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1.
Ann Med ; 51(7-8): 333-344, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31714153

RESUMO

Albumin is the most abundant plasma protein and albumin infusion is commonly used. Conventionally, the biologic and therapeutic effects of albumin have been thought to be due to its oncotic properties. However, albumin has a variety of biologic functions, including molecular transport, anti-oxidation, anti-inflammation, endothelial stabilisation, anti-thrombotic effects, and the adjustment of capillary permeability. Despite this, the functions of albumin have not been thoroughly investigated. Recent studies have shown non-alcoholic fatty liver disease (NAFLD), viral hepatitis, cirrhosis, and liver failure to be associated with impairments in albumin function, which are associated with impairments in liver function and disease prognosis. Post-translational modifications of albumin cause structural modifications that affect protein function. Recently, the concentration of albumin associated with normal function, the 'efficient albumin concentration', has been attracting more interest. In addition, although many biologic markers, including albumin concentration, are widely used for the assessment of early liver dysfunction in patients with liver diseases, the predictive values are unsatisfactory. However, clinical evidence has suggested that albumin function may represent a novel biomarker of early impairment in liver function. In this review, we summarise the factors affecting albumin function and discuss the clinical significance of impairments in albumin function in various liver diseases.Key messagesThe importance of albumin depends not only on its concentration, but also on its various physiological functions.Impaired albumin function has been reported in a variety of liver diseases, and is associated with disease severity and prognosis, thereby proposing the concept of 'effective albumin concentration'.Albumin dysfunction occurs earlier than other conventional indicators, and albumin dysfunction may be a new biomarker of early impairment in liver function.Many exogenous and endogenous factors lead to post-translational modifications of albumin, which alters the three-dimensional structure of albumin, resulting in a decrease in its biological activity.

2.
Front Oncol ; 9: 897, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31620360

RESUMO

Background: Recently, blockade of immune checkpoint has emerged as one of the most potential treatments for solid tumors. Programmed cell death ligand 1(PD-L1), a member of the B7 family of molecules, plays a crucial role in tumor immunobiology. However, the prognostic significance of PD-L1 in cholangiocarcinoma (CCA) patients remains controversial. This study aimed to inquire into the prognostic and clinicopathological significance of PD-L1 in CCA via a meta-analysis. Methods: We searched PubMed, the Cochrane Library, Embase, Web of Science and Google Scholar up to April 2019, regardless of the region or language, for studies on the correlation between clinicopathology/prognosis and PD-L1 in patients with CCA. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to investigate the prognostic significance of PD-L1 expression in cholangiocarcinoma. The odds ratios (ORs) were also determined to explore the association between PD-L1 expression and clinicopathological features. Results: Our meta-analysis included 11 studies with 1,066 patients. The meta-analysis of these studies indicated a trend that high PD-L1 expression indicated a poor OS, but the result was not statistically significant (HR = 1.62, 95% CI [0.98-2.68], p = 0.063). For DFS, although the pooled result is not statistically significant, it trends toward being significant that high PD-L1 expression indicated improved DFS (HR = 0.80, 95% CI [0.62, 1.04], p = 0.092). In subgroup analyses, the results were not consistent across the subgroups that were divided based on the publication year (before 2018: HR = 1.92, 95% CI [1.34-2.75], p < 0.001; after 2018: HR = 1.42, 95% CI [0.70-2.89], p = 0.335). Moreover, PD-L1 expression in TCs significantly correlated with the AJCC TNM stage of CCA (OR = 0.52, 95% CI [0.27, 0.99], p = 0.09). Conclusion: Our meta-analyses revealed that PD-L1 expressed in TCs was significantly correlated with the AJCC TNM stage of CCA. Based on the included studies, we found that PD-L1 indeed expressed in both TCs and ICs in CCA patients, raising the possibility of the use of anti-PD-1/PD-L1 therapy for CCA patients. In contrast, expression of PD-L1 did not seem to be associated with patient outcome in our study. The prognostic role of PD-L1 in CCA demands further investigation.

