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Sclerosing extramedullary hematopoietic tumor (SEMHT) is a rare tumor that can occur in association with some chronic myeloproliferative neoplasms, particularly myelofibrosis. The morphology of SEMHT can mimic that of a wide variety of other lesions, both macroscopically and microscopically. SEMHT originating from the colon is extremely rare. The present study reports a case of SEMHT in the colon with involvement of the peri-intestinal lymph nodes. On the basis of the clinical symptoms and endoscopic results, a malignant tumor of colon was suspected. Pathological examination revealed the deposition of collagen and hematopoietic components in the fibrous mucus background. Immunohistochemical staining for CD61 confirmed the presence of atypical megakaryocytes, while immunohistochemical staining for myeloperoxidase and glycophorin A highlighted the existence of granulocyte and erythrocyte precursors, respectively. These findings combined with a clinical history of myelofibrosis led to the final diagnosis of SEMHT. The presence of atypical megakaryocytes with immature hematopoietic cell morphology and a good understanding of the clinical history of the patient are essential to prevent misdiagnosis. The present case emphasizes the necessity of reviewing previous hematological history and considering clinical findings together with the associated pathological results.
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Not required for Clinical Vignette.
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Neoplasias das Glândulas Suprarrenais , Hemangioma , Humanos , Diagnóstico Diferencial , Hemangioma/diagnóstico por imagem , Hemangioma/cirurgia , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/cirurgiaRESUMO
Perianal skin Paget disease (PPD) is an unusual subtype of extramammary Paget disease, which is usually caused by a primary intraepithelial adnexal tumor and secondary spread from colorectal adenocarcinoma. The reports of secondary PPD associated with non-invasive colorectal adenoma are rare. We report a rare case of non-invasive colorectal-adenoma-associated PPD. In this case, the intraepithelial Paget cells of perianal skin manifested with colorectal phenotype by immunohistochemistry, and adjacent adenomas had high-grade intraepithelial neoplasia but not invasion. Although this is a rare manifestation of PPD, understanding this phenomenon is important to prevent overdiagnosis and invasive overtreatment. Clinical management is variable and, therefore, close follow-up examination is necessary.
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Adenocarcinoma , Neoplasias do Ânus , Doença de Paget Extramamária , Neoplasias Cutâneas , Humanos , Neoplasias do Ânus/diagnóstico , Neoplasias do Ânus/tratamento farmacológico , Neoplasias do Ânus/patologia , Neoplasias Cutâneas/patologia , Doença de Paget Extramamária/diagnóstico , Pele/patologiaRESUMO
Angioleiomyoma is a type of pericyte tumor with a benign biological behavior. It typically features proliferation of mature perivascular smooth muscle cells around blood vessels. Angioleiomyoma may be categorized into solid, cavernous or venous subtypes. Usually, it occurs in the dermis or subcutaneous tissue, while the rare cavernous subtype is most common in the upper extremities. Only a small number of cases of angioleiomyoma located in the mediastinum have been reported to date. In addition, there are few reports of mediastinal angioleiomyoma described as a cavernous histopathological subtype. The present study reported a case of mediastinal angioleiomyoma presenting as an unusual cavernous histopathological subtype. The histopathological and immunohistochemical features, based on which a diagnosis of cavernous angioleiomyoma was confirmed, were desmin- and smooth muscle actin-positive expression in spindle tumor cells, as well as ETS-related gene (ERG)- and CD31-positive expression in vascular endothelial cells. Cavernous angioleiomyoma of the mediastinum rarely occurs in the clinical setting but should be considered as a differential diagnosis of mediastinal tumors.
