with unexplained abdominal pain. Dual-layer spectral-detector computed tomography (DLCT) revealed a mixed density mass in the pancreatic body and tail. The patient was transferred to our hospital after previous failed surgical resection at other hospitals. The patient and her family strongly desired surgery. After a thorough preoperative evaluation and adequate preparation, a large mass with the greatest dimension of 8.0 cm was successfully resected. The final pathological diagnosis was malignant paraganglioma. The patient was discharged in good condition 2 wk postoperatively. CONCLUSION: The rare malignant pancreatic paraganglioma reported here was difficult to diagnose preoperatively. Early filling of the draining vein may be a crucial diagnostic imaging feature. DLCT can provide more precise information for surgical resection through dual-energy imaging.

4.
Front Plant Sci ; 13: 843725, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35519810

RESUMO

Cadmium (Cd) pollution is widely detected in soil and has been recognized as a major environmental problem. Tamarix hispida is a woody halophyte, which can form natural forest on the desert and soil with 0.5 to 1% salt content, making it an ideal plant for the research on response to abiotic stresses. However, no systematic study has investigated the molecular mechanism of Cd tolerance in T. hispida. In the study, RNA-seq technique was applied to analyze the transcriptomic changes in T. hispida treated with 150 µmol L-1 CdCl2 for 24, 48, and 72 h compared with control. In total, 72,764 unigenes exhibited similar sequences in the Non-redundant nucleic acid database (NR database), while 36.3% of all these unigenes may be new transcripts. In addition, 6,778, 8,282, and 8,601 DEGs were detected at 24, 48, and 72 h, respectively. Functional annotation analysis indicated that many genes may be involved in Cd stress response, including ion bonding, signal transduction, stress sensing, hormone responses and ROS metabolism. A ThUGT gene from the abscisic acid (ABA) signaling pathway can enhance Cd resistance ability of T. hispida by regulating the production of ROS under Cd stress and inhibit absorption of Cd. The new transcriptome resources and data that we present in this study for T. hispida may facilitate investigation of molecular mechanisms governing Cd resistance.

5.
Int J Biol Sci ; 17(4): 995-1009, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33867824

RESUMO

Homoharringtonine (HHT), a natural alkaloid derived from the cephalotaxus, exhibited its anti-cancer effects in hematological malignancies clinically. However, its pesticide effects and mechanisms in treating solid tumors remain unclear. In this study, we found that HHT was capable of inhibiting tumor growth after 5-days treatment of breast cancer cells, MCF-7, in vivo. Furthemore, HHT also significantly inhibited the cancer cell growth and induced cell apoptosis in vitro. miRNA sequencing proved miR-18a-3p was noticeably downregulated in the cells after HHT treatment. Moreover, downregulating miR-18a-3p increased HHT-induced cell apoptosis; our data supported that HHT suppressed miR-18a-3p expression and inhibited tumorigenesis might via AKT-mTOR signaling pathway. In conclusion: our study proved that HHT suppressed breast cancer cell growth and promoted apoptosis mediated by regulating of the miR-18a-3p-AKT-mTOR signaling pathway, HHT may be a promising antitumor agent in breast cancer treatment.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Mepesuccinato de Omacetaxina/uso terapêutico , MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Apoptose/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Mepesuccinato de Omacetaxina/farmacologia , Humanos , Células MCF-7 , Transdução de Sinais/efeitos dos fármacos
6.
Mikrochim Acta ; 187(3): 194, 2020 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-32124079

