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BACKGROUND: While treatment advancements have prolonged the lives of patients with head and neck cancer, the subgroups of these patients at higher risk for cardiovascular disease (CVD) mortality remain unclear. METHODS: We analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database for patients diagnosed with head and neck cancer from 2000 to 2019. We compared their CVD mortality against the general US population using standardized mortality ratios (SMRs). RESULTS: Our analysis included 474,366 patients, identifying that 14% of deaths were due to CVD, with an SMR of 1.19. Notably, patients under the age of 39 had a CVD SMR increase of over 100-fold. Those with distant tumor stages showed the highest CVD SMR of 1.52 (95% CI 1.50-1.54). An upward trend in SMR to 2.53 (95% CI 2.51-2.56) was observed from 2011 to 2019. Within the initial 5-year post-diagnosis, the SMR for CVD was 3.17 (95% CI 3.14-3.20), which exceeded the general population's rates but declined in the 5-20-year range after diagnosis. Patients who did not any therapy had the greatest CVD SMR of 2.26 (95% CI 2.24-2.28). Hypopharyngeal cancer patients exhibited the highest CVD SMR of 1.54 (95% CI 1.52-1.56). CONCLUSIONS: The study highlights that head and neck cancer patients, especially younger individuals and those with advanced disease stages, face substantial CVD mortality risks. The CVD SMR peaks within 5 years following diagnosis. Patients abstaining from treatment bear the highest risk of CVD mortality. Cardioprotective measures should be considered critical for this patient population.
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Doenças Cardiovasculares , Neoplasias de Cabeça e Pescoço , Programa de SEER , Humanos , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/epidemiologia , Masculino , Feminino , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/epidemiologia , Pessoa de Meia-Idade , Incidência , Idoso , Adulto , Estados Unidos/epidemiologia , Idoso de 80 Anos ou mais , Fatores de RiscoRESUMO
Anti-DNER antibody is associated with paraneoplastic cerebellar degeneration (PCD) and Hodgkin's disease (HD). However, recent studies reported cases absence of HD and that non-tumor anti-DNER antibody-associated ataxia was not well characterized. We present a case of acute cerebellar ataxia and nystagmus with detected anti-DNER antibody. Brain magnetic resonance imaging (MRI) showed cerebellar atrophy. High titer of anti-DNER antibody was detected in CSF and serum. Positron emission tomography (PET) scanning was unremarkable at a 10-month follow up. The patient improved significantly after immunosuppressive therapy with intravenous steroids, immunoglobulin followed by rituximab. Our study suggest that the presence of such anti-neuronal antibodies might not come along with malignancy and that early onset non-tumor patients are more likely to have a better outcome after immunotherapy. Early diagnosis and timely immunosuppressive therapy may prove beneficial for these patients.
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The "hot cross bun" sign (HCBs) is a cruciform hyperintensity on T2-weighted imaging within the pons initially found in patients diagnosed as multiple system atrophy. However, recent findings have broadened the disease spectrum presented with HCBs. Here is a case report at an academic medical center. Cerebral magnetic resonance imaging (MRI), electroneuromyography, serum, and CSF analysis were performed. Literature is comprehensively reviewed. We investigated a woman presented with blurred speech and cerebellar ataxia. Her MRI showed the vertical line of HCBs 2 weeks after disease onset and gradually enhanced, presenting as an intact HCBs in a year. Glutamic acid decarboxylase 65-kDa isoform (GAD65) antibody IgG was detected in serum and CSF. The patient was diagnosed as GAD65 associated cerebellar ataxia and treated with corticosteroid and rituximab. We found 6 previously reported autoimmune cerebellar ataxia patients with HCBs. Anti-KLHL-11, anti-Homer-3, anti-Ri, and anti-Amphiphysin were associated. All patients had cerebellar ataxia with other neurological symptoms. Five patients were diagnosed with tumor. First-line immunotherapy including corticosteroid, intravenous immunoglobulin, and plasma exchange for most patients was unsatisfied. This case highlights the importance of considering GAD65 IgG evaluation in patients with progressive cerebellar syndrome and HCBs. Early diagnosis and therapy are challenging but imperative. Further studies are required in regard to therapeutic management.
