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1.
BMC Cancer ; 24(1): 1229, 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-39369213

RESUMO

OBJECTIVE: To evaluate the diagnostic efficacy of a deep learning (DL) model based on PET/CT images for distinguishing and predicting various pathological subtypes of invasive lung adenocarcinoma. METHODS: A total of 250 patients diagnosed with invasive lung cancer were included in this retrospective study. The pathological subtypes of the cancer were recorded. PET/CT images were analyzed, including measurements and recordings of the short and long diameters on the maximum cross-sectional plane of the CT image, the density of the lesion, and the associated imaging signs. The SUVmax, SUVmean, and the lesion's long and short diameters on the PET image were also measured. A manual diagnostic model was constructed to analyze its diagnostic performance across different pathological subtypes. The acquired images were first denoised, followed by data augmentation to expand the dataset. The U-Net network architecture was then employed for feature extraction and network segmentation. The classification network was based on the ResNet residual network to address the issue of gradient vanishing in deep networks. Batch normalization was applied to ensure the feature matrix followed a distribution with a mean of 0 and a variance of 1. The images were divided into training, validation, and test sets in a ratio of 6:2:2 to train the model. The deep learning model was then constructed to analyze its diagnostic performance across different pathological subtypes. RESULTS: Statistically significant differences (P < 0.05) were observed among the four different subtypes in PET/CT imaging performance. The AUC and diagnostic accuracy of the manual diagnostic model for different pathological subtypes were as follows: APA: 0.647, 0.664; SPA: 0.737, 0.772; PPA: 0.698, 0.780; LPA: 0.849, 0.904. Chi-square tests indicated significant statistical differences among these subtypes (P < 0.05). The AUC and diagnostic accuracy of the deep learning model for the different pathological subtypes were as follows: APA: 0.854, 0.864; SPA: 0.930, 0.936; PPA: 0.878, 0.888; LPA: 0.900, 0.920. Chi-square tests also indicated significant statistical differences among these subtypes (P < 0.05). The Delong test showed that the diagnostic performance of the deep learning model was superior to that of the manual diagnostic model (P < 0.05). CONCLUSIONS: The deep learning model based on PET/CT images exhibits high diagnostic efficacy in distinguishing and diagnosing various pathological subtypes of invasive lung adenocarcinoma, demonstrating the significant potential of deep learning techniques in accurately identifying and predicting disease subgroups.


Assuntos
Adenocarcinoma de Pulmão , Aprendizado Profundo , Fluordesoxiglucose F18 , Neoplasias Pulmonares , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Estudos Retrospectivos , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/classificação , Idoso , Adulto , Compostos Radiofarmacêuticos , Idoso de 80 Anos ou mais
2.
Int J Colorectal Dis ; 39(1): 166, 2024 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-39419860

RESUMO

AIM: Postoperative gastrointestinal dysfunction (POGD) is a common complication following colorectal surgery. This study aimed to investigate the incidence and risk factors of POGD after minimally invasive surgery and to assess the relationship between robotic surgery, POGD, and their outcomes. METHOD: Patients who had undergone minimally invasive colorectal surgery at our institution between July 2018 and November 2023 were retrospectively enrolled. POGD was diagnosed based on the presence of two or more intestinal symptoms within 72 h or more after surgery. Risk factors were identified through regression analyses, and the impact of POGD on outcomes was assessed using linear regression.The association between those factors was assessed using subgroup analysis and hierarchical regression. RESULTS: A total of 226 patients were included in the analysis, including 33 with POGD. POGD occurred in 14.6% of patients, with a lower incidence in robotic surgery (7.3%) than in laparoscopic surgery (19.8%). Multivariate analysis indicated that robotic surgery had a protective effect, while blood loss exceeding 50 ml was an independent risk factor for POGD. POGD was also correlated with longer length of stays and higher costs. The association between POGD, length of stay, and cost varied depending on the surgical platform. Robotic surgery exacerbated the effect of POGD on short-term outcomes, which aligned with the observed significant interaction effect. CONCLUSION: POGD remains a prevalent postoperative disease. Preventive strategies, including meticulous hemostasis techniques and robotic surgery, should be prioritized by healthcare professionals to reduce POGD risk, improve short-term outcomes, and preserve healthcare resources.