RESUMO

A controllable approach for preparing a portable colloidal photonic crystal (CPC) array chip is presented. The approach was inspired by the confinement effect of nanoparticle self-assembly on patterned surface. Hydrophobic polydimethylsiloxane substrate with reproducible micro-region array was fabricated by soft-lithography. The substrate was employed as the patterned template for self-assembly of monodisperse polystyrene nanoparticles. The CPC units can be prepared in several minutes, and exhibit consistent reflection wavelength. By adjusting the size of polystyrene nanoparticles and the shape of micro-regions, CPC units with multiple structure, colors and geometries were obtained. The CPC array chip features fluorescence enhancement owing to the optical modulation capability of the periodic nanostructure of the self-assembled CPC. With the reflection wavelength (523 nm) of green CPC units overlapping the emission wavelength (520 nm, with excitation wavelength of 490 nm) of 6-carboxyfluorescein-labeled DNA probe, the fluorescence intensity increased more than 10-fold. For signal-amplified assay of adenosine, the concentration range of linear response was 5.0 × 10-5 mol L-1 to 1.0 × 10-3 mol L-1, and the limit of detection was 1.3 × 10-6 mol L-1. Because of the enhancement effect of photonic crystal, the fluorescence images were more readable from the CPC array chip, compared with those from the planar substrate. The chip has potential applications in multiplex determination with high-throughput via encoding strategy based on the tunable structure, color or geometric shape. Graphical abstractSchematic diagram of signal-enhanced fluorescent detection of adenosine based on the colloidal photonic crystal array chip (PDMS, polydimethylsiloxane; PS NPs, polystyrene nanoparticles; CPC, colloidal photonic crystal; GO, graphene oxide; FAM, 6-carboxyfluorescein).


Assuntos
Adenosina/análise , Técnicas Biossensoriais/métodos , Fluoresceínas/química , Corantes Fluorescentes/química , Dispositivos Lab-On-A-Chip , Coloides , Cristalização , Sondas de DNA/química , Dimetilpolisiloxanos/química , Interações Hidrofóbicas e Hidrofílicas , Limite de Detecção , Fótons , Espectrometria de Fluorescência , Propriedades de Superfície
7.
Neuroophthalmology ; 43(1): 18-25, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30723520

RESUMO

PURPOSE: To determine the positive yield (utility rate) of temporal artery biopsy (TAB) in patients with suspected giant cell arteritis (GCA). STUDY DESIGN: Systematic review (CRD42017078508) and meta-regression. MATERIALS AND METHODS: All articles concerning TAB for suspected GCA with English language abstracts from 1998 to 2017 were retrieved. Articles were excluded if they exclusively reported positive TAB, or only cases of known GCA. Where available, the pre-specified predictors of age, sex, vision symptoms, jaw claudication, duration of steroid treatment prior to TAB, specimen length, bilateral TAB, and use of ultrasound/MRI (imaging) were recorded for meta-regression. RESULTS: One hundred and thirteen articles met eligibility criteria. The I 2 was 92%, and with such high heterogeneity, meta-analysis is unsuitable. The median yield of TAB was 0.25 (95% confidence interval 0.21 to 0.27), with interquartile range 0.17 to 0.34. On univariate meta-regression age (coefficient 0.012, p = 0.025) was the only statistically significant patient factor associated with TAB yield. CONCLUSIONS: Systematic review revealed high heterogeneity in the yield of TAB. The median utility rate of 25% and its interquartile range provides a benchmark for decisions regarding the under/overutilization of TAB and aids in the evaluation of non-invasive alternatives for the investigation of GCA.

8.
Int J Neurosci ; 128(3): 199-207, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28931339

RESUMO

BACKGROUND: Limb-girdle muscular dystrophy type 2I (LGMD2I) is an autosomal recessive hereditary disorder caused by mutations in the fukutin-related protein (FKRP) gene. Although the features of the disorder in European patients have been summarized, Asian patients with LGMD2I have rarely been reported. Thus, the clinical differences in LGMD2I between Asian and European patients and the associated genetic changes remain unclear. METHODS: We reported detailed clinical data as well as results from muscle biopsy, muscle MRI and genetic analysis of the FKRP gene in two unrelated Chinese families with LGMD2I. Additionally, a review of the literature focusing on the clinical and mutational features of LGMD2I in Asian patients was performed. RESULTS: The muscle biopsy results showed dystrophic features. Immunohistochemical staining revealed decreased glycosylations on α-dystroglycan. The muscle MRI results showed that the gluteus maximus, adductor, biceps femoris, vastus intermedius and vastus lateralis were severely affected. The patients in the two families harbored the same compound heterozygous mutations (c.545A>G and c.948delC). One patient showed significant clinical improvement after corticosteroid treatment. CONCLUSION: Our study expanded the reported spectrum of Asian LGMD2I patients. Our literature review revealed that pathogenic mutations in the FKRP gene in Asian LGMD2I patients are compound heterozygous rather than homozygous. Compound heterozygous Asian patients have a mild phenotype but frequently show respiratory and cardiac impairments. Corticosteroids may be beneficial for the treatment of LGMD2I and should be further investigated.