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OBJECTIVE: The mechanisms of lung injury in acute respiratory distress syndrome (ARDS) are not well understood.Piezo1 was recently identified as a mechanotransduction protein. The present study found the expression of Piezo1 in type II pneumocytes and investigated its role in mediating ARDS-related lung injury. METHODS: Sprague-Dawley rats were used to establish an ARDS model, the expression of Piezo1,lung injuries, apoptosis as well as calcium influx were assessed. RESULTS: Piezo1 was expressed in type II pneumocytes as shown by immunofluorescence staining and expression was increased in the ARDS model. Knockdown of Piezo1 reduced apoptosis which was related to the elevation of Bcl-2.Calcium influx played a vital role in Piezo1-induced apoptosis. CONCLUSION: Piezo1 was expressed in type II pneumocytes. Mechanical stretch of alveoli during ARDS induced activation of the Piezo1 channel,which resulted in calcium influx. The increased intracellular Ca2+ induced the apoptosis of type II pneumocytes, which may be related to the Bcl-2 pathway.
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Células Epiteliais Alveolares/metabolismo , Apoptose/fisiologia , Proteínas de Membrana/biossíntese , Síndrome do Desconforto Respiratório/metabolismo , Estresse Mecânico , Células A549 , Células Epiteliais Alveolares/patologia , Animais , Humanos , Ratos , Ratos Sprague-Dawley , Síndrome do Desconforto Respiratório/patologiaRESUMO
The primary purpose of this study was to assess the serum levels of homocysteine (HCY) at admission to the presence of post-stroke depression (PSD). From September 2014 to December 2015, first-ever acute ischemic stroke patients within the first 24 h after stroke onset were consecutively recruited and followed-up for 3 months. Based on the symptoms, diagnoses of depression were made in accordance with DSM-IV criteria for depression. By the time of 3 month after stroke, 238 had finished the follow-up and included in our study. Totally, 65 out of the 238 patients were diagnosed as depression (27.3%; 95% CI 19.6-35.4%). The results showed significantly higher HCY levels in patients with depression [21.4 (IQR 16.5-23.4) mmol/L vs. 14.1 (IQR 11.2-18.5) mmol/L, P < 0.0001) at admission than patients without depression. In multivariate logistic regression analysis, HCY was an independent predictor of PSD with an adjusted OR of 1.07 (95% CI 1.01-1.22; P = 0.013). Based on the ROC curve, the optimal cut-off value of serum HCY levels as an indicator for prediction of PSD was projected to be 16.5 mmol/L, which yielded a sensitivity of 82.5% and a specificity of 63.6%, with the area under the curve at 0.745 (95% CI 0.672-0.818; P < 0.0001). An increased risk of PSD was associated with serum HCY levels ≥16.5 mmol/L (adjusted OR 6.13, 95% CI 3.32-14.16; P < 0.001) after adjusting for above-recorded confounders. Elevated serum levels of HCY at admission were associated with depression 3-month after stroke, suggesting that these alterations might participate in the pathophysiology of depression symptoms in stroke patients.
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Depressão/sangue , Depressão/etiologia , Homocisteína/sangue , Acidente Vascular Cerebral/complicações , Idoso , Isquemia Encefálica/complicações , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Admissão do Paciente , Escalas de Graduação Psiquiátrica , Curva ROC , Estatísticas não Paramétricas , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/etiologia , Tomografia Computadorizada por Raios XRESUMO
According to the rate of living-free radical hypothesis, higher metabolic rates should increase reactive oxygen species (ROS) production. However, the "uncoupling to survive" hypothesis postulates that uncoupling proteins (UCPs) can decrease ROS production by lowering the potential of the inner mitochondrial membrane, in which case the correlation between metabolic rate and ROS levels would be a negative rather than positive. In this study, we examined energy intake, oxidative stress levels, antioxidant activity and the expression of UCPs in brown adipose tissue (BAT), and in the liver, heart, skeletal muscle and brain, of striped hamsters (Cricetulus barabensis) acclimated to either 5 °C or 32.5 °C. The energy intake of hamsters acclimated to 5 °C increased by 70.7%, whereas the energy intake of hamsters acclimated to 32.5 °C decreased by 31.3%, relative to hamsters kept at room temperature (21 °C) (P<0.05). Malonadialdehyde (MDA) levels, total antioxidant capacity (T-AOC) and glutathione peroxidase (GSH-PX) activity in BAT significantly decreased in 5 °C group, but increased in 32.5 °C group, relative to the 21 °C group. Neither ROS levels (i.e. H2O2 levels), nor antioxidants in skeletal muscle, liver, heart or brain tissue, were affected by temperature. UCP1 expression in BAT was significantly up-regulated in 5 °C group, but down-regulated in 32.5 °C group, relative to the 21 °C group. UCP3 expression of skeletal muscle was also up-regulated significantly in hamsters acclimated to 5 °C. These results suggest that the relationship between ROS levels and metabolic rate was negative, rather than positive. UCP1 expression in BAT may have played a role in lowering ROS levels.