Assuntos
Cirurgia Colorretal , Complicações Pós-Operatórias , Procedimentos Cirúrgicos Robóticos , Humanos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Fatores de Risco , Masculino , Feminino , Incidência , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Cirurgia Colorretal/efeitos adversos , Resultado do Tratamento , Idoso , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Fatores de Tempo , Tempo de Internação , Gastroenteropatias/etiologia , Gastroenteropatias/cirurgia , Gastroenteropatias/epidemiologia , Laparoscopia/efeitos adversos , Estudos Retrospectivos , Adulto
3.
New Microbes New Infect ; 62: 101469, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39282140

RESUMO

Background: Collecting and standardizing clinical research data is a very tedious task. This study is to develop an intelligent data collection tool, named CHB-EDC, for real-world cohort studies of chronic hepatitis B (CHB), which can assist in standardized and efficient data collection. Methods: CHB_EDC is capable of automatically processing various formats of data, including raw data in image format, using internationally recognized data standards, OCR, and NLP models. It can automatically populate the data into eCRFs designed in the REDCap system, supporting the integration of patient data from electronic medical record systems through commonly used web application interfaces. This tool enables intelligent extraction and aggregation of data, as well as secure and anonymous data sharing. Results: For non-electronic data collection, the average accuracy of manual collection was 98.65 %, with an average time of 63.64 min to collect information for one patient. The average accuracy CHB-EDC was 98.66 %, with an average time of 3.57 min to collect information for one patient. In the same data collection task, CHB-EDC achieved a comparable average accuracy to manual collection. However, in terms of time, CHB-EDC significantly outperformed manual collection (p < 0.05). Our research has significantly reduced the required collection time and lowered the cost of data collection while ensuring accuracy. Conclusion: The tool has significantly improved the efficiency of data collection while ensuring accuracy, enabling standardized collection of real-world data.

4.
Expert Rev Gastroenterol Hepatol ; 18(6): 283-292, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38937981

RESUMO

INTRODUCTION: Alcoholic liver disease (ALD) encompasses a spectrum of liver conditions, including liver steatosis, alcoholic hepatitis (AH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). microRNAs (miRNAs) have garnered significant interest as potential biomarkers for ALD. METHODS: We searched PubMed, Embase, Web of Science and Cochrane Central Register of Controlled Trials (CENTRAL) systemically from inception to June 2024. All extracted data was stratified according to the stages of ALD. The vote-counting strategy performed a meta-analysis on miRNA expression profiles. RESULTS: We included 40 studies. In serum of individuals with alcohol-use vs. no alcohol-use, miRNA-122 and miRNA-155 were upregulated, and miRNA-146a was downregulated. In patients with ALD vs. healthy controls, miRNA-122 and miRNA-155 were also upregulated, and miRNA-146a was downregulated. However, in patients with AH vs. healthy individuals, only the serum miRNA-122 level was upregulated. Due to insufficient data on diagnostic accuracy, we failed to conclude the ability of miRNAs to distinguish between different stages of ALD-related liver fibrosis. The results for ALD-related HCC were also insufficient and controversial. CONCLUSIONS: Circulating miRNA-122 was the most promising biomarker to manage individuals with ALD. More studies were needed for the diagnostic accuracy of miRNAs in ALD. REGISTRATION: This protocol was registered on the International Prospective Register of Systematic Reviews (PROSPERO) (www.crd.york.ac.uk/prospero/) with registration number CRD42023391931.