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Background: The IBCSG 23-01 and AMAROS trials both reported that axillary lymph node dissection (ALND) did not change survival rates in breast cancer patients with positive nodes detected by sentinel lymph node biopsy (SLNB). The aim of this study was to determine whether breast cancer patients with mastectomy and false-negative frozen section (FS) in SLNB could forgo ALND. Materials and Methods: This was a retrospective study of cN0 patients diagnosed with primary invasive breast cancer treated by mastectomy and SLNB at our institute between January 2010 and December 2014. Patients with false-negative FS in SLNB were separated by the following management of axillary lymph node dissection in the non-ALND group (nonprocess or axillary radiation only) and ALND group (with or without radiation). Results: A total of 212 patients were included, 86 and 126 patients in the non-ALND and ALND groups, respectively. The positive rate of non-sentinel lymph nodes (SLNs) was 15.87% (20/126) in the ALND group. In multivariate analysis, we found that patients with larger tumor size (>2 cm) (OR, 1.989; p = 0.030) and multifocal lesions (OR, 3.542; p = 0.029) tended to receive ALND. The positivity of non-SLNs in the ALND group was associated with SLN macrometastasis (OR, 3.551; p = 0.043) and lymphovascular invasion (OR, 6.158; p = 0.003). Also, removing more SLNs (≥3) was related to negativity in non-SLNs (OR, 0.255; p = 0.016). After a median follow-up of 59.43 months, RFS and OS of the two groups were similar (p = 0.994 and 0.441). In subgroup analysis, we found that 97 patients who met the inclusive criteria of the IBCSG 23-01 trial had similar RFS and OS between the non-ALND and ALND groups (p = 0.856 and 0.298). The positive rate of non-SLNs was 9.62% (5/52). Also, in 174 patients who met the criteria of the AMAROS trial, RFS and OS in the non-ALND and ALND groups were similar (p = 0.930 and 0.616). The positive rate of non-SLNs was 18.27% (19/104). Conclusion: ALND can be carefully omitted in selected breast cancer patients with mastectomy and false-negative FS in SLNB. SLNB is relatively sufficient in the IBCSG 23-01-eligible patients, and axillary radiation was an effective option in the AMAROS-eligible patients.
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BACKGROUND: Ductal carcinoma in situ with microinvasion (DCISM) was defined as one or more foci of invasion beyond the basement membrane within 1 mm. The size of primary lesion is associated with axillary status and prognosis in patients with invasive breast cancer; thus, it is of interest to determine whether multiple foci of microinvasion are associated with a higher risk of positive axillary status or worse long-term outcomes in patients with DCISM. METHODS: This study identified 359 patients with DCISM who had undergone axillary evaluation at our institute from January 2006 to December 2015. Patients were categorized as one focus or multiple foci (≥2 foci) according to the pathological results. Clinicopathological features, axillary status, and disease-free survival rate were obtained and analyzed. RESULTS: Of 359 patients, 233 (64.90%) had one focus of microinvasion and 126 (35.10%) had multiple foci. Overall, 242 (67.41%) and 117 (32.59%) patients underwent sentinel lymph nodes biopsy (SLNB) and axillary lymph nodes dissection (ALND), respectively. Isolated tumor cells were found in four (1.11%) patients and axillary metastasis rate was 2.51%. Neither axillary evaluation methods (P = 0.244) nor axillary metastasis rate (P = 0.559) was significantly different between patients with one focus and multiple foci. In univariate analysis, patients with multiple foci tended to have larger tumor size (P < 0.001), higher nuclear grade (P = 0.001), and higher rate of lymphatic vascular invasion (P = 0.034). Also, the proportion of positive HER2 (P = 0.027) and Ki67 level (P = 0.004) increased in patients with multiple foci, while in multivariate analysis, only tumor size showed significant difference (P = 0.009). Patients with multiple foci were more likely to receive chemotherapy (56.35 vs 40.77%; P = 0.028). At median 5.11 years follow-up, overall survival rate was 99.36%. Patients with multiple microinvasive foci had worse disease-free survival rate compared with one-focus patients (98.29 vs 93.01%, P = 0.032). CONCLUSION: Even though the numbers of microinvasion were different and patients with multiple foci of microinvasion tended to have larger tumor size, there was no higher risk of axillary involvement compared with patients with one focus of microinvasion, while patients with multiple microinvasive foci had worse DFS rate. Thus, DCISM patients with multiple foci of microinvasion may be the criterion for more aggressive local-regional treatment. Optimization of adjuvant therapy in DCISM patients is required.