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Antioxidantes/metabolismo , Cricetulus/fisiologia , Expressão Gênica , Canais Iônicos/genética , Proteínas Mitocondriais/genética , Estresse Oxidativo/fisiologia , Temperatura , Aclimatação/fisiologia , Tecido Adiposo Marrom/metabolismo , Animais , Encéfalo/metabolismo , Cricetinae , Cricetulus/genética , Cricetulus/metabolismo , Ingestão de Energia/fisiologia , Metabolismo Energético/fisiologia , Glutationa Peroxidase/metabolismo , Fígado/metabolismo , Malondialdeído/metabolismo , Músculos/metabolismo , Miocárdio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteína Desacopladora 1RESUMO
Conventional therapies for autoimmune diseases produce nonspecific immune suppression, which are usually continued lifelong to maintain disease control, and associated with a variety of adverse effects. In this study, we found that spleen-derived dendritic cells (DCs) from the ongoing experimental autoimmune myasthenia gravis (EAMG) rats can be induced into tolerogenic DCs by atorvastatin in vitro. Administration of these tolerogenic DCs to EAMG rats on days 5 and 13 post immunization (p.i.) resulted in improved clinical symptoms, which were associated with increased numbers of CD4(+)CD25(+) T regulatory (Treg) cells and Foxp3 expression, decreased lymphocyte proliferation among lymph node mononuclear cells (MNC), shifted cytokine profile from Th1/Th17 to Th2 type cytokines, decreased level of anti-R97-116 peptide (region 97-116 of the rat acetylcholine receptor α subunit) IgG antibody in serum. These tolerogenic DCs can migrate to spleen, thymus, popliteal and inguinal lymph nodes after they were injected into the EAMG rats intraperitoneally. Furthermore, these tolerogenic DCs played their immunomodulatory effects in vivo mainly by decreased expression of CD86 and MHC class II on endogenous DCs. All these data provided us a new strategy to treat EAMG and even human myasthenia gravis (MG).
