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1.
Zhonghua Xue Ye Xue Za Zhi ; 45(5): 436-444, 2024 May 14.
Artigo em Chinês | MEDLINE | ID: mdl-38964917

RESUMO

Objective: To construct a novel chimeric antigen receptor T (CAR-T) cell targeting CD138 and to investigate its cytotoxicity against myeloma cells. Methods: The hybridoma strain that can stably secrete the CD138 monoclonal antibody (mAb) was prepared and obtained through monoclonal antibody screening technology. The hybridoma strain cells were intraperitoneally injected into mice to produce ascites containing monoclonal antibodies, which were then collected and purified to obtain pure CD138 mAb. Further examinations were performed to assess the biological characteristics of CD138 mAb. The variable region sequence of this antibody was amplified through reverse transcription polymerase chain reaction and was used as the antigen recognition domain of CD138 CAR, which was subsequently expressed on the surface of T cells by lentiviral infection. Flow cytometry was employed to assess the phenotype of CD138 CAR-T cells. In vitro cytotoxicity and degranulation assays were performed to evaluate their antitumor effects. Results: ① We successfully prepared anti-human CD138 antibody hybridoma cell lines and screened a hybridoma cell strain, 5G2, which could persistently and stably secrete the anti-CD138 antibody. ② The purified CD138 (5G2) mAb can especially recognize CD138(+) cells with a binding affinity constant (K(D)) of 6.011×10(-9) mol/L and showed no significant binding activity with CD138(-) cells. ③The variable region sequence of the CD138 (5G2) antibody was obtained using molecular cloning technology, and CD138 (5G2) CAR was successfully constructed and expressed on T cells through lentivirus infection and, concurrently, demonstrated effective binding to recombinant human CD138 protein.④ The proliferation of T cells transduced with the CD138 (5G2) CAR was highly efficient. The phenotype analysis revealed that CD138 (5G2) CAR-T cells exhibited a greater tendency to differentiate into central memory T cells and memory stem T cells, with a reduced proportion of terminally differentiated effector memory subsets. ⑤CD138 (5G2) CAR-T cells demonstrated specific cytotoxicity against CD138(+) myeloma cell line H929, whereas CD138(-) cell line K562 remained unaffected. The percentage of residual H929 cells was (12.92±8.02) % after co-culturing with CD138 (5G2) CAR-T cells, while (54.25±15.79) % was left in the Vector-T group (E∶T=1∶2; P<0.001). ⑥Results of degranulation assays demonstrated a significant activation of CD138 (5G2) CAR-T cells after co-culture with the H929 cell line, whereas no significant activation was observed in Vector-T cells [ (25.78±3.35) % vs (6.13±1.30) %, P<0.001]. ⑦After co-culturing with CD138(+) cells, CD138 (5G2) CAR-T cells exhibited a significant increase in cytokine secretion compared to the Vector-T group [interleukin-2: (1 697.52±599.05) pg/ml vs (5.07±1.17) pg/ml, P<0.001; interferon-γ: (3 312.20±486.38) pg/ml vs (9.28±1.46) pg/ml, P<0.001; and tumor necrosis factor-α: (1 837.43±640.49) pg/ml vs (8.75±1.65) pg/ml, P<0.001]. However, no significant difference was observed in cytokine secretion levels between the two groups after co-culturing with CD138(-) cells. Conclusion: This study successfully prepared a novel monoclonal antibody against CD138, and CAR-T cells constructed with the antigen recognition domain derived from this 5G2 mAb demonstrated effective antitumor activity against myeloma cells. This can be used as a new option for the detection of the CD138 antigen and proposes a novel strategy for multiple myeloma immunotherapy.


Assuntos
Mieloma Múltiplo , Receptores de Antígenos Quiméricos , Sindecana-1 , Linfócitos T , Mieloma Múltiplo/terapia , Mieloma Múltiplo/imunologia , Receptores de Antígenos Quiméricos/imunologia , Camundongos , Animais , Humanos , Sindecana-1/imunologia , Linfócitos T/imunologia , Hibridomas , Imunoterapia Adotiva/métodos , Linhagem Celular Tumoral , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos T/genética , Anticorpos Monoclonais/imunologia
2.
Sci Rep ; 14(1): 12931, 2024 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-38839816

RESUMO

The present study aimed to investigate endothelial glycocalyx (eGCx) damage in cats with feline hemotropic mycoplasmosis caused by Mycoplasma haemofelis using selected biomarkers and to determine the diagnostic and prognostic significance of these biomarkers. The study included 25 cats with feline hemotropic mycoplasmosis and 10 healthy cats. Clinical examination, blood gas analysis, complete blood count, and biochemical analysis were performed. Hemotropic mycoplasmosis diagnosed by microscopic examination and molecularly confirmed by PCR targeting the Mycoplasma haemofelis 16s rRNA gene. To evaluate endothelial glycocalyx damage, syndecan-1, endothelin-1 (ET-1), asymmetric dimethylarginine (ADMA), and vascular endothelial growth factor-A (VEGF-A) concentrations were measured using cat-specific commercial ELISA kits. Of the cats with feline hemotropic mycoplasmosis, 14 (56%) survived and 11 (44%) died. While syndecan-1 and ET-1 concentrations were significantly higher in cats with hemotropic mycoplasmosis compared to the control group (p < 0.001), no statistically significant difference was found for ADMA and VEGF-A concentrations (p > 0.05). Endothelial glycocalyx biomarkers showed significant correlations with each other and with hematological parameters (p < 0.01). The results of the ROC analysis showed that ET-1 with area under the curve (AUC) of 0.821 (p < 0.01) and VEGF-A with AUC of 0.805 (p < 0.010) were found to be significant prognostic indicators. In conclusion, this study demonstrated that serum syndecan-1 and ET-1 can be used as diagnostic and serum ET-1 and VEGF-A as prognostic biomarkers in cats with hemotropic mycoplasmosis. Our results indicate the development of eGCx damage in feline hemotropic mycoplasmosis and suggest that glycocalyx disruption may contribute to the pathogenesis of the disease.