Assuntos
Biomarcadores , Hepatopatias Alcoólicas , MicroRNAs , Humanos , MicroRNAs/sangue , MicroRNAs/genética , Hepatopatias Alcoólicas/genética , Hepatopatias Alcoólicas/sangue , Biomarcadores/sangue , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/sangue , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/sangue
5.
Sci Adv ; 10(10): eadl0026, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38457511

RESUMO

Achieving regioselective synthesis in complex molecules with multiple reactive sites remains a tremendous challenge in synthetic chemistry. Regiodivergent palladium-catalyzed C─H arylation of complex antitumor drug osimertinib with various aryl bromides via the late-stage functionalization strategy was demonstrated here. This reaction displayed a switch in regioselectivity under complete base control. Potassium carbonate (K2CO3) promoted the arylation of acrylamide terminal C(sp2)-H, affording 34 derivatives. Conversely, sodium tert-butoxide (t-BuONa) mediated the aryl C(sp2)-H arylation of the indole C2 position, providing 27 derivatives. The derivative 3r containing a 3-fluorophenyl group at the indole C2 position demonstrated similar inhibition of EGFRT790M/L858R and superior antiproliferative activity in H1975 cells compared to osimertinib, as well as similar antiproliferative activity in A549 cells and antitumor efficacy in xenograft mouse model bearing H1975 cells. This approach provides a "one substrate-multi reactions-multiple products" strategy for the structural modification of complex drug molecules, creating more opportunities for the fast screening of pharmaceutical molecules.


Assuntos
Acrilamidas , Compostos de Anilina , Neoplasias Pulmonares , Paládio , Pirimidinas , Humanos , Animais , Camundongos , Paládio/química , Receptores ErbB , Mutação , Inibidores de Proteínas Quinases , Indóis/química , Catálise
6.
J Gastroenterol Hepatol ; 39(5): 847-857, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38240493

RESUMO

BACKGROUND: Patients with nonalcoholic fatty liver disease (NAFLD) are reported to have a higher risk of osteoporosis/fractures; however, the causal relationship remains unclear. METHODS: Publicly available genome-wide association studies (GWASs) were used for Mendelian randomization (MR) analysis. GWASs of NAFLD and fractures were obtained from the FinnGen Consortium. GWASs of bone mineral density (BMD) were derived from a meta-analysis. GWASs of obesity, diabetes, liver function, and serum lipid-related metrics were used to clarify whether the accompanying NAFLD symptoms contributed to fractures. Moreover, two additional GWASs of NAFLD were applied. RESULTS: A causal association was not observed between NAFLD and BMD using GWASs from the FinnGen Consortium. However, a causal relationship between NAFLD and femoral neck-BMD (FN-BMD), a suggestive relationship between fibrosis and FN-BMD, and between NAFLD and osteoporosis were identified in replication GWASs. Genetically proxied body mass index (BMI), high-density lipoprotein (HDL), and hip circumference increased the likelihood of lower limb fractures. The waist-to-hip ratio decreased, whereas glycated hemoglobin (HbA1C) and homeostasis model assessment of ß-cell function (HOMA-B) increased the risk of forearm fractures. Low-density lipoprotein (LDL) reduced, whereas HbA1C increased the incidence of femoral fractures. Alkaline phosphatase (ALP) raised the risk of foot fractures. However, after a multivariate MR analysis (adjusted for BMI), all the relationships became insignificant. CONCLUSIONS: NAFLD caused reduced BMD, and genetically predicted HDL, LDL, HbA1C, HOMA-B, ALP, hip circumference, and waist-to-hip ratio causally increased the risk of fractures. BMI may mediate causal relationships. Larger GWASs are required to verify this finding.


Assuntos
Índice de Massa Corporal , Densidade Óssea , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Hepatopatia Gordurosa não Alcoólica , Osteoporose , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/complicações , Humanos , Densidade Óssea/genética , Osteoporose/genética , Osteoporose/etiologia , Relação Cintura-Quadril , Fraturas Ósseas/etiologia , Fraturas Ósseas/genética , Fraturas Ósseas/epidemiologia , Hemoglobinas Glicadas/metabolismo , Colo do Fêmur/diagnóstico por imagem , Risco , Lipoproteínas HDL/sangue
8.
Stem Cell Rev Rep ; 20(2): 447-454, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37993759

