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1.
Liver Int ; 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33647177

RESUMO

BACKGROUND&AIMS: Magnetic resonance imaging (MRI) is the first-line tool for the noninvasive diagnosis of hepatocellular carcinoma (HCC) in patients with chronic liver diseases. We performed a meta-analysis to compare the performance of MRI using extracellular contrast agents (ECA-MRI) with that using gadoxetic acid (EOB-MRI) for diagnosing HCC. METHODS: We searched multiple databases for studies comparing the diagnostic performance of ECA-MRI with that of EOB-MRI in patients with suspected HCC until May 31, 2020. The bivariate random-effects model was used to pool the performance and further subgroup analysis was performed. RESULTS: Eight studies were included evaluating a total of 1002 patients. ECA-MRI revealed significantly higher per-lesion sensitivity in the diagnosis of HCC than EOB-MRI did (0.76 versus 0.63, P = 0.002). For modified EOB-MRI (mEOB-MRI) using extended washout to the transitional phase (TP) or hepatobiliary phase (HBP), the sensitivity increased compared with that of EOB-MRI using restrictive washout in the portal venous phase (PVP) (0.74 versus 0.63, P = 0.07). No significant difference among the specificities of ECA-MRI, EOB-MRI, and mEOB-MRI (0.96, 0.98, and 0.93, respectively) was found. The sensitivity for lesions < 20 mm was significantly lower than that for lesions ≥ 20mm (0.66 versus 0.87, P = 0.01) only for ECA-MRI, which achieved higher sensitivity in Asian patients or with a 3.0 T scanner. CONCLUSIONS: ECA-MRI outperforms EOB-MRI in per-lesion sensitivity for diagnosing HCC, while mEOB-MRI shows a trend toward improved sensitivity compared with EOB-MRI with slightly decreased specificity.

2.
J Mater Chem B ; 9(6): 1625-1637, 2021 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-33475658

RESUMO

Radiotherapy occupies an essential position in curing and palliating a wide range of solid tumors based on DNA damage responses to eradicate cancer cells. However, the tumor microenvironment generally exhibits the characteristics of hypoxia and glutathione overexpression, which play a critical role in radioresistance, to prevent irreparable breaks to DNA and necrocytosis of cancer cells. Herein, polyethylene glycol (PEG) functionalized manganese ferrite nanoparticles (MnFe2O4-PEG) are designed to enable self-sufficiency of oxygen by continuously catalyzing the decomposition of endogenous hydrogen peroxide. Simultaneously, the nano-platform can consume GSH to reduce the loss of reactive oxygen species in radiotherapy and achieve better therapeutic effects at the cellular and animal levels. In addition, the MnFe2O4-PEG could act as an optimal T1- and T2-weighted contrast medium for tumor-specific magnetic resonance imaging. This work proposes a systematically administered radiosensitizer that can selectively reside in tumor sites via the enhanced permeability and retention effect to relieve hypoxia and reduce GSH concentration, combined with dual-mode magnetic resonance imaging, achieving precise and effective image-guided tumor therapy.