Assuntos
Saúde da Família , Distrofia Muscular do Cíngulo dos Membros/genética , Mutação/genética , Proteínas/genética , Adolescente , Adulto , Povo Asiático , Pré-Escolar , Testes Genéticos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/patologia , Distrofia Muscular do Cíngulo dos Membros/patologia , Pentosiltransferases , Adulto Jovem
9.
Neuromuscul Disord ; 27(8): 715-722, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28318817

RESUMO

The development of clinical trials for Duchenne muscular dystrophy (DMD) in China faces many challenges due to limited information about epidemiological data, natural history and clinical management. To provide these detailed data, we developed a comprehensive database based on registered DMD patients from South China and analysed their clinical and mutational characteristics. The database included DMD registrants confirmed by clinical presentation, family history, genetic detection, prognostic outcome, and/or muscle biopsy. Clinical data were collected by a registry form. Mutations of dystrophin were detected by multiplex ligation-dependent probe amplification (MLPA) and Sanger sequencing. Currently, 132 DMD patients from 128 families in South China have been registered, and 91.7% of them were below 10 years old. In mutational detection, large deletions were the most frequent type (57.8%), followed by small deletion/insertion mutations (14.1%), nonsense mutations (13.3%), large duplications (10.9%), and splice site mutations (3.1%). Clinical analysis revealed that most patients reported initial symptoms between 1 and 3 years of age, but the diagnostic age was more frequently between 6 and 8 years. 81.4% of patients were ambulatory. Baseline cardiac assessments at diagnosis were conducted in 39.4% and 29.5% of patients by echocardiograms and electrocardiograms, respectively. Only 22.7% of registrants performed baseline respiratory assessments. A small numbers of patients (20.5%) were treated with glucocorticoids. 13.3% of patients were eligible for stop codon read-through therapy, and 48.4% of patients would potentially benefit from exon skipping. The top five exon skips applicable to the largest group of registrants were skipping of exons 51 (14.8% of total mutations), 53 (12.5%), 45 (7.0%), 55 (4.7%), and 44 (3.9%). In conclusion, our database provided information on the natural history, diagnosis and management status of DMD in South China, as well as potential molecular therapies suitable for these patients. This comprehensive database will promote future experimental therapies in China.


Assuntos
Distrofia Muscular de Duchenne/epidemiologia , Distrofia Muscular de Duchenne/genética , Adolescente , Idade de Início , Criança , Pré-Escolar , China , Bases de Dados Factuais , Distrofina/genética , Família , Seguimentos , Humanos , Lactente , Masculino , Distrofia Muscular de Duchenne/tratamento farmacológico , Distrofia Muscular de Duchenne/fisiopatologia , Mutação , Sistema de Registros , Adulto Jovem
10.
Chin Med J (Engl) ; 129(12): 1425-31, 2016 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-27270537