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Melanoma is a common type of cutaneous tumor, but current drug treatments do not satisfy clinical practice requirements. At present, mitochondrial uncoupling is an effective antitumor treatment. Triclosan, a common antimicrobial, also acts as a mitochondrial uncoupler. The aims of the present study were to investigate the effects of triclosan on melanoma cells and the underlying mechanisms. Mitochondrial membrane potential (MMP), mitochondrial morphology, mitochondrial reactive oxygen species (mito-ROS), intracellular superoxide anion and [Ca2+]i were measured using confocal microscopy. It was found that triclosan application was associated with decreased A375 cell viability in a dose- and time-dependent manner and these effects may have cell specificity. Furthermore, triclosan induced MMP depolarization, ATP content decrease, mito-ROS and [Ca2+]i level increases, excessive mitochondrial fission, AMP-activated protein kinase (AMPK) activation and STAT3 inhibition. Moreover, these aforementioned effects were reversed by acetylcysteine treatment. Triclosan acute treatment also induced mitochondrial swelling, which was reversed after AMPK-knockdown associated with [Ca2+]i overload. Cell death was caused by STAT3 inhibition but not AMPK activation. Moreover, triclosan induced autophagy via the ROS/AMPK/p62/microtubule-associated protein 1A/1B-light chain 3 (LC3) signaling pathway, which may serve a role in feedback protection. Collectively, the present results suggested that triclosan increased mito-ROS production in melanoma cells, following induced cell death via the STAT3/Bcl-2 pathway and autophagy via the AMPK/p62/LC3 pathway.
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Increasing evidence has suggested that special AT-rich sequence-binding protein 2 (SATB2) may be involved in the progression of numerous types of human cancer; however, the biological function of SATB2 in oral squamous cell carcinoma (OSCC) occurrence and progression remains relatively unknown. The present study aimed to investigate the potential role of SATB2 in the regulation of biological characteristics of OSSC during hypoxia. The expression of SATB2 in SCC9 cells was knocked down using small interfering RNA. Western blotting was used to determine the protein expression levels of SATB2, autophagy-related proteins microtubule-associated protein light chain (LC)3-I/II and Beclin-1, and stemness markers such as Oct-4 (POU class 5 homeobox 1), Sox-2 (SRY-box 2) and Nanog (nanog homeobox). Transmission electron microscopy and monodansylcadaverine staining were used to detect the presence of autophagosomes. Furthermore, the self-renewal capacity of cells was analyzed using colony forming assays; the cell proliferative, migratory and invasive ability were evaluated using CCK-8, wound healing and Transwell assays, respectively; and the cell cycle distribution and rate of apoptosis were detected using flow cytometry. The expression levels of SATB2, autophagy-related proteins and stemness markers were significantly increased in SCC9 cells following hypoxic treatment. Meanwhile, the genetic knockdown of SATB2 inhibited hypoxia-mediated autophagy by decreasing the expression levels of Beclin-1, and preventing the conversion of LC3-I to LC3-II and the accumulation of autophagosomes. The knockdown of SATB2 also inhibited the hypoxia-induced colony-forming ability and the expression of stemness markers. Functionally, it also inhibited the proliferative, migratory and invasive abilities of SCC9 cells, while inducing apoptosis and cell cycle arrest under hypoxia. In conclusion, the present study suggested that SATB2 may function as an oncogene in OSCC cells, and targeting SATB2 may be a potential therapeutic strategy for the treatment of OSCC.
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Decompression has been considered a valuable tool for odontogenic cystic lesions to minimize cyst size with low morbidity and recurrence. However, whether decompression has a role in regulating stem cell properties of orofacial bone marrow stromal cells (BMSCs) around the cysts has not been fully investigated. The present study compared the stem cell marker profile and osteogenic differentiation potential of orofacial BMSCs prior to and following marsupialization (preBMSCs vs. postBMSCs) in the same individuals. The results demonstrated that postBMSCs proliferated significantly faster, displayed higher colonyforming unitfibroblast capacity and demonstrated higher expression of octamer binding protein 4, Nanog and SRYrelated HMG box 2 when compared with the preBMSCs. Notably, the osteogenic potential was greater in the postBMSCs compared with in preBMSCs, by demonstrating that the protein and mRNA expression levels of osteopontin, runtrelated transcription factor 2, osteocalcin, alkaline phosphatase and osterix were upregulated in preBMSCs. Furthermore, the phosphorylated levels of extracellular signalregulated kinase and cJun Nterminal kinase were enhanced in postBMSCs. In conclusion, the study indicated that decompression influences the stem cell properties of orofacial BMSCs, and further studies are needed to verify the findings.
