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Accurate detection of homologous recombination deficiency (HRD) in cancer patients is paramount in clinical applications, as HRD confers sensitivity to poly (ADP-ribose) polymerase (PARP) inhibitors. With the advances in genome sequencing technology, mutational profiling on a genome-wide scale has become readily accessible, and our knowledge of the genomic consequences of HRD has been greatly expanded and refined. Here, we review the recent advances in HRD detection methods. We examine the copy number and structural alterations that often accompany the genome instability that results from HRD, describe the advantages of mutational signature-based methods that do not rely on specific gene mutations, and review some of the existing algorithms used for HRD detection. We also discuss the choice of sequencing platforms (panel, exome, or whole-genome) and catalog the HRD detection assays used in key PARP inhibitor trials.
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Two-dimensional conjugated metal-organic frameworks (2D cMOFs) are emerging as promising materials for electrochemical energy storage (EES). Despite considerable interest, an understanding of their electrochemical stability and the factors contributing to their degradation during cycling is largely lacking. Here we investigate three Cu-based MOFs and report that the dissolution of 2D cMOFs into electrolytes is a prevalent and significant degradation pathway. Several factors, such as the inherent solubility of ligands in electrolyte solvents and the duration of charge-discharge cycling exert a strong influence on the dissolution process. When these factors combine within a MOF, severely limited cycling stability is observed, with dissolution accounting for up to 80% of capacity degradation. Conversely, excellent cycling stability is observed when testing a Cu-MOF with a sparingly soluble ligand within an optimized potential window. Overall, these findings represent essential insights into the electrochemical stability of 2D cMOFs, offering crucial guidelines for their targeted development in EES applications.
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Purpose: This study contributes to the evolving understanding of the pivotal involvement of Sirtuins (SIRTs) in various human cancers, with a particular focus on elucidating their expression patterns and clinical relevance within the context of hepatocellular carcinoma (HCC). The investigation involves a comprehensive analysis of mRNA expression and prognostic implications associated with distinct SIRTs in HCC. Patients and Methods: Initial data pertaining to SIRT expression in HCC patients were collated from publicly accessible databases. Subsequently, the expression levels of select members of the SIRT family were validated using clinicopathological specimens from HCC patients. Additionally, HCC tissue microarray was employed to scrutinize the correlation between SIRT7 expression and HCC prognosis. Results: The findings indicated a substantial upregulation of SIRT2, SIRT3, SIRT4, SIRT6, and SIRT7 in HCC tissues. Survival analysis underscored a pronounced association between elevated mRNA levels of SIRT3, SIRT6, and SIRT7 and an adverse prognosis for HCC patients. Particularly, SIRT7 emerged as a potential independent risk factor for poor prognosis in HCC patients. Examination of the HCC tissue microarray revealed heightened expression of SIRT7 in 68 cases (54.8%) of HCC tissues. Multivariate analysis established high SIRT7 expression as an independent risk factor for diminished Disease-Free Survival (DFS) and Overall Survival (OS) in HCC patients. Conclusion: The aberrant expression of SIRT7 presents itself may be as a novel biomarker for predicting the prognosis of HCC patients.
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Insertion of active retroelements-L1s, Alus, and SVAs-can disrupt proper genome function and lead to various disorders including cancer. However, the role of de novo retroelements (DNRTs) in birth defects and childhood cancers has not been well characterized due to the lack of adequate data and efficient computational tools. Here, we examine whole-genome sequencing data of 3,244 trios from 12 birth defect and childhood cancer cohorts in the Gabriella Miller Kids First Pediatric Research Program. Using an improved version of our tool xTea (x-Transposable element analyzer) that incorporates a deep-learning module, we identified 162 DNRTs, as well as 2 pseudogene insertions. Several variants are likely to be causal, such as a de novo Alu insertion that led to the ablation of a whole exon in the NF1 gene in a proband with brain tumor. We observe a high de novo SVA insertion burden in both high-intolerance loss-of-function genes and exons as well as more frequent de novo Alu insertions of paternal origin. We also identify potential mosaic DNRTs from embryonic stages. Our study reveals the important roles of DNRTs in causing birth defects and predisposition to childhood cancers.
