RESUMO
BACKGROUND: Irritable bowel syndrome is common in children and exhibits a high placebo response. This study was to explore the placebo response rate and its influencing factors in children with irritable bowel syndrome. METHODS: A systematic search was performed on Pubmed, Embase, MEDLINE, Cochrane Library, CNKI, Wanfang, and CBM from database inception to March 2022. Randomized controlled trials of irritable bowel syndrome in children were included in the study. The primary outcome was the placebo response rate of improvement. RESULTS: Thirteen studies were included, with 445 patients in the placebo group. The rate of improvement and abdominal pain disappearance were 28.2% (95% CI, 16.6-39.9%) and 5% (95% CI, 0-18.4%). The placebo response based on the abdominal pain score was 0.675 (95% CI, 0.203-1.147). The mode of administration (P < 0.01), dosing schedule (P < 0.01), and clinical outcome assessor (P = 0.04) have a significant impact on the magnitude of placebo effect. CONCLUSIONS: The placebo response rate for pediatric irritable bowel syndrome was 28.2%. In clinical trials, reducing dosing frequency, selecting appropriate dosage forms, and using patient-reported outcomes can help mitigate the placebo effect. IMPACT: This is the first meta-analysis to assess the placebo response rates for improvement and disappearance in children with IBS. The finding suggested that the mode of administration, dosing schedule, and clinical outcome assessor could potentially influence the magnitude of the placebo effect in children with IBS. This study would provide a basis for estimating sample size in clinical trial design with a placebo control.
Assuntos
Dor Abdominal , Síndrome do Intestino Irritável , Efeito Placebo , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Dor Abdominal/tratamento farmacológico , Síndrome do Intestino Irritável/tratamento farmacológico , Placebos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
BACKGROUND: Neuroinflammation is an important component mechanism in the development of depression. Exosomal transfer of MDD-associated microRNAs (miRNAs) from neurons to microglia might exacerbate neuronal cell inflammatory injury. RESULTS: By sequence identification, we found significantly higher miR-9-5p expression levels in serum exosomes from MDD patients than healthy control (HC) subjects. Then, in cultured cell model, we observed that BV2 microglial cells internalized PC12 neuron cell-derived exosomes while successfully transferring miR-9-5p. MiR-9-5p promoted M1 polarization in microglia and led to over releasing of proinflammatory cytokines, such as interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), which exacerbated neurological damage. Furthermore, we identified suppressor of cytokine signaling 2 (SOCS2) as a direct target of miR-9-5p. Overexpression of miR-9-5p suppressed SOCS2 expression and reactivated SOCS2-repressed Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathways. Consistently, we confirmed that adeno-associated virus (AAV)-mediated overexpression of miR-9-5p polarized microglia toward the M1 phenotype and exacerbated depressive symptoms in chronic unpredictable mild stress (CUMS) mouse mode. CONCLUSION: MiR-9-5p was transferred from neurons to microglia in an exosomal way, leading to M1 polarization of microglia and further neuronal injury. The expression and secretion of miR-9-5p might be novel therapeutic targets for MDD.
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Exossomos , MicroRNAs , Animais , Depressão , Exossomos/metabolismo , Humanos , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Microglia/metabolismo , Neurônios/metabolismoRESUMO
Exposure to microgravity results in cardiovascular deconditioning, and cerebrovascular oxidative stress injury has been suggested to occur. To elucidate the mechanism for this condition, we investigated whether simulated microgravity induces mitochondrial dysfunction in rat arteries. Four-week hindlimb unweighting (HU) was used to simulate microgravity in rats. Mitochondrial reactive oxygen species (ROS), mitochondrial membrane potential (Δψm), mitochondrial permeability transition pore (mPTP) opening, mitochondrial respiratory control ratio (RCR), MnSOD/GPx activity and expression, and mitochondrial malondialdehyde (MDA) were examined in rat cerebral and mesenteric VSMCs. Compared with the control rats, mitochondrial ROS levels, mPTP opening, and MDA content increased significantly (P<0.001, P<0.01, and P<0.01, respectively), Δψm, RCR, MnSOD/GPx activity (P<0.001 for Δψm and RCR; P<0.05 for MnSOD; and P<0.001 for GPx activity) and protein abundance of mitochondrial MnSOD/GPx-1 decreased (P<0.001 for MnSOD and GPx-1) in HU rat cerebral but not mesenteric arteries. Chronic treatment with NADPH oxidase inhibitor apocynin and mitochondria-targeted antioxidant mitoTempol promoted recovery of mitochondrial function in HU rat cerebral arteries, but exerted no effects on HU rat mesenteric arteries. Therefore, simulated microgravity resulted in cerebrovascular mitochondrial dysfunction, and crosstalk between NADPH oxidase and mitochondria participated in the process.