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Diferenciação Celular , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Osteogênese , Adulto , Biomarcadores , Proliferação de Células , Separação Celular , Feminino , Humanos , Imunofenotipagem , Sistema de Sinalização das MAP Quinases , Masculino , Cistos Odontogênicos , Células-TroncoRESUMO
Litsea cubeba is one of aromatic medicinal plant belonging to family Lauraceae. The roots, stems and fruits of L. cubeba have been widely applied as folk medicines in some districts in China for relieving rheumatism and cold, regulating Qi (meridian) to alleviate pain. Previous studies revealed that this species contains major alkaloids, in specific aporphines, and minor flavonoids, lignans as well. Related pharmacological investigations demonstrated its activities and clinical applications on cardiovascular diseases, anti-cancer, against rheumatoid arthritis, relieving asthma and anti-allergic effects, as anti-oxidants, and so on. As an effort for further exploration of this bioactive ingredients and potential drug development, this paper summarizes most phytochemical and pharmacological results. Further, future prospects are also included.
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Litsea/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Animais , Tratamento Farmacológico , Humanos , Estrutura MolecularRESUMO
A phytochemical investigation on the aerial parts of a Tibetan medicine Meconopsis horridula, by solvent extraction, repeated chromatographies on silica gel, Sephadex LH-20, and preparative TLC techniques, led to the isolation of 9 compounds. By spectroscopic analysis and comparison of its 1H and 13C-NMR data with those in literatures, their structures were identified as oleracein E(1), N-( trans-p-coumaroyl) tyramine (2), chrysoeriol (3), apigenin (4), hydnocarpin (5), p-coumaric acid glucosyl ester (6), stigmast-5-ene-3beta-ylformate (7), 3beta-hydroxy-7alpha-ethoxy-24beta-ethylcholest-5-ene (8), and beta-sitosterol (9), respectively, among which compounds 6-8 were isolated from the genus for the first time,and 1,3 were isolated from the species for the first time. A MTT method was applied to evaluate the cytotoxic activity of compounds 14 against the human hepatocellular liver carcinoma cell line (HepG2), and compound 1 showed significant cytotoxicity against HepG2,with its inhibitory rate of 52.2% at 10 micromol x L(-1).
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Papaveraceae/química , Extratos Vegetais/química , Medicina Tradicional Tibetana , Estrutura Molecular , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
OBJECTIVE: To explore the association of Jab1 (c-Jun activation domain binding protein 1) expression during carcinogenesis and clinicopathological characteristics of colorectal carcinoma (CRC) . METHODS: Tissue specimens were obtained from 80 cases of CRC from January 2007 to December 2008. And the expression of Jab1 protein for each specimen was detected by immunohistochemistry (EnVision). Six representative paired samples of cancerous and paired adjacent normal tissues were collected for Western blot. The relationships between the expression level of Jab1 protein and the clinicopathological characteristics of primary CRC were retrospectively analyzed. RESULTS: A high-level expression of Jab1 was present in cancerous tissues but not in paired adjacent normal tissues. The positive expression rate of Jab1 protein was as high as 96.3% (77/80) . And its high expression rate was 82.5% (66/80) , low expression rate 17.5% (14/80) and 8.8% (7/80) in cancerous and paired adjacent normal tissues respectively (P < 0.05) . Its expression was correlated with differentiation, invasion depth, TNM stage and lymph node metastasis (all P < 0.05) . Jab1 was significantly correlated with Ki-67 (r = 0.548, P < 0.01) and inversely with p27(kip1) (r = -0.461, P < 0.01). CONCLUSIONS: An over-expression of Jab1 protein might play an important role in the pathogenesis of CRC. Thus it may become a novel diagnostic marker and a therapeutic target in patients with CRC.