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Células Dendríticas/efeitos dos fármacos , Ácidos Heptanoicos/farmacologia , Imunoterapia , Miastenia Gravis Autoimune Experimental/terapia , Pirróis/farmacologia , Linfócitos T Reguladores/imunologia , Animais , Atorvastatina , Proliferação de Células , Citocinas/genética , Citocinas/metabolismo , Células Dendríticas/imunologia , Células Dendríticas/transplante , Feminino , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Linfonodos/citologia , Linfonodos/imunologia , Miastenia Gravis Autoimune Experimental/imunologia , Ratos , Ratos Endogâmicos Lew , Baço/citologia , Baço/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/metabolismo , Linfócitos T Reguladores/metabolismo , Timo/citologia , Timo/imunologia , Regulação para CimaRESUMO
Er(3+)-doped yttrium-stabilized zirconia upconversion powders Zr(0.92-x)Y0.08O(1.96-0.5x):xEr(3+) (x = 0.001~0.11) were synthesized via chemical coprecipitation method at 1200 °C for 3 hours. Phase structure and upconversion luminescence spectra of the samples were characterized by X-ray diffractometer and fluorescence spectrometer, respectively. The proposed upconversion mechanism of the samples was discussed. The results indicate that good crystallinity cubic ZrO2 solid solution can be stabilized by introducing 8 mol% yttrium ions. Size and valent differences between trivalent Y(3+) and quadrivalent Zr(4+) ions generate asymmetry and oxygen vacancies, which contribute to the stability of upconversion luminescence properties and luminescence intensity increase of the samples, and expand its practical application fields. Under 980 nm excitation, the samples emit green light centered at 539 nm ((2)H11/2-->(4)I15/2), 552 nm ((4)S3/2-->(4)I15/2) and red light at 656 and 680 nm ((4)F9/2-->(4)I15/2). When Er(3+) doping concentration (0.1 mol%) is low, the main green emission of samples is ascribed to the excited state absorption (ESA) processes; With the Er(3+) concentration increases from 0.1% to 11 mol%, there exist three cross relaxation (CR) processes: (2)H11/2+(4)I15/2-->(4)I9/2+(4)Ii3/2, (4)F7/2+(4)I11/2-->2 (4)F9/2 and (4)I15/2+(4)I9/2-->2 (4)I13/2, causing that the red emissions increase markedly whereas the green emissions decrease. When Er(3+) doping concentration (9 mol%) is high, the sample mainly presents red luminescence due to the dominated CR processes in upconversion process.
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OBJECTIVE: To study the effects of (E)-2-(4-bromophenyl)-1-(3, 4-dihydroxyphenyl) ethanone oxime (BDEO) on the proliferation and activation of the mice' s splenic lymphocytes and the peripheral blood lymphocytes induced by Concanavalin A (Con A) in vitro and in vivo, and its molecular mechanism. METHODS: During the lymphocyte proliferation and activation induced by Con A in vitro, MTT and cell counting were used to detect the transformation rates and survival rates of lymphocytes, and ELISA was used to measure the activity of caspase-9; moreover, the levels of Bax, Bcl-2 and caspase-3 were determined by Western blot, in order to observe the effects of BDEO on cell proliferation and activation. The effects of administration of Con A [15 mg/(kg x d)] and BDEO [(3, 6 mg/(kg x d)] by intraperitoneal injection on transformation rates of spleen cells and peripheral blood lymphocyte, as well as phagocytosis rate of peritoneal macrophages in mice were also observed in vivo. RESULTS: 0.3-1 micromol/L BDEO significantly inhibited the transformation rates and growth of mice lymphocyte (P < 0.05). The activity of caspase-9 and the levels of mitochondrial pro-apoptotic protein Bax and Bak gradually increased, then decreased as the BDEO continually accumulated. Anti-apoptotic protein Bcl-2 as well as mitochondrial Cyt C levels first decreased then increased gradually, and cytoplasmic Cyt C, cleaved caspase-9 and cleaved caspase-3 levels showed firstly a increase, then decrease gradually. Additionally, administration of BDEO by intraperitoneal injection significantly inhibited proliferation of spleen lymphocytes and peripheral blood lymphocyte, as well as phagocytosis of peritoneal macrophagesin in mice. CONCLUSION: BDEO might regulate the proliferation and activation of lymphocytes through activation of caspase-3 mainly via a mitochondrial intrinsic pathway; the inhibiting effect on the proliferation and transformation rate of lymphocytes was significant when the concentration of BDEO was relatively low; as the concentration accumulated increasingly, the inhibiting effect reduced. The results indicated that BDEO has immunosuppressive activity.
