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Converting M2 macrophages into an M1 phenotype in the tumor microenvironment, provides a new direction for tumor treatment. Here, we further report CVPW-1, a new polysaccharide of 1.03 × 106 Da that was isolated from Coriolus versicolor. Its monosaccharide was composed of mannose, glucose, and galactose at a ratio of 1.00:8.73:1.68. The backbone of CVPW-1 was composed of (1 â 3)-linked α-D-Glcp residues and (1 â 3,6)-linked α-D-Glcp residues that branched at O-6. The branch consisted of (1 â 6)-linked α-D-Glcp residues and (1 â 4)-linked α-D-Glap, and some branches were terminated with (1â)-linked ß-D-Manp residues according to the results of HPLC, FT-IR, GC-MS, 1D and 2D NMR. Meanwhile, CVPW-1 could polarize M2 macrophages to M1 phenotypein vitro by binding to TLR4 and inducing the activation of Akt, JNK and NF-κB. This process involved reversing the functional inhibition of CD8+ T lymphocytes by inhibiting the expression of TREM2 in M2 macrophages. The in vivo experiments showed that oral administration of CVPW-1 could inhibit the growth of tumor in mice and polarize TAMs to M1 phenotype. Thus, the novel polysaccharide CVPW-1 from Coriolus versicolor might activate a variety of immune cells and then play an anti-tumor role. These results demonstrated that CVPW-1 could be developed as a potential immuno-oncology treatment reagent.
Assuntos
Neoplasias , Polyporaceae , Microambiente Tumoral , Animais , Camundongos , Espectroscopia de Infravermelho com Transformada de Fourier , Polissacarídeos/farmacologia , Polissacarídeos/química , Macrófagos , Fenótipo , Neoplasias/tratamento farmacológicoRESUMO
INTRODUCTION: New-onset postoperative atrial fibrillation (POAF) is a common complication following coronary artery bypass grafting (CABG) surgery. OBJECTIVE: To explore predictive factors and potential mechanisms of new-onset POAF in isolated off-pump CABG patients. METHODS: Retrospective observational case-control study of 233 patients undergoing isolated off-pump CABG surgery between August 2018 and July 2020 at the Department of Thoracic and Cardiovascular Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School. Associations between predictor variables and new-onset POAF were identified. The main outcome was new-onset POAF after CABG surgery. RESULTS: A total of 75 (32.19%) patients developed new-onset POAF after CABG surgery. The new-onset POAF patients had advanced age, higher baseline systolic blood pressure, more preoperative use of diuretic drug, more transfusion of blood products, atrial dilation and postoperative positive inotropic drug treatment. Nineteen variates entered the multivariable logistic regression model with a Hosmer-Lemeshow test score of 7.565 (P=0.477). Postoperative left atrial enlargement, postoperative drainage in the first 24 hours and total length of hospital stay were statistically significant, while postoperative right atrial enlargement (OR and 95% CI, 7.797 [0.200, 304.294], P=0.272) and left atrial enlargement (3.524 [1.141, 10.886], P=0.029) assessed by echocardiography had the largest OR value. CONCLUSION: Atrial enlargement is strongly associated with new-onset POAF in patients with isolated off-pump CABG, thus it highlights the advantage of echocardiography as a useful tool for predicting new-onset POAF. Careful monitoring and timely intervention should be considered for these patients.
