RESUMO
PURPOSE: Myeloid-derived suppressors cells (MDSCs) are heterogeneous immunosuppressive cells, closely related to the development, efficacy and prognosis in various tumors. The relationship between clinicopathological characteristics, efficacy of neoadjuvant chemoimmunotherapy (NCIO) and circulating MDSCs in patients with non-small cell lung cancer (NSCLC) was investigated in this study. METHODS: This study analyzed the clinical data of patients diagnosed at Department of Thoracic Surgery, Beijing Chest Hospital from November 2020 to August 2021. MDSCs and T cells subgroups were measured in fresh peripheral blood mononuclear cells(PBMCs) at baseline. Flow cytometry was used to detect MDSCs and T cells subgroups. RESULTS: A total of 78 patients with NSCLC and 20 patients with benign nodule underwent direct surgery. 23 patients with NSCLC scheduled to accept NCIO before surgery. NSCLC had elevated levels of total MDSCs, PMN-MDSCs and M-MDSCs compared to patients with benign nodule. MDSCs subgroups were correlated to the pTNM stage in NSCLC patients. The frequency of total MDSCs were moderately positively correlated with regulatory T cells (Tregs)(r = 0.3597, P < 0.01) and negatively correlated with CD4 + T cells(r = 0.2714, P < 0.05). The baseline levels of total MDSCs, PMN-MDSCs and Tregs in pCR patients were significantly decreased than those of non-pCR patients (P < 0.05). CONCLUSION: Circulating MDSCs were increased in NSCLC patients. MDSC subgroups were related to pTNM stage in NSCLC patients. Total MDSCs were positively correlated with Tregs levels and negatively correlated with CD4 + T cells in peripheral blood. The level of MDSCs and Tregs in peripheral blood may have potential value in predicting pathological response in NSCLC.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Células Supressoras Mieloides , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Leucócitos Mononucleares/patologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Células Supressoras Mieloides/patologia , Terapia NeoadjuvanteRESUMO
PURPOSE: The aim of the present study was to elucidate the functional role of hsa-miR-328-3p/STAT3 pathway in the effects of propofol on gastric cancer proliferation. METHODS: Bioinformatics was used to analyze the molecular expression differences of hsa-miR-328-3p/STAT3 axis in stomach adenocarcinoma (n = 435) and normal samples (n = 41) from TCGA database. The expression of the above molecules in gastric cancer cells SGC-7901 and normal gastric mucosal cells GES-1 was verified via qPCR. The dual-luciferase assay was carried out to confirm the interaction between hsa-miR-328-3p and STAT3. Subsequently, the cell proliferation and the expression of the above molecules in SGC-7901 and GES-1 cells were evaluated after 10 µM propofol treatment. Finally, we analyzed whether propofol still inhibited the proliferation of gastric cancer by suppressing STAT3 pathway after hsa-miR-328-3p down-regulation. RESULTS: Compared with normal samples, the expression of hsa-miR-328-3p was significantly down-regulated in stomach adenocarcinoma samples, while the expression of STAT3 and downstream target genes (MMP2, CCND1 and COX2) was up-regulated. The results were consistent with those in GES-1 and SGC-7901 cell lines. Meanwhile, we found that hsa-miR-328-3p can bind to the 3'-UTR of the potential target gene STAT3. Furthermore, propofol significantly inhibited the proliferation of gastric cancer cell line SGC-7901, where hsa-miR-328-3p was up-regulated and the expression of STAT3 and downstream proliferation-related target genes were down-regulated. However, the growth inhibition of propofol on SGC-7901 cell was significantly reversed after the inhibition of hsa-miR-328-3p. CONCLUSIONS: To sum up, propofol suppressed the STAT3 pathway via up-regulating hsa-miR-328-3p to inhibit gastric cancer proliferation.
