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1.
J Gastrointest Surg ; 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32128681

RESUMO

BACKGROUND: To define early versus late recurrence based on post-recurrence survival (PRS) among patients undergoing curative resection for hepatocellular carcinoma (HCC). METHODS: Patients who underwent curative-intent resection for HCC between 2000 and 2017 were identified from an international multi-institutional database. The optimal cut-off time point to discriminate early versus late recurrence was determined relative to PRS. RESULTS: Among 1004 patients, 443 (44.1%) patients experienced recurrence with a median recurrence-free survival time of 12 months. A cut-off time point of 8 months was defined as the optimal threshold based on sensitivity analyses relative to PRS for early (n = 165, 37.2%) versus late relapse (n = 278, 62.8%) (p = 0.008). Early recurrence was associated with worse PRS (median PRS, 27.0 vs. 43.0 months, p = 0.019), as well as overall survival (OS) (median OS, 32.0 versus 74.0 months, p < 0.001) versus late recurrence. In addition, patients who recurred early were more likely to recur at extra- ± intrahepatic (35.5% vs. 19.8%, p = 0.003) sites and were less likely to have the recurrence treated with curative intent (33.8% vs. 45.7%, p = 0.08). Patients undergoing curative re-treatment of late recurrence had a comparable OS with patients who had no recurrence (median OS, 139.0 vs. 140.0 months); patients with early recurrence had inferior OS after curative re-treatment versus patients with no recurrence (median OS, 69.0 vs. 140.0 months, p = 0.036), yet still better than patients who received palliative treatment for early recurrence (median OS, 69.0 vs. 21.0 months, p < 0.001). CONCLUSIONS: Eight months was identified as the cut-off value to differentiate early versus late recurrence. Curative-intent treatment for recurrent intrahepatic tumors was associated with reasonable long-term outcomes.

2.
Int Immunopharmacol ; 82: 106377, 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32163858

RESUMO

BACKGROUND: CTLA-4 is involved in the immune dysfunction of hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC). This study analyzed the association of circulating CTLA-4 levels and CTLA4 polymorphisms with disease condition and progression in chronic HBV infection. METHODS: Serum CTLA-4 levels and CTLA4 rs231775 and rs5742909 polymorphisms were determined in patients with various HBV-related diseases [53 asymptomatic HBV carrier status (ASC), 147 chronic hepatitis, 130 cirrhosis and 102 HCC] and nearly a 10-year follow-up. RESULTS: Serum CTLA-4 levels were stepwisely increased from ASC, chronic hepatitis, cirrhosis to HCC and independently associated with HCC (OR 2.628, P < 0.001). HCC patients had lower frequencies of rs231775 genotype GA, genotype AA and allele A than ASC, chronic hepatitis and cirrhosis patients. Rs231775 genotype GG was independently associated with HCC (OR 2.324, P = 0.010) and higher CTLA-4 levels in patients with HBV infection. In the follow-up, higher baseline CTLA-4 levels and CTLA4 rs231775 genotype GG significantly associated with disease progression from chronic hepatitis to cirrhosis (OR 2.561, P = 0.011 and OR 2.799, P = 0.015, respectively) or from cirrhosis to HCC (OR 2.673, P = 0.008 and OR 2.097, P = 0.023, respectively) and with a shorter overall survival in HCC patients (HR 0.317, P = 0.018 and HR 0.682, P = 0.026, respectively). Rs5742909 had no significant association with CTLA-4 levels and disease progression. CONCLUSION: CTLA-4 levels and CTLA4 rs231775 polymorphism associate with the disease condition and progression and HCC development in chronic HBV infection and their determination may be used for monitoring disease progression and predicting patient prognosis.