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Actinidia arguta, the most widely distributed Actinidia species and the second cultivated species in the genus, can be distinguished from the currently cultivated Actinidia chinensis on the basis of its small and smooth fruit, rapid softening, and excellent cold tolerance. Adaptive evolution of tetraploid Actinidia species and the genetic basis of their important agronomic traits are still unclear. Here, we generated a chromosome-scale genome assembly of an autotetraploid male A. arguta accession. The genome assembly was 2.77 Gb in length with a contig N50 of 9.97 Mb and was anchored onto 116 pseudo-chromosomes. Resequencing and clustering of 101 geographically representative accessions showed that they could be divided into two geographic groups, Southern and Northern, which first diverged 12.9 million years ago. A. arguta underwent two prominent expansions and one demographic bottleneck from the mid-Pleistocene climate transition to the late Pleistocene. Population genomics studies using paleoclimate data enabled us to discern the evolution of the species' adaptation to different historical environments. Three genes (AaCEL1, AaPME1, and AaDOF1) related to flesh softening were identified by multi-omics analysis, and their ability to accelerate flesh softening was verified through transient expression assays. A set of genes that characteristically regulate sexual dimorphism located on the sex chromosome (Chr3) or autosomal chromosomes showed biased expression during stamen or carpel development. This chromosome-level assembly of the autotetraploid A. arguta genome and the genes related to important agronomic traits will facilitate future functional genomics research and improvement of A. arguta.
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Actinidia , Genoma de Planta , Tetraploidia , Actinidia/genética , Evolução Molecular , Adaptação Fisiológica/genética , Evolução BiológicaRESUMO
Characterizing somatic mutations in the brain is important for disentangling the complex mechanisms of aging, yet little is known about mutational patterns in different brain cell types. Here, we performed whole-genome sequencing (WGS) of 86 single oligodendrocytes, 20 mixed glia, and 56 single neurons from neurotypical individuals spanning 0.4-104 years of age and identified >92,000 somatic single-nucleotide variants (sSNVs) and small insertions/deletions (indels). Although both cell types accumulate somatic mutations linearly with age, oligodendrocytes accumulated sSNVs 81% faster than neurons and indels 28% slower than neurons. Correlation of mutations with single-nucleus RNA profiles and chromatin accessibility from the same brains revealed that oligodendrocyte mutations are enriched in inactive genomic regions and are distributed across the genome similarly to mutations in brain cancers. In contrast, neuronal mutations are enriched in open, transcriptionally active chromatin. These stark differences suggest an assortment of active mutagenic processes in oligodendrocytes and neurons.
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Envelhecimento , Encéfalo , Neurônios , Oligodendroglia , Humanos , Envelhecimento/genética , Envelhecimento/patologia , Cromatina/genética , Cromatina/metabolismo , Mutação , Neurônios/metabolismo , Neurônios/patologia , Oligodendroglia/metabolismo , Oligodendroglia/patologia , Análise da Expressão Gênica de Célula Única , Sequenciamento Completo do Genoma , Encéfalo/metabolismo , Encéfalo/patologia , Polimorfismo de Nucleotídeo Único , Mutação INDEL , Bancos de Espécimes Biológicos , Células Precursoras de Oligodendrócitos/metabolismo , Células Precursoras de Oligodendrócitos/patologiaRESUMO
The consensus has been reached on the benefits of surgical drainage. However, catheter-related blockage and retrograde infection remain bottleneck problems in the treatment process. To this end, with Huashan Hospital, Fudan University, as the main inventors, a drainage tube dredging umbrella and anti-retrograde infection kit have been designed and applied for the national utility model patent (patent number: ZL 2023 2 1300036.2). The main body of the kit consists of a catheter dredging umbrella, drainage tube, and drainage bag. Several isolation layers are installed in the drainage bag to form a maze structure and a reflux valve is added, thereby increasing the distance and resistance of liquid reflux, greatly reducing the possibility of liquid reflux entering the drainage tube, so as to reduce the risk of retrograde infection through physical means. When the drainage tube is blocked, the drainage tube and joint tube of the drainage bag can be separated, the unblocking umbrella can be inserted into the blockage through the guide wire, the cannula can be inserted along the guide wire, the guide wire is pulled to release the dredging umbrella in the contraction state, and the dredging umbrella can be pulled back in the expansion state until the blockage is removed from the drainage tube. The operating procedure is standardized and simple. While preventing retrograde infection (anti-retrograde infection kit), the catheter dredging umbrella could effectively address the issue of catheter blockage. It has certain clinical promotion and application value.