Assuntos
Artérias Cerebrais/fisiopatologia , Mitocôndrias/metabolismo , Simulação de Ausência de Peso/efeitos adversos , Acetofenonas/farmacologia , Animais , Artérias Cerebrais/ultraestrutura , Glutationa Peroxidase/metabolismo , Elevação dos Membros Posteriores , Masculino , Potencial da Membrana Mitocondrial/fisiologia , Artérias Mesentéricas/ultraestrutura , Mitocôndrias/efeitos dos fármacos , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Poro de Transição de Permeabilidade Mitocondrial , NADPH Oxidases/metabolismo , Compostos Organofosforados/farmacologia , Piperidinas/farmacologia , Ratos , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismoRESUMO
BACKGROUND AIMS: Currently available treatment methods for advanced plasmacytoma include surgery, chemotherapy, radiotherapy, immunomodulatory agents, hematopoietic stem cell transplantation and donor lymphocyte infusion. We report a case of advanced refractory multiple solitary plasmacytomas in a 68-year-old Asian man with multiple bone lesions, in whom autologous cytokine-induced killer (CIK) cells were administered in an effort to eliminate residual tumor lesions. METHODS: CIK cells were infused monthly for 21 courses. RESULTS: The patient has survived 63 months since the first hospital visit without disease progression for 40 months. CONCLUSIONS: This case represents the first report of autologous CIK cell immunotherapy used successfully to suppress multiple solitary plasmacytomas and resolve bone lesions.
Assuntos
Neoplasias Ósseas/terapia , Vacinas Anticâncer , Células Matadoras Induzidas por Citocinas/transplante , Transplante de Células-Tronco Hematopoéticas , Imunoterapia/métodos , Plasmocitoma/terapia , Idoso , Povo Asiático , Neoplasias Ósseas/imunologia , Células Matadoras Induzidas por Citocinas/imunologia , Intervalo Livre de Doença , Humanos , Masculino , Plasmocitoma/imunologia , Transplante AutólogoRESUMO
Immune checkpoint inhibitors (ICIs) have become an important cornerstone of many tumour treatments. However, the toxicity profile of immune-chemotherapy combination treatment approaches among older adult cancer patients is still unclear. Patients with any cancer who received camrelizumab-based immunotherapy were eligible for inclusion. The primary endpoints were adverse events (AEs) and immune-related adverse events (irAEs), which were defined based on Naranjo's algorithm. Patients were stratified by age (≥ 70 years and < 70 years), and comparisons were made based on the type of camrelizumab-based therapy (monotherapy, combined chemotherapy, or combined anti-VEGF therapy). A total of 185 patients were administered camrelizumab-based immunotherapy, 55 (30%) of whom were ≥ 70 years old. A total of 146 (78.9%) patients received camrelizumab-based combination treatment. The incidence of all-grade AEs was 56.8% (105 patients), while that of irAEs was 36.8% (68 patients). There was no difference in the percentage of patients experiencing any grade or grade ≥ 3 AEs between age groups. However, the frequency of irAEs (both any grade and grade ≥ 3) significantly differed by age group (P = 0.001 and 0.009, respectively). The results of multivariable analysis revealed that age ≥ 70 years was the only independent risk factor for irAEs. The results of subgroup analysis revealed that the incidence of irAEs was higher in older patients treated with camrelizumab-chemotherapy, while the incidence rates were similar between age groups in the monotherapy and combination anti-VEGF treatment subgroups. Immune-related diabetes mellitus occurred more frequently among older adults. The spectrum of irAEs showed that combination immunotherapy had more widely effects on the organ system than monotherapy. In this study, older (≥ 70 years) patients had a higher risk of all-grade and high-grade irAEs when receiving camrelizumab chemotherapy combination treatment. Notably, long-term random glucose monitoring should be performed during ICI-based immunotherapy in older cancer patients.