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Benzoína/análogos & derivados , Proliferação de Células/efeitos dos fármacos , Ativação Linfocitária/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Oximas/farmacologia , Animais , Benzoína/farmacologia , Caspase 3/metabolismo , Caspase 9/metabolismo , Concanavalina A , Camundongos , Mitocôndrias/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Baço/citologia , Proteína X Associada a bcl-2/metabolismoRESUMO
Background: The Scn3b gene encodes for Navß3, a pivotal regulatory subunit of the fast sodium channel in cardiomyocytes. However, its mutation status in the Chinese population suffering from Brugada Syndrome (BrS) has not been characterized, and the contributory pathophysiological mechanisms to disease pathology remain undefined. Methods and Results: A Scn3b (c.260C>T, p.P87l) mutation was identified in a patient with BrS of Chinese descent. Functional analyses demonstrated that sodium channel activation for the wild type, mutant samples, and co-expression of both commenced at -55â mv and peaked at -25â mv. The mutant group exhibited a notable reduction, approximately 60%, in peak sodium channel activation current (INa) at -25â mv. The parameters for half-maximal activation voltages (V1/2) and slope factors (k) showed no significant differences when comparing wild type, mutant, and combined expression groups (P = 0.98 and P = 0.65, respectively). Additionally, no significant disparities were evident in terms of the steady-state sodium channel inactivation parameters V1/2 and k (with P-values of 0.85 and 0.25, respectively), nor were there significant differences in the activation time constant τ (P = 0.59) and late sodium current density (P = 0.23) across the wild-type, mutant, and co-expressed groups. Confocal imaging and Western blot analysis demonstrated decreased plasma membrane localization of SCN3B and SCN5A in the P87l group. Computational simulations of cardiac action potentials suggested that SCN3B P87l can alter the morphology of the action potentials within the endocardium and epicardium while reducing the peak of depolarization. Conclusions: The pathogenic impact of the Scn3b P87l mutation predominantly originates from a reduction in peak INa activation current coupled with decreased cell surface expression of Nav1.5 and Navß3. These alterations may influence cardiac action potential configurations and contribute to the risk of ventricular arrhythmias in individuals with BrS.
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The management of chronic wounds in diabetes remains challenging due to the complexity of impaired wound healing, delayed healing, susceptibility to infection, and elevated risk of reopening, highlighting the need for effective chronic wound management with innovative approaches such as multifunctional hydrogels. Here, we have produced HA-DA@rhCol hydrogels consisting of dopamine-modified hyaluronic acid and recombinant human collagen type-III (rhCol) by oxidative coupling of the catechol group using the H2O2/HRP catalytic system. The post-reactive hydrogel has a good porous structure, swelling rate, reasonable degradation, rheological and mechanical properties, and the catechol group and dopamine impart to the hydrogel tissue adhesiveness, antioxidant capacity, and excellent photothermal effects leading to superior in vitro antimicrobial activity. In addition, the ability of rhCol to confer hydrogels to promote angiogenesis and wound repair has also been investigated. Cytotoxicity and hemolysis tests demonstrated the good biocompatibility of the hydrogel. Wound closure, collagen deposition and immunohistochemical examination confirmed the ability of the hydrogel to promote diabetic wound healing. In summary, the adhesive hemostatic antioxidative hydrogel with rhCol to promote wound healing in diabetic rat is an excellent chronic wound dressing.
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BACKGROUND: The objective of antiviral therapy for chronic viral hepatitis B infection (CHB) is to achieve a functional cure. An important viral marker in the serum of patients with CHB is the serum hepatitis B core-related antigen (HBcrAg). However, there is limited research on HBcrAg in juvenile patients with CHB. In this study, we aimed to investigate the correlation between serum HBcrAg and other hepatitis B virus (HBV) markers in children with CHB and its predictive significance for prognosis during antiviral therapy. METHODS: A single-center retrospective study was conducted involving 79 children with CHB, aged between 0 and 16 years. All the children were treated with interferon [or combined nucleos(t)ide analogs] for 48 weeks. HBcrAg, hepatitis B surface antigen (HBsAg), and HBV DNA were measured before treatment, and at 12 and 48 weeks after treatment. The enrolled children were classified into the seroclearance group and the nonseroclearance group based on the therapeutic outcome. RESULTS: HBsAg seroclearance was observed in 28 out of 79 patients and hepatitis B e antigen seroconversion without HBsAg seroclearance was observed in 14 out of 79 patients following the conclusion of the treatment, with baseline HBcrAg titer levels showing no statistical significance in both the seroclearance and nonseroclearance groups (Pâ =â 0.277). HBsAg and HBV DNA were positively correlated with HBcrAg in children with CHB (R2â =â 0.3289, 0.4388). The area under the receiver operating characteristic curve of the decrease in HBcrAg at 12 weeks of treatment as a predictor of seroclearance at 48 weeks of treatment, exhibited a value of 0.77. CONCLUSION: A decrease in serum HBcrAg levels in children with hepatitis B serves as a prognostic indicator.