3.
Biomed Pharmacother ; 126: 110101, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32199226

RESUMO

BACKGROUND: Abnormal activation of pancreatic stellate cells (PSCs) plays a crucial role in the pathogenesis of chronic pancreatitis (CP). Irisin, an exercise-induced hormone, has been shown to mitigate liver fibrosis by inhibiting the activation of hepatic stellate cells. However, the effect of irisin in CP has not been evaluated. METHODS: This study aimed to determine whether irisin is protective in CP. CP was induced by 6 IP injections of cerulein (50 µg/kg/body weight). HPSCs were treated with 5 ng/ml TGF-ß1 as in vitro experiment. RESULTS: Our results showed that repeated cerulein injection induced severe pancreatic injury and fibrosis in mice and the serum irisin level in cerulein-treated mice decreased as in CP patients. Excessive oxidative and ER stress was also present in the pancreas of cerulein-treated mice. Irisin treatment significantly alleviated pancreatic injury and fibrosis, which was associated with reduced oxidative and ER stress. In cultured PSCs, irisin directly inhibited TGF-ß-induced α-SMA and collagen I expression. This effect appears to be mediated through downregulation of kindlin-2 and inhibition of the SMAD2/3 pathway. CONCLUSIONS: Irisin alleviated pancreatic injury and fibrosis, which was associated with reduced oxidative and ER stress. Thus, irisin may offer therapeutic potential for patients with CP.

4.
Cell Death Dis ; 11(3): 189, 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32184393

RESUMO

Adrenomedullin (ADM) is a multifunctional peptide that is expressed by many surface epithelial cells, but its relevance to Helicobacter pylori (H. pylori)-induced gastritis is unknown. Here, we found that gastric ADM expression was elevated in gastric mucosa of H. pylori-infected patients and mice. In H. pylori-infected human gastric mucosa, ADM expression was positively correlated with the degree of gastritis; accordingly, blockade of ADM resulted in decreased inflammation within the gastric mucosa of H. pylori-infected mice. During H. pylori infection, ADM production was promoted via PI3K-AKT signaling pathway activation by gastric epithelial cells in a cagA-dependent manner, and resulted in increased inflammation within the gastric mucosa. This inflammation was characterized by the increased IFN-γ-producing T cells, whose differentiation was induced via the phosphorylation of AKT and STAT3 by ADM derived from gastric epithelial cells. ADM also induced macrophages to produce IL-12, which promoted the IFN-γ-producing T-cell responses, thereby contributing to the development of H. pylori-associated gastritis. Accordingly, blockade of IFN-γ or knockout of IFN-γ decreased inflammation within the gastric mucosa of H. pylori-infected mice. This study identifies a novel regulatory network involving H. pylori, gastric epithelial cells, ADM, macrophages, T cells, and IFN-γ, which collectively exert a pro-inflammatory effect within the gastric microenvironment.

5.
Mater Sci Eng C Mater Biol Appl ; 110: 110711, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32204023

RESUMO

Nanofibrous scaffolds with structural and compositional gradients exhibit great potential to modulate zonal differentiation of stem cells for the regeneration of soft-to-hard tissue interface. Here, the response of bone marrow stem cells (BMSCs) to electrospun gradient nanofibrous scaffolds was investigated to demonstrate their potential capabilities for interfacial tissue regeneration. The electrospun scaffolds showed gradient distribution of BMP-2/nanoHA contents and the fiber orientations gradually changed from random to align. Biomimetic mineralization demonstrated that calcium and phosphorus elements can deposit onto the surface of the nanofibers in a gradient manner similar to nanoHA content. BMSCs cultured on the gradient nanofibrous scaffolds exhibited high cell viability and cell morphology gradually changed from disorder to highly align similar to the underlying fiber orientation. BMP-2/nanoHA content gradients in the nanofibrous scaffolds were found to effectively promote the zonal expression of bone-specific genes like osteocalcin (OCN), Runt-related transcription factor 2 (Runx2) and alkaline phosphatase (ALP). Immunofluorescent staining of osteopontin (OPN) and OCN further confirmed osteoblastic phenotypic maturation on the regions of the scaffolds with a higher level of nanoHA and BMP-2 contents after cultured 28 days. These results indicated that the gradient nanofibrous scaffolds enable to guide zonal differentiation of BMSCs in vitro, which might be useful to realize multitissue regeneration in one construct for the regeneration of soft-to-hard tissue interface.