Assuntos
Biomarcadores , Doenças do Gato , Glicocálix , Mycoplasma , Fator A de Crescimento do Endotélio Vascular , Animais , Gatos , Glicocálix/metabolismo , Biomarcadores/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Doenças do Gato/microbiologia , Doenças do Gato/sangue , Doenças do Gato/diagnóstico , Mycoplasma/genética , Masculino , Feminino , Infecções por Mycoplasma/veterinária , Infecções por Mycoplasma/sangue , Infecções por Mycoplasma/microbiologia , Endotelina-1/sangue , Sindecana-1/sangue , Arginina/análogos & derivados , Arginina/sangue , Arginina/metabolismo
3.
Cells ; 13(11)2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38891113

RESUMO

Tigilanol tiglate (TT, also known as EBC-46) is a novel, plant-derived diterpene ester possessing anticancer and wound-healing properties. Here, we show that TT-evoked PKC-dependent S985 phosphorylation of the tyrosine kinase MET leads to subsequent degradation of tyrosine phosphorylated p-Y1003 and p-Y1234/5 MET species. PKC inhibition with BIM-1 blocked S985 phosphorylation of MET and led to MET cell surface accumulation. Treatment with metalloproteinase inhibitors prevented MET-ECD release into cell culture media, which was also blocked by PKC inhibitors. Furthermore, unbiased secretome analysis, performed using TMT-technology, identified additional targets of TT-dependent release of cell surface proteins from H357 head and neck cancer cells. We confirm that the MET co-signalling receptor syndecan-1 was cleaved from the cell surface in response to TT treatment. This was accompanied by rapid cleavage of the cellular junction adhesion protein Nectin-1 and the nerve growth factor receptor NGFRp75/TNFR16. These findings, that TT is a novel negative regulator of protumorigenic c-MET and NGFRp75/TNFR16 signalling, as well as regulating Nectin-1-mediated cell adhesion, further contribute to our understanding of the mode of action and efficacy of TT in the treatment of solid tumours.


Assuntos
Neoplasias de Cabeça e Pescoço , Proteínas Proto-Oncogênicas c-met , Humanos , Proteínas Proto-Oncogênicas c-met/metabolismo , Fosforilação/efeitos dos fármacos , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/genética , Linhagem Celular Tumoral , Secretoma/metabolismo , Diterpenos/farmacologia , Proteínas de Membrana/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sindecana-1/metabolismo , Nectinas/metabolismo , Proteína Quinase C/metabolismo
4.
BMC Womens Health ; 24(1): 372, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38918774

RESUMO

BACKGROUND: To investigate the impact of chronic endometritis (CE) on the recurrence of endometrial polyps (EPs) in premenopausal women after transcervical resection of endometrial polyps (TCRP). METHODS: This prospective study enrolled 507 women who underwent TCRP between January 1, 2022 and December 31, 2022. The patients were divided into a CE group (n = 133) and non-CE group (n = 374) based on the expression of CD138 in the endometrium. The EP recurrence rate at 1 year after TCRP was compared between the CE and non-CE groups and between groups with mild CE and severe CE. The impact of CD138 expression by resected EPs on EP recurrence also was investigated. RESULTS: The EP recurrence rate at 1 year post-TCRP was higher in the CE group than in the non-CE group (25.6% vs. 10.4%) and also higher in the severe CE group than in the mild CE group (34.5% vs. 18.7%). Additionally, the EP recurrence rate was higher among patients with CD138-expressing EPs than among those with EPs lacking CD138 expression (30.5% vs. 6.5%). The odds ratio (OR) for EP recurrence in the CE cohort compared with the non-CE cohort was 3.10 (95% confidence interval [CI] 1.84-5.23) after adjustment for EP number and precautions against EP recurrence. The ORs for EP recurrence in patients with mild CE and severe CE were 2.21 (95%CI 1.11-4.40) and 4.32 (95%CI 2.26-8.26), respectively. Similarly, the OR for EP recurrence in cases with CD138-expressing EPs relative to cases with EPs lacking CD138 expression was 6.22 (95%CI 3.59-10.80) after adjustment for EP number and precautions against EP recurrence. CONCLUSIONS: CE multiplied the recurrence rate of EPs in premenopausal women after TCRP, and this effect positively correlated with CE severity. CD138 expression by EPs also was associated with a higher risk for EP recurrence.


Assuntos
Endometrite , Pólipos , Recidiva , Humanos , Feminino , Estudos Prospectivos , Adulto , Pólipos/cirurgia , Endometrite/epidemiologia , Endometrite/etiologia , Doença Crônica , Sindecana-1/metabolismo , Pessoa de Meia-Idade , Doenças Uterinas/cirurgia , Doenças Uterinas/etiologia , Fatores de Risco
5.
Recenti Prog Med ; 115(5): 238-242, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38708535

RESUMO

Plasma cell multiple myeloma (MM) is a multiform clinical entity characterized by different laboratory hallmarks. This case shows a rare entity of plasma cell myeloma: the entire plasma cell population lack the CD138 expression. In this case, a careful analysis of laboratory finding, particular flow cytometry gating strategies and the use of other ancillary laboratory tests, guide the clinicians to correct diagnosis. The correct evaluation of pre-analytical phase and the correct gating strategy are the necessary conditions to produce robust and solid flow cytometric results. The diagnostic implications of CD138-negative plasma cell are strictly linked to stem cell-like clonogenic features, such as possible more aggressive clinical behaviour and increasing probability of chemotherapy resistance. At this time, clinical laboratory remains the main reference point to MM diagnosis.