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To determine the transfection efficiency about PBase to piggyBac transposon in transfecting to Toxoplasma gondii, T. gondii RH strain tachyzoites were transfected with plasmid PB-Toxo-RFP which was expressed piggyBac transposon with a red fluorescent protein and Toxo-PBase plasmid which is a transposable enzyme. T. gondii tachyzoites were transfected with PB-Toxo-RFP plasmid alone as control group. The expression of red fluorescent protein was detected by flow cytometry at 24 h after transfection. The transposition efficiency in PB-Toxo-RFP+Toxo-PBase group and PB-Toxo-RFP group was 73% and 43%, respectively (P < 0.01). It suggests that the PBase transposase can improve the transfection efficiency of piggyBac transposon in T. gondii tachyzoites.
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Elementos de DNA Transponíveis , Toxoplasma/genética , Toxoplasma/metabolismo , Transposases/metabolismo , Vetores Genéticos , Plasmídeos , Toxoplasma/classificação , TransfecçãoRESUMO
OBJECTIVE: To investigate the effects of snakegourd root polysaccharide on apoptosis of human breast cancer cells (MCF-7 cells). METHODS: Colorimetric MTT assay was used to measure the inhibition of snakegourd root polysaccharide on MCF-7 cells. The morphological changes of MCF-7 cells were observed by fluorescence microscope after DAPI staining and transmission electron microscope. The apoptosis of MCF-7 cells was examined by DNA agarose gel electrophoresis analysis of DNA fragmentation amd flow cytometry. The activity of Caspase-3 and Caspase-8 was detected by colorimetric assay. RESULTS: Polysaccharide of snakegourd root significantly inhibited MCF-7 cells in a dose-and time-dependent manner. The nuclear condensation and marginalization were observed by DAPI staining and transmission electron microscope. The characteristic ladder of apoptosis in DNA electrophoresis was detected in MCF-7 cells treated with 10.0 µmol/L polysaccharide of snakegourd root at d 2. The activities of Caspase-3 and Caspase-8 were increased in a time-dependent manner. The rates of apoptosis in MCF-7 cells were (5.2 ±1.3)%, (13.1 ±4.7)%, (27.6 ±6.8)% and (43.8 ±9.8)% treated with 1.0,5.0,10.0 and 20.0 µmol/L snakegourd root polysaccharide at d 2,respectively. The maximal activities of intracellular Caspase-3 and Caspase-8 were (2.32 ±0.12)U/µg and (1.92 ±0.11)U/µg at d 2 and d 1, respectively when MCF-7 cells were treated with 10.0 µmol/L. CONCLUSION: The polysaccharide of snakegourd root can induce the apoptosis of MCF-7 cells,which is associated with the activation of intracellular Caspase-3 and Caspase-8.
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Apoptose/efeitos dos fármacos , Polissacarídeos/farmacologia , Trichosanthes/química , Caspase 3/metabolismo , Caspase 8/metabolismo , Humanos , Células MCF-7 , Raízes de Plantas/químicaRESUMO
Statins have anti-inflammatory and immune-regulating properties. To investigate the effects of atorvastatin on experimental autoimmune neuritis (EAN), an animal model of Guillain-Barré syndrome (GBS), atorvastatin was administered to Lewis rats immunized with bovine peripheral myelin in complete Freund's adjuvant. We found that atorvastatin ameliorated the clinical symptoms of EAN, decreased the numbers of inflammatory cells as well as IFN-γ(+) and IL-17(+) cells in sciatic nerves, decreased the CD80 expression and increased the number of CD25(+)Foxp3(+) cells in mononuclear cells (MNC), and decreased the levels of IFN-γ in MNC culture supernatants. These data provide strong evidence that atorvastatin can act as an inhibitor in EAN by inhibiting the immune response of Th1 and Th17, decreasing the expression of co-stimulatory molecule, and up-regulating the number of T regulatory cells. These data demonstrated that statins could be used as a therapeutic strategy in human GBS in future.