Assuntos
Anticorpos Monoclonais Humanizados , Imunoterapia , Neoplasias , Humanos , Idoso , Masculino , Feminino , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias/tratamento farmacológico , Imunoterapia/efeitos adversos , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fatores Etários , Estudos RetrospectivosRESUMO
BACKGROUND: With the intensification of social aging, the susceptibility of the elderly population to diseases has attracted increasing attention, especially chronic heart failure (CHF) that accounts for a large proportion of the elderly. AIM: To evaluate the application value of health concept model-based detailed behavioral care in elderly patients with CHF. METHODS: This study recruited 116 elderly CHF patients admitted from October 2018 to October 2020 and grouped them according to the nursing care that they received. The elderly patients who underwent health concept model-based detailed behavioral care were included in a study group (SG; n = 62), and those who underwent routine detailed behavioral nursing intervention were included as a control group (CG; n = 54). Patients' negative emotions (NEs), quality of life (QoL), and nutritional status were assessed using the self-rating anxiety/ depression scale (SAS/SDS), the Minnesota Living with Heart Failure Ques-tionnaire (MLHFQ), and the Modified Quantitative Subjective Global Assessment (MQSGA) of nutrition, respectively. Differences in rehabilitation efficiency, NEs, cardiac function (CF) indexes, nutritional status, QoL, and nursing satisfaction were comparatively analyzed. RESULTS: A higher response rate was recorded in the SG vs the CG after intervention (P < 0.05). After care, the left ventricular ejection fraction was higher while the left ventricular end-diastolic dimension and left ventricular end systolic diameter were lower in the SG compared with the CG (P < 0.05). The post-intervention SAS and SDS scores, as well as MQSGA and MLHFQ scores, were also lower in the SG (P < 0.05). The SG was also superior to the CG in the overall nursing satisfaction rate (P < 0.05). CONCLUSION: Health concept model-based detailed behavioral care has high application value in the nursing care of elderly CHF patients, and it can not only effectively enhance rehabilitation efficiency, but also mitigate patients' NEs and improve their CF and QoL.
RESUMO
The elderly population is susceptible to haematological malignancies, and these elderly patients are intolerant to cytotoxic drugs. Therefore, the exploration of a safe and reliable strategy exclusive of chemotherapy is critical in improving the prognosis of elderly patients with haematological malignancies. We evaluated the safety and the efficacy of autologous cytokine-induced killer (CIK) cells combined with recombinant human interleukin 2 (rhIL-2) in the treatment of haematological malignancies in elderly patients. Peripheral blood mononuclear cells were isolated from 20 elderly patients with haematological malignancies, then augmented by priming with interferon gamma, rhIL-2 and CD3 monoclonal antibody. The autologous CIK cells (2-3 × 10(9)) were transfused back to patients, followed by a subcutaneous injection of IL-2 (1 mU/day) for 10 consecutive days. The regimen was repeated every 4 weeks. The host cellular immune function, tumour-related biological parameters, imaging characteristics, disease condition, quality of life and survival time were assessed. Fourteen patients received 8 cycles of transfusion and 6 received 4 cycles. No adverse effects were observed. The percentages of CD3(+), CD3(+) CD8(+) and CD3(+) CD56(+) cells were significantly increased (p < 0.05), and the levels of serum ß2 microglobulin and lactate dehydrogenase (LDH) were markedly decreased (p < 0.05) after autologous CIK cell transfusion. Cancer-related symptoms were profoundly alleviated, as demonstrated by the improved quality of life (p < 0.01). Complete remission was observed in 11 patients, persistent partial remission in 7 patients and stable disease in 2 patients. At the end of follow-up, the mean survival time was 20 months. Transfusion with autologous CIK cells plus rhIL-2 treatment is safe and effective for treating haematological malignancies in elderly patients.