Assuntos
Citometria de Fluxo , Mieloma Múltiplo , Plasmócitos , Sindecana-1 , Idoso , Humanos , Masculino , Citometria de Fluxo/métodos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/patologia , Plasmócitos/patologia , Sindecana-1/metabolismo , Sindecana-1/análise
6.
Sci Rep ; 14(1): 10477, 2024 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714743

RESUMO

Endothelial glycocalyx (eGC) covers the inner surface of the vessels and plays a role in vascular homeostasis. Syndecan is considered the "backbone" of this structure. Several studies have shown eGC shedding in sepsis and its involvement in organ dysfunction. Matrix metalloproteinases (MMP) contribute to eGC shedding through their ability for syndecan-1 cleavage. This study aimed to investigate if doxycycline, a potent MMP inhibitor, could protect against eGC shedding in lipopolysaccharide (LPS)-induced sepsis and if it could interrupt the vascular hyperpermeability, neutrophil transmigration, and microvascular impairment. Rats that received pretreatment with doxycycline before LPS displayed ultrastructural preservation of the eGC observed using transmission electronic microscopy of the lung and heart. In addition, these animals exhibited lower serum syndecan-1 levels, a biomarker of eGC injury, and lower perfused boundary region (PBR) in the mesenteric video capillaroscopy, which is inversely related to the eGC thickness compared with rats that only received LPS. Furthermore, this study revealed that doxycycline decreased sepsis-related vascular hyperpermeability in the lung and heart, reduced neutrophil transmigration in the peritoneal lavage and inside the lungs, and improved some microvascular parameters. These findings suggest that doxycycline protects against LPS-induced eGC shedding, and it could reduce vascular hyperpermeability, neutrophils transmigration, and microvascular impairment.


Assuntos
Doxiciclina , Glicocálix , Lipopolissacarídeos , Sepse , Glicocálix/metabolismo , Glicocálix/efeitos dos fármacos , Animais , Sepse/tratamento farmacológico , Sepse/metabolismo , Doxiciclina/farmacologia , Ratos , Masculino , Permeabilidade Capilar/efeitos dos fármacos , Pulmão/patologia , Pulmão/metabolismo , Pulmão/efeitos dos fármacos , Sindecana-1/metabolismo , Ratos Wistar , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Neutrófilos/metabolismo , Neutrófilos/efeitos dos fármacos , Inibidores de Metaloproteinases de Matriz/farmacologia
7.
Am J Reprod Immunol ; 91(5): e13858, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38762781

RESUMO

PROBLEM: In the current study we aimed to investigate Syndecan 1 (SDC1) levels in pregnant women diagnosed with fetal growth restriction (FGR) and the relationship between SDC1 levels and clinical and doppler parameters in FGR cases associated with endothelial dysfunction, angiogenesis and uteroplacental insufficiency METHOD OF STUDY: A total of 90 pregnant women included in the study, (45 with FGR, 45 healthy control) matched by week of gestation and maternal age. Venous blood samples were collected and plasma concentrations of SDC1 were determined by a specific immunoassay. Doppler examination was performed to evaluate the relationship between the SDC1 levels and placental blood supply. RESULTS: Doppler parameters; mean UtA-PI (p < .001), CPR (p = .002) and CPUR (p < .001) were different between the groups, however MCA PI, umbilical artery PI and umbilical artery S/D were not (p > .05). While gestational age at delivery, birth weight, APGAR score at 1 and 5 min were significantly lower (all, p < .001) in the study group, non-reassure fetal heart rate tracing (p = .09) and NICU admission (p = .02) were significantly higher. SDC 1 level was 2,00 ± 1,47 ng/mL and 2,34 ± 1,12 ng/mL in the FGR and control groups, respectively (p = .008). In the study group SDC 1 level was 1,69 ± 2,00 in those with gestational age below 32 weeks and 2,13 ± 1,18 in those with gestational age above 32 weeks and there was a statistically significant difference between the groups (p = .015). Plasma SDC 1 concentration of 2,1850 ng/mL or less had a sensitivity of 70%, a specificity of 72%, area under the ROC curve .65 (p < .005). CONCLUSIONS: Low maternal plasma SDC1 level may be associated with placental insufficiency and FGR. Low levels of SDC1 may be helpful as a predictor for the development of FGR during gestation.


Assuntos
Biomarcadores , Retardo do Crescimento Fetal , Sindecana-1 , Humanos , Sindecana-1/sangue , Retardo do Crescimento Fetal/sangue , Feminino , Gravidez , Adulto , Biomarcadores/sangue , Idade Gestacional , Recém-Nascido , Artérias Umbilicais/diagnóstico por imagem , Placenta/metabolismo , Endotélio Vascular/fisiopatologia
8.
Biochem Biophys Res Commun ; 716: 150019, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38703555

RESUMO

- Acute respiratory distress syndrome (ARDS)/acute lung injury (ALI) is a life-threatening condition marked by severe lung inflammation and increased lung endothelial barrier permeability. Endothelial glycocalyx deterioration is the primary factor of vascular permeability changes in ARDS/ALI. Although previous studies have shown that phospholipase D2 (PLD2) is closely related to the onset and progression of ARDS/ALI, its role and mechanism in the damage of endothelial cell glycocalyx remains unclear. We used LPS-induced ARDS/ALI mice (in vivo) and LPS-stimulated injury models of EA.hy926 endothelial cells (in vitro). We employed C57BL/6 mice, including wild-type and PLD2 knockout (PLD2-/-) mice, to establish the ARDS/ALI model. We applied immunofluorescence and ELISA to examine changes in syndecan-1 (SDC-1), matrix metalloproteinase-9 (MMP9), inflammatory cytokines (TNF-α, IL-6, and IL-1ß) levels and the effect of external factors, such as phosphatidic acid (PA), 1-butanol (a PLD inhibitor), on SDC-1 and MMP9 expression levels. We found that PLD2 deficiency inhibits SDC-1 degradation and MMP9 expression in LPS-induced ARDS/ALI. Externally added PA decreases SDC-1 levels and increases MMP9 in endothelial cells, hence underlining PA's role in SDC-1 degradation. Additionally, PLD2 deficiency decreases the production of inflammatory cytokines (TNF-α, IL-6, and IL-1ß) in LPS-induced ARDS/ALI. In summary, these findings suggest that PLD2 deficiency plays a role in inhibiting the inflammatory process and protecting against endothelial glycocalyx injury in LPS-induced ARDS/ALI.