RESUMO

Stem cell therapy holds great promise for future clinical practice for treatment of advanced liver diseases. However, the fate of stem cells after transplantation, including the distribution, viability, and the cell clearance, has not been fully elucidated. Herein, recent advances regarding the imaging tools for stem cells tracking mainly in chronic liver diseases with the advantages and disadvantages of each approach have been described. Magnetic resonance imaging is a promising clinical imaging modality due to non-radioactivity, excellent penetrability, and high spatial resolution. Fluorescence imaging and radionuclide imaging demonstrate relatively increased sensitivity, with the latter excelling in real-time monitoring. Reporter genes specialize in long-term tracing. Nevertheless, the disadvantages of low sensitivity, radiation, exogenous gene risk are inevitably present in each of these means, respectively. In this review, we aim to comprehensively evaluate the current state of methods for tracking of stem cell, highlighting their strengths and weaknesses, and providing insights into their future potential. Multimodality imaging strategies may overcome the inherent limitations of single-modality imaging by combining the strengths of different imaging techniques to provide more comprehensive information in the clinical setting.


Assuntos
Hepatopatias , Transplante de Células-Tronco , Humanos , Transplante de Células-Tronco/métodos , Genes Reporter , Imageamento por Ressonância Magnética/métodos , Hepatopatias/terapia
9.
RNA Biol ; 21(1): 1-15, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38113132

RESUMO

Nonalcoholic fatty liver disease (NAFLD), which affects approximately 25% of the global population, is an urgent health issue leading to various metabolic comorbidities. Circular RNAs (circRNAs), covalently closed RNA molecules, are characterized by ubiquity, diversity, stability, and conservatism. Indeed, they participate in various biological processes via distinct mechanisms that could modify the natural history of NAFLD. In this review, we briefly introduce the biogenesis, characteristics, and biological functions of circRNAs. Furthermore, we summarize circRNAs expression profiles in NAFLD by intersecting seven sequencing data sets and describe the cellular roles of circRNAs and their potential advantages as biomarkers of NAFLD. In addition, we emphatically discuss the exosomal non-coding RNA sorting mechanisms and possible functions in recipient cells. Finally, we extensively discuss the potential application of targeting disease-related circRNAs and competing endogenous RNA networks through gain-of-function and loss-of-function approaches in targeted therapy of NAFLD.


Assuntos
Hepatopatia Gordurosa não Alcoólica , RNA Circular , Humanos , RNA Circular/genética , RNA Circular/metabolismo , Hepatopatia Gordurosa não Alcoólica/genética , Relevância Clínica , RNA/genética , RNA/metabolismo , Biomarcadores
10.
Clin Case Rep ; 11(9): e7912, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37700775

RESUMO

Key Clinical Message: We report a young man with isolated elevated AST. He had no other evidence of liver or other related diseases. All the tests and examination reports were negative. The final diagnosis of macro-AST was confirmed by PEG precipitation tests. Abstract: Elevated liver enzymes, such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), may commonly indicate liver injury. However, macro-AST is generally a benign condition that may be considered as pathologic by clinicians. A young man with isolated elevated AST for more than 10 years who have taken extensive tests and examinations was diagnosed with macro-AST in our article. Thus, in patients with isolated AST-elevation, polyethylene glycol (PEG) precipitation test was recommended to test whether macro-AST could be diagnosed.

11.
Front Endocrinol (Lausanne) ; 14: 1196831, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37534206

RESUMO

Background: Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease that affects approximately one-quarter of the global population and is becoming increasingly prevalent worldwide. The lack of current noninvasive tools and efficient treatment is recognized as a significant barrier to the clinical management of these conditions. Extracellular vesicles (EVs) are nanoscale vesicles released by various cells and deliver bioactive molecules to target cells, thereby mediating various processes, including the development of NAFLD. Scope of review: There is still a long way to actualize the application of EVs in NAFLD diagnosis and treatment. Herein, we summarize the roles of EVs in NAFLD and highlight their prospects for clinical application as a novel noninvasive diagnostic tool as well as a promising therapy for NAFLD, owing to their unique physiochemical characteristics. We summarize the literatures on the mechanisms by which EVs act as mediators of intercellular communication by regulating metabolism, insulin resistance, inflammation, immune response, intestinal microecology, and fibrosis in NAFLD. We also discuss future challenges that must be resolved to improve the therapeutic potential of EVs. Major conclusions: The levels and contents of EVs change dynamically at different stages of diseases and this phenomenon may be exploited for establishing sensitive stage-specific markers. EVs also have high application potential as drug delivery systems with low immunogenicity and high biocompatibility and can be easily engineered. Research on the mechanisms and clinical applications of EVs in NAFLD is in its initial phase and the applicability of EVs in NAFLD diagnosis and treatment is expected to grow with technological progress.