Assuntos
Células Matadoras Induzidas por Citocinas/transplante , Neoplasias Hematológicas/cirurgia , Imunoterapia Adotiva , Síndromes Mielodisplásicas/cirurgia , Terapia de Salvação , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais , Células Cultivadas/efeitos dos fármacos , Células Cultivadas/transplante , Comorbidade , Feminino , Neoplasias Hematológicas/tratamento farmacológico , Humanos , Interferon gama/farmacologia , Interleucina-2/farmacologia , Interleucina-2/uso terapêutico , L-Lactato Desidrogenase/sangue , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/cirurgia , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/cirurgia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/cirurgia , Síndromes Mielodisplásicas/tratamento farmacológico , Projetos Piloto , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Indução de Remissão , Timopentina/farmacologia , Timopentina/uso terapêutico , Resultado do Tratamento , Microglobulina beta-2/análiseRESUMO
OBJECTIVE: To observe the effects of down-regulation of long non-coding RNA HOX antisense intergenic RNA myeloid 1 (LncRNA-HOTAIRM1) to the proliferation and apoptosis of Jurkat in human leukemia T lymphocytes, and explore its mechanism. METHODS: Jurkat cells were cultured in vitro and randomly divided into control group, HOTAIRM1 siRNA-NC group and HOTAIRM1 siRNA group; the expressions of LncRNA-HOTAIRM1 mRNA, KIT receptor tyrosine kinase (KIT) mRNA and serine threonine kinase (AKT) mRNA in Jurkat cells were detected by real-time fluorescence quantification (RT-qPCR); the proliferation of Jurkat cells in each groups was detected by CCK-8 method; the apoptosis of Jurkat cells in each groups was detected by Annexin V-FITC/PI double staining; the expressions of KIT, AKT, p-KIT, p-AKT, B-lymphoma-2 gene (BCL-2) and Caspase-3 were detected by Western blot. RESULTS: Compared with the cells in the control group and HOTAIRM1 siRNA-NC group, the expression level of LncRNA-HOTAIRM1 mRNA, cell survival rate, expression levels of KIT mRNA, AKT mRNA, p-KIT, p-AKT and BCL-2 proteins in Jurkat cells in HOTAIRM1 siRNA group were significantly lower (P<0.05), while the expression level of Cleared Caspase-3 protein and Jurkat cell apoptosis rate were significantly higher (P<0.05). CONCLUSION: LncRNA-HOTAIRM1 may inhibit Jurkat cell proliferation and induce apoptosis through KIT/AKT signaling pathway.
Assuntos
RNA Longo não Codificante , Apoptose , Proliferação de Células , Regulação para Baixo , Humanos , Células Jurkat , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/genéticaRESUMO
A highly sensitive and selective Ag(+) detection method was developed based on the Ag(+)-mediated formation of G-quadruplex-hemin DNAzymes. In this method, two unlabelled oligonucleotides with different lengths are used. In the absence of Ag(+), the two oligonucleotides hybridize to each other to form an intermolecular duplex. The addition of Ag(+) can disrupt the intermolecular duplex and promote a part of the sequence of the longer oligonucleotide to fold into an intramolecular duplex, in which cytosine-cytosine (C-C) mismatches are stabilized by C-Ag(+)-C base pairs. As a result, the G-rich sequence of the same oligonucleotide can fold into a G-quadruplex, which is able to bind hemin to form a catalytically active G-quadruplex-hemin DNAzyme. This can be reflected by an absorbance increase when monitored in the H(2)O(2)-ABTS (2,2'-azinobis(3-ethylbenzothiozoline)-6-sulfonic acid) reaction system by using UV-vis absorption spectroscopy. This 'turn-on' process allows the detection of aqueous Ag(+) at concentrations as low as 20 nM using a simple colorimetric technique. Considering that Cysteine (Cys) is a strong binder of Ag(+), the presence of Cys may disrupt the C-Ag(+)-C base pairs in the intramolecular duplex, resulting in the reformation of the intermolecular duplex and the decrease of the catalytic activity of the sensing system. Therefore, the Ag(+)-sensing system can be further developed as a Cys-sensing system. This method allows the detection of Cys with a detection limit of 25 nM. With the development of the studies on DNA-metal base pairs, this Ag(+)-sensing method can be easily extended to the analysis of other metal ions.