Assuntos
Lesão Pulmonar Aguda , Glicocálix , Lipopolissacarídeos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fosfolipase D , Síndrome do Desconforto Respiratório , Animais , Fosfolipase D/metabolismo , Fosfolipase D/genética , Glicocálix/metabolismo , Síndrome do Desconforto Respiratório/metabolismo , Síndrome do Desconforto Respiratório/patologia , Síndrome do Desconforto Respiratório/induzido quimicamente , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/etiologia , Camundongos , Humanos , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Sindecana-1/metabolismo , Sindecana-1/genética , Citocinas/metabolismo , Linhagem Celular
9.
Biomed Pharmacother ; 175: 116621, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38677244

RESUMO

BACKGROUND: Extracellular neutrophil extracellular traps (NETs) play an important role in acute lung injury (ALI), but their mechanisms are still unclear. The aim of this study is to explore the effects of NETs on endothelial glycocalyx/HGF/cMET pathway and ferroptosis in ALI and elucidate their potential mechanisms. METHODS: Plasma was collected from healthy and sepsis patients to test for differences in neutrophil elastase (NE) expression of NETs components. In addition, LPS-ALI mice and endothelial cell injury models were established, and NETs were disrupted by siPAD4 (a driver gene for NETs) and sivelestat (an inhibitor of the NETs component) in the mice and by sivelestat in the endothelial cell injury models, and the effects of NETs on the SDC-1/HS/HGF/cMET pathway were studied. To verify the relationship between NETs and ferroptosis, Fer1, a ferroptosis inhibitor, was added as a positive control to observe the effect of NETs on ferroptosis indicators. RESULTS: The expression level of NE was significantly higher in the plasma of sepsis patients. In ALI mice, intervention in the generation of NETs reduced pulmonary vascular permeability, protected the integrity of SDC-1/HS and promoted the downstream HGF/cMET pathway. In addition, sivelestat also improved the survival rate of mice, decreased the serious degree of ferroptosis. In the endothelial cells, the results were consistent with those of the ALI mice. CONCLUSION: The study indicates that inhibiting the production of NETs can protect the normal conduction of the SDC-1/HS/HGF/cMET signalling pathway and reduce the severity of ferroptosis.


Assuntos
Lesão Pulmonar Aguda , Células Endoteliais , Armadilhas Extracelulares , Ferroptose , Lipopolissacarídeos , Camundongos Endogâmicos C57BL , Transdução de Sinais , Sindecana-1 , Animais , Ferroptose/efeitos dos fármacos , Ferroptose/fisiologia , Humanos , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Lesão Pulmonar Aguda/patologia , Lesão Pulmonar Aguda/metabolismo , Células Endoteliais/metabolismo , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/patologia , Armadilhas Extracelulares/metabolismo , Armadilhas Extracelulares/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Sindecana-1/metabolismo , Sepse/metabolismo , Sepse/patologia , Feminino , Pessoa de Meia-Idade , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Modelos Animais de Doenças
10.
J Cell Mol Med ; 28(9): e18336, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38686489

RESUMO

Diabetic kidney disease (DKD), a primary microvascular complication arising from diabetes, may result in end-stage renal disease. Epigenetic regulation of endothelial mesenchymal transition (EndMT) has been recently reported to exert function in metabolic memory and DKD. Here, we investigated the mechanism which Sirt7 modulated EndMT in human glomerular endothelial cells (HGECs) in the occurrence of metabolic memory in DKD. Lower levels of SDC1 and Sirt7 were noted in the glomeruli of both DKD patients and diabetes-induced renal injury rats, as well as in human glomerular endothelial cells (HGECs) with high blood sugar. Endothelial-to-mesenchymal transition (EndMT) was sustained despite the normalization of glycaemic control. We also found that Sirt7 overexpression associated with glucose normalization promoted the SDC1 expression and reversed EndMT in HGECs. Furthermore, the sh-Sirt7-mediated EndMT could be reversed by SDC1 overexpression. The ChIP assay revealed enrichment of Sirt7 and H3K18ac in the SDC1 promoter region. Furthermore, hypermethylated in cancer 1 (HIC1) was found to be associated with Sirt7. Overexpression of HIC1 with normoglycaemia reversed high glucose-mediated EndMT in HGECs. The knockdown of HIC1-mediated EndMT was reversed by SDC1 upregulation. In addition, the enrichment of HIC1 and Sirt7 was observed in the same promoter region of SDC1. The overexpressed Sirt7 reversed EndMT and improved renal function in insulin-treated diabetic models. This study demonstrated that the hyperglycaemia-mediated interaction between Sirt7 and HIC1 exerts a role in the metabolic memory in DKD by inactivating SDC1 transcription and mediating EndMT despite glucose normalization in HGECs.


Assuntos
Nefropatias Diabéticas , Células Endoteliais , Hiperglicemia , Fatores de Transcrição Kruppel-Like , Sirtuínas , Sindecana-1 , Sindecana-1/metabolismo , Sindecana-1/genética , Humanos , Animais , Hiperglicemia/metabolismo , Hiperglicemia/genética , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/patologia , Ratos , Masculino , Células Endoteliais/metabolismo , Sirtuínas/metabolismo , Sirtuínas/genética , Transição Epitelial-Mesenquimal/genética , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/complicações , Ratos Sprague-Dawley , Glomérulos Renais/metabolismo , Glomérulos Renais/patologia , Epigênese Genética , Regulação da Expressão Gênica , Regiões Promotoras Genéticas , Transição Endotélio-Mesênquima
11.
Neurol Neuroimmunol Neuroinflamm ; 11(3): e200230, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38669615