Assuntos
Vesículas Extracelulares , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/terapia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Vesículas Extracelulares/metabolismo , Biomarcadores/metabolismo , Comunicação Celular , Sistemas de Liberação de Medicamentos
12.
Eur J Med Chem ; 260: 115722, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37595546

RESUMO

Autophagy is well-known to be a lysosome-mediated catabolic process for maintaining cellular and organismal homeostasis, which has been established with many links to a variety of human diseases. Compared with the therapeutic strategy for inhibiting autophagy, activating autophagy seems to be another promising therapeutic strategy in several contexts. Hitherto, mounting efforts have been made to discover potent and selective small-molecule activators of autophagy to potentially treat human diseases. Thus, in this perspective, we focus on summarizing the complicated relationships between defective autophagy and human diseases, and further discuss the updated progress of a series of small-molecule activators targeting autophagy in human diseases. Taken together, these inspiring findings would provide a clue on discovering more small-molecule activators of autophagy as targeted candidate drugs for potential therapeutic purposes.


Assuntos
Autofagia , Sistemas de Liberação de Medicamentos , Humanos , Homeostase , Lisossomos
13.
Clin Case Rep ; 11(8): e7784, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37564607

RESUMO

Key Clinical Message: Progressive multifocal leukoencephalopathy (PML) is a rare opportunistic infection of the brain caused by reactivation of the JC virus, which can lead to a lytic infection of oligodendrocytes. We report a patient with HIV who developed PML. Abstract: Progressive multifocal leukoencephalopathy (PML) is a rare opportunistic infection of the brain caused by reactivation of the John Cunningham virus (JCV), which can lead to a lytic infection of oligodendrocytes. Herein, we report the case of a patient with HIV who developed PML that presented as a progressive disturbance of consciousness and movement. The patient's clinical symptoms progressively deteriorated, and positive JC viral DNA in his cerebrospinal fluid (CSF) helped us diagnose him with PML. Magnetic resonance imaging (MRI) showed multiple asymmetric subcortical and deep white-matter lesions. Although we administered immunoreconstructive therapy, the patient's condition gradually worsened. Therefore, we suggest that PML should be considered if such lesions are found in MRIs of HIV patients.

14.
Stem Cell Res Ther ; 14(1): 231, 2023 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-37649110

RESUMO

BACKGROUND: Stem cells play a therapeutic role mainly through immunoregulation. However, the immunomodulatory function of stem cells may be affected by inflammation-related factors in patients' serum. Therefore, this study aims to investigate the possible mechanism by which acute-on-chronic liver failure (ACLF) patient serum influences the efficacy of hUC-MSCs. METHODS: The serum of surviving and dead ACLF patients was collected to culture hUC-MSCs in vitro, and the hUC-MSCs cultured in the serum of ACLF patients were used to treat acute liver failure (ALF) rats. The therapeutic effect on the rats was evaluated by a survival curve, the transaminase level and liver histopathology. The expression of cytokines in hUC-MSCs was detected by Q-PCR and ELISA. RESULTS: Serum pretreatment reduced the therapeutic effect of hUC-MSCs on ALF, especially pretreatment in the serum from dead ACLF patients. After hUC-MSCs were cultured in the serum of surviving or dead ACLF patients, the most differentially expressed factor was IL-8. Interfering with the expression of IL-8 in hUC-MSCs can improve the therapeutic effect of hUC-MSCs on ALF. The high level of IL-1ß in the serum of dead ACLF patients causes the increased expression of IL-8 in hUC-MSCs through the activation of the NF-κB signaling pathway. Meanwhile, we found that the neutralizing IL-1ß in serum from dead ACLF patients can improve the therapeutic effect of hUC-MSCs on ALF. CONCLUSION: The high level of IL-1ß in ACLF serum can promote the expression of IL-8 in hUC-MSCs through the NF-κB signaling pathway, thus reducing the effect of hUC-MSCs on ALF.