Assuntos
Cisteína/análise , DNA Catalítico/química , Quadruplex G , Hemina/química , Prata/análise , Espectrofotometria Ultravioleta/métodos , Dicroísmo Circular , Oligonucleotídeos/químicaRESUMO
OBJECTIVE: To detect the effect of extracellular Ca2+ concentrations on test results of coagulation-related parameters. METHODS: Blood samples of outpatient medical volunteers were collected and then different doses of calcium chloride added. The rate of platelet aggregation (n = 42), prothrombin time (PT), thrombin time (TT) and activated partial thromboplastin time (APTT) (n = 21) and parameters of thromboelastography (n = 30) were detected according to the standard protocols by plasma turbidimetry, coagulation and recalcification respectively. RESULTS: When the plasma Ca2+ concentration was in the range of 0.1 - 33.7 mmol/L, the rate of platelet aggregation gradually increased with a increasing concentration of Ca2+. And the rates induced by adenosine diphosphate (ADP) and arachidonic acid (AA) were (51.8 +/- 9.6)% - (94.7 +/- 4.8)% and (64.4 +/- 12.2)% - (93.2 +/- 5.5)% respectively. When the Ca2+ concentration was 39.0 mmol/L, the rate decreased markedly [ADP (9.1 +/- 5.3)%, AA (11.1 +/- 4.5)%, both P < 0.01]. When the Ca2+ concentration was in the range of 0.1 - 33.7 mmol/L, the values of PT gradually increased with a increasing concentration of Ca2+. The values of TT changed in "V"-type and became minimum when the calcium concentration was 4.4 mmol/L. The values of APTT decreased with higher calcium concentrations and could not be determined when the concentration increased above 0.5 mmol/L. When the Ca2+ concentration was in the range of 0.4 - 27.3 mmol/L, the values of reaction time and coagulation time of thromboelastography changed in "V"-type and became nearly minimal at the Ca2+ concentration of about 2.1 mmol/L. The values of alpha angle and maximum amplitude changed in "V"-type and became maximal at the Ca2+ concentration of 2.1 mmol/L. CONCLUSIONS: The effect of Ca2+ concentration on the testing results of coagulation-related parameters is significant. A high calcium ( > or = 39 mmol/L) can inhibit the platelet aggregation, coagulation factor activity and blood coagulation. The Ca2+ concentration of 2.1 mmol/L seems to be the optimal concentration for thromboelastography by recalcification method.
Assuntos
Cálcio/sangue , Agregação Plaquetária , Tempo de Protrombina , Tromboelastografia , Idoso , Coagulação Sanguínea , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial , Tempo de TrombinaRESUMO
OBJECTIVE: To identify differential proteins in the seminal plasma of healthy fertile men and non-obstructive azoospermia patients by the shotgun proteomic strategy. METHODS: Six seminal plasma samples from 3 healthy fertile and 3 non-obstructive azoospermia volunteers were collected by Percoll isolation, balanced-mixed, and followed by separation of the mixture by SDS-PAGE. The proteins were subjected to in-gel enzymolysis and isolation of peptide fragments, and then identified by the shotgun proteomic strategy. Then comparative analyses were made between the two groups on the identified proteins with the unique peptide count > or = 2 and = 1 but with the peptide count > or = 4. RESULTS: A total of 213 differential proteins were identified, 133 in the non-obstructive azoospermia patients and 80 in the healthy fertile men. According to the molecular function, these differential proteins mainly fell into the types of signal transduction, cytoskeleton and catalytic activity, especially oxidoreductase activity in the latter type. Eighteen of the differential proteins were found to be of particular significance, including dynein heavy chain, fatty acid synthase, and tubulin alpha-6 chain. CONCLUSION: The differential proteins identified in this study were many in number and various in function, which not only demonstrated the value of the shotgun proteomic strategy in protein identification, but also suggested the complicated pathogenesis and varied types of non-obstructive azoospermia. The samples must be selected strictly based on their gene and histological types. Non-obstructive azoospermia was shown to be related with the M phase of the mitotic cell cycle at the protein level, but its specific mechanism remains unknown.
Assuntos
Azoospermia/metabolismo , Proteoma/análise , Sêmen/química , Azoospermia/fisiopatologia , Estudos de Casos e Controles , Humanos , Masculino , Proteômica/métodos , Motilidade dos EspermatozoidesRESUMO
OBJECTIVE: To identify asthenozoospermia-associated proteins in seminal plasma by the shotgun proteomic strategy. METHODS: Six seminal plasma samples were collected by Percoll respectively from healthy fertile and asthenozoospermia volunteers, balanced, mixed, and then the mixture was separated by SDS-PAGE. The proteins in the gel were enzymolyzed, extracted and identified by the shotgun proteomic strategy. The identified proteins with the unique peptide count > or =2 or the unique peptide count=1 but the total count > or =4 were compared between the two groups. RESULTS: A total of 172 differential proteins were identified, of which, 89 were exclusively from the asthenozoospermia and 83 exclusively from the healthy fertile men. According to the molecular function, these differential proteins were mainly the types of signal transduction and catalytic activity. CONCLUSION: Functionally, 10 of the proteins are particularly important, which include annexin VI isoform 2, isoform 1 of interleukin-6 receptor subunit beta precursor, Mr 400,000 protein, cytosolic dynein heavy chain, alpha-actinin-4, receptor-type tyrosine-protein phosphatase eta precursor, vitamin D-binding protein precursor, protein S100-A11, protein S100-A9 and ANXA4.