6.
Surg Endosc ; 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32016520

RESUMO

BACKGROUND: Laparoscopic splenectomy (LS) has been proven to be a safe and advantageous procedure. To ensure that resections of appropriate difficulty are selected, an objective preoperative grading of difficulty is required. We aimed to develop a predictive difficulty grading of LS based on intraoperative complications. METHODS: A total of 272 non-traumatic patients who underwent LS were identified from a regional medical center. Patients were randomized into a training cohort (n = 222) and a validation cohort (n = 50). Data on demographics, medical and surgical history, operative and pathological characteristics, and postoperative outcome details were collected. Univariate and multivariate analyses of risk factors for intraoperative complications were performed to develop a difficulty scoring system. The Spearman correlation coefficient was used to evaluate the relationship between the difficulty grading score and intraoperative outcomes. Receiver operating characteristic (ROC) curve was used to evaluate the discriminatory power of this scoring system. RESULTS: Three preoperative factors (spleen weight, esophagogastric varices, and INR) had a significant effect on operative time, bleeding, and conversion to open surgery. We created a difficulty grading score with three levels of difficulty: low (≤ 4 points), medium (5-6 points), and high (≥ 7 points), based on the three preoperative parameters. The correlation was highly significant (P < 0.01) according to Spearman's correlation. The area under the ROC curve was 0.695 (95% CI 0.630-0.755). The external validation showed significant correlations with the present model, with an AUC of 0.725 (95% CI 0.580-0.842). The comparison between our difficulty score and the previous grading system in the 272-patient cohort presented a significant difference in the AUC (0.701, 95% CI 0.643-0.755 vs. 0.644, 95% CI 0.584-0.701, P = 0.0452). CONCLUSION: The present difficulty scoring system, based on preoperative factors, has good performance in predicting the risk of intraoperative complications of LS and could be helpful for enabling appropriate case selection with respect to the current experience of a surgeon.

7.
Chem Commun (Camb) ; 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32057067

RESUMO

An interesting chemiluminescence (CL) phenomenon of cyclic peroxides originating from tetrahydrofuran hydrogen peroxide (THF-HPO) in the presence of BSA-stabilized Au NCs (Au@BSA NCs) was found for the first time. In this CL system, Au@BSA NCs can greatly accelerate the decomposition of THF-HPO, and then chemiluminescence resonance energy transfer (CRET) occurs between excited dioxetane derivatives and the Au@BSA NCs, yielding enhanced CL emission which can be further enhanced more than 10 times by the addition of copper ions. Based on this, a synergistic CL nanoprobe with a special signal amplification strategy was developed.

8.
Anal Chem ; 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32093470

RESUMO

Fluoride ion detection in water focuses much attention due to the serious healthy impact in human pathologies. For fluoride recognition, the chemical affinity between fluoride and silicon has been developed on the basis of the degradation mechanism. However, most fluorescent probes are the "turn off" type due to the aggregation of the degradational products. Herein, we first developed an "off-on" hydrophilic luminescent polymer composed of amino-functionalized polyhedral oligomeric silsesquioxane (AE-POSS) and perylene diimides (PDIs) for fluoride ion in water. The AE-PDI polymer was "turned off" because of the photoinduced electron transfer (PET) between PDI and AE-POSS, and then after reaction with F-, the fluorescent emission could "turn on" obviously because the PET was blocked by the degradation of the cage. The PET from amino-POSS to PDI was proved by FL spectrum and energies of HOMO and LUMO orbitals. 29Si, 19F NMR, and 1H NMR titration, XRD, FTIR, size analysis, and ion chromatography were applied to demonstrate the degradation mechanism. These results indicated that the higher quantum yield could be obtained by introducing the amide group in the PDI and the products of AE-PDI polymer might exist in the form of complex compounds with partial condensation of organosiloxane. With high selectivity and sensitivity (detection limit of 16.2 ppb), this probe was successfully applied for F- detection in actual water samples.