RESUMO

BACKGROUND AND OBJECTIVES: The aim of this study was to identify novel biomarkers for multiple sclerosis (MS) diagnosis and prognosis, addressing the critical need for specific and prognostically valuable markers in the field. METHODS: We conducted an extensive proteomic investigation, combining analysis of (1) CSF proteome from symptomatic controls, fast and slow converters after clinically isolated syndromes, and patients with relapsing-remitting MS (n = 10 per group) using label-free quantitative proteomics and (2) oligodendrocyte secretome changes under proinflammatory or proapoptotic conditions using stable isotope labeling by amino acids in cell culture. Proteins exhibiting differential abundance in both proteomic analyses were combined with other putative MS biomarkers, yielding a comprehensive list of 87 proteins that underwent quantification through parallel reaction monitoring (PRM) in a novel cohort, comprising symptomatic controls, inflammatory neurologic disease controls, and patients with MS at various disease stages (n = 10 per group). The 11 proteins that passed this qualification step were subjected to a new PRM assay within an expanded cohort comprising 158 patients with either MS at different disease stages or other inflammatory or noninflammatory neurologic disease controls. RESULTS: This study unveiled a promising biomarker signature for MS, including previously established candidates, such as chitinase 3-like protein 1, chitinase 3-like protein 2, chitotriosidase, immunoglobulin kappa chain region C, neutrophil gelatinase-associated lipocalin, and CD27. In addition, we identified novel markers, namely cat eye syndrome critical region protein 1 (adenosine deaminase 2, a therapeutic target in multiple sclerosis) and syndecan-1, a proteoglycan, also known as plasma cell surface marker CD138 and acting as chitinase 3-like protein 1 receptor implicated in inflammation and cancer signaling. CD138 exhibited good diagnostic accuracy in distinguishing MS from inflammatory neurologic disorders (area under the curve [AUC] = 0.85, CI 0.75-0.95). CD138 immunostaining was also observed in the brains of patients with MS and cultured oligodendrocyte precursor cells but was absent in astrocytes. DISCUSSION: These findings identify CD138 as a specific CSF biomarker for MS and suggest the selective activation of the chitinase 3-like protein 1/CD138 pathway within the oligodendrocyte lineage in MS. They offer promising prospects for improving MS diagnosis and prognosis by providing much-needed specificity and clinical utility. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that CD138 distinguishes multiple sclerosis from other inflammatory neurologic disorders with an AUC of 0.85 (95% CI 0.75-0.95).


Assuntos
Biomarcadores , Esclerose Múltipla Recidivante-Remitente , Sindecana-1 , Humanos , Biomarcadores/líquido cefalorraquidiano , Adulto , Feminino , Masculino , Esclerose Múltipla Recidivante-Remitente/líquido cefalorraquidiano , Esclerose Múltipla Recidivante-Remitente/diagnóstico , Pessoa de Meia-Idade , Sindecana-1/líquido cefalorraquidiano , Estudos de Coortes , Proteômica , Esclerose Múltipla/líquido cefalorraquidiano , Esclerose Múltipla/diagnóstico , Oligodendroglia/metabolismo
12.
BMC Anesthesiol ; 24(1): 154, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649813

RESUMO

BACKGROUND: Various factors can cause vascular endothelial damage during cardiovascular surgery (CVS) with cardiopulmonary bypass (CPB), which has been suggested to be associated with postoperative complications. However, few studies have specifically investigated the relationship between the degree of vascular endothelial damage and postoperative acute kidney injury (pAKI). The objectives of this study were to measure perioperative serum syndecan-1 concentrations in patients who underwent CVS with CPB, evaluate their trends, and determine their association with pAKI. METHODS: This was a descriptive and case‒control study conducted at the National University Hospital. Adult patients who underwent CVS with CPB at a national university hospital between March 15, 2016, and August 31, 2020, were included. Patients who were undergoing preoperative dialysis, had preoperative serum creatinine concentrations greater than 2.0 mg dl-1, who were undergoing surgery involving the descending aorta were excluded. The perioperative serum syndecan-1 concentration was measured, and its association with pAKI was investigated. RESULTS: Fifty-two patients were included. pAKI occurred in 18 (34.6%) of those patients. The serum syndecan-1 concentration increased after CPB initiation and exhibited bimodal peak values. The serum syndecan-1 concentration at all time points was significantly elevated compared to that after the induction of anesthesia. The serum syndecan-1 concentration at 30 min after weaning from CPB and on postoperative day 1 was associated with the occurrence of pAKI (OR = 1.10 [1.01 to 1.21], P = 0.03]; OR = 1.16 [1.01 to 1.34], P = 0.04]; and the cutoff values of the serum syndecan-1 concentration that resulted in pAKI were 101.0 ng ml-1 (sensitivity = 0.71, specificity = 0.62, area under the curve (AUC) = 0.67 (0.51 to 0.83)) and 57.1 ng ml-1 (sensitivity = 0.82, specificity = 0.56, AUC = 0.71 (0.57 to 0.86)). Multivariate logistic regression analysis revealed that the serum syndecan-1 concentration on postoperative day 1 was associated with the occurrence of pAKI (OR = 1.02 [1.00 to 1.03]; P = 0.03). CONCLUSION: The serum syndecan-1 concentration at all time points was significantly greater than that after the induction of anesthesia. The serum syndecan-1 concentration on postoperative day 1 was significantly associated with the occurrence of pAKI. TRIAL REGISTRATION: This study is not a clinical trial and is not registered with the registry.