3.
J Gerontol A Biol Sci Med Sci ; 76(3): e78-e84, 2021 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-33355656

RESUMO

BACKGROUND: Skeletal muscle depletion is common in old adults and individuals with chronic comorbidities, who have an increased risk of developing severe coronavirus disease 2019 (COVID-19), which is defined by hypoxia requiring supplemental oxygen. This study aimed to determine the association between skeletal muscle depletion and clinical outcomes in patients with severe COVID-19. METHODS: One hundred and sixteen patients with severe COVID-19 who underwent chest computed tomography scan on admission were included in this multicenter, retrospective study. Paraspinal muscle index (PMI) and radiodensity (PMD) were measured using computed tomography images. The primary composite outcome was the occurrence of critical illness (respiratory failure requiring mechanical ventilation, shock, or intensive care unit admission) or death, and the secondary outcomes were the duration of viral shedding and pulmonary fibrosis in the early rehabilitation phase. Logistic regression and Cox proportional hazards models were employed to evaluate the associations. RESULTS: The primary composite outcome occurred in 48 (41.4%) patients, who were older and had lower PMD (both p < .05). Higher PMD was associated with reduced risk of critical illness or death in a fully adjusted model overall (odds ratio [OR] per standard deviation [SD] increment: 0.87, 95% confidence interval [CI]: 0.80-0.95; p = .002) and in female patients (OR per SD increment: 0.71, 95% CI: 0.56-0.91; p = .006), although the effect was not statistically significant in male patients (p = .202). Higher PMD (hazard ratio [HR] per SD increment: 1.08, 95% CI: 1.02-1.14; p = .008) was associated with shorter duration of viral shedding among female survivors. However, no significant association was found between PMD and pulmonary fibrosis in the early rehabilitation phase, or between PMI and any outcome in both men and women. CONCLUSIONS: Higher PMD, a proxy measure of lower muscle fat deposition, was associated with a reduced risk of disease deterioration and decreased likelihood of prolonged viral shedding among female patients with severe COVID-19.

4.
Nano Lett ; 21(1): 414-423, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33356313

RESUMO

Salmonella selectively colonizes into the hypoxic tumor region and exerts antitumor effects via multiple mechanisms, while the tumor colonized Salmonella recruits host neutrophils into the tumor, presenting a key immunological restraint to compromise the Salmonella efficacy. Here, we develop a combinatorial strategy by employing silver nanoparticles (AgNPs) to improve the efficacy and biosafety of Salmonella. The AgNPs were decorated with sialic acid (SA) to allow selective recognition of L-selectin on neutrophil surfaces, based on which the tumor-homing of AgNPs was achieved by neutrophil infiltration in the Salmonella colonized tumor. The tumor-targeting AgNPs exert the functions of (1) local depletion of neutrophils in tumors to boost the efficacy of Salmonella, (2) direct killing tumor cells via L-selectin-mediated intracellular delivery, and (3) clearing the residual Salmonella after complete tumor eradication to minimize the side effects. With a single tail vein injection of such combination treatment, the tumor was eliminated with high biosafety, resulting in a superior therapeutic outcome.

5.
Med Image Anal ; 67: 101836, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33129141

RESUMO

The recent global outbreak and spread of coronavirus disease (COVID-19) makes it an imperative to develop accurate and efficient diagnostic tools for the disease as medical resources are getting increasingly constrained. Artificial intelligence (AI)-aided tools have exhibited desirable potential; for example, chest computed tomography (CT) has been demonstrated to play a major role in the diagnosis and evaluation of COVID-19. However, developing a CT-based AI diagnostic system for the disease detection has faced considerable challenges, which is mainly due to the lack of adequate manually-delineated samples for training, as well as the requirement of sufficient sensitivity to subtle lesions in the early infection stages. In this study, we developed a dual-branch combination network (DCN) for COVID-19 diagnosis that can simultaneously achieve individual-level classification and lesion segmentation. To focus the classification branch more intensively on the lesion areas, a novel lesion attention module was developed to integrate the intermediate segmentation results. Furthermore, to manage the potential influence of different imaging parameters from individual facilities, a slice probability mapping method was proposed to learn the transformation from slice-level to individual-level classification. We conducted experiments on a large dataset of 1202 subjects from ten institutes in China. The results demonstrated that 1) the proposed DCN attained a classification accuracy of 96.74% on the internal dataset and 92.87% on the external validation dataset, thereby outperforming other models; 2) DCN obtained comparable performance with fewer samples and exhibited higher sensitivity, especially in subtle lesion detection; and 3) DCN provided good interpretability on the loci of infection compared to other deep models due to its classification guided by high-level semantic information. An online CT-based diagnostic platform for COVID-19 derived from our proposed framework is now available.