RESUMO

BACKGROUND: Lipid storage myopathy (LSM) is a genetically heterogeneous group with variable clinical phenotypes. Late-onset multiple acyl-coenzyme A dehydrogenation deficiency (MADD) is a rather common form of LSM in China. Diagnosis and clinical management of it remain challenging, especially without robust muscle biopsy result and genetic detection. As the noninvasion and convenience, muscle magnetic resonance imaging (MRI) is a helpful assistant, diagnostic tool for neuromuscular disorders. However, the disease-specific MRI patterns of muscle involved and its diagnostic value in late-onset MADD have not been systematic analyzed. METHODS: We assessed the MRI pattern and fat infiltration degree of the lower limb muscles in 28 late-onset MADD patients, combined with detailed clinical features and gene spectrum. Fat infiltration degree of the thigh muscle was scored while that of gluteus was described as obvious or not. Associated muscular atrophy was defined as obvious muscle bulk reduction. RESULTS: The mean scores were significantly different among the anterior, medial, and posterior thigh muscle groups. The mean of fat infiltration scores on posterior thigh muscle group was significantly higher than either anterior or medial thigh muscle group (P < 0.001). Moreover, the mean score on medial thigh muscle group was significantly higher than that of anterior thigh muscle group (P < 0.01). About half of the patients displayed fat infiltration and atrophy in gluteus muscles. Of 28 patients, 12 exhibited atrophy in medial and/or posterior thigh muscle groups, especially in posterior thigh muscle group. Muscle edema pattern was not found in all the patients. CONCLUSIONS: Late-onset MADD patients show a typical muscular imaging pattern of fat infiltration and atrophy on anterior, posterior, and medial thigh muscle groups, with major involvement of posterior thigh muscle group and gluteus muscles and a sparing involvement of anterior thigh compartment. Our findings also suggest that muscle MRI of lower limbs is a helpful tool in guiding clinical evaluation on late-onset MADD.


Assuntos
Flavoproteínas Transferidoras de Elétrons/genética , Erros Inatos do Metabolismo Lipídico/genética , Erros Inatos do Metabolismo Lipídico/patologia , Extremidade Inferior/patologia , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Distrofias Musculares/genética , Distrofias Musculares/patologia , Adolescente , Adulto , Idade de Início , Criança , Pré-Escolar , Feminino , Humanos , Erros Inatos do Metabolismo Lipídico/metabolismo , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Atrofia Muscular/genética , Atrofia Muscular/metabolismo , Atrofia Muscular/patologia , Distrofias Musculares/metabolismo , Mutação/genética , Adulto Jovem
11.
J Neurol Sci ; 364: 19-23, 2016 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-27084208

RESUMO

OBJECTIVE: To explore the risk factors associated with acute/subacute cerebral infarction (ASCI) in HIV-negative patients with cryptococcal meningitis (CM). METHODS: This case-control study included 10 HIV-negative CM patients with ASCI and 30 age- and sex-matched HIV-negative control (1:3) CM patients without ASCI. The clinical manifestations and neuroimaging findings were collected. Risk factors for ASCI in the HIV-negative CM patients were confirmed by conditional logistic regression analysis. RESULTS: Among the 10 HIV-negative CM patients with ASCI, all cases had lacunar infarctions. Single infarctions were found in 6 patients, and multiple infarctions in 4. Hydrocephalus (p=0.020, OR=23.77, 95% CI, 1.67-339.33) and smoking (p=0.039, OR=11.63, 95% CI, 1.14-118.96) were found to be independently associated with the occurrence of ASCI. CONCLUSIONS: Hydrocephalus and smoking may increase the risk of ASCI in HIV-negative CM patients. In the clinical course, cerebral infarction should be strongly suspected in CM patients with hydrocephalus or smoking histories.


Assuntos
Infarto Cerebral/etiologia , Meningite Criptocócica/complicações , Fatores de Risco , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Infarto Cerebral/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Hidrocefalia/etiologia , Masculino , Meningite Criptocócica/diagnóstico por imagem , Pessoa de Meia-Idade , Estudos Retrospectivos , Estatísticas não Paramétricas , Adulto Jovem
12.
Chin Med J (Engl) ; 129(2): 142-6, 2016 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-26830983