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Anti-Infecciosos , Drenagem , Humanos , Cânula , Consenso , HospitaisRESUMO
Mutational signature analysis is a recent computational approach for interpreting somatic mutations in the genome. Its application to cancer data has enhanced our understanding of mutational forces driving tumorigenesis and demonstrated its potential to inform prognosis and treatment decisions. However, methodological challenges remain for discovering new signatures and assigning proper weights to existing signatures, thereby hindering broader clinical applications. Here we present Mutational Signature Calculator (MuSiCal), a rigorous analytical framework with algorithms that solve major problems in the standard workflow. Our simulation studies demonstrate that MuSiCal outperforms state-of-the-art algorithms for both signature discovery and assignment. By reanalyzing more than 2,700 cancer genomes, we provide an improved catalog of signatures and their assignments, discover nine indel signatures absent in the current catalog, resolve long-standing issues with the ambiguous 'flat' signatures and give insights into signatures with unknown etiologies. We expect MuSiCal and the improved catalog to be a step towards establishing best practices for mutational signature analysis.
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Música , Neoplasias , Humanos , Neoplasias/genética , Mutação , Carcinogênese/genética , Mutação INDELRESUMO
RBCK1 is an important E3 ubiquitin ligase, which plays an important role in many major diseases. However, the function and mechanism of RBCK1 in pan-cancer and its association with immune cell infiltration have not been reported. The purpose of this study is to find out the expression of RBCK1 in cancer, and to explore the relationship between RBCK1 and the prognosis of patients. Our results show that the expression of RBCK1 is up-regulated in a variety of malignant tumors, and is closely related to the prognosis of patients. Further studies have shown that RBCK1 regulates protein expression in the nucleus and plays an important role in ribosome and valine, leucine, and isoleucine degradation. Genetic variation analysis showed that RBCK1 was mainly involved in missense mutations in multiple tumors, and mutated patients showed poor prognoses. Further studies showed that RBCK1 may be interacted with proteins such as RNRPB, MCRS1, TRIB3, MKKS and ARPC3. Through protein interaction analysis, we found 43 proteins interacting with RBCK1 in liver cancer. We also analyzed immune cell infiltration and found that RBCK1 expression was positively correlated with T cells and macrophages, while it was negatively correlated with neutrophils, NK cells, and DCs in liver cancer. Finally, we confirmed experimentally that RBCK1 can significantly inhibit the apoptosis and invasion of HCC. Therefore, we speculate that RBCK1 plays an important regulatory role in the occurrence and development of HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Chlorocebus aethiops , Neoplasias Hepáticas/genética , Prognóstico , Proteínas de Ligação a RNA , Fatores de Transcrição/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismoRESUMO
Despite the overall efficacy of immune checkpoint blockade (ICB) for mismatch repair deficiency (MMRD) across tumor types, a sizable fraction of patients with MMRD still do not respond to ICB. We performed mutational signature analysis of panel sequencing data (n = 95) from MMRD cases treated with ICB. We discover that T>C-rich single base substitution (SBS) signatures-SBS26 and SBS54 from the COSMIC Mutational Signatures catalog-identify MMRD patients with significantly shorter overall survival. Tumors with a high burden of SBS26 show over-expression and enriched mutations of genes involved in double-strand break repair and other DNA repair pathways. They also display chromosomal instability (CIN), likely related to replication fork instability, leading to copy number losses that trigger immune evasion. SBS54 is associated with transcriptional activity and not with CIN, defining a distinct subtype. Consistently, cancer cell lines with a high burden of SBS26 and SBS54 are sensitive to treatments targeting pathways related to their proposed etiology. Together, our analysis offers an explanation for the heterogeneous responses to ICB among MMRD patients and supports an SBS signature-based predictor as a prognostic biomarker for differential ICB response.