Assuntos
/diagnóstico por imagem , Redes Neurais de Computação , Pneumonia Viral/diagnóstico por imagem , Tomografia Computadorizada por Raios X , /classificação , Humanos , Pneumonia Viral/classificação , Radiografia Torácica , Sensibilidade e Especificidade
6.
Nat Commun ; 11(1): 4968, 2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-33009413

RESUMO

The outbreak of coronavirus disease 2019 (COVID-19) has rapidly spread to become a worldwide emergency. Early identification of patients at risk of progression may facilitate more individually aligned treatment plans and optimized utilization of medical resource. Here we conducted a multicenter retrospective study involving patients with moderate COVID-19 pneumonia to investigate the utility of chest computed tomography (CT) and clinical characteristics to risk-stratify the patients. Our results show that CT severity score is associated with inflammatory levels and that older age, higher neutrophil-to-lymphocyte ratio (NLR), and CT severity score on admission are independent risk factors for short-term progression. The nomogram based on these risk factors shows good calibration and discrimination in the derivation and validation cohorts. These findings have implications for predicting the progression risk of COVID-19 pneumonia patients at the time of admission. CT examination may help risk-stratification and guide the timing of admission.


Assuntos
Infecções por Coronavirus/diagnóstico , Progressão da Doença , Pneumonia Viral/diagnóstico , Pneumonia , Tomografia Computadorizada por Raios X/métodos , Adulto , Betacoronavirus , China , Técnicas de Laboratório Clínico , Coinfecção , Infecções por Coronavirus/patologia , Infecções por Coronavirus/fisiopatologia , Feminino , Hospitalização , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Linfócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos , Pandemias , Pneumonia Viral/patologia , Pneumonia Viral/fisiopatologia , Análise de Regressão , Estudos Retrospectivos , Medição de Risco , Fatores de Risco
7.
EMBO Mol Med ; 12(11): e12305, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33034128

RESUMO

Type 2 innate lymphoid cells (ILC2s) are a subset of ILCs with critical roles in immunoregulation. However, the possible role of ILC2s as immunotherapy against allograft rejection remains unclear. Here, we show that IL-33 significantly prolonged islet allograft survival. IL-33-treated mice had elevated numbers of ILC2s and regulatory T cells (Tregs). Depletion of Tregs partially abolished the protective effect of IL-33 on allograft survival, and additional ILC2 depletion in Treg-depleted DEREG mice completely abolished the protective effects of IL-33, indicating that ILC2s play critical roles in IL-33-mediated islet graft protection. Two subsets of ILC2s were identified in islet allografts of IL-33-treated mice: IL-10 producing ILC2s (ILC210 ) and non-IL-10 producing ILC2s (non-ILC10 ). Intravenous transfer of ILC210 cells, but not non-ILC10 , prolonged islet allograft survival in an IL-10-dependent manner. Locally transferred ILC210 cells led to long-term islet graft survival, suggesting that ILC210 cells are required within the allograft for maximal suppressive effect and graft protection. This study has uncovered a major protective role of ILC210 in islet transplantation which could be potentiated as a therapeutic strategy.