Assuntos
Astenozoospermia/fisiopatologia , Proteômica , Sêmen/química , Proteínas de Plasma Seminal/isolamento & purificação , Adulto , Eletroforese em Gel de Poliacrilamida , Humanos , Masculino , Proteína de Ligação a Vitamina D/isolamento & purificaçãoAssuntos
Amifostina/administração & dosagem , Azacitidina/análogos & derivados , Células Matadoras Induzidas por Citocinas/transplante , Leucemia Mieloide Aguda/terapia , Síndromes Mielodisplásicas/terapia , Idoso de 80 Anos ou mais , Azacitidina/administração & dosagem , Células Cultivadas , Terapia Combinada/métodos , Decitabina , Gerenciamento Clínico , Progressão da Doença , Quimioterapia Combinada , Humanos , Leucemia Mieloide Aguda/diagnóstico , Masculino , Síndromes Mielodisplásicas/diagnóstico , Transplante AutólogoRESUMO
OBJECTIVE: To identify proteins in the seminal plasma of healthy fertile men. METHODS: Three seminal plasma samples were collected from healthy fertile volunteers by Percoll isolation, and then the balanced mixture of the seminal plasma was separated by SDS-PAGE. The proteins in the gel band underwent enzymoloysis, and was extracted and identified by shotgun proteomic strategy. RESULTS: A total of 331 proteins were identified, with the molecular weight (MW) ranging from 8 000 to 572 068 and the isoelectric point (pI) from 4.36 to 11.05. Based on the molecular function and biological process of the proteins, 51 (15.4%) were classified as transport proteins, 11 (3.32%) as cell movement proteins, 63 (19.03%) as signal transduction proteins, 147 (44.4%) as proteases, 38 (11.5%) as enzyme regulator proteins, 21 (6.3%) as programmed cell death proteins, 12 (3.62%) as structural proteins and 59 (17.8%) as proteins with unknown molecular function. CONCLUSION: Shotgun proteomic strategy is a good method for protein identification. Annexin A, Annexin-associated proteins and the Ras-related protein Rab were the major members of the signal transducer proteins identified. Ca2+ and G protein signal pathways may play a most important role in the extracellular signal transduction into cells, but the interactions between these proteins remain unknown. The great quantity of enzymes and enzyme regulator proteins identified in the seminal plasma may be closely related with the maintenance of sperm motility and metabolism.
Assuntos
Fertilidade , Proteômica/métodos , Sêmen/química , Proteínas de Plasma Seminal/isolamento & purificação , Adulto , Humanos , Masculino , Motilidade dos EspermatozoidesRESUMO
OBJECTIVE: To investigate the effects of the combination of alpha-keto acid and low-protein diet on the levels of serum cytokines in patients performing continuous ambulatory peritoneal dialysis (CAPD) and to explore the relationship between inflammation and malnutrition in CAPD patients. METHODS: Eighty-nine CAPD patients were randomized into three groups, and 78 cases completed a one-year follow-up and with complete data. There were 31 cases in low-protein diet plus alpha-keto acid group, 26 cases in low-protein diet group and 21 cases in routine-protein diet group. The levels of serum albumin (Alb), prealbumin (PA), retinol-binding protein (RBP), transferrin (TRF), cholesterol (TC), triglycerides (TG), leptin, and triceps skinfold thickness (TSF), mid-arm muscle circumference (MAMC), body mass index (BMI) were measured. The changes of serum interleukin-1alpha (IL-1alpha), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and C-reactive protein (CRP) were also detected. RESULTS: Compared with low-protein diet group, serum levels of PA, RBP and TRF were significantly increased both in low-protein diet plus alpha-keto acid and routine-protein diet groups ( P<0.01), however, there was no significant difference in the levels of PA, RBP and TRF between low-protein diet plus alpha-keto acid group and routine-protein diet group. There was an increased tendency in the content of Alb, TC, TG, BMI, TSF and MAMC, but there were no significant differences. The plasma levels of IL-1alpha, IL-6 and TNF-alpha in low-protein diet plus alpha-keto acid group were decreased as compared with the routine-protein diet group, but there were no significant differences. The plasma level of CRP in low-protein diet plus alpha-keto acid group was lower than that in the routine-protein diet group ( P<0.01). CONCLUSION: The combination of alpha-keto acid and low-protein diet can ameliorate malnutrition and micro-inflammation in CAPD patients.