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Inspired by the natural skeletal muscles, this paper presents a novel shape memory alloy-based artificial muscle matrix (AMM) with advantages of a large output force and displacement, flexibility, and compactness. According to the composition of the AMM, we propose a matrix control strategy to achieve independent control of the output force and displacement of the AMM. Based on the kinematics simulation and experiments, we obtained the output displacement and bearing capacity of the smart digital structure (SDS) and confirmed the effectiveness of the matrix control strategy to achieve force and displacement output independently and controllably. A bionic mechanical ankle actuated by AMM was proposed to demonstrate the actuating capability of the AMM. Experimental results show that the angle and force of the bionic mechanical ankle are output independently and have a significant gradient. In addition, by using a self-sensing method (resistance self-feedback) and PD control strategy, the output angle and force of the bionic mechanical ankle can be maintained for a long time without overheating of the AMM.
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Contamination by pathogens, such as bacteria, can irritate a wound and prevent its healing, which may affect the physical fitness of the infected person. As such, the development of more novel nano-biomaterials able to cope with the inflammatory reaction to bacterial infection during the wound healing process to accelerate wound healing is required. Herein, a halofuginonesilver nano thermosensitive hydrogel (HTPM&AgNPs-gel) was prepared via a physical swelling method. HTPM&AgNPs-gel was characterized based on thermogravimetric analysis, differential scanning calorimetry, morphology, injectability, and rheological mechanics that reflected its exemplary nature. Moreover, HTPM&AgNPs-gel was further tested for its ability to facilitate healing of skin fibroblasts and exert antibacterial activity. Finally, HTPM&AgNPs-gel was tested for its capacity to accelerate general wound healing and treat bacterially induced wound damage. HTPM&AgNPs-gel appeared spherical under a transmission electron microscope and showed a grid structure under a scanning electron microscope. Additionally, HTPM&AgNPs-gel demonstrated excellent properties, including injectability, temperature-dependent swelling behavior, low loss at high temperatures, and appropriate rheological properties. Further, HTPM&AgNPs-gel was found to effectively promote healing of skin fibroblasts and inhibit the proliferation of Escherichia coli and Staphylococcus aureus. An evaluation of the wound healing efficacy demonstrated that HTPM&AgNPs-gel had a more pronounced ability to facilitate wound repair and antibacterial effects than HTPM-gel or AgNPs-gel alone, and exhibited ideal biocompatibility. Notably, HTPM&AgNPs-gel also inhibited inflammatory responses in the healing process. HTPM&AgNPs-gel exhibited antibacterial, anti-inflammatory, and scar repair features, which remarkably promoted wound healing. These findings indicated that HTPM&AgNPs-gel holds great clinical potential as a promising and valuable wound healing treatment.