8.
Aging Dis ; 11(5): 1069-1081, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33014523

RESUMO

Coronavirus disease 2019 (COVID-19) is a global pandemic associated with a high mortality. Our study aimed to determine the clinical risk factors associated with disease progression and prolonged viral shedding in patients with COVID-19. Consecutive 564 hospitalized patients with confirmed COVID-19 between January 17, 2020 and February 28, 2020 were included in this multicenter, retrospective study. The effects of clinical factors on disease progression and prolonged viral shedding were analyzed using logistic regression and Cox regression analyses. 69 patients (12.2%) developed severe or critical pneumonia, with a higher incidence in the elderly and in individuals with underlying comorbidities, fever, dyspnea, and laboratory and imaging abnormalities at admission. Multivariate logistic regression analysis indicated that older age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.02-1.06), hypertension without receiving angiotensinogen converting enzyme inhibitors or angiotensin receptor blockers (ACEI/ARB) therapy (OR, 2.29; 95% CI, 1.14-4.59), and chronic obstructive pulmonary disease (OR, 7.55; 95% CI, 2.44-23.39) were independent risk factors for progression to severe or critical pneumonia. Hypertensive patients without receiving ACEI/ARB therapy showed higher lactate dehydrogenase levels and computed tomography (CT) lung scores at about 3 days after admission than those on ACEI/ARB therapy. Multivariate Cox regression analysis revealed that male gender (hazard ratio [HR], 1.22; 95% CI, 1.02-1.46), receiving lopinavir/ritonavir treatment within 7 days from illness onset (HR, 0.75; 95% CI, 0.63-0.90), and receiving systemic glucocorticoid therapy (HR, 1.79; 95% CI, 1.46-2.21) were independent factors associated with prolonged viral shedding. Our findings presented several potential clinical factors associated with developing severe or critical pneumonia and prolonged viral shedding, which may provide a rationale for clinicians in medical resource allocation and early intervention.

9.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(7): 752-758, 2020 Jul 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-32879077

RESUMO

OBJECTIVES: To investigate whether necrostatin-1 (Nec-1) can protect islet cells from the damage induced by TNF-α. METHODS: After isolation and purification, the neonatal porcine islet cell clusters (NICCs) were divided into 3 groups (islets 10 000 IEQ/group): a Nec-1 group (Nec-1+TNF-α was added to the culture medium), a TNF-α group (TNF-α was added to the culture medium), and a control group (pure medium). The number of cells was observed after 48 h of co-culture. The cell death was evaluated by AO/EB staining. Insulin secretion and DNA of islets were detected by chemiluminescence and nucleic acid quantitative analysis. RT-PCR assay was used to examine the mRNA expressions of insulin gene, glueogan gene and somatostatin gene. Flow cytometry analysis was used to detect the viability of B cells. RESULTS: The number of islets in Nec-1 group, TNF-α group and the control group were (8 425±2 187), (4 325±778), and (7 122±1 558) IEQ, respectively. Compared to the other two groups, the number of dead cells in TNF-α group was greatly increased. The insulin/DNA values in the Nec-1 group, TNF-α group and blank control group were (13.21±3.15), (2.47±0.45), and (7.44±0.97) mIU/mg, respectively. Compared to the TNF-α group and the control group, the mRNA relative expression levels of insulin gene (6.73±1.07), glucagon gene (10.13±1.98), somatostatin gene (8.57±1.11) were significantly increased in the Nec-1 group (all P<0.05), the rate of live cells (97.32±1.87)% and live B cells (90.86±3.68)% were increased significantly in the Nec-1 group (all P<0.05). CONCLUSIONS: TNF-α can induce neonatal porcine islet cells damage, which is attenuated in the presence of Nec-1. Nec-1 can increase the content of endocrine cells in NICCs.


Assuntos
Ilhotas Pancreáticas , Fator de Necrose Tumoral alfa/genética , Animais , Imidazóis , Indóis , Insulina , Suínos
10.
Mol Med Rep ; 22(4): 3191-3200, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32945429