Assuntos
Adenocarcinoma/patologia , Anestésicos Intravenosos/farmacologia , Proliferação de Células/efeitos dos fármacos , MicroRNAs/metabolismo , Propofol/farmacologia , Fator de Transcrição STAT3/metabolismo , Neoplasias Gástricas/patologia , Regiões 3' não Traduzidas , Adenocarcinoma/metabolismo , Linhagem Celular Tumoral , Biologia Computacional , Ciclina D1/genética , Ciclina D1/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Regulação para Baixo , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Humanos , Luciferases/metabolismo , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , MicroRNAs/antagonistas & inibidores , Fator de Transcrição STAT3/genética , Neoplasias Gástricas/metabolismo , Regulação para CimaRESUMO
OBJECTIVE: To delineate the association of postoperative complications with clinicopathologic factors and to identify risk factors for tumor recurrence and mortality after tumor resection in patients with colorectal cancer (CRC). METHODS: The clinical data of 1144 patients with CRC who underwent surgical intervention between 2003 and 2013 were retrieved. Correlations of postoperative complications with clinicopathologic factors were examined using univariate analysis. Risk factors for tumor recurrence and mortality of the patients after tumor resection were identified using multivariate Cox proportional hazards models. Time to relapse and overall survival were analyzed using log-rank test of Kaplan-Meier analysis. RESULTS: Blood carcinoembryonic antigen (CEA) significantly correlated with early symptoms, preoperative manifestations, and tumor pathology. Low differentiation grade of tumor increased the risk of recurrence after surgery in all patients with CRC. In the same cohort of patients, elevated blood CEA, low differentiation grade of tumor, laparotomy, smoking history, and TNM stage IV and III increased the mortality risk after tumor resection. In patients with advanced colon cancer, risk for postoperative mortality was increased by blood CEA, advanced tumor stage, and low tumor differentiation grade; while in those with advanced rectal cancer, blood CEA, pathologic type other than mucinous/adenocarcinoma, and laparotomy were identified as significant risk factors. In both groups of patients, postoperative chemotherapy significantly reduced the risk of mortality. CONCLUSIONS: The present work has identified clinical factors increasing the risk of recurrence as well as mortality after surgery in more than 1,000 patients with CRC. Postoperative chemotherapy is associated with a significant reduction in the risk of mortality. All of these findings should provide insights into the better management of critically ill patients with CRC.
Assuntos
Neoplasias Colorretais/cirurgia , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Complicações Pós-Operatórias/mortalidade , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Idoso , Feminino , Seguimentos , Humanos , Masculino , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
This study aimed to explore the roles of monocyte chemotactic protein 1 (MCP-1) and nuclear factor kappa B (NF-κB) in immune response to spinal tuberculosis in a New Zealand white rabbit model. Forty-eight New Zealand white rabbits were collected and divided into four groups: experimental group (n=30, spinal tuberculosis model was established), the sham group (n=15, sham operation was performed) and the blank group (n=3). The qRT-PCR assay and western blotting were applied to detect the mRNA and protein expressions of MCP-1 and NF-κB in peripheral blood. ELISA was used to measure serum levels of MCP-1, NF-κB, IFN-γ, IL-2, IL-4, and IL-10. Flow cytometry was adopted to assess the distributions of CD4+, CD8+ lymphocytes and CD4+ CD25+ Foxp3 lymphocyte subsets. Compared with the sham and blank groups, the mRNA and protein expressions of MCP-1 and NF-κB in the experimental group were significantly increased. The experimental group had lower serum levels of IL-2 and IFN-γ and higher serum level of IL-10 than the sham and blank groups. In comparison to the sham and blank groups, CD4+ T lymphocyte subsets percentage, CD4+/CD8+ ratio and CD4+ CD25+ Foxp3+ Tregs subsets accounting for CD4+ lymphocyte in the experimental group were lower, while percentage of CD8+ T lymphocyte subsets was higher. Our study provided evidence that higher expression of MCP-1 and NF-κB may be associated with decreased immune function of spinal tuberculosis, which can provide a new treatment direction for spinal tuberculosis.
Assuntos
Quimiocina CCL2/metabolismo , Imunidade Celular/imunologia , NF-kappa B/metabolismo , Tuberculose da Coluna Vertebral/imunologia , Animais , Western Blotting , Quimiocina CCL2/sangue , Citocinas/sangue , Citocinas/imunologia , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Masculino , NF-kappa B/sangue , Coelhos , Reação em Cadeia da Polimerase em Tempo RealRESUMO
This study aimed to explore the roles of monocyte chemotactic protein 1 (MCP-1) and nuclear factor kappa B (NF-κB) in immune response to spinal tuberculosis in a New Zealand white rabbit model. Forty-eight New Zealand white rabbits were collected and divided into four groups: experimental group (n=30, spinal tuberculosis model was established), the sham group (n=15, sham operation was performed) and the blank group (n=3). The qRT-PCR assay and western blotting were applied to detect the mRNA and protein expressions of MCP-1 and NF-κB in peripheral blood. ELISA was used to measure serum levels of MCP-1, NF-κB, IFN-γ, IL-2, IL-4, and IL-10. Flow cytometry was adopted to assess the distributions of CD4+, CD8+ lymphocytes and CD4+ CD25+ Foxp3 lymphocyte subsets. Compared with the sham and blank groups, the mRNA and protein expressions of MCP-1 and NF-κB in the experimental group were significantly increased. The experimental group had lower serum levels of IL-2 and IFN-γ and higher serum level of IL-10 than the sham and blank groups. In comparison to the sham and blank groups, CD4+ T lymphocyte subsets percentage, CD4+/CD8+ ratio and CD4+ CD25+ Foxp3+ Tregs subsets accounting for CD4+ lymphocyte in the experimental group were lower, while percentage of CD8+ T lymphocyte subsets was higher. Our study provided evidence that higher expression of MCP-1 and NF-κB may be associated with decreased immune function of spinal tuberculosis, which can provide a new treatment direction for spinal tuberculosis.