9.
BMC Infect Dis ; 20(1): 145, 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32066406

RESUMO

BACKGROUND: Pyogenic liver abscess (PLA) is an inflammatory disease with increasing incidence. When it occurs with diabetes mellitus (DM), the risk of recurrence and mortality may increase. However, the effect of DM on the short-term prognosis of PLA patients after hospitalization remained unknown. METHODS: Two hundred twenty-seven PLA patients who received treatment at the First Affiliated Hospital of Xi'an Jiaotong University from January 2011 to January 2018 were retrospectively enrolled. They were divided into two groups as the DM group (n = 61) and the Non-DM group (n = 166). In the DM group, HbA1C level < 7% was considered to be good-control of glycaemia (n = 23). The clinical characteristics and overall short-term survival were analyzed. RESULTS: The proportion of PLA patients with DM was 26.87%. In the DM group, there was a higher incidence of hypertension and Candida spp. infection. Conservative administration and percutaneous drainage were mainly used in patients with good- (60.87%) and poor-control (60.53%) of glycaemia, respectively. During follow-up, 24 (10.57%) died due to uncontrolled systemic infections and other serious complications. Compared with PLA patients without DM, patients in the DM group had significantly increased 6-month mortality rate after discharge (Log-Rank test, P = 0.021). Poor-control of glycaemia did not reduce the six-month survival, while the recurrence rate of PLA within 3 months showed an almost 3-fold increase (13.16% vs. 4.35%). Further multivariate analyses found that DM was the only independent risk factor for the PLA six-month survival (odds ratio [OR]: 3.019, 95% confidence interval [CI]: 1.138-8.010, P = 0.026). However, the blood glucose level had no significant effect on the short-term survival of PLA patients with DM (Log-Rank test, P = 0.218). CONCLUSIONS: In PLA patients, DM aggravated short-term mortality and blood glucose levels should be well controlled.

10.
Anal Chem ; 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32030974

RESUMO

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death, which is demanding powerful diagnosis tools. Although the traditionally used serological biomarker alpha-fetoprotein (AFP) cannot meet the  requirement of accurate diagnosis, its isoform alpha-fetoprotein L3 (AFP-L3) ratio in total AFP is emerging as a highly specific alternative. The routine electrophoretic blotting methods for analyzing AFP-L3 isoform ratio are reliable but often lack speediness, sensitivity, or accuracy. Herein, an elemental mass spectrometric strategy was established to simultaneously detect total AFP and AFP-L3 for the accurate HCC diagnosis. The metal isotopes inside colloidal gold nanoparticle (AuNP) and colloidal silver nanoparticle (AgNP) reporters were used to sensitively detect total AFP and AFP-L3, respectively. AFP-L3 and total AFP were accurately and simultaneously detected with the limits of detection (LODs) of 0.1 ng mL-1 and 0.2 ng mL-1, respectively. The proposed method was successfully validated in a series of human serum samples. The assay procedure was greatly simplified and less time-consuming for the AFP-L3 isoform ratio evaluation, when compared to clinical routine chromatographic/electrophoretic methods. Thanks to the highly multiplex ability of mass spectrometry, the proposed method provides great potential for the analysis of multiple isoforms of various disease biomarkers.

11.
Chem Commun (Camb) ; 56(12): 1891-1894, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-31956863

RESUMO

In this work, NH2-functionalized BPQDs (N-BPQDs) were purposely synthesized by using an ultrasound exfoliation technique combined with solvothermal treatment. The surface modification of BPQDs allowed engineering the energy gap and accelerating the electron transfer between the electron/hole donors and N-BPQDs, which played an important role in producing efficient chemiluminescence (CL) with the assistance of persulfate (K2S2O8). This work sheds new light on revealing the relationship between the BPQD structures and their optical properties.

12.
Oxid Med Cell Longev ; 2020: 6946037, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31976032

RESUMO

An aged liver has decreased reparative capacity during ischemia-reperfusion (IR) injury. A recent study showed that plasma irisin levels predict telomere length in healthy adults. The aim of the present study is to clarify the role of irisin, telomerase activity, and autophagy during hepatic IR in the elderly. To study this, hepatic IR was established in 22-month- and 3-month-old rats and primary hepatocytes were isolated. The results showed that the old rats exhibited more serious liver injury and lower levels of irisin expression, telomerase activity, autophagy ability, and mitochondrial function than young rats during hepatic IR. Irisin activated autophagy and improved mitochondrial function via increasing telomerase activity in aged hepatocytes. Inhibition of telomerase activity by BIBP1532 abolished the protective role of irisin in hepatocytes during hypoxia and reoxygenation. Additionally, this study proved irisin increased the telomerase activity via inhibition of the phosphorylation of JNK during hepatic IR. Administration of exogenous irisin significantly mitigated the inflammation, oxidative stress, apoptosis, and liver injury in an old rat model of hepatic IR. In conclusion, irisin improves autophagy of aged hepatocytes via increasing telomerase activity in hepatic IR. Irisin exhibits conspicuous benefits in increasing reparative capacity of an aged liver during hepatic IR.