Assuntos
Insuficiência Hepática Crônica Agudizada , Interleucina-1beta , Interleucina-8 , Animais , Ratos , Insuficiência Hepática Crônica Agudizada/terapia , Interleucina-8/genética , NF-kappa B , Transdução de Sinais , Humanos , Interleucina-1beta/sangue
15.
Biomolecules ; 13(3)2023 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-36979495

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is currently the most common cause of chronic liver disease worldwide. Early identification and prompt treatment are critical to optimize patient management and improve long-term prognosis. Long non-coding RNA (lncRNA) and circular RNA (circRNA) are recently emerging non-coding RNAs, and are highly stable and easily detected in the circulation, representing a promising non-invasive approach for predicting NAFLD. A literature search of the Pubmed, Embase, Web of Science, and Cochrane Library databases was performed and 36 eligible studies were retrieved, including 18 on NAFLD, 13 on nonalcoholic steatohepatitis (NASH), and 11 on fibrosis and/or cirrhosis. Dynamic changes in lncRNA expression were associated with the occurrence and progression of NAFLD, among which lncRNA NEAT1, MEG3, and MALAT1 exhibited great potential as biomarkers for NAFLD. Moreover, mitochondria-located circRNA SCAR can drive metaflammation and its inhibition might be a promising therapeutic target for NASH. In this systematic review, we highlight the great potential of lncRNA/circRNA for early diagnosis and progression assessment of NAFLD. To further verify their clinical value, large-cohort studies incorporating lncRNA and circRNA expression both in liver tissue and blood should be conducted. Additionally, detailed studies on the functional mechanisms of NEAT1, MEG3, and MALAT1 will be essential for elucidating their roles in diagnosing and treating NAFLD, NASH, and fibrosis.


Assuntos
Hepatopatia Gordurosa não Alcoólica , RNA Longo não Codificante , Humanos , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/diagnóstico , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Circular/genética , Fígado/metabolismo , Fibrose
16.
Int J Mol Sci ; 24(2)2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36674813

RESUMO

Ectopic fat deposition in the liver, known as non-alcoholic fatty liver disease (NAFLD), affects up to 30% of the worldwide population. miRNA-122, the most abundant liver-specific miRNA, protects hepatic steatosis and inhibits cholesterol and fatty acid synthesis in NAFLD. Previously, we have shown that compared with its expression in healthy controls, miRNA-122 decreased in the liver tissue but gradually increased in the serum of patients with non-alcoholic fatty liver disease and non-alcoholic steatohepatitis, suggesting that miRNA-122 could have been transported to the serum. Here, we aimed to confirm and unravel the mechanism of transportation of miRNA-122 to extra-hepatocytes. Our findings showed a decrease in the intra-hepatocyte miRNA-122 and an increase in the extra-hepatocyte (medium level) miRNA-122, suggesting the miRNA-122 "escaped" from the intra-hepatocyte due to an increased extra-hepatocyte excretion. Using bioinformatics tools, we showed that miRNA-122 binds to circPI4KB, which was further validated by an RNA pull-down and luciferase reporter assay. The levels of circPI4KB in intra- and extra-hepatocytes corresponded to that of miRNA-122, and the overexpression of circPI4KB increased the miRNA-122 in extra-hepatocytes, consequently accomplishing a decreased protective role of miRNA-122 in inhibiting the lipid deposition. The present study provides a new explanation for the pathogenesis of the hepatic lipid deposition in NAFLD.