RESUMO

Hepatic fibrosis (HF) is a common complication of numerous chronic liver diseases, but predominantly results from persistent liver inflammation or injury. If left untreated, HF can progress and develop into liver cirrhosis and even hepatocellular carcinoma. However, the underlying molecular mechanisms of HF remain unknown. The present study aimed to investigate the role of 11ß­hydroxysteroid dehydrogenase­1 (11ß­HSD1) during the development of hepatic fibrosis. An experimental rat model of liver fibrosis was induced using porcine serum. 11ß­HSD1 gene expression levels and enzyme activity during hepatic fibrogenesis were assessed. 11ß­HSD1 gene knockdown using small interfering RNA and overexpression were performed in LX2­human hepatic stellate cells (HSCs). HSCs were stimulated with transforming growth factor­ß1 (TGF­ß1). Cell cycle distribution, proliferation, collagen secretion and 11ß­HSD1 gene activity in HSCs were compared before and after stimulation. As hepatic fibrosis progressed, 11ß­HSD1 gene expression and activity increased, indicating a positive correlation with typical markers of liver fibrosis. 11ß­HSD1 inhibition markedly reduced the degree of fibrosis. The cell proliferation was increased, the number of cells in the G0/G1 phase decreased and the number of cells in the S and G2/M phases increased in the pSuper transfected group compared with the N group. In addition, the overexpression of 11ß­HSD1 enhanced the TGF­ß1­induced activation of LX2­HSCs and enzyme activity of connective tissue growth factor. 11ß­HSD1 knockdown suppressed cell proliferation by blocking the G0/G1 phase of the cell cycle, which was associated with HSC stimulation and inhibition of 11ß­HSD1 enzyme activity. In conclusion, increased 11ß­HSD1 expression in the liver may be partially responsible for hepatic fibrogenesis, which is potentially associated with HSC activation and proliferation.

12.
Theranostics ; 10(20): 9303-9314, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32802193

RESUMO

The proteins expressed on exosomes have emerged as promising liquid-biopsy biomarkers for cancer diagnosis. However, molecular profiling of exosomal proteins remains technically challenging. Herein, we report a nanozyme-assisted immunosorbent assay (NAISA) that enables sensitive and rapid multiplex profiling of exosomal proteins. This NAISA system is based on the installation of peroxidase-like nanozymes onto the phospholipid membranes of exosomes, thus avoiding the need for post-labelling detection antibodies. The exosomal proteins are determined by a sensitive nanozyme-catalyzed colorimetric assay less than 3 h, without the need for multi-step incubation and washing operations. Using NAISA to profile exosomal proteins from different cell lines and clinical samples, we reveal that tumor-associated exosomal proteins can serve as promising biomarkers for accurate cancer diagnosis in a cooperative detection pattern. Methods: Exosomes were engineered with DSPE-PEG-SH through hydrophobic interaction, and then were assembled with gold nanoparticles (2 nm) to produce Exo@Au nanozyme. The proteins on Exo@Au could be selectively captured by their specific antibodies seeded into a 96-well plate. The immobilized Exo@Au shows peroxidase-like activity to perform colorimetric assays by reaction with 3,3',5,5'-tetramethylbenzidine (TMB) and H2O2. The protein levels of exosomes were recorded on a microplate reader. Results: The NAISA platform is capable of profiling multiple exosomal proteins from both cancer cell lines and clinical samples. The expression levels of exosomal proteins, such as CD63, CEA, GPC-3, PD-L1 and HER2, were used to classify different cancer cell lines. Moreover, the protein profiles have been applied to differentiate healthy donors, hepatitis B patients, and hepatic cell carcinoma (HCC) patients with high accuracy. Conclusion: The NAISA nanozyme was allowed to rapidly profile multiple exosomal proteins and could have great promise for early HCC diagnosis and identification of other cancer types.

13.
Cell Transplant ; 29: 963689720934413, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32543895

RESUMO

Islet transplantation is a promising ß-cell replacement therapy for type 1 diabetes, which can reduce glucose lability and hypoglycemic episodes compared with standard insulin therapy. Despite the tremendous progress made in this field, challenges remain in terms of long-term successful transplant outcomes. The insulin independence rate remains low after islet transplantation from one donor pancreas. It has been reported that the islet-related inflammatory response is the main cause of early islet damage and graft loss after transplantation. The production of interleukin-1ß (IL-1ß) has considered to be one of the primary harmful inflammatory events during pancreatic procurement, islet isolation, and islet transplantation. Evidence suggests that the innate immune response is upregulated through the activity of Toll-like receptors and The NACHT Domain-Leucine-Rich Repeat and PYD-containing Protein 3 inflammasome, which are the starting points for a series of signaling events that drive excessive IL-1ß production in islet transplantation. In this review, we show recent contributions to the advancement of knowledge of IL-1ß in islet transplantation and discuss several strategies targeting IL-1ß for improving islet engraftment.