Assuntos
Animais , Masculino , Coelhos , Quimiocina CCL2/metabolismo , Imunidade Celular/imunologia , NF-kappa B/metabolismo , Tuberculose da Coluna Vertebral/imunologia , Western Blotting , Quimiocina CCL2/sangue , Citocinas/sangue , Citocinas/imunologia , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , NF-kappa B/sangue , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Four Hyriopsis cumingii populations, a breeding population (BP), a cultured population (FP), two wild populations from Poyang Lake (PY) and Dongting Lake (DT), and an H. schlegelii population were collected (JX), and the first filial generations (F1) were bred synchronously. The shell nacre polymorphisms, population genetic diversity, and genetic structures of the F1 of each population were analyzed and compared using CIELAB colorimetric measurements and microsatellite markers. The color parameters of the shell nacre (L*, a*, dE*) in the BP were significantly different from those in the FP, PY, and JX populations (P < 0.05), whereas the shell nacre color did not differ significantly between the left and right sides of the shells within the same population (P > 0.05). The BP had relatively darker nacre at the posterior end of the shell, and the color parameters (L*, a*, b*, and dE*) differed significantly from those at the front end (P < 0.05). The five populations showed relatively high levels of genetic diversity (HO = 0.733-0.829). The genetic distance between the H. cumingii populations and H. schlegelii was the greatest, whereas that within the H. cumingii populations and between the FP and the PY population was the smallest. All the individuals tested in this study were optimally grouped into four theoretical populations. In conclusion, the BP was significantly different from the base populations of PY and DT in terms of genetic background and phenotypic parameters of shell nacre color, with potential for further genetic improvement.
Assuntos
Bivalves/classificação , Bivalves/genética , Repetições de Microssatélites , Locos de Características Quantitativas , Exoesqueleto , Animais , Cruzamento , Evolução Molecular , Feminino , Água Doce , Variação Genética , Genética Populacional , Masculino , Fenótipo , FilogeniaRESUMO
The triangle sail mussel, Hyriopsis cumingii, is the most important freshwater pearl mussel in China. However, the mechanisms underlying its chitin-mediated shell and nacre formation remain largely unknown. Here, we characterized a chitin synthase (CS) gene (HcCS1) in H. cumingii, and analyzed its possible physiological function. The complete ORF sequence of HcCS1 contained 6903 bp, encoding a 2300-amino acid protein (theoretical molecular mass = 264 kDa; isoelectric point = 6.22), and no putative signal peptide was predicted. A myosin motor head domain, a CS domain, and 12 transmembrane domains were found. The predicted spatial structures of the myosin head and CS domains were similar to the electron microscopic structure of the heavy meromyosin subfragment of chicken smooth muscle myosin and the crystal structure of bacterial cellulose synthase, respectively. This structural similarity indicates that the functions of these two domains might be conserved. Quantitative reverse transcription PCR results showed that HcCS1 was present in all detected tissues, with the highest expression levels detected in the mantle. The HcCS1 transcripts in the mantle were upregulated following shell damage from 12 to 24 h post-damage, and they peaked (approximately 1.5-fold increase) at 12 h after shell damage. These findings suggest that HcCS1 was involved in shell regeneration, and that it might participate in shell and nacre formation in this species via chitin synthesis. HcCS1 might also dynamically regulate chitin deposition during the process of shell and nacre formation with the help of its conserved myosin head domain.
Assuntos
Exoesqueleto/metabolismo , Bivalves/genética , Quitina Sintase/genética , Quitina/biossíntese , Nácar/metabolismo , Sequência de Aminoácidos , Animais , Bivalves/classificação , Bivalves/enzimologia , Galinhas , Quitina Sintase/química , Quitina Sintase/metabolismo , Água Doce , Expressão Gênica , Glucosiltransferases/química , Glucosiltransferases/genética , Ponto Isoelétrico , Modelos Moleculares , Dados de Sequência Molecular , Peso Molecular , Subfragmentos de Miosina/química , Subfragmentos de Miosina/genética , Fases de Leitura Aberta , Filogenia , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Alinhamento de Sequência , Homologia Estrutural de ProteínaRESUMO
5-Azacytidine has been shown to be an effective anti-pancreatic cancer drug, but the mechanism remains unknown. In the current study, we explored the effect of 5-azacytidine on abnormal activation of the Wnt-ß-catenin signaling pathway in pancreatic cancer cells. The human pancreatic cancer cell line Bxpc-3 was treated with different concentrations of 5-azacytidine for various times. The proliferation and early apoptosis of the cells were evaluated using the CCK8 method and flow cytometry, respectively. mRNA and protein expression of ß-catenin, c-myc, and cyclinD1 were detected using real-time fluorescent quantitative polymerase chain reaction and Western blot analysis, respectively. The proliferation of Bxpc-3 cells was suppressed by 5-azacytidine. The early apoptosis of the cells was significantly enhanced over time and with increasing drug concentrations. The expression of ß-catenin, c-myc, and cyclinD1 were down-regulated, showing significant differences between different concentrations and treatment times (P < 0.05). 5-Azacytidine suppressed the proliferation of pancreatic cancer cells by inhibiting the Wnt/ß-catenin signaling pathway, particularly the expression of ß-catenin, c-myc, and cyclinD1. This study may provide a new potential strategy for diagnosing and treating pancreatic cancer.