3.
Front Oncol ; 9: 47, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30891423

RESUMO

Background: Immune checkpoint inhibitors targeting the programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway are a paradigm-shifting cancer therapy. Programmed cell death ligand 2 (PD-L2) is another ligand of PD-1, but its prognostic significance in solid cancer patients after surgery remains controversial. In this study, we aimed to reveal the prognostic implication of PD-L2 in solid tumors through a meta-analysis. Methods: We searched PubMed, Embase and the Cochrane library for studies reporting the relationship between PD-L2 expression and prognosis or clinicopathological features in solid cancer patients after surgery from inception to January 2018, with language restricted to English. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were determined to explore the prognostic value of PD-L2 expression. Odds ratios (ORs) were also calculated to investigate the relationship between PD-L2 expression and clinicopathological parameters. Results: Sixteen studies incorporating 3,533 patients were included in our meta-analysis. The pooled results revealed that PD-L2 overexpression was a weak negative predictor for overall survival (OS; HR = 1.38, 95% CI = 1.05-1.81, P = 0.021), as well as a strong predictor for poor disease-free survival (DFS)/progression-free survival (PFS) (HR = 1.44, 95% CI = 1.15-1.81, P = 0.001). In subgroup analyses, high PD-L2 expression revealed an unfavorable prognostic prediction for OS in hepatocellular carcinoma (HCC) (HR = 1.60, 95% CI = 1.12-2.29, P = 0.011) and for DFS/PFS in HCC (HR = 1.50, 95%CI = 1.04-2.16, P = 0.031) as well as clear cell renal cell carcinoma (HR = 1.45, 95% CI = 1.03-2.03, P = 0.033). Moreover, PD-L2 expression implied a weak trend toward the presence of lymphatic metastasis (presence vs. absence, OR = 1.61, 95% CI = 0.98-2.65, P = 0.061). Conclusion: High PD-L2 expression may promote tumor metastasis and predict unfavorable prognosis in solid cancer patients after surgery, especially in HCC.

4.
Pediatr Res ; 85(4): 518-526, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30188503

RESUMO

BACKGROUND: Time-restricted feeding regimen (TRF), that is, no food consumption for 14-16 h during the light phase per day, attenuates the fattening traits and metabolic disorders in adults. This study aims to further investigate whether TRF would be protective against similar nutritional challenges in juvenile mice. METHODS: Mice in the experimental group were treated with TRF during the first 4 weeks (considered to be the childhood phase of mice) before switching to ad libitum (AD) feeding pattern as adults; the control group with all subjects sticks to AD mode. Body weight was monitored, and serum biochemistry, sexual maturity, immune function, and gut microbiota were assessed at a certain timing. RESULTS: Mice treated with TRF during the childhood period (from weaning age) but went through AD feeding pattern as adults demonstrated the tendency of higher body weight, higher levels of serum glucose, shrunken Langerhans islets, fatty liver disease, thickening of aortic walls, delayed sexual development, increased proportion of T regulatory cells, and unhealthy gut microbiota. CONCLUSION: Childhood TRF causes pleiotropic adverse effects, including severe irreversible metabolic disorders, depressed immune function, and retarded puberty. Microbiota set the stage for TRF to employ downstream reactions on the above changes.

7.
Front Physiol ; 9: 536, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29867575

RESUMO

Neurogenic airway inflammation in chronic cough and bronchial asthma related to gastroesophageal reflux (GER) is involved in the esophageal-bronchial reflex, but it is unclear whether this reflex is mediated by central neurons. This study aimed to investigate the regulatory effects of the dorsal vagal complex (DVC) on airway inflammation induced by the esophageal perfusion of hydrochloric acid (HCl) following the microinjection of nuclei in the DVC in guinea pigs. Airway inflammation was evaluated by measuring the extravasation of Evans blue dye (EBD) and substance P (SP) expression in the airway. Neuronal activity was indicated by Fos expression in the DVC. The neural pathways from the lower esophagus to the DVC and the DVC to the airway were identified using DiI tracing and pseudorabies virus Bartha (PRV-Bartha) retrograde tracing, respectively. HCl perfusion significantly increased plasma extravasation, SP expression in the trachea, and the expression of SP and Fos in the medulla oblongata nuclei, including the nucleus of the solitary tract (NTS) and the dorsal motor nucleus of the vagus (DMV). The microinjection of glutamic acid (Glu) or exogenous SP to enhance neuronal activity in the DVC significantly potentiated plasma extravasation and SP release induced by intra-esophageal perfusion. The microinjection of γ-aminobutyric acid (GABA), lidocaine to inhibit neuronal activity or anti-SP serum in the DVC alleviated plasma extravasation and SP release. In conclusion, airway inflammation induced by the esophageal perfusion of HCl is regulated by DVC. This study provides new insight for the mechanism of airway neurogenic inflammation related to GER.