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Carcinoma/metabolismo , Neoplasias Colorretais/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Peptídeo Hidrolases/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Complexo do Signalossomo COP9 , Carcinoma/patologia , Neoplasias Colorretais/patologia , Feminino , Humanos , Imuno-Histoquímica , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos RetrospectivosAssuntos
Neoplasias da Mama/metabolismo , Carcinoma/metabolismo , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Proteínas Quinases Associadas a Fase S/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Carcinoma/patologia , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fosforilação , Prognóstico , Treonina/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Species of the genus Cynomorium (Cynomoriaceae), including C. songaricum Rupr. and C. coccineum L., have a long history of use in traditional medicine to treat various ailments such as impotence, premature ejaculation, kidney-yang deficiency, spermatorrhea, colic, and stomach ulcers. In addition, these species are used in health foods, tea, and cosmetics. AIM OF THE REVIEW: The aim of this review is to provide comprehensive information on the botany, traditional uses, phytochemistry, pharmacological research, and toxicology of C. songaricum and C. coccineum and to explore the therapeutic potential and future research opportunities of these species. MATERIALS AND METHODS: All available information on C. songaricum and C. coccineum was collected via electronic search (using PubMed, ACS, CNKI, Google Scholar, Baidu Scholar, and Web of Science). RESULTS: The ethnomedical uses of C. songaricum and C. coccineum in Saudi Arabia, China, Afghanistan, Mongolia, and Iran for several types of ailments were recorded. A phytochemical investigation revealed the presence of flavonoids, terpenoids, phloroglucinol adducts, saccharides, phenylpropanoids, steroids, organic acids, and other compounds. The crude extracts and pure compounds from C. songaricum and C. coccineum exhibited a wide spectrum of in vitro and in vivo pharmacological activity, including anti-fatigue, anti-hypoxia, anti-oxidation, anti-diabetic, immune system modulating, and antiviral activity. CONCLUSIONS: Cynomorium species have emerged as a source of traditional medicine. Many studies have provided evidence for the therapeutic efficacy of these species in treating various conditions and possible mechanisms. However, further research is required for the development of new drugs and therapies for the treatment of various diseases, especially cancer and diabetes. Therefore, this review on the ethnopharmacology, phytochemistry, and toxicity of Cynomorium species will provide helpful data for further studies and commercial exploitation of the species.
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Cynomorium , Medicamentos de Ervas Chinesas/farmacologia , Etnofarmacologia , Medicina Tradicional Chinesa , Fitoterapia , Animais , China , Conservação dos Recursos Naturais , Cynomorium/química , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/toxicidade , Humanos , Plantas MedicinaisRESUMO
AIM: To investigate sex hormone and androgen receptor (AR) levels and to evaluate their relationship with diabetes mellitus (DM) in senile men. METHODS: The cross-sectional study included 492 elderly men comprising 104 healthy subjects (mean age 71.4 ± 5.2 years), 259 subjects without DM (71.5 ± 5.0 years) and 129 DM patients (73.0 ± 6.3 years). Plasma concentrations of total testosterone (TT), free testosterone (FT), dehydroepiandrosterone sulphate, sex hormone-binding globulin (SHBG), estradiol (E(2)), luteinising hormone) and follicle-stimulating hormone (FSH) were determined. AR-positive cells were measured by flow cytometry. RESULTS: TT concentrations were significantly lower in the DM group (13.8 ± 4.7 nmol/l) than in the healthy (17.1 ± 6.1 nmol/l) and non-diabetes groups (15.8 ± 6.0 nmol/l; all P < 0.01). FT, SHBG, AR-positive proportion (AR%) and AR fluorescence intensity showed a decreasing trend among the healthy, non-DM and DM groups, but the differences were not significant. TT, E(2), E(2)/testosterone and SHBG were negatively correlated with blood glucose. SHBG was positively correlated and TT and AR% were negatively correlated with the course of DM. Logistic multiple regression analysis revealed that age, waist/hip ratio, FSH, SHBG and AR% are potential risk factors for DM. CONCLUSIONS: Low levels of TT, SHBG and AR may be potential risk factors for DM in elderly men.