13.
Anal Chem ; 92(3): 2876-2881, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-31910615

RESUMO

The most convenient method for the clinical routine analysis of disease biomarkers is homogeneous immunoassay, which minimizes the requirements for automation and time-/lab-consumption. Despite great success, because sample constituents are not removed by a separation or washing step, a major challenge in conducting homogeneous immunoassays for the practical application is the matrix effect-related inaccuracy. Herein, to guarantee an accurate quantification, a self-validated homogeneous immunoassay was proposed, by simultaneously scrutinizing both frequency and intensity of single gold nanoparticles. The two analytical modes of single particle inductively coupled plasma mass spectrometry (ICPMS) correlated well with each other, resulting in a self-validation mechanism for the accurate immunoassay. Both two modes of the proposed method provided linear ranges of 2 orders of magnitude and LODs of pM level. Thanks to the self-validated strategy and the high tolerance of the matrix effect of ICPMS, the proposed homogeneous immunoassay was successfully demonstrated in a series of human serum samples, with results in good accordance with clinical routine methods.

14.
FASEB J ; 34(1): 1169-1181, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914631

RESUMO

BHLHE40, a member of the basic helix-loop-helix transcription factor family, has been reported to play an important role in inflammatory diseases. However, the regulation and function of BHLHE40 in Helicobacter pylori (H pylori)-associated gastritis is unknown. We observed that gastric BHLHE40 was significantly elevated in patients and mice with H pylori infection. Then, we demonstrate that H pylori-infected GECs express BHLHE40 via cagA-ERK pathway. BHLHE40 translocates to cell nucleus, and then binds to cagA protein-activated p-STAT3 (Tyr705). The complex increases chemotactic factor CXCL12 expression (production). Release of CXCL12 from GECs fosters CD4+ T cell infiltration in the gastric mucosa. Our results identify the cagA-BHLHE40-CXCL12 axis that contributes to inflammatory response in gastric mucosa during H pylori infection.

15.
Ann Surg ; 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31972643

RESUMO

OBJECTIVES: To determine the prognostic implication of the number and station of LNM, and the minimal number of LNs needed for evaluation to accurately stage patients with intrahepatic cholangiocarcinoma (ICC). BACKGROUND: Impact of the number and station of LNM on long-term survival, and the minimal number of LNs needed for accurate staging of ICC patients remain poorly defined. METHODS: Data on patients who underwent curative-intent resection for ICC was collected from 15 high-volume centers worldwide. External validation was performed using the SEER registry. Primary outcomes included overall (OS), disease-specific, and recurrence-free survival. RESULTS: Among 603 patients who underwent curative-intent resection, median and 5-year OS were 30.6 months and 30.4%. Patients with 1 or 2 LNM had comparable worse OS versus patients with no nodal disease (median OS, 1 LNM 18.0, 2 LNM 20.0 vs no LNM 45.0 months, both P < 0.001), yet better OS versus patients with 3 or more LNM (median OS, 1-2 LNM 19.8 vs ≥3 LNM 16.0 months, P < 0.01). On multivariable analysis, a proposed new nodal staging with N1 (1-2 LNM) (Ref. N0, HR 2.40, P < 0.001) and N2 (≥3 LNM) [Ref. N0, hazard ratio (HR) 3.85, P < 0.001] categories were independently associated with incrementally worse OS. Patients with no nodal metastasis, 1-2 LNM and ≥3 LNM also had an increasingly worse disease-specific survival, and recurrence-free survival (both P < 0.05). Total number of LNs examined ≥6 had the greatest discriminatory power relative to OS among patients with 1-2 LNM, and patients with ≥3 LNM in both the multi-institutional (area under the curve 0.780) and SEER database (area under the curve 0.820) (n = 1036). Among patients who underwent an adequate regional lymphadenectomy (total number of LNs examined ≥6), LNM beyond the HDL was associated with worse OS versus LNM within the HDL only (median OS, 14.0 vs 24.0 months, HR 2.41, P = 0.003). CONCLUSION: Standard lymphadenectomy of at least 6 LNs is strongly recommended and should include examination beyond station 12 to have the greatest chance of accurate staging. The proposed new nodal staging of N0, N1, and N2 should be considered to stratify outcomes among patients after curative-intent resection of ICC.