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Citocinas/metabolismo , Ácidos Heptanoicos/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Neurite Autoimune Experimental/tratamento farmacológico , Neurite Autoimune Experimental/imunologia , Pirróis/farmacologia , Subpopulações de Linfócitos T/efeitos dos fármacos , Animais , Atorvastatina , Bovinos , Feminino , Síndrome de Guillain-Barré/tratamento farmacológico , Síndrome de Guillain-Barré/imunologia , Humanos , Imunização , Interferon gama/metabolismo , Interleucina-17/metabolismo , Bainha de Mielina/imunologia , Neurite Autoimune Experimental/patologia , Ratos , Ratos Endogâmicos Lew , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/patologia , Subpopulações de Linfócitos T/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th17/efeitos dos fármacos , Células Th17/imunologiaRESUMO
OBJECTIVE: In order to develop a promising HCV gene vaccine candidate to induce effective immune response and explore the application of magnetic nanoparticles as gene delivery system. METHODS: The DNA fragment containing multi-epitope antigen gene of HCV with five conserved mimotopes was synthesized and cloned into plasmid pcDNA3.1 (+). The Fe3O4 modified with chitoson was prepared and the cytotoxicity of the magnetic material was detected in vitro. Analysis of recombinant plasmid in vitro expression, and its immunogenicity loaded by CTS-Fe3O4 in mice were evaluated in detail. RESULTS: The HCV multi-epitope gene vaccine pcDNA3.1 (+)-MA was successfully constructed and recognized by 81% HCV positive sera. There was no cytotoxicity of CTS-Fe3O4 when its concentration was equal or less than 1 mmol/L. Both the antibody production and T-cell activity were induced. CONCLUSION: It was believed that DNA encoding MA was an attractive approach for the therapeutic and prophylactic vaccines against HCV and the Fe3O4 modified with chitoson showed excellent target, safety and adjuvant effect as gene carrier.
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Quitosana/química , Epitopos/genética , Hepacivirus/imunologia , Vacinas de DNA/imunologia , Vacinas contra Hepatite Viral/imunologia , Animais , Feminino , Óxido Ferroso-Férrico/química , Hepacivirus/genética , Hepatite C/prevenção & controle , Humanos , Magnetismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/química , Vacinas de DNA/genética , Vacinas contra Hepatite Viral/síntese químicaRESUMO
Objective: We conducted a survey to assess vaccination coverage, vaccination willingness, and variables associated with vaccination hesitancy to provide evidence on coronavirus disease (COVID-19) vaccination strategies. Methods: This anonymous questionnaire study conducted a multicenter, cross-sectional survey of outpatients and inpatients with epilepsy (PWE) registered in epilepsy clinics, in 2021, in 10 hospitals in seven cities of Shandong Province. Results: A total of 600 questionnaires were distributed, and 557 valid questionnaires were returned. A total of 130 people were vaccinated against COVID-19. Among 427 unvaccinated participants, 69.32% (296/427) were willing to receive the COVID-19 vaccine in the future, and the remaining 30.68% (131/427) were unwilling to receive vaccination. Most (89.9%) of the participants believed that the role of vaccination was crucial in response to the spread of COVID-19. A significant association was found between willingness to receive the COVID-19 vaccine and the following variables: age, marital status, level of education, occupation, residence, seizure type, and seizure control after antiepileptic drug therapy. It is noteworthy that education level, living in urban areas, and seizure freedom were significantly related to willingness to receive COVID-19 vaccination. Conclusions: Vaccination is a key measure for the prevention and control of COVID-19, and most PWE are willing to be vaccinated. Vaccine safety, effectiveness, and accessibility are essential in combatting vaccine hesitation and increasing vaccination rates.