Assuntos
Fibrilação Atrial , Humanos , Estudos Retrospectivos , Estudos de Casos e Controles , Ponte de Artéria Coronária/efeitos adversos , Ecocardiografia , Complicações Pós-Operatórias/etiologia , Fatores de RiscoRESUMO
ABSTRACT Introduction: New-onset postoperative atrial fibrillation (POAF) is a common complication following coronary artery bypass grafting (CABG) surgery. Objective: To explore predictive factors and potential mechanisms of new-onset POAF in isolated off-pump CABG patients. Methods: Retrospective observational case-control study of 233 patients undergoing isolated off-pump CABG surgery between August 2018 and July 2020 at the Department of Thoracic and Cardiovascular Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School. Associations between predictor variables and new-onset POAF were identified. The main outcome was new-onset POAF after CABG surgery. Results: A total of 75 (32.19%) patients developed new-onset POAF after CABG surgery. The new-onset POAF patients had advanced age, higher baseline systolic blood pressure, more preoperative use of diuretic drug, more transfusion of blood products, atrial dilation and postoperative positive inotropic drug treatment. Nineteen variates entered the multivariable logistic regression model with a Hosmer-Lemeshow test score of 7.565 (P=0.477). Postoperative left atrial enlargement, postoperative drainage in the first 24 hours and total length of hospital stay were statistically significant, while postoperative right atrial enlargement (OR and 95% CI, 7.797 [0.200, 304.294], P=0.272) and left atrial enlargement (3.524 [1.141, 10.886], P=0.029) assessed by echocardiography had the largest OR value. Conclusion: Atrial enlargement is strongly associated with new-onset POAF in patients with isolated off-pump CABG, thus it highlights the advantage of echocardiography as a useful tool for predicting new-onset POAF. Careful monitoring and timely intervention should be considered for these patients.
RESUMO
The induction of autophagy by nanoparticles causes nanotoxicity, but appropriate modulation of autophagy by nanoparticles may have therapeutic potential. Multiwalled carbon nanotubes (MWCNTs) interact with cell membranes and membrane-associated molecules before and after internalization. These interactions alter cellular signaling and impact major cell functions such as cell cycle, apoptosis, and autophagy. In this work, we demonstrated that MWCNT-cell interactions can be modulated by varying densely distributed surface ligands on MWCNTs. Using a fluorescent autophagy-reporting cell line, we evaluated the autophagy induction capability of 81 surface-modified MWCNTs. We identified strong and moderate autophagy-inducing MWCNTs as well as those that did not induce autophagy. Variation of the surface ligand structure of strong autophagy nanoinducers led to the induction of different autophagy-activating signaling pathways, presumably through their different interactions with cell surface receptors.
Assuntos
Autofagia/efeitos dos fármacos , Nanomedicina , Nanotubos de Carbono/química , Células HEK293 , Humanos , Receptores de Superfície Celular/metabolismo , Transdução de Sinais/efeitos dos fármacos , Propriedades de Superfície , Serina-Treonina Quinases TOR/metabolismoRESUMO
To investigate shallow groundwater quality in Taihu plain, south of Jiangsu province, 56 samples were collected in north area (C area), north east area (W area) and east area (S area). The concentrations of priority 16 polycyclic aromatic hydrocarbons (PAHs) were analyzed by HP 6890-GC. Hierarchical cluster analysis (HCA) and Molecular ratios were used to characterize their possible pollution sources. Concentrations of total priority 16 PAHs in shallow groundwater samples ranged from below method detection limits (< MDLs) to 32.45 microg/L with the average value of 4.42 microg/L, which were predominated by three and four-ring PAHs. High contents of PAHs were found in the vicinity of industrial areas. Ratios of specific PAH compounds including phenanthrene/anthracene (Phe/Ant), fluoranthene/pyrene (FL/Pyr), chrysene/ benzo(a)/anthracene (Chr/BaA), low-molecular-weight PAH/high-molecular-weight PAH (LPAH/HPAH) were calculated to evaluate the possible sources of PAH contamination. These ratios reflected a mixed pattern of pyrolytic and petrogenic inputs of PAHs with different proportion in shallow groundwater. Hierarchical cluster analysis (HCA) results showed that the abnormal benzo (k) fluoranthene concentration dominated the HCA results in C area, the abnormal benzo(a)anthracene concentration dominated the HCA results in W area, and the abnormal benzo (b) fluoranthene concertration dominated the HCA results in S area. At level 0.05, FL, AcPy, Acp, Phe and Bap in C area had Pearson correlation between 0.680 and 0.712. BP, BaA and Bap in W area had Pearson correlation between 0.724 and 0.773. AcPy and Flu in S area had Pearson correlation 0.659, which meant that these PAHs listed in each areas might came from the same kind of sources.