14.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(3): 262-268, 2020 Mar 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-32386017

RESUMO

OBJECTIVES: To investigate imaging features of the coronavirus disease 2019 (COVID-19), and to provide concrete evidences for diagnosis of COVID-19. METHODS: Imaging data of the first chest CT examination and clinical data (age, sex, clinical history, epidemiological history, and laboratory tests) of 163 patients with COVID-19 from 2 hospitals were collected for retrospective analysis. Imaging features of the first chest CT examination and the correspondence between CT manifestations and the nucleic acid test results of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were analyzed. RESULTS: The first chest CT images of 163 COVID-19 patients showed that 92.02% of lesions were ground-glass opacity (GGO), 76.69% were consolidation, and 73.62% were GGO together with consolidation. Multiple lesions were found in 71.17% patients and multiple lobules in 86.50% patients. Lesions in 53.37% patients were found with bronchial inflation signs and those in 36.20% patients presented with "crazy paving" pattern, while only 7.36% were found with hilar node enlargement and pleural effusion. First CT findings of 18 patients were found to be inconsistent with the results of pathogen examination. CONCLUSIONS: COVID-19 patients showed specific features in the first chest CT examination. The combination of the first chest CT imaging features and SARS-CoV-2 nucleic acid test results as well as reexamination if necessary can help to make the diagnosis of SARS-CoV-2 infection accurately.


Assuntos
Betacoronavirus , Infecções por Coronavirus/diagnóstico por imagem , Pneumonia Viral/diagnóstico por imagem , Humanos , Pandemias , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
15.
J Diabetes Res ; 2020: 3847171, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32455132

RESUMO

Transplantation of umbilical cord mesenchymal stem cells (UC-MSCs) is currently considered a novel therapeutic strategy for diabetic nephropathy (DN). However, the mechanisms by which UC-MSCs ameliorate renal fibrosis in DN are not well understood. Herein, we firstly investigated the therapeutic effects of mouse UC-MSC infusion on kidney structural and functional impairment in streptozotocin- (STZ-) induced diabetic mice. We found that the repeated injection with mUC-MSCs alleviates albuminuria, glomerulus injury, and fibrosis in DN mouse models. Next, mesangial cells were exposed to 5.6 mM glucose, 30 mM glucose, or mUC-MSC-conditioned medium, and then we performed western blotting, immunofluorescence, wound healing assay, and cell proliferation assay to measure extracellular matrix (ECM) proteins and matrix metalloproteinases (MMPs), myofibroblast transdifferentiation (MFT), and cell proliferation. We demonstrated that mUC-MSC paracrine decreased the deposition of fibronectin and collagen I by inhibiting TGF-ß1-triggered MFT and cell proliferation mediated by PI3K/Akt and MAPK signaling pathways, and elevating the levels of MMP2 and MMP9. Importantly, we provided evidence that the antifibrosis role of mUC-MSC paracrine in DN might be determined by exosomes shed by MSCs. Together, these findings reveal the mechanisms underlying the therapeutic effects of UC-MSCs on renal fibrosis in DN and provide the evidence for DN cell-free therapy based on UC-MSCs in the future.