RESUMO

BACKGROUND: Late-onset multiple acyl-CoA dehydrogenase deficiency (MADD) is the most common type of lipid storage myopathies in China. Most patients with late-onset MADD are well responsive to riboflavin. Up to now, these patients are often treated with glucocorticoids as the first-line drug because they are misdiagnosed as polymyositis without muscle biopsy or gene analysis. Although glucocorticoids seem to improve the fatty acid metabolism of late-onset MADD, the objective evaluation of their rationalization on this disorder and comparison with riboflavin treatment are unknown. METHODS: We performed a historical cohort study on the efficacy of the two drugs among 45 patients with late-onset MADD, who were divided into glucocorticoids group and riboflavin group. Detailed clinical information of baseline and 1-month follow-up were collected. RESULTS: After 1-month treatment, a dramatic improvement of muscle strength was found in riboflavin group (P < 0.05). There was no significant difference in muscle enzymes between the two groups. Significantly, the number of patients with full recovery in glucocorticoids group was less than the number in riboflavin group (P < 0.05). On the other hand, almost half of the patients in riboflavin group still presented high-level muscle enzymes and weak muscle strength after 1-month riboflavin treatment, meaning that 1-month treatment duration maybe insufficient and patients should keep on riboflavin supplement for a longer time. CONCLUSIONS: Our results provide credible evidences that the overall efficacy of riboflavin is superior to glucocorticoids, and a longer duration of riboflavin treatment is necessary for patients with late-onset MADD.


Assuntos
Glucocorticoides/uso terapêutico , Deficiência Múltipla de Acil Coenzima A Desidrogenase/tratamento farmacológico , Riboflavina/uso terapêutico , Adolescente , Adulto , Idade de Início , Criança , Estudos de Coortes , Feminino , Humanos , Erros Inatos do Metabolismo Lipídico/terapia , Masculino , Distrofias Musculares/terapia , Adulto Jovem
13.
Infect Immun ; 83(4): 1577-86, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25644007

RESUMO

Cryptococcosis due to a highly virulent fungus, Cryptococcus gattii, emerged as an infectious disease on Vancouver Island in Canada and surrounding areas in 1999, causing deaths among immunocompetent individuals. Previous studies indicated that C. gattii strain R265 isolated from the Canadian outbreak had immune avoidance or immune suppression capabilities. However, protective immunity against C. gattii has not been identified. In this study, we used a gain-of-function approach to investigate the protective immunity against C. gattii infection using a dendritic cell (DC)-based vaccine. Bone marrow-derived dendritic cells (BMDCs) efficiently engulfed acapsular C. gattii (Δcap60 strain), which resulted in their expression of costimulatory molecules and inflammatory cytokines. This was not observed for BMDCs that were cultured with encapsulated strains. When Δcap60 strain-pulsed BMDCs were transferred to mice prior to intratracheal R265 infection, significant amelioration of pathology, fungal burden, and the survival rate resulted compared with those in controls. Multinucleated giant cells (MGCs) that engulfed fungal cells were significantly increased in the lungs of immunized mice. Interleukin 17A (IL-17A)-, gamma interferon (IFN-γ)-, and tumor necrosis factor alpha (TNF-α)-producing lymphocytes were significantly increased in the spleens and lungs of immunized mice. The protective effect of this DC vaccine was significantly reduced in IFN-γ knockout mice. These results demonstrated that an increase in cytokine-producing lymphocytes and the development of MGCs that engulfed fungal cells were associated with the protection against pulmonary infection with highly virulent C. gattii and suggested that IFN-γ may have been an important mediator for this vaccine-induced protection.


Assuntos
Criptococose/imunologia , Cryptococcus gattii/imunologia , Células Dendríticas/transplante , Cápsulas Fúngicas/imunologia , Vacinas Fúngicas/imunologia , Animais , Células da Medula Óssea/imunologia , Terapia Baseada em Transplante de Células e Tecidos , Criptococose/prevenção & controle , Células Dendríticas/imunologia , Cápsulas Fúngicas/genética , Células Gigantes/imunologia , Interferon gama/genética , Interferon gama/imunologia , Interleucina-17/imunologia , Pulmão/imunologia , Pulmão/microbiologia , Linfócitos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fator de Necrose Tumoral alfa/imunologia , Vacinação
14.
Med Chem ; 10(8): 836-42, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24773350