16.
J Cell Mol Med ; 24(1): 996-1009, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31701659

RESUMO

Disruption of the gut barrier results in severe clinical outcomes with no specific treatment. Metabolic disorders and destruction of enterocytes play key roles in gut barrier dysfunction. Irisin is a newly identified exercise hormone that regulates energy metabolism. However, the effect of irisin on gut barrier function remains unknown. The therapeutic effect of irisin on gut barrier dysfunction was evaluated in gut ischemia reperfusion (IR). The direct effect of irisin on gut barrier function was studied in Caco-2 cells. Here, we discovered that serum and gut irisin levels were decreased during gut IR and that treatment with exogenous irisin restored gut barrier function after gut IR in mice. Meanwhile, irisin decreased oxidative stress, calcium influx and endoplasmic reticulum (ER) stress after gut IR. Moreover, irisin protected mitochondrial function and reduced enterocyte apoptosis. The neutralizing antibody against irisin significantly aggravated gut injury, oxidative stress and enterocyte apoptosis after gut IR. Further studies revealed that irisin activated the AMPK-UCP 2 pathway via binding to the integrin αVß5 receptor. Inhibition of integrin αVß5, AMPK or UCP 2 abolished the protective role of irisin in gut barrier function. In conclusion, exogenous irisin restores gut barrier function after gut IR via the integrin αVß5-AMPK-UCP 2 pathway.

17.
Cell Mol Gastroenterol Hepatol ; 9(1): 145-160, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31562937

RESUMO

BACKGROUND & AIMS: Toll-like receptor 2 (TLR2) and TLR3 regulate hepatic immunity under pathological conditions, but their functions and potential drug targets in alcoholic liver disease (ALD) remain poorly understood. METHODS: ALD-associated liver injury were induced in TLR2 knockout (TLR2-/-), TLR3-/-, TLR2-/- bone marrow transplanted (BMT), TLR3-/- BMT, IL-10-/- mice, and their wild-type littermates through ethanol challenge with or without co-administered epigallocatechin-3-gallate (EGCG). Moreover, Kupffer cells were depleted by GdCl3 injection to evaluate their pathogenic roles in ALD. RESULTS: We identified that deficiency of TLR2 and TLR3 significantly alleviated and aggravated ALD-induced liver injury, respectively. Mechanistically, Kupffer cell inactivation, M1 to M2 polarization, and IL-10 production via STAT3 activation contributed to hepatic protection mediated by concurrent TLR2 inhibition and TLR3 agonism. These findings were further confirmed in TLR2 and TLR3 BMT mice. We also identified a novel ALD-protective agent EGCG which directly interacted with Kupffer cell TLR2/3 to induce IL-10 production. Deficiency of IL-10 aggravated ALD injury and blunted EGCG-mediated hepatoprotection while depletion of Kupffer cells partially recovered liver injury but abolished EGCG's actions. CONCLUSIONS: Altogether, our results illustrate the divergent roles of Kupffer cells TLR2/3 in ALD progression via anti-inflammatory cytokine IL-10 production.

18.
Surg Endosc ; 34(2): 580-589, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31011863

RESUMO

BACKGROUND: Irreversible electroporation (IRE) is an emerging tissue ablation technique, which is safe for sites where thermal-basis techniques are not suitable. The aim of this study is to evaluate the safety and efficacy of magnetic anchoring electrode (MAE)-assisted IRE for normal gastric tissue ablation in a rabbit model. METHODS: IRE (500 V, 100 µs, 99 pulses, 1 Hz) of the gastric wall was performed in 24 adult New Zealand rabbits with a novel catheter-mounted MAE with fluoroscopy and a surgical approach. Procedure time, procedure-related bleeding, perforation, and other complications were recorded. Animals were sacrificed at 30 min, 1 day, 3 days, 7 days, 14 days, and 28 days post-IRE. The stomach was removed en bloc, and the diameter of each lesion was measured. Histopathological analyses by Hematoxylin-Eosin (H&E), masson trichrome, alpha-smooth muscle action (α-SMA), and terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) were performed. RESULTS: Gastric tissue ablation with MAE-assisted IRE was successfully performed without any interruption. No perforation or bleeding was observed during IRE or throughout the follow-up period. A demarcated hemorrhage was found in the ablated area upon gross examination. H&E staining showed complete cell death with inflammatory infiltration, edema, and hemorrhaging. TUNEL presented diffuse positive cells in the ablated area. The tissue scaffold was well preserved without damage as indicated by Masson trichrome staining. Ulceration was observed starting from 3 days post-IRE. The mucosal layer was gradually recovered and regenerated within 14-28 days. No other complication was observed post-IRE. CONCLUSIONS: MAE-assisted IRE is safe and effective for normal gastric tissue ablation and the gastric wall recovered in 14-28 days post-IRE.