Assuntos
Dieta com Restrição de Proteínas , Cetoácidos/uso terapêutico , Falência Renal Crônica/terapia , Estado Nutricional , Diálise Peritoneal Ambulatorial Contínua , Idoso , Idoso de 80 Anos ou mais , Citocinas/sangue , Feminino , Humanos , Inflamação/terapia , Masculino , Desnutrição/prevenção & controle , Pessoa de Meia-IdadeRESUMO
G-protein-coupled receptor (GPCR)-related proteins are dysregulated and the GPCR CC-chemokine receptor 10 (CCR10) is significantly upregulated in inflammation-driven HCC. However, CCR10's role in inflammation-driven hepatocarcinogenesis remains unknown. The aim of this study was to evaluate the role of CCR10 in inflammation-driven hepatocarcinogenesis. Via a targeted gene expression microarray screening alterations in GPCR family gene expression, we found CCR10 to be significantly upregulated in hepatocytes isolated from inflammation-driven human HCC tumors and matching paracancerous tissues. Tetrachloromethane (CCl4)-induced and diethylnitrosamine (DEN)-induced murine models of inflammatory hepatocarcinogenesis displayed significant hepatocellular TNF and CCR10 upregulation. Exogenous TNF applied to HepG2 and LO2 cell lines as well as wild-type (WT) mice significantly upregulated hepatocellular CCR10 expression, Akt phosphorylation, PCNA expression, and hepatocellular proliferation. Additionally, exogenous TNF significantly upregulated secretion of the natural CCR10 ligand-agonist CCL28 from both cell lines. Transgenic CCR10-knockout (CCR10 KO) in DEN-treated mice significantly increased hepatocellular apoptosis levels and significantly lowered compensatory hepatocellular proliferation but did not affect upstream TNF expression. In addition, DEN-treated CCR10 KO mice showed a significantly lower liver weight/body weight ratio, significantly lower liver tumor incidence, and significantly smaller tumors. Moreover, exogenous CCR10 expression significantly raised xenograft tumor growth in Balb/c nude mice. In vitro, CCR10 transfection or CCL28 treatment in HepG2 and LO2 cell lines significantly increased Akt phosphorylation, PCNA expression, and cell proliferation, while CCR10 silencing or Akt inhibition produced the opposite effects. In vivo, hepatocytes isolated from HCC tumor tissue and matching paracancerous tissue in DEN-treated CCR10 KO mice showed significantly lower Akt phosphorylation and PCNA expression relative to WT hepatocytes. In conclusion, inflammation-induced TNF promotes hepatocellular CCR10 expression and downstream PI3K/Akt-mediated hepatocarcinogenesis. CCR10 appears to function as a linkage between TNF stimulation and downstream PI3K/Akt pathway activation and shows promise as a potential therapeutic target for inflammation-driven HCC.
Assuntos
Carcinoma Hepatocelular/genética , Regulação Neoplásica da Expressão Gênica , Hemangioma/genética , Neoplasias Hepáticas Experimentais/genética , Neoplasias Hepáticas/genética , Fosfatidilinositol 3-Quinases/genética , Receptores CCR10/genética , Adolescente , Adulto , Idoso , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Tetracloreto de Carbono/administração & dosagem , Carcinogênese/genética , Carcinogênese/metabolismo , Carcinogênese/patologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Quimiocinas CC/genética , Quimiocinas CC/metabolismo , Dietilnitrosamina/administração & dosagem , Feminino , Hemangioma/metabolismo , Hemangioma/patologia , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas Experimentais/induzido quimicamente , Neoplasias Hepáticas Experimentais/metabolismo , Neoplasias Hepáticas Experimentais/patologia , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Fosfatidilinositol 3-Quinases/metabolismo , Antígeno Nuclear de Célula em Proliferação/genética , Antígeno Nuclear de Célula em Proliferação/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores CCR10/metabolismo , Transdução de Sinais , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Hepatocellular carcinoma (HCC) is one of the most prevalent and aggressive malignant tumors. The involvement of N-myc (and STAT) interactor (NMI) and its possible functional mechanisms in HCC progression still remain to be elucidated. In this study, we found that NMI was overexpressed in metastatic HCC cell lines compared with non-metastatic ones; and the expression levels of NMI in the HCC samples with metastasis were higher than that in the non-metastatic specimens. Furthermore, NMI depletion significantly decreased HCC cell proliferation and invasiveness in vitro, and also inhibited tumor growth and lung metastasis in vivo in nude mice models bearing human HCC. By contrast, NMI stable overexpression can enhance the malignant behaviors obviously. Moreover, we further verified that NMI promotes the expression of BDKRB2 and mediates the activation of MAPK/ERK signaling pathway according to the bidirectional perturbations of NMI expression in vivo or in vitro of HCC. Taken together, NMI is a pro-metastatic molecule and partially responsible for HCC tumor growth and motility. NMI could improve its downstream target BDKRB2 expression to induce ERK1/2 activation, and thereby further evoke malignant progression of HCC.