RESUMO

Estrogen receptors (ERs) are members of a superfamily of ligand-modulated nuclear receptors, which have been associated with an increased risk of cardiovascular diseases and breast cancer. Based on molecular docking studies, 1,4-dihydrothieno[3',2':5,6]thiopyrano[4,3-c]pyrazole-3-carboxamide derivatives as estrogen receptor inhibitors with a new scaffold , have been synthesized and tested for the antitumor activity on the ER expressing (ER dependent) human MCF-7 breast cancer cell line. According to the biological activity evaluation, compound 6a demonstrated the most potent antiproliferative activity (relative inhibitory rate: 100%). Several of these compounds exhibited moderate antitumor activity and worthy of further modification to obtain more potent anticancer candidate drugs.


Assuntos
Amidas/síntese química , Antineoplásicos/síntese química , Receptor alfa de Estrogênio/antagonistas & inibidores , Pirazóis/síntese química , Amidas/química , Amidas/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Feminino , Expressão Gênica , Humanos , Ligantes , Células MCF-7 , Simulação de Acoplamento Molecular , Pirazóis/química , Pirazóis/farmacologia , Relação Estrutura-Atividade
15.
Artigo em Chinês | MEDLINE | ID: mdl-24195819

RESUMO

OBJECTIVE: To discuss the indications, surgery methods and effects of the BAHA implantation by analyzing the patients' medical records of bone-anchored hearing aids(BAHA). METHODS: Retrospective analyzed the records of 16 patients of BAHA implantation, including nine males and seven females. Their average age was 31 years old (8-53ys). Nine of them were congenital ear malformation, two were chronic suppurative otitis media, two were otosclerosis and three were unilateral severe sensorineural deafness. We evaluated their pure tone audiometry (PTA), speech audiometry and temporal CT before the surgery, and evaluated the aided PTA in soundfield and speech audiometry in sound field. RESULTS: These patients received BAHA implantation and installed the speech processor their months later. The average preoperative PTA measurements (PTA at 0.5, 1, 2, 4 kHz) was (63.2 ± 19.0) dB HL and postoperative aided PTA in sound field was (35.5 ± 10.9)dB HL. The average improvement in Hearing In Noise Test (HINT) was 37.0% ± 31.7%. The average improvement in Mandarin Speech Test was 76.0% ± 19.7%. After 4-16 months' follow-up, no significant complications were recorded. CONCLUSION: BAHA is a safe and effective bone implantable hearing device.


Assuntos
Auxiliares de Audição , Audiometria , Audiometria de Tons Puros , Audiometria da Fala , Condução Óssea , Orelha , Feminino , Audição , Perda Auditiva Neurossensorial , Testes Auditivos , Humanos , Masculino , Ruído , Otosclerose , Próteses e Implantes , Estudos Retrospectivos , Som
16.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 32(6): 744-7, 2012 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-22978092

RESUMO

OBJECTIVE: To explore the effects of Fuzheng Paidu Tablet (FPT) on serum levels of tumor necrosis factor-alpha (TNF-alpha) and neopterin (NPI) in patients with asymptomatic human immunodeficiency virus (HIV) carriers. METHODS: Using flow cytometry detection technology, CD T lymphocyte in anticoagulant blood sample of 32 asymptomatic HIV infection patients who were taking FPT for 6 months was detected and compared with before treatment. The serum levels of TNF-alpha and NPI were determined using ELISA method and compared with 22 healthy volunteers. RESULTS: After 6 months of treatment by FPT, the CD4+ T lymphocyte of asymptomatic HIV carriers increased from (368.63 +/- 111.54)/mm3 to (412.72 +/- 159.63)/mm3. Before treatment the serum levels of TNF-alpha [(20.05 +/- 13.08) nmol/L] and NPI [(9.55 +/- 2.52) nmol/L] were obviously higher than those of the healthy volunteers [(12.20 +/- 4.07) nmol/L and (5.91 +/- 1.43) nmol/L] (P < 0.05). After 6 months of treatment by FPT, they were lower after treatment than before treatment (P < 0.05). But there was no statistical difference in the serum TNF-alpha level [(11.06 +/- 4.71) nmol/L] when compared with the healthy volunteers group (P > 0.05). But the serum NPI level [(8.08 +/- 2.13) nmol/L] was still higher than that of the healthy volunteers group (P < 0.05). CONCLUSIONS: One of the pathological factors for asymptomatic HIV infection is abnormal immune activation represented by increased serum levels of TNF-alpha and NPI. FPT could lower the serum levels of TNF-alpha and NPI in asymptomatic HIV infection patients, which was one of its possible mechanisms for its efficacy.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Infecções por HIV/sangue , Neopterina/sangue , Fator de Necrose Tumoral alfa/sangue , Adulto , Idoso , Contagem de Linfócito CD4 , Estudos de Casos e Controles , Medicamentos de Ervas Chinesas/uso terapêutico , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Comprimidos
17.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 32(6): 828-30, 2012 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-22978114