19.
J Surg Res ; 245: 249-256, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31421370

RESUMO

BACKGROUND: Technical improvement of gastrojejunostomy is critical in bariatric and metabolic surgery. In this study, a novel magnetic compression approach for gastrojejunostomy was evaluated. MATERIALS AND METHODS: Both cylindrical and rectangular magnets were used in rabbits, and the magnets were named according to their location. All the magnets were perorally introduced into the stomach. The position of the jejunal magnet was controlled by a connecting line. When the jejunal magnet spontaneously entered the jejunum, the gastric magnet was introduced into the stomach. An extracorporeal magnet was used to guide these two magnets together, and the magnet pair was left to create a side-to-side anastomosis. The state of the animals and extrusion time of the magnets were observed. The anastomoses were evaluated by burst pressure and histology. RESULTS: Gastrojejunostomy was successfully established in all animals. Cylindrical and rectangular magnets spontaneously entered the jejunum through the pylorus within 2.4 ± 0.5 and 6.0 ± 0.8 d, respectively (P < 0.01). The cylindrical and rectangular magnet pairs fell off within 15.3 ± 0.8 and 11.9 ± 1.1 d, respectively (P < 0.01). The burst pressures were statistically similar between the two types of magnets (P > 0.05). Histological examination showed sealed anastomoses with mild inflammation of the mucosa and fibrosis within the submucosa. CONCLUSIONS: The feasibility and efficacy of establishing gastrojejunostomy by guidewire introduction of magnets, which were guided together with an extracorporeal magnet, were confirmed in rabbits. In humans, with the clinical use of this procedure, surgery would be greatly simplified.


Assuntos
Derivação Gástrica/instrumentação , Gastrostomia/instrumentação , Jejunostomia/instrumentação , Imãs , Animais , Desenho de Equipamento , Estudos de Viabilidade , Feminino , Derivação Gástrica/efeitos adversos , Derivação Gástrica/métodos , Gastrostomia/efeitos adversos , Gastrostomia/métodos , Jejunostomia/efeitos adversos , Jejunostomia/métodos , Masculino , Modelos Animais , Pressão , Coelhos
20.
J Ethnopharmacol ; 248: 112357, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31693919

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Gogi berry is a traditional food supplement and medical herbal which has been widely used in Eastern Asian countries. Lycium barbarum polysaccharides (LBP) are the major active components of Gogi berry and have been proved to possess a lot of biological activities. AIM OF THE STUDY: We aimed to delineate the protective effect and mechanism of LBP on hepatic encephalopathy (HE). MATERIALS AND METHODS: We investigated the protective mechanism of LBP in a thioacetamide (TAA, intraperitoneally injected, 400 mg/kg) induced acute HE mice model. Key phenotypes of clinical HE were phenocopied in the mice model, including high mortality, severe hepatic histology injury, increased hepatic oxidative stress, apoptosis, enhanced circulating levels of pro-inflammatory cytokines and ammonia, suppressed tryptophan hydroxylase activity, and deficits in locomotor activity. RESULTS: The pathological alterations were effectively ameliorated by the oral administration with LBP (5 mg/kg, oral gavage, everyday), which were mediated by regulating MAPK pathways in both the liver and brain. Knockout of pro-inflammatory cytokines TNF-α or IL-6 effectively ameliorated impaired mice locomotor activity and MAPK activation in the brain. In an in vitro TNF-α-, IL-6-, or ammonia-induced microglia damaged cell model, cell injuries were evidently protected by the co-administration with LBP (50 µg/ml). CONCLUSION: LBP ameliorated the hepatic/brain injuries and impaired locomotor activities in a HE mice model. Pro-inflammatory cytokines may serve as communicating molecules linking the liver and brain for the HE pathogenesis, partly through MAPK regulation.

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