Assuntos
Carcinoma Hepatocelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Neoplasias Hepáticas/genética , Sistema de Sinalização das MAP Quinases , Receptor B2 da Bradicinina/genética , Animais , Western Blotting , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/terapia , Linhagem Celular Tumoral , Progressão da Doença , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/terapia , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Interferência de RNA , Terapêutica com RNAi/métodos , Receptor B2 da Bradicinina/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Carga Tumoral/genética , Ensaios Antitumorais Modelo de Xenoenxerto/métodosRESUMO
OBJECTIVE: To evaluate the value of a new platelet function test PFA P2Y (PFA-200) in monitoring clopidogrel treatment for cardiovascular disease in elderly patients. METHODS: Fifty-six elderly patients receiving clopidogrel therapy in the Department of Cardiology of General Hospital of PLA from March to August in 2016 and 85 healthy volunteers were recruited for analysis. All the subjects underwent PFA P2Y, LTA (light transmittance aggregometry) and TEG (Thromboelastograph) tests, and Spearman correlation coefficients were used to test the associations between test results. The agreement among the 3 platelet function test methods was assessed using Cohen's kappa coefficient. RESULTS: Correlation coefficient (r) was -0.701 (P<0.001) between PFA P2Y and LTA, and 0.475 (P<0.001) between PFA P2Y and TEG. The agreement was 75% between PFA P2Y and LTA and 67.9% between PFA P2Y and TEG. The κ value was 0.434 (P=0.001) between PFA P2Y and LTA and 0.242 (P=0.046) between PFA P2Y and TEG. With ADP-induced maximum platelet aggregation rate of LTA >50% as the laboratory clopidogrel resistance, the cut-off value of PFA P2Y was 119 s (AUC=0.733) with a sensitivity of 75.6% and a specificity of 73.3%. CONCLUSION: PFA P2Y has a moderate correlation and agreement with LTA, but has a poor correlation and agreement with TEG. PFA P2Y can be useful for assessing the effects of clopidogrel therapy and the association of the cut-off value (119 s) with the long-term clinical ischemic events needs be confirmed in further study.
Assuntos
Plaquetas , Doenças Cardiovasculares/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Testes de Função Plaquetária , Ticlopidina/análogos & derivados , Bioensaio , Testes de Coagulação Sanguínea , Clopidogrel , Humanos , Agregação Plaquetária , Sensibilidade e Especificidade , Ticlopidina/uso terapêuticoRESUMO
This study was purposed to evaluate the effectiveness and safety of autologous cytokine induced killer (CIK) cells combined with chemotherapy in treatment of elderly patients with acute myeloid leukemia. Peripheral blood mononuclear cells (PBMNC) were isolated from 5 elderly patients with acute myeloid leukemia, and then augmented by priming with interferon gamma (IFN-γ) followed by IL-2 and monoclonal antibody (mAb) against CD3. The autologous CIK cells thus obtained were infused back to individual patients, 28 days as one cycle. The changes in cellular immune function, incidence of infection, independence of hematoglobin or blood transfusion, and progression of disease were observed and assessed before and after therapy. The results showed that the 46 cycles of CIK cell infusion were performed for 5 patients, no adverse reaction was observed in these patients. The percentages of CD3(+), CD3(+)CD8(+) and CD3(+)CD56(+) increased significantly (P < 0.05), The therapy of CIK could significantly reduce the incidence of infection (P < 0.05) and shorten the time of high fever in AML patients (P < 0.05). CIK also could reduce the volume of erythrocyte infusion to maintenance hematoglobin level (P < 0.05). We found that although CIK could not change the outcome of AML, the combination of CIK and chemotherapy could control patients' condition and prolong their survival during the development and end stage of AML. It is concluded that autologous CIK cells combined with chemotherapy is safe and efficacious for the elderly patients with acute myeloid leukemia.