Assuntos
Antimetabólitos Antineoplásicos/farmacologia , Azacitidina/farmacologia , Proliferação de Células/efeitos dos fármacos , Pâncreas/efeitos dos fármacos , beta Catenina/genética , Linhagem Celular Tumoral , Ciclina D1/antagonistas & inibidores , Ciclina D1/genética , Ciclina D1/metabolismo , Regulação da Expressão Gênica , Humanos , Pâncreas/metabolismo , Pâncreas/patologia , Proteínas Proto-Oncogênicas c-myc/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Transdução de Sinais , beta Catenina/antagonistas & inibidores , beta Catenina/metabolismoRESUMO
Hyperglycemia is common in critical patients and high blood glucose levels have a negative effect on their prognosis. The aim of this study was to investigate the effect of hyperglycemia and glycosylated hemoglobin (GHb) in critical patients. A total of 648 critical patients were enrolled in the study and received a random blood glucose test when they entered the emergency department. If blood glucose was more than 11.1 mM, a GHb test was followed within 24 h. All patients were followed up for 28 days. According to diabetes mellitus (DM) history, GHb value, and outcome of follow-up, patients were divided into different groups, and mortality rates were calculated, respectively. Hyperglycemia was found in 67.44% (437/648) of patients, and 51.49% (225/437) and 48.51% (212/437) had normal and elevated GHb levels, respectively. At the end of the follow-up period, 14 of the normal GHb patients and 32 of the elevated GHb patients died (6.22 and 15.09%, respectively). In the normal GHb group, 53 had a DM history, 23 were newly diagnosed with DM, and 149 had hospital-related hyperglycemia (HRH); the mortality rates were 11.32% (6/53), 8.70% (2/23), and 4.03% (6/149), respectively. In the elevated GHb group, 114 had a DM history, 83 were newly diagnosed with DM, and 15 had HRH; the mortality rates were 13.16% (15/114), 19.27% (16/83), and 6.67% (1/15), respectively. Hyperglycemia and GHb might play important roles in the prognosis and assessment for critical patients, and the prognosis would vary according to the different causes of hyperglycemia.
Assuntos
Estado Terminal , Hemoglobinas Glicadas/metabolismo , Hiperglicemia/sangue , Idoso , Idoso de 80 Anos ou mais , Glicemia/metabolismo , Diabetes Mellitus/sangue , Diabetes Mellitus/diagnóstico , Feminino , Seguimentos , Humanos , Hiperglicemia/diagnóstico , Masculino , Pessoa de Meia-Idade , Prognóstico , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Fatores de Risco , Fatores de TempoRESUMO
Hyriopsis cumingii is an economically important freshwater pearl mussel with high pearl quality that is endemic in China. Investigation of genes relevant to shell formation is important for increased pearl output. The substances that form mollusk shells are secreted by epithelial cells in the mantle, the proliferation of which influences secretion ability. This study focused on the proliferation-related 37-kDa laminin receptor precursor (37LRP) of H. cumingii. The full-length cDNA (1133 bp) encoding this 300-amino acid protein was cloned from the mantle. Quantitative fluorescence analysis showed that 37LRP expressed in eight tissues, with the highest expression observed in the liver, and its expression pattern in the mantle reflected shell repair. During repair, 37LRP expression was higher in the experimental shell repair group than that in the control group, exhibiting an initial increase followed by a decrease in expression, and returning to basal levels on completion of the repair. A similar trend was also observed with respect to immunity and cellular metabolism. Expression of the 37LRP protein in the experimental group was significantly higher than that in the control group at the first and second days after shell injury. After 4 days, 37LRP expression in the experimental group was lower than that in the control group. In situ hybridization revealed a strong positive signal corresponding to the 37LRP mRNA at the horny grooves of the mantle, evagination, and in epithelial cells of the velum, which implicated these areas in the repair and formation of the cuticle, prismatic layer, and nacre.