Assuntos
Injúria Renal Aguda , Ponte Cardiopulmonar , Complicações Pós-Operatórias , Sindecana-1 , Humanos , Sindecana-1/sangue , Masculino , Ponte Cardiopulmonar/efeitos adversos , Feminino , Injúria Renal Aguda/sangue , Injúria Renal Aguda/etiologia , Estudos Retrospectivos , Pessoa de Meia-Idade , Complicações Pós-Operatórias/sangue , Idoso , Estudos de Casos e Controles , Procedimentos Cirúrgicos Cardiovasculares/efeitos adversos
13.
Microvasc Res ; 154: 104683, 2024 07.
Artigo em Inglês | MEDLINE | ID: mdl-38522507

RESUMO

BACKGROUND: Microvascular dysfunction plays a central role in organ dysfunction during septic shock. Endothelial glycocalyx (eGC) damage could contribute to impaired microcirculation. The aim was to assess whether several eGC-damaged biomarkers are associated with microvascular dysfunction in resuscitated septic shock patients. METHODS: This cross-sectional study included resuscitated septic shock patients (N = 31), and a group of healthy individuals (N = 20). The eGC damage biomarkers measured were syndecan-1 (SDC-1), soluble CD44 (CD44s), hyaluronic acid (HYAL) in blood sample; sulfated glycosaminoglycans (GAGs) in urine sample; and thrombomodulin (TBML) in blood sample as biomarker of endothelial cell damage. Microcirculation was assessed through sublingual videocapillaroscopy using the GlycoCheck™, which estimated the perfused vascular density (PVD); the perfused boundary region (PBR), an inverse parameter of the eGC thickness; and the microvascular health score (MVHS). We defined a low MVHS (<50th percentile in septic patients) as a surrogate for more impaired microvascular function. RESULTS: The SDC-1, CD44s, TBML and GAGs levels were correlated with impaired microvascular parameters (PVD of vessels with diameter < 10 µm, MVHS and flow-adjusted PBR); p < 0.05 for all comparisons, except for GAGs and flow-adjusted PBR. The SDC-1 [78 ng/mL (interquartile range (IQR) 45-336) vs. 48 ng/mL (IQR 9-85); p = 0.052], CD44s [796ρg/mL (IQR 512-1995) vs. 526ρg/mL (IQR 287-750); p = 0.036], TBML [734ρg/mL (IQR 237-2396) vs. 95ρg/mL (IQR 63-475); p = 0.012] and GAGs levels [0.42 ρg/mg (IQR 0.04-1.40) vs. 0.07 ρg/mg (IQR 0.02-0.20); p = 0.024]; were higher in septic patients with more impaired sublingual microvascular function (low MVHS vs. high MVHS). CONCLUSION: SDC-1, CD44s, TBML and GAGs levels were associated with impaired microvascular function in resuscitated septic shock patients.


Assuntos
Biomarcadores , Glicocálix , Receptores de Hialuronatos , Ácido Hialurônico , Microcirculação , Choque Séptico , Sindecana-1 , Trombomodulina , Humanos , Glicocálix/metabolismo , Choque Séptico/fisiopatologia , Choque Séptico/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Biomarcadores/sangue , Sindecana-1/sangue , Estudos Transversais , Receptores de Hialuronatos/metabolismo , Idoso , Trombomodulina/sangue , Ácido Hialurônico/sangue , Estudos de Casos e Controles , Ressuscitação , Glicosaminoglicanos , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Angioscopia Microscópica , Microvasos/fisiopatologia , Microvasos/patologia , Adulto , Densidade Microvascular , Soalho Bucal/irrigação sanguínea
14.
Anticancer Res ; 44(4): 1611-1618, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38537984

RESUMO

BACKGROUND/AIM: A three-dimensional network constructed using glycocalyx (GCX) extends throughout the cancer cell nest in human colorectal cancer (CRC). GCX was found to be closely related to cancer. We examined the prognostic correlation and potential of syndecan-1 (SDC1), a representative proteoglycan of GCX, as a biomarker. PATIENTS AND METHODS: We analyzed SDC1 in the transcriptomic profiles of a major publicly available CRC cohort from The Cancer Genome Atlas (TCGA) using a computational algorithm. We investigated serum SDC1 levels preoperatively and on postoperative day seven in 48 patients with stage I-III CRC who underwent surgery during July-December 2019 at Gifu University Hospital. RESULTS: For TCGA, no significant differences existed between the high and low SDC1 expression groups regarding disease-free, disease-specific, and overall survival for stage I-III, and only overall survival for stage IV was significantly different. In our study, among the 48 patients, 17 (no recurrence), 13 (1 recurrence), and 18 (10 recurrences) had stage I-III, respectively. Preoperative and postoperative day 7 SDC1 levels for patients with stage I-III were 10.7±2.3 and 9.9±3.1 ng/ml (p=0.40), 11.1±1.7 and 10.1±0.8 ng/ml (p=0.07), and 10.3±2.0 and 9.5±1.4 ng/ml (p=0.15), respectively. In stage II and III, patients were divided into two groups according to differences between preoperative and postoperative SDC1 levels (SDC1pre-pro). SDC1pre-pro ≤0 group significantly prolonged disease-free survival compared with SDC1pre-pro >0 group (p=0.048). CONCLUSION: Dynamic change in serum SDC1 levels serves as a prognostic biomarker for stage II and III colorectal cancer.


Assuntos
Neoplasias Colorretais , Sindecana-1 , Humanos , Biomarcadores Tumorais/sangue , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/cirurgia , Intervalo Livre de Doença , Prognóstico , Sindecana-1/sangue
15.
Acta Neurochir (Wien) ; 166(1): 153, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38536487