8.
Front Physiol ; 9: 452, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29765332

RESUMO

Background and Objective: Galectin-9 (Gal-9) is one of the galectin family members which are known as proteins with ß-galactoside-binding affinity. Accumulative evidence suggest that Gal-9 plays multifaceted roles in tumor biology. However, the prognostic significance of Gal-9 in solid cancer patients remains controversial. The objective of the study was to clarify the prognostic significance of Gal-9 in solid tumors via meta-analysis. Methods: We searched PubMed, Embase and the Cochrane library for studies that report the correlation between Gal-9 expression and prognosis or clinicopathological parameters in solid cancer patients from inception to October 2017, with no language restriction. We calculated pooled hazard ratio (HR) and 95% confidence interval (CI) to investigate the prognostic significance of Gal-9 expression in solid tumors. We also calculated Odds ratio (OR) to explore the association between Gal-9 expression and clinicopathological features. Results: We included Fourteen studies with 2326 patients in our meta-analysis. The synthetic results revealed that high Gal-9 expression indicated improved overall survival (OS; HR = 0.70, 95% CI = 0.51-0.71, P = 0.006) but had no correlation with disease-free survival (DFS)/recurrence-free survival (RFS) (HR = 0.85, 95% CI = 0.51-1.41, P = 0.527) in solid tumors. In stratified analyses, high Gal-9 expression was significantly correlated with improved OS in hepatocellular carcinoma and colon cancer and with improved DFS/RFS in gastric cancer and non-small cell lung cancer. In addition, ethnicity and the method of data extraction didn't affect the positive prognostic values of high Gal-9 expression. Moreover, high Gal-9 expression was significantly correlated with a smaller depth of invasion (TI/TII vs. TIII/TIV, OR = 2.80, 95% CI = 1.97-3.96, P < 0.001), an earlier histopathological stage (I/II vs. III/IV, OR = 3.00, 95% CI = 2.04-4.42, P < 0.001), negative lymph node metastasis (Presence vs. Absence, OR = 0.47, 95% CI = 0.25-0.89, P = 0.020) and negative distal tumor metastasis (Presence vs. Absence, OR = 13.85, 95% CI = 3.50-54.76, P < 0.001). Conclusion: Gal-9 expression indicates beneficial outcome in patients with solid tumors and is correlated with the pathogenesis of solid tumors. Gal-9 may serve as a prognostic biomarker and an emerging therapeutic target against solid tumors.

10.
Ann Transl Med ; 6(Suppl 2): S116, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30740437
11.
Physiol Res ; 66(6): 1021-1028, 2017 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-28937249

RESUMO

Neuronal activity in the medulla oblongata and neurogenic inflammation of airways were investigated in a guinea pig model induced by repeated intra-esophageal instillation of hydrochloric acid (HCl) after vagotomy. Unilateral vagotomy was performed in the vagotomy group, while a sham-operation was performed in the sham group. Operation was not conducted in sham control group. Airway inflammation was observed with hematoxylin and eosin (HE) staining. C-fos protein was measured by immunohistochemistry (IHC) and Western blot (WB). Substance P was examined by IHC and enzyme-linked immuno sorbent assay (ELISA). Airway microvascular permeability was detected by evans blue dye (EBD) fluorescence. Inflammation of airway was observed in the trachea and bronchi after chronic HCl perfusion into the lower esophagus, and was alleviated after unilateral vagotomy. C-fos expression in the medulla oblongata was lower in the vagotomy group compared to the sham control and sham groups. Substance P-like immunoreactivity (SP-li), concentration and microvascular leakage in airway were lower in the vagotomy group than that in the other groups. Our results suggest that vagotomy improved neurogenic inflammation of airways and decreased neuronal activities, the afferent nerves and neurons in medulla oblongata may be involved in neurogenic inflammation of airways mediated by esophageal-bronchial reflex.