Assuntos
MicroRNAs , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/metabolismo , Metabolismo dos Lipídeos/genética , Fígado/metabolismo , Hepatócitos/metabolismo , Lipídeos
17.
Oncogene ; 42(8): 586-600, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36550358

RESUMO

The MRE11-RAD50-NBS1 (MRN) complex plays a crucial role in DNA double-strand breaks (DSBs) sensing and initiation of signaling cascades. However, the precise mechanisms by which the recruitment of MRN complex is regulated has yet to be elucidated. Here, we identified TRIpartite motif-containing protein 24 (TRIM24), a protein considered as an oncogene overexpressed in cancers, as a novel signaling molecule in response to DSBs. TRIM24 is essential for DSBs-induced recruitment of MRN complex and activation of downstream signaling. In the absence of TRIM24, MRN mediated DSBs repair is remarkably diminished. Mechanistically, TRIM24 is phosphorylated by ataxia-telangiectasia mutated (ATM) and then recruited to DSBs sites, facilitating the accumulation of the MRN components to chromatin. Depletion of TRIM24 sensitizes human hepatocellular carcinoma cells to cancer therapy agent-induced apoptosis and retards the tumor growth in a subcutaneous xenograft tumor mouse model. Together, our data reveal a novel function of TRIM24 in response to DSBs through regulating the MRN complex, which suggests that TRIM24 may be a potential therapeutic molecular target for tumor treatment.


Assuntos
Proteínas de Transporte , Proteínas de Ciclo Celular , Quebras de DNA de Cadeia Dupla , Animais , Humanos , Camundongos , Hidrolases Anidrido Ácido/metabolismo , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Proteínas de Ciclo Celular/metabolismo , Reparo do DNA , Enzimas Reparadoras do DNA/genética , Enzimas Reparadoras do DNA/metabolismo , Proteína Homóloga a MRE11/genética , Proteína Homóloga a MRE11/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo
18.
Dig Dis Sci ; 68(4): 1605-1614, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36227429

RESUMO

BACKGROUND: The association between hepatitis B and concomitant diseases, such as fatty liver, T2DM, MetS, and Hp infection, remains unclear. AIM: The present study was to illustrate the association and explore the co-contribution on abnormal transaminase and progression of liver stiffness. METHODS: A total of 95,998 participants underwent HBsAg screening in West China Hospital from 2014 to 2017. Multivariable logistic regression was used to determine the adjusted odds ratios. RESULTS: The prevalence of HBsAg-positive rate was 8.30% of our included study population. HBsAg positive was associated with negative risk of fatty liver (odds ratio [OR] 0.71, 95% confidence interval [CI] 0.65-0.78, p < 0.001) and MetS (OR 0.74, 95% CI 0.67-0.84, p < 0.001), and with positive risk of Hp infection (OR 1.09, 95% CI 1.02-1.17, p = 0.012) and T2DM (OR 1.18, 95% CI 1.01-1.40, p = 0.043). Besides, HBsAg-positive patients with T2DM had higher risk of elevated ALT (OR 2.09, 95% CI 1.69-2.83, p < 0.001 vs OR 1.59, 95% CI 1.51-1.68, p < 0.001), AST (OR 2.69, 95% CI 1.98-3.65, p < 0.001 vs OR 1.89, 95% CI 1.76-2.02, p < 0.001) than HBV alone. In addition to HBV, T2DM also can increase the risk of liver fibrosis (OR 3.23, 95% CI 1.35-7.71, p = 0.008) and cirrhosis (OR 4.31, 95% CI 1.41-13.20, p = 0.010). CONCLUSION: Hepatitis B patients have a lower risk of fatty liver and MetS, and a higher risk of T2DM and Hp infection. Besides, T2DM might be possibly associated with abnormal liver transaminase and fibrosis progression in HBsAg-positive patients.