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Nanopartículas Metálicas , Piperidinas , Quinazolinonas , Prata , Humanos , Prata/farmacologia , Prata/química , Staphylococcus aureus , Cicatrização , Nanopartículas Metálicas/química , Antibacterianos/farmacologia , Hidrogéis/química , Anti-Inflamatórios/farmacologiaRESUMO
BACKGROUND: Surgery plays an important role in the treatment of neuroblastoma. Perioperative complications may impact the course of neuroblastoma treatment. To date, comprehensive analyses of complications and risk factors have been lacking. METHODS: Patients with retroperitoneal neuroblastoma undergoing tumor resection were retrospectively analyzed between 2014 and 2021. The data collected included clinical characteristics, operative details, operative complications and postoperative outcomes. Risk factors for perioperative complications of retroperitoneal neuroblastoma were analyzed. RESULTS: A total of 571 patients were enrolled in this study. Perioperative complications were observed in 255 (44.7%) patients. Lymphatic leakage (28.4%), diarrhea (13.5%), and injury (vascular, nerve and organ; 7.5%) were the most frequent complications. There were three operation-related deaths (0.53%): massive hemorrhage (n = 1), biliary tract perforation (n = 1) and intestinal necrosis (n = 1). The presence of image-defined risk factors (IDRFs) [odds ratio (OR) = 2.09, P < 0.01], high stage of the International Neuroblastoma Risk Group staging system (INRGSS) (OR = 0.454, P = 0.04), retroperitoneal lymph node metastasis (OR = 2.433, P = 0.026), superior mesenteric artery encasement (OR = 3.346, P = 0.003), and inferior mesenteric artery encasement (OR = 2.218, P = 0.019) were identified as independent risk factors for perioperative complications. CONCLUSIONS: Despite the high incidence of perioperative complications, the associated mortality rate was quite low. Perioperative complications of retroperitoneal neuroblastoma were associated with IDRFs, INRGSS, retroperitoneal lymph node metastasis and vascular encasement. Patients with high-risk factors should receive more serious attention during surgery but should not discourage the determination to pursue total resection of neuroblastoma. Video Abstract (MP4 94289 KB).
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Neuroblastoma , Criança , Humanos , Estudos Retrospectivos , Incidência , Metástase Linfática , Neuroblastoma/epidemiologia , Neuroblastoma/cirurgia , Fatores de Risco , Complicações Pós-Operatórias/epidemiologia , Estadiamento de NeoplasiasRESUMO
Lysophosphatidic acid acyltransferases (LPAATs) catalyze the formation of phosphatidic acid (PA), a central metabolite in both prokaryotic and eukaryotic organisms for glycerolipid biosynthesis. Phaeodactylum tricornutum contains at least two plastid-localized LPAATs (ptATS2a and ptATS2b), but their roles in lipid synthesis remain unknown. Both ptATS2a and ptATS2b could complement the high temperature sensitivity of the bacterial plsC mutant deficient in LPAAT. In vitro enzyme assays showed that they prefer lysophosphatidic acid over other lysophospholipids. ptATS2a is localized in the plastid inner envelope membrane and CRISPR/Cas9-generated ptATS2a mutants showed compromised cell growth, significantly changed plastid and extra-plastidial membrane lipids at nitrogen-replete condition and reduced triacylglycerols (TAGs) under nitrogen-depleted condition. ptATS2b is localized in thylakoid membranes and its knockout led to reduced growth rate and TAG content but slightly altered molecular composition of membrane lipids. The changes in glycerolipid profiles are consistent with the role of both LPAATs in the sn-2 acylation of sn-1-acyl-glycerol-3-phosphate substrates harboring 20:5 at the sn-1 position. Our findings suggest that both LPAATs are important for membrane lipids and TAG biosynthesis in P. tricornutum and further highlight that 20:5-Lyso-PA is likely involved in the massive import of 20:5 back to the plastid to feed plastid glycerolipid syntheses.
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Aciltransferases , Lipídeos de Membrana , Triglicerídeos , Aciltransferases/metabolismo , Plastídeos/metabolismo , Ácidos Fosfatídicos , NitrogênioRESUMO
The consensus has been