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OBJECTIVE: To construct Syk recombinant adenovirus with which vascular smooth muscle cells (VSMC) were infected, and to investigate the effect of Syk on the proliferation of VSMC. METHODS: Syk adenovirus recombinant plasmid pDC315-GFP-Syk was constructed by using pDC315-GFP adenovirus vector system. The recombinant adenoviral vector (pDC315-GFP-Syk) was packaged and amplified in HEK 293 cells. The VSMC of rat pulmonary vascular smooth muscle cells were isolated and cultured in vitro and transfected with Syk adenovirus. The mRNA and protein express level of Syk, SM22alpha and alpha-SM-actin of rat pulmonary vascular smooth muscle cells were detected by RT-PCR and Western blot. RESULTS: The recombinant adenovirus carrying rat Syk was constructed successfully. The titer of Syk adenovirus was 10(11) pfu/mL after purification. The expression of Syk mRNA (741638.70 +/- 35213.53) and protein (2.14 +/- 0.71) in VSMC transfected with Syk adenovirus was significantly higher (P < 0.01) than that of empty adenovirus after transfection at fifth day. The mRNA express of alpha-SM-actin (0.80 +/- 0.04) and SM22a (1.00 +/- 0.01) was significantly decreased (P < 0.05) in VSMC. Meanwhile, the protein express of alpha-SM-actin (0.61 +/- 0.10) and SM22alpha (0.18 +/- 0.06) was also significantly decreased (P < 0.01) in VSMC. CONCLUSION: These data indicated that Syk played an important role in vascular remodeling by changing the phenotypes of VSMC.
Assuntos
Adenoviridae/metabolismo , Vetores Genéticos/genética , Músculo Liso Vascular/citologia , Proteínas Tirosina Quinases/biossíntese , Adenoviridae/genética , Animais , Células Cultivadas , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Fenótipo , Proteínas Tirosina Quinases/genética , Artéria Pulmonar/citologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Quinase Syk , TransfecçãoRESUMO
OBJECTIVE: To investigate the clinic features and treatment of seventh day syndrome (7DS) following living donor liver transplantation (LDLT). METHODS: From January 2002 to March 2009, 8 patients were diagnosed with 7DS following LDLT. A retrospective analysis was made on the clinical data containing liver and renal functions, coagulation function, sonographic and histological features and effectiveness of the treatments. RESULTS: Rapid deterioration of liver function happened 1-2 weeks after operations, followed by renal dysfunction. There was a reduction of velocity or bidirectional blood flow in the portal vein. Massive coagulative necrosis with disruption of lobular architecture occurred in 3.3% of cases, with a mortality of 87.5%. The steroid pulse and OKT3 (anti-CD3 antibody) therapy showed minimal effects. Prolonged application of i.v. methylprednisolone may be helpful with the delay of 7DS. CONCLUSION: The 7DS may be an immune-mediated graft failure. The prevention and control of 7DS is difficult due to lack of research evidence.
Assuntos
Rejeição de Enxerto/etiologia , Transplante de Fígado/efeitos adversos , Doadores Vivos , Insuficiência Renal/etiologia , Adulto , China/epidemiologia , Humanos , Falência Hepática/sangue , Falência Hepática/etiologia , Falência Hepática/patologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/mortalidade , Estudos Retrospectivos , SíndromeRESUMO
OBJECTIVE: To investigate the role of spleen tyrosine kinase (Syk) in rat pulmonary vascular smooth muscle cells (PVSMCs) proliferation induced by platelet-derived growth factor-BB (PDGF-BB). METHODS: PVSMCs from male Sprague-Dawley rats were cultured in vitro and the cells of passages 3-5 were used in the experiment. PVSMCs were stimulated by PDGF-BB and were treated with three different doses of piceatannol, a Syk selective inhibitor. Cell proliferation was assessed by methyl thiazolyl tetrazolium (MTT) assay. DNA synthesis was measured by ³H-thymidine incorporation (³H-TdR). Cellular cycle was observed by flow cytometry. Syk mRNA and protein expression were detected using real-time quantitative PCR and Western blot, respectively. RESULTS: The expression of Syk protein of PVSMCs was significantly up-regulated following PDGF-BB stimulation. PDGF-BB stimulation dramatically increased PVSMCs proliferation. After piceatannol treatment, both Syk mRNA and protein expression decreased and the proliferation of PVSMCs was inhibited in a dose-dependent manner. CONCLUSIONS: Syk may promote PVSMCs proliferation induced by PDGF-BB.