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Glicemia/análise , Diabetes Mellitus , Hormônios Esteroides Gonadais , Receptores Androgênicos , Fatores Etários , Idoso , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/metabolismo , Hormônio Foliculoestimulante/metabolismo , Hormônios Esteroides Gonadais/análise , Hormônios Esteroides Gonadais/metabolismo , Humanos , Modelos Logísticos , Hormônio Luteinizante/metabolismo , Masculino , Receptores Androgênicos/análise , Receptores Androgênicos/metabolismo , Fatores de Risco , Globulina de Ligação a Hormônio Sexual/metabolismo , Relação Cintura-QuadrilRESUMO
Integrin-mediated substrate adhesion of endothelial cells leads to dynamic rearrangement of the actin cytoskeleton. Protein kinase C (PKC) stimulates reorganization of microfilaments and adhesion, while the responses of Schwann cells during adhesion and migration are unknown, so we examined the expression changes of SSeCKS and F-actin in Schwann cells after exposure to fibronectin. Src (sarcoma) suppressed C kinase substrate (SSeCKS) is a PKC substrate that may play an important role in regulating actin cytoskeleton. We found that SSeCKS was localized to focal adhesion sites soon after Schwann cells adhesion and that SSeCKS increased during the process of cell spreading. Using small interfering RNAs specific to SSeCKS, we showed that Schwann cells in which SSeCKS expression was inhibited reduced cellular adhesion, spreading and promoted cellular migration on fibronectin through reorganization of actin stress fibers and blocking formation of focal adhesions. These results demonstrated SSeCKS modulate Schwann cells adhesion, spreading and migration by reorganization of the actin cytoskeleton.
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Proteínas de Ancoragem à Quinase A/fisiologia , Proteínas de Ciclo Celular/fisiologia , Células de Schwann/fisiologia , Quinases da Família src/fisiologia , Proteínas de Ancoragem à Quinase A/genética , Animais , Adesão Celular , Proteínas de Ciclo Celular/genética , Linhagem Celular , Membrana Celular/metabolismo , Movimento Celular , Citosol/metabolismo , Fibronectinas/fisiologia , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Adesões Focais/fisiologia , Técnicas de Silenciamento de Genes , Transporte Proteico , RNA Interferente Pequeno/genética , Ratos , Fibras de Estresse/fisiologiaRESUMO
Peripheral nerve transection has been implicated to cause a production of neuronal nitric oxide synthase (nNOS), which may influence a range of post-axotomy processes necessary for neuronal survival and nerve regeneration. Carboxy-terminal post synaptic density protein/Drosophila disc large tumor suppressor/zonula occuldens-1 protein (PDZ) ligand of neuronal nitric oxide synthase (CAPON), as an adaptor, interacts with nNOS via the PDZ domain helping regulate nNOS activity at postsynaptic sites in neurons. And Dexras1, a small G protein mediating multiple signal transductions, has been reported to form a complex with CAPON and nNOS. A role for the physiologic linkage by CAPON of nNOS to Dexras1 has suggested that NO-mediated activation of Dexras1 is markedly enhanced by CAPON. We investigated the changes in mRNA for CAPON, Dexras1 and nNOS in the sciatic nerve, dorsal root ganglia and lumbar spinal cord of adult rat following sciatic axotomy by TaqMan quantitative real-time PCR and in situ hybridization combined with immunofluorescence. Signals of mRNA for CAPON and Dexras1 were initially expressed in these neural tissues mentioned, transiently increased at certain time periods after sciatic axotomy and finally recovered to the basal level. It was also found that nNOS mRNA underwent a similar change pattern during this process. These results suggest that CAPON as well as Dexras1 may be involved in the different pathological conditions including nerve regeneration, neuron loss or survival and even pain process, possibly via regulating the nNOS activity or through the downstream targets of Dexras1.