16.
Clin Nutr ; 39(10): 3132-3139, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32057535

RESUMO

BACKGROUND & AIMS: Sarcopenia is associated with a higher rate of complications and is an independent predictor of poor outcomes in cirrhosis. The aim of this study was to investigate the association between sarcopenia and the risk of hepatocellular carcinoma (HCC) among patients with cirrhosis. METHODS: Four hundred and ninety-two patients with cirrhosis and no evidence of HCC from 2008 to 2017 were enrolled, who had baseline abdominal computed tomography (CT) analyzed for identification of sarcopenia according to the previously established sex-specific cutoffs. The main endpoint of follow-up was the occurrence of HCC. RESULTS: The majority of patients were male (365/492, 74.2%), and sarcopenia were present in 238 (48.4%) patients at baseline. During a median follow-up of 3.6 years, 54 (11.0%) patients developed HCC. The cumulative incidence of HCC was significantly higher in male patients with sarcopenia than those without sarcopenia (P = 0.001), but not in female patients (P = 0.26). Multivariate Cox regression analysis showed that sarcopenia (hazard ratio [HR], 2.27; 95% confidence interval [CI], 1.09-4.74) was a significant independent factor for HCC development in male patients with cirrhosis, which was consistently identified through competing-risk analysis (subdistribution HR, 2.20; 95% CI, 1.02-4.72). After propensity score matching, male cirrhotic patients with sarcopenia still had a higher risk of HCC than those without sarcopenia (P = 0.02). CONCLUSION: Sarcopenia is associated with an increased risk of developing HCC among male patients with cirrhosis. Therefore, nutritional assessment and necessary interventions in specific cirrhotic patients need to be valued.

17.
Future Med Chem ; 12(9): 835-852, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32107934

RESUMO

Drug-induced liver injury (DILI) has been a long-standing concern of modern medicine, and the single most frequent reason for drug nonapprovals and postapproval restrictions or withdrawals. Chemical probes for early diagnosis of DILI has triggered a tremendous interest in the field of molecular imaging. In this review, we make a brief summary of the recently developed chemical probes and their applications in DILI imaging with special attention to the design of chemical probes, mechanism of their actions and their performances in DILI imaging.

19.
Xenotransplantation ; 27(1): e12556, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31578787

RESUMO

BACKGROUND: The dysfunction of islet grafts is generally attributed to hypoxia-induced damage. Mesenchymal stem cells (MSCs) are currently thought to effectively protect cells from various risk factors via regulating autophagy. In our study, we investigated if human umbilical cord-derived MSCs could ameliorate hypoxia-induced apoptosis in porcine islets by modulating autophagy, and we explored the underlying mechanisms. METHODS: Neonatal porcine islet cell clusters (NICCs) were cultured with human umbilical cord-derived MSC conditioned medium (huc-MSC-CM) and RPMI-1640 medium (control) under hypoxic conditions (1% O2 ) in vitro. NICCs were treated with 3-methyladenine (3-MA) and chloroquine (CQ) to examine the role of huc-MSC-CM in regulating autophagy. Finally, the levels of several cytokines secreted by huc-MSCs were detected by ELISAs, and the corresponding inhibitors were applied to investigate which cytokine mediates the protective effects of huc-MSC-CM. The effects of huc-MSC-CM on NICCs viability and autophagy were examined using AO/PI staining, flow cytometry analysis, transmission electron microscopy (TEM) and confocal fluorescence microscopy analysis. The insulin secretion of NICCs was tested with an insulin immunoradiometric assay kit. RESULTS: Compared to the control, the huc-MSC-CM treatment improved the viability of NICCs, inhibited apoptosis, increased autophagic activity and the levels of PI3K class III and phosphorylated Akt, while the ratio of phosphorylated mTOR/mTOR was reduced. These changes were reversed by CQ and 3-MA treatments. High concentrations of IL-6 were detected in hu-MSC-CM. Furthermore, recombinant IL-6 pre-treatment exerted similar effects as huc-MSC-CM, and these effects were reversed by a specific inhibitor of IL-6 (Sarilumab). CONCLUSIONS: Our results demonstrated that huc-MSC-CM improved islet viability and function by increasing autophagy through the PI3K/Akt/mTOR pathway under hypoxic conditions. Additionally, IL-6 plays an important role in the function of huc-MSC-CM.

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