RESUMO

AIDS is a serious threat to the human health. Although highly active anti-retroviral therapy (HAART) has obviously prohibited the progress of AIDS, a yearly increasing problems of human immunodeficiency virus (HIV) drug resistance have arousing more attention, affecting the clinical efficacy of HAART, and even resulting in treatment failure. We are lack of exchangeable medicines, while the therapeutic course of AIDS treatment is longer. It is not feasible to monitor and detect the drug resistance of medicine takers by taking the exchangeable medicines as the outcome. Better indications have been obtained by combining the experiences for Chinese medicine and pharmacy (CMP) intervention and CMP's intervening HIV drug resistance by clinical trails. Based on retrospective studies on the HIV biological features, reasons for HIV drug resistance, the occurrence, the predisposing population, and the mutation sites, the authors addressed it is a good opportunity for CMP in intervening HIV drug resistance at present situation in China. Meanwhile, the authors also raised too much difficulties and challenges. We hope CMP's intervention can minimize and delay the generation of drug resistance to the utmost, solve key problems in HIV/AIDS prevention and control in China.


Assuntos
Farmacorresistência Viral/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , HIV/efeitos dos fármacos , Fármacos Anti-HIV/farmacologia , Humanos
18.
Artigo em Chinês | MEDLINE | ID: mdl-19558884

RESUMO

OBJECTIVE: To investigate the clinical features, differential diagnosis and management of congenital stenosis of external auditory canal (CSEAC) with cholesteatoma. METHODS: The clinical information for 10 cases of CSEAC with cholesteatoma was retrospectively reviewed. RESULTS: The patients' ages ranged from 4.75 to 22 years (average 12 years). The diameter of the external auditory canal (EAC) was < 2 mm. All 10 ears had a history of postural fistulae or sinuses. Bone erosion of EAC was distinctly shown in high-resolution computed tomography (HRCT) of all cases, as well as soft tissue masses, which led to enlargement of the bony canals. All patients underwent canaloplasty; eight ears received hearing reconstructions at the same time. Cholesteatoma in EACs was confirmed during the operations, accompanied by compression and destruction of the post-superior and/or inferior bony wall. Postoperative pathologic examinations proved the diagnosis of cholesteatoma, and excluded any tissue of bronchial cleft cyst or fistula. After a follow-up 1 to 3 years, no recurrent cholesteatoma was found in any of the 10 cases. All reconstructed EACs were clean and smooth. The hearing levels in the eight ears that received hearing reconstructions improved 20 - 35 dBHL. CONCLUSIONS: In CSEAC with cholesteatoma, the bony wall of EAC is most commonly involved. This involvement will lead to bone erosion of the EAC and may subsequently lead to the formation of postural or cervical sinuses. HRCT of temporal bone can show characteristic signs of soft tissue mass in EAC, with adjacent bone erosion.