RESUMO

BACKGROUND: Previously, we revealed noticeable dynamic fluctuations in syndecan-1 levels in the peripheral blood of post-stroke patients. We further investigated the clinical prognostic value of syndecan-1 as a biomarker of glycoprotein damage in patients with acute ischaemic stroke (AIS). METHODS: We examined 105 patients with acute large vessel occlusion in the anterior circulation, all of whom underwent mechanical thrombectomy (MT). Peripheral blood syndecan-1 levels were measured 1 day after MT, and patients were categorised into favourable and unfavourable prognostic groups based on the 90-day modified Rankin Scale (mRS) score. Additionally, we compared the clinical outcomes between groups with high and low syndecan-1 concentrations. RESULTS: The findings revealed a significantly lower syndecan-1 level in the group with an unfavourable prognosis compared to those with a favourable prognosis (p < 0.01). In the multivariable logistic regression analysis, lower syndecan-1 levels were identified as a predictor of unfavourable prognosis (odds ratio (OR) = 0.965, p = 0.001). Patients displaying low syndecan-1 expression in the peripheral blood (< 29.51 ng/mL) experienced a > twofold increase in the rates of unfavourable prognosis and mortality. CONCLUSIONS: Our study demonstrates that syndecan-1, as an emerging, easily detectable stroke biomarker, can predict the clinical outcomes of patients with AIS. After MT, low levels of syndecan-1 in the peripheral blood on the first day emerged as an independent risk factor for an unfavourable prognosis, suggesting that lower syndecan-1 levels might signify worse clinical presentation and outcomes in stroke patients undergoing this procedure.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Sindecana-1 , Humanos , Biomarcadores , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/cirurgia , AVC Isquêmico/complicações , AVC Isquêmico/diagnóstico , AVC Isquêmico/cirurgia , Prognóstico , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/cirurgia , Acidente Vascular Cerebral/etiologia , Sindecana-1/sangue , Sindecana-1/química , Trombectomia/efeitos adversos , Resultado do Tratamento
16.
Head Neck Pathol ; 18(1): 23, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38504068

RESUMO

BACKGROUND: Dysregulation of the MAPK pathway appears to exert a pivotal role in the pathogenesis of ameloblastomas, since BRAF p.V600E has been reported in over 65% of the tumors. Therefore, the purpose of this study was to investigate whether the BRAF p.V600E is related to biological behavior and disease-free survival in patients with conventional ameloblastomas. METHODS: This is a retrospective cohort study based on the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) recommendations. The study population consisted of individuals treated for conventional ameloblastomas. Clinical, imaging, histomorphological, immunohistochemical (Ki67 and CD138/syndecan-1), and molecular BRAF p.V600E mutation analyses were performed. Bivariate statistical analysis was performed through chi-square and Fisher's exact tests. Kaplan-Meier analysis with log-rank test and Cox proportional hazards regression were used to identify predictors of disease-free survival, with a significance level of 5%. RESULTS: Forty-one individuals were included, with a male-to-female ratio of 1.15:1. BRAF p.V600E mutation was identified in 75.6% of the tumors. No association between the BRAF mutational status and other clinical, imaging, histomorphological, and immunohistochemical variables was observed. Only the initial treatment modality was significantly associated with a better prognosis in univariate (p = 0.008) and multivariate (p = 0.030) analyses, with a hazard ratio of 9.60 (95%IC = 1.24-73.89), favoring radical treatment. CONCLUSION: BRAF p.V600E mutation emerges as a prevalent molecular aberration in ameloblastomas. Nevertheless, it does not seem to significantly affect the tumor proliferative activity, CD138/syndecan-1-mediated cell adhesion, or disease-free survival outcomes.


Assuntos
Ameloblastoma , Humanos , Masculino , Feminino , Intervalo Livre de Doença , Ameloblastoma/genética , Ameloblastoma/patologia , Proteínas Proto-Oncogênicas B-raf/genética , Sindecana-1/genética , Estudos Retrospectivos , Mutação
17.
PLoS Negl Trop Dis ; 18(3): e0012071, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38536887

RESUMO

Dengue shock (DS) is the most severe complication of dengue infection; endothelial hyperpermeability leads to profound plasma leakage, hypovolaemia and extravascular fluid accumulation. At present, the only treatment is supportive with intravenous fluid, but targeted endothelial stabilising therapies and host immune modulators are needed. With the aim of prioritising potential therapeutics, we conducted a prospective observational study of adults (≥16 years) with DS in Vietnam from 2019-2022, comparing the pathophysiology underlying circulatory failure with patients with septic shock (SS), and investigating the association of biomarkers with clinical severity (SOFA score, ICU admission, mortality) and pulmonary vascular leak (daily lung ultrasound for interstitial and pleural fluid). Plasma was collected at enrolment, 48 hours later and hospital discharge. We measured biomarkers of inflammation (IL-6, ferritin), endothelial activation (Ang-1, Ang-2, sTie-2, VCAM-1) and endothelial glycocalyx breakdown (hyaluronan, heparan sulfate, endocan, syndecan-1). We enrolled 135 patients with DS (median age 26, median SOFA score 7, 34 required ICU admission, 5 deaths), together with 37 patients with SS and 25 healthy controls. Within the DS group, IL-6 and ferritin were associated with admission SOFA score (IL-6: ßeta0.70, p<0.001 & ferritin: ßeta0.45, p<0.001), ICU admission (IL-6: OR 2.6, p<0.001 & ferritin: OR 1.55, p<0.001) and mortality (IL-6: OR 4.49, p = 0.005 & ferritin: OR 13.8, p = 0.02); both biomarkers discriminated survivors and non-survivors at 48 hours and all patients who died from DS had pre-mortem ferritin ≥100,000ng/ml. IL-6 most strongly correlated with severity of pulmonary vascular leakage (R = 0.41, p<0.001). Ang-2 correlated with pulmonary vascular leak (R = 0.33, p<0.001) and associated with SOFA score (ß 0.81, p<0.001) and mortality (OR 8.06, p = 0.002). Ang-1 was associated with ICU admission (OR 1.6, p = 0.005) and mortality (OR 3.62, p = 0.006). All 4 glycocalyx biomarkers were positively associated with SOFA score, but only syndecan-1 was associated with ICU admission (OR 2.02, p<0.001) and mortality (OR 6.51, p<0.001). This study highlights the central role of hyperinflammation in determining outcomes from DS; the data suggest that anti-IL-1 and anti-IL-6 immune modulators and Tie2 agonists may be considered as candidates for therapeutic trials in severe dengue.