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Proteínas Adaptadoras de Transdução de Sinal/genética , Óxido Nítrico Sintase Tipo I/metabolismo , Óxido Nítrico/biossíntese , Neuropatia Ciática/metabolismo , Proteínas ras/genética , Animais , Axotomia , Sobrevivência Celular/genética , Feminino , Gânglios Espinais/metabolismo , Gânglios Espinais/patologia , Gânglios Espinais/fisiopatologia , Regulação Enzimológica da Expressão Gênica/genética , Hibridização In Situ , Substâncias Macromoleculares/metabolismo , Masculino , Regeneração Nervosa/genética , Células do Corno Posterior/metabolismo , Células do Corno Posterior/patologia , Células do Corno Posterior/fisiopatologia , RNA Mensageiro/análise , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neuropatia Ciática/genética , Neuropatia Ciática/fisiopatologia , Raízes Nervosas Espinhais/metabolismo , Raízes Nervosas Espinhais/patologia , Degeneração Walleriana/genética , Degeneração Walleriana/metabolismo , Degeneração Walleriana/fisiopatologiaRESUMO
OBJECTIVE: To investigate the association between catecholamine-beta-adrenoceptor (beta-AR)-adenosine 3', 5'-monophosphate (cAMP) system and long-term prognosis in patients with chronic heart failure (CHF). METHODS: The study population comprised 73 patients with CHF (EF: 23% +/- 10%) with a mean follow-up of 3.8 +/- 1.9 years. Plasma levels of norepinephrine (NE) were measured using high performance lipid chromatography, beta-adrenergic receptor density (Bmax) and the content of cAMP in peripheral lymphocytes were calculated using 3H-dihydroalpneolo as ligand and competitive immunoassay, respectively. Deaths due to cardiovascular events within the follow-up period were registered. RESULTS: The total mortality was 64.7%, 57.4% of which was for cardiogenic (worsening heart failure: 32.4%; sudden death: 25.0%). In the cardiogenic death group, plasma levels of NE and epinephrine (E) (3.74 nmol/L +/- 0.09 nmol/L and 3.17 nmol/L +/- 1.0 nmol/L) and the contents of peripheral lymphocyte cAMP (3.64 pmol/mg protein +/- 1.4 pmol/mg protein) were significantly increased as compared with the survival group (2.68 nmol/L +/- 0.07 nmol/L, 2.41 nmol/L +/- 0.24 nmol/L and 2.73 pmol/mg protein +/- 0.9 pmol/mg protein, respectively, all P < 0.01). In the sudden death group, plasma levels of NE and E (5.01 nmol/L +/- 0.06 nmol/L and 4.13 nmol/L +/- 0.08 nmol/L) were significantly increased as compared with the worsening heart failure group (2.49 nmol/L +/- 0.07 nmol/L and 2.33 nmol/L +/- 0.8 nmol/L, all P < 0.001) and to the survival group (2.68 nmol/L +/- 0.07 nmol/L and 2.41 nmol/L +/- 0.14 nmol/L, all P < 0.01). The incidences of sudden death were 0%, 75%, and 100% (chi(2) = 16.018, P < 0.01) in patients with plasma NE < 2.5 nmol/L, NE 2.5 nmol/L - 4.5 nmol/L, and NE > 4.5 nmol/L, respectively. In the worsening heart failure group, the content of peripheral lymphocyte cAMP (4.46 pmol/mg protein +/- 0.18 pmol/mg protein) was significantly increased compared with the sudden death group (2.39 pmol/mg protein +/- 0.9 pmol/mg protein, P < 0.001) and to the survival group (2.73 pmol/mg protein +/- 1.1 pmol/mg protein, P < 0.001). The worsening heart failure death occurences were 5.0%, 72.2%, and 100% (chi(2) = 14.26, P < 0.01) in patients with a content of peripheral lymphocyte cAMP < 2.5 nmol/L, cAMP 2.5 nmol/L - 4.5 nmol/L, and cAMP > 4.5 nmol/L, respectively. Bmax in peripheral lymphocyte was not significantly different (P > 0.05) among the sudden death, worsening heart failure, and survival groups in CHF patients. CONCLUSIONS: Plasma levels of catecholamine increase significantly, and Bmax and the contents of cAMP in peripheral lymphocytes decrease significantly in patients with CHF. High plasma catecholamine levels may be associated with sudden death, and high intralymphocyte cAMP content may be associated with worsening heart failure in CHF patients.