Assuntos
Colesteatoma/cirurgia , Fístula Cutânea/cirurgia , Meato Acústico Externo/anormalidades , Otopatias/cirurgia , Adolescente , Criança , Pré-Escolar , Colesteatoma/complicações , Colesteatoma/diagnóstico , Constrição Patológica/congênito , Fístula Cutânea/complicações , Fístula Cutânea/diagnóstico , Otopatias/congênito , Otopatias/diagnóstico , Feminino , Humanos , Masculino , Estudos Retrospectivos , Adulto Jovem
19.
Artigo em Chinês | MEDLINE | ID: mdl-16270873

RESUMO

OBJECTIVE: To describe the relevant factors of endoscopic surgery in patients with nasal septal perforation. METHODS: Twenty-three patients with nasal septal perforation were treated under nasal endoscope. Four kinds of reconstruction materials were used to accomplish the closure of perforation: residual osseous septum or temporalis fascia, inverting septal mucoperichondrial flap, autologous connective tissue insert overlaid with mucous flaps and turbinate flap. The reconstructed septum was packed by moist dressing with silicone or plastic splints. RESULTS: Seven patients underwent direct closure. Inverting flap repair for five cases, shifting flap closure for ten cases, and repair with turbinate flap in one case. During the follow-up ranging from four weeks to seven months, the successful reconstruction was achieved in 19 cases (82.6%). The problems in the remaining four cases were: mucosal flap displacement, fascia flap shrank and so caused reperforation, two perforations present with only the larger one repaired, the mucosal flap was smaller in size than the perforation. CONCLUSIONS: Intranasal endoscopic reconstruction surgery is a reasonable management for nasal septal perforation.


Assuntos
Endoscopia , Septo Nasal , Doenças Nasais/cirurgia , Procedimentos Cirúrgicos Otorrinolaringológicos/métodos , Feminino , Humanos , Masculino , Septo Nasal/lesões
20.
Artigo em Chinês | MEDLINE | ID: mdl-16229169

RESUMO

OBJECTIVE: To evaluate the stability of hearing results and complications in long-term following-up who underwent reconstruction surgery. METHODS: Six hundreds and seventy five cases (700 ears) of congenital aural atresia were reviewed from January 1984 to January 2001 at the Department of Otorhinolaryngology Head and Neck Surgery, Tongren hospital. Except 40 ears undone hearing reconstruction, 635 cases (660 ears) underwent long-term following-up for 3 to 19 years, with an average of 7.9 years. RESULTS: Stenosis and recurrent infection of the external auditory canal (EAC) were the most frequent complications. Stenosis was seen in 120 ears, and 2 ears re-atresia, with an incidence of 18.48% (122/660). Recurrent infection of the cavity and canal skin happened in 6 ears. Closure of the air-bone gap (ABG) post-operation were gained in all cases, and ABG gains 20 dB or more occurred in 512 ears (77.57%), but 30 dB or more in 231 ears (35%). Following-up results: Stable hearing results gained in 450 ears over the length of following-up; the hearing worsened than that of 3 weeks postoperatively occurred in 160 ears, including 2 ears with sensorineural hearing loss. Hearing deteriorated more than 20 dB happened in 35 ears, and 10-15 dB in others cases but still be improved compared with that of preoperation. CONCLUSIONS: Atresiaplasty surgery in individuals with congenital aural atresia can yield reliable, lasting hearing results in 68.2% (450/660), with a low incidence of complications; the initial improved hearing deteriorated gradually over the first 6 months post-operation, which are related with the stenosis and infection of canal. Cavity adhesion, bony EAC re-growth, ossicular chain re-fixation or displace may affect the hearing results in some cases. Even unilateral aural atresia may benefit from the reconstruction surgery and achieve serviceable hearing results.


Assuntos
Otopatias/congênito , Otopatias/cirurgia , Audição , Procedimentos Cirúrgicos Otológicos , Adolescente , Adulto , Criança , Pré-Escolar , Pavilhão Auricular/anormalidades , Orelha Externa/anormalidades , Orelha Média/anormalidades , Feminino , Humanos , Masculino , Procedimentos de Cirurgia Plástica , Resultado do Tratamento , Adulto Jovem
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