Assuntos
Sepse , Dengue Grave , Choque Séptico , Adulto , Humanos , Sindecana-1 , Estudos Prospectivos , Vietnã/epidemiologia , Interleucina-6 , Biomarcadores , Ferritinas , Prognóstico , Unidades de Terapia Intensiva , Sepse/complicações
18.
Int Immunopharmacol ; 132: 111828, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38552294

RESUMO

PURPOSE: Urethral hypospadias, a common congenital malformation in males, is closely linked with disruptions in uroepithelial cell (UEC) processes. Evidence exists reporting that urine-derived exosomes (Urine-Exos) enhance UEC proliferation and regeneration, suggesting a potential role in preventing hypospadias. However, the specific influence of Urine-Exos on urethral hypospadias and the molecular mechanisms involved are not fully understood. This study focuses on investigating the capability of Urine-Exos to mitigate urethral hypospadias and aims to uncover the underlying molecular mechanisms. METHODS: Bioinformatics analysis was performed to identify key gene targets in Urine-Exos potentially involved in hypospadias. Subsequent in vitro and in vivo experiments were conducted to validate the regulatory effects of Urine-Exos on hypospadias. RESULTS: Bioinformatics screening revealed syndecan-1 (SDC1) as a potential pivotal gene for the prevention of hypospadias. In vitro experiments demonstrated that Urine-Exos enhanced the proliferation and migration of UECs by transferring SDC1 and inhibiting cell apoptosis. Notably, Urine-Exos upregulated ß-catenin expression through SDC1 transfer, further promoting UEC proliferation and migration. These findings were confirmed in a congenital hypospadias rat model induced by di(2-ethylhexyl) phthalate (DEHP). CONCLUSION: This study reveals the therapeutic potential of Urine-Exos in hypospadias, mediated by the SDC1/ß-catenin axis. Urine-Exos promote UEC proliferation and migration, thereby inhibiting the progression of hypospadias. These findings offer new insights and potential therapeutic targets for the management of congenital malformations.


Assuntos
Proliferação de Células , Exossomos , Hipospadia , Sindecana-1 , beta Catenina , Hipospadia/metabolismo , Exossomos/metabolismo , Animais , Masculino , Humanos , Sindecana-1/metabolismo , Ratos , beta Catenina/metabolismo , beta Catenina/genética , Ratos Sprague-Dawley , Células Epiteliais/metabolismo , Apoptose , Movimento Celular , Modelos Animais de Doenças , Urina
19.
Immunogenetics ; 76(3): 145-154, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38451352

RESUMO

Syndecan-1 (Sdc-1), a transmembrane heparan sulfate protein, is implicated in several pathophysiological processes including rheumatoid arthritis (RA). The exact role of Syndican-1 in this autoimmune disease is still undetermined. This study explores the involvement level of Sdc-1 in the development of RA in a collagen II-induced arthritis mice model. RA was induced in two mice strains (wild-type BALB/c group and Sdc-1 knockout) by collagen II. Mice underwent regular clinical observations and scoring. After sacrifice, leg biopsies were taken from mice for histological examination, using a variety of stains. In addition, proteins were extracted, and molecular assessment of TNF-α was performed using the western blot technique. In the Sdc-1 knockout group, clinical scoring results showed a significantly more severe experimental RA; histology showed a significant increase in bone erosion, cartilage destruction, inflammation, and less granulated mast cells than the wild-type. In addition, molecular assessment of TNF-α showed more increase in expression in the Sdc-1 knockout models compared to the wild-type. Data suggest that lack of Sdc-1 enhances the inflammatory characteristics in RA. However, more molecular studies and investigations are needed to determine its exact role and possible mechanisms involved.


Assuntos
Artrite Experimental , Artrite Reumatoide , Sindecana-1 , Fator de Necrose Tumoral alfa , Animais , Masculino , Camundongos , Artrite Experimental/genética , Artrite Experimental/patologia , Artrite Experimental/imunologia , Artrite Reumatoide/genética , Artrite Reumatoide/patologia , Artrite Reumatoide/metabolismo , Artrite Reumatoide/imunologia , Colágeno Tipo II/genética , Modelos Animais de Doenças , Camundongos Endogâmicos BALB C , Camundongos Knockout , Sindecana-1/genética , Sindecana-1/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/genética
20.
PLoS One ; 19(2): e0294918, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38408050

RESUMO

BACKGROUND: Variation of circulating concentrations of putative biomarkers of intestinal barrier function over the day and after acute physiological interventions are poorly documented on humans. This study aimed to examine the stability and pharmacokinetics of changes in plasma concentrations of intestinal Fatty-acid -binding -protein (IFABP), Lipopolysaccharide-binging-protein (LBP), soluble CD14, and Syndecan-1 after acute stress and high fat-high-carbohydrate meal. METHODS: In a single-blinded, cross-over, randomised study, healthy volunteers received on separate days corticotropin-releasing hormone (CRH, 100 µg) or normal saline (as placebo) intravenously in random order, then a HFHC meal. Participants were allowed low caloric food. Markers of intestinal barrier function were measured at set timed intervals from 30 minutes before to 24 hours after interventions. RESULTS: 10 participants (50% female) completed all three arms of the study. IFABP decreased by median 3.6 (IQR 1.4-10)% from -30 minutes to zero time (p = 0.001) and further reduced by 25 (20-52)% at 24 hours (p = 0.01) on the low caloric diet, but did not change in response to the meal. Syndecan-1, LBP and sCD14 were stable over a 24-hour period and not affected acutely by food intake. LBP levels 2 hours after CRH reduced by 0.61 (-0.95 to 0.05) µg/ml compared with 0.16 (-0.3 to 0.5) µg/ml post placebo injection (p = 0.05), but other markers did not change. CONCLUSION: Concentrations of IFABP, but not other markers, are unstable over 24 hours and should be measured fasting. A HFHC meal does not change intestinal permeability. Transient reduction of LPB after CRH confirms acute barrier dysfunction during stress.


Assuntos
Hormônio Liberador da Corticotropina , Sindecana-1 , Humanos , Feminino , Masculino , Hormônio Liberador da Corticotropina/metabolismo , Função da Barreira Intestinal , Lipopolissacarídeos , Biomarcadores
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