Assuntos
Diabetes Mellitus Tipo 2 , Fígado Gorduroso , Hepatite B , Humanos , Vírus da Hepatite B , Antígenos de Superfície da Hepatite B , Hepatite B/complicações , Hepatite B/epidemiologia , Cirrose Hepática/diagnóstico , Cirrose Hepática/epidemiologia , Cirrose Hepática/complicações , Fígado Gorduroso/complicações , Alanina Transaminase , Diabetes Mellitus Tipo 2/complicações
19.
Asian J Surg ; 46(2): 841-849, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36123208

RESUMO

BACKGROUND: Pseudolymphoma is a rare, benign, nonspecific condition that forms a mass-like lesion characterized by the proliferation of non-neoplastic lymphocytes. Lacking of specific clinical symptoms, serological markers, and imaging features, the diagnosis is difficult. We reporte five cases of hepatic pseudolymphoma and provide a systematic review of existing literatures to improve our understanding of this rare liver disease. METHODS: We followed-up five cases of hepatic pseudolymphoma in West China Hospital from January 2002 to January 2022. We also summarized the cases of hepatic pseudolymphoma from January 1981 to December 2021 through the PubMed database and comprehensively analyzed the characteristics of the cases. RESULTS: The pathologic features of the five cases were characterized by benign lymphoid tissue hyperplasia, lymphoid follicle formation, and a polarized germinal center. Immunohistochemistry, in situ hybridization, and gene rearrangement revealed non-malignant lymphoma. Besides, a total of 116 cases have been reported in the PubMed database from 1981 to 2021. The incidence of hepatic pseudolymphoma is higher in middle-aged and elderly women and has been reported more frequently in Asia. All cases were pathologically diagnosed, among which 85.95% of the patients were treated by surgery. CONCLUSIONS: Hepatic pseudolymphoma is an extremely rare benign disease, mainly in middle-aged and elderly women. Without distinctive clinical and imaging characteristics, pathological diagnosis is the highly reliable method at present. Thus, in the absence of risk factors for a primary liver tumor or metastatic tumor in middle-aged and elderly women, the possibility of pseudolymphoma should be considered to avoid extensive treatments.


Assuntos
Hepatopatias , Neoplasias Hepáticas , Pseudolinfoma , Pessoa de Meia-Idade , Idoso , Humanos , Feminino , Pseudolinfoma/diagnóstico , Pseudolinfoma/patologia , Hepatopatias/cirurgia , Neoplasias Hepáticas/patologia , Imuno-Histoquímica , Diagnóstico Diferencial
20.
Quant Imaging Med Surg ; 12(12): 5433-5451, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36465825

RESUMO

Background: For patients with hepatocellular carcinoma (HCC) undergoing hepatectomy, insufficient remnant liver regenerative capacity can lead to liver failure. The aim of this study was to evaluate the potential role of magnetic resonance elastography (MRE) for the preoperative prediction of liver regeneration in patients with HCC after partial hepatectomy (PH). Methods: A total of 54 patients with HCC undergoing MRE prior to PH were retrospectively included. The total functional liver, volume of preoperative future liver remnant (LVpre), and volume of postoperative liver remnant (LVpost), respectively, were measured, and the regeneration index (RI) and parenchymal hepatic resection rate (PHRR) were manually calculated. Univariate and multivariate logistic regression analyses were conducted to identify factors associated with a high RI, and receiver operating characteristic (ROC) curves were employed to evaluate the diagnostic performance of the liver stiffness (LS) values. Patients were classified into three subgroups based on the value of PHRR: low PHRR (<30%), intermediate PHRR (30-50%), and high PHRR (>50%). Subsequently, Spearman correlation analysis was used to investigate the relationship between LS values and RI in the subgroups. Results: Multivariable analysis revealed a low LS value was associated with greater odds of a high RI [odds ratio (OR), 0.049; 95% confidence interval (CI): 0.002 to 0.980]. An optimal cutoff value of 3.30 kPa was used to divide all patients into a low RI group and a high RI group with an area under the curve (AUC) value of 0.882 (95% CI: 0.767 to 0.996). A significant negative relationship between RI and LS values (r=-0.799; P<0.001) was observed in the intermediate PHRR subgroup. Conclusions: The LS values based on MRE may serve as a potential preoperative predictor of liver regeneration for patients with HCC undergoing PH.

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