Assuntos
Esôfago/inervação , Ácido Clorídrico , Pulmão/inervação , Bulbo/fisiopatologia , Inflamação Neurogênica/cirurgia , Pneumonia Aspirativa/cirurgia , Vagotomia , Animais , Permeabilidade Capilar , Cobaias , Pulmão/metabolismo , Masculino , Bulbo/metabolismo , Inflamação Neurogênica/induzido quimicamente , Inflamação Neurogênica/fisiopatologia , Pneumonia Aspirativa/induzido quimicamente , Pneumonia Aspirativa/fisiopatologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Reflexo Anormal , Substância P/metabolismo
12.
Oncotarget ; 8(24): 39658-39672, 2017 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-28487498

RESUMO

The clinicopathologic and prognostic significance of regulatory T cells (Tregs) in patients with hepatocellular carcinoma (HCC) remains controversial. We performed a meta-analysis to resolve this issue. PubMed, Embase, Cochrane library, and the Web of Science were searched to identify eligible studies performed up to November 2016. A total of 3,854 HCC patients from 27 cohort studies were included. The meta-analysis revealed that high levels of Tregs were associated with poor overall survival (OS; HR = 1.95, P < 0.00001) and disease-free survival (DFS; HR = 1.82, P < 0.00001). However, the prognostic effect varied greatly according to the site of the Tregs. Higher intratumoral and peripheral blood levels of Tregs were associated with shorter OS and DFS, whereas a high peritumoral Tregs level was not associated with decreased OS and DFS. Trial design, therapy and method of detection had no effect on prognosis of Tregs. Moreover, the patients with high Tregs infiltration had multiple tumors, high AFP level, poor differentiation, later TNM stage, and vascular invasion. The present study demonstrates that high levels of intratumoral and peripheral blood Tregs predict multiple tumors, high AFP level, poor differentiation, later TNM stage, and vascular invasion and might be a promising prognostic factor in patients with HCC.


Assuntos
Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Linfócitos T Reguladores/imunologia , Carcinoma Hepatocelular/imunologia , Humanos , Neoplasias Hepáticas/imunologia , Prognóstico
13.
Oncotarget ; 8(66): 110406-110414, 2017 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-29299157

RESUMO

Background: Although patients with Barcelona clinic liver cancer stage B or C hepatocellular carcinoma derive survival benefit from hepatectomy, prognostic factors and management after curative resection are unclear. This study aims to evaluate predictive factors, therapy and prognosis of intra-hepatic recurrences after curative resection of Barcelona clinic liver cancer stage B or C hepatocellular carcinoma. Methods: We retrospectively analyzed 397 patients with Barcelona clinic liver cancer stage B or C hepatocellular carcinoma who underwent curative resections from January 1989 to October 2011. Intra-hepatic recurrences were classified into early (<2 year) and late (≥2 year) recurrences. Results: Overall survival rates in our cohort were 1-year: 81.4%; 3-year: 48.5%; and 5-year: 28.2%. Early and late intra-hepatic recurrences developed in 104 patients and 73 patients, respectively. In univariate analysis, overall survival for the non-recurrence group was significantly better than for the recurrence group (P<0.001), and overall survival for the late recurrence group was significantly better than for the early recurrence group (P<0.001). In multivariate analysis, total tumor size, tumor number and vascular invasion were significant risk factors for tumor recurrence (P<0.001). The overall survival of patients with late recurrence who received curative treatment was comparable to those who never had tumor recurrences (P=0.140). Conclusion: Time to recurrence and feasibility of curative treatment are the best determinants for prognosis in Barcelona clinic liver cancer stage B or C hepatocellular carcinoma. Curative treatments may prolong overall survival of patients with late recurrences, but should be avoided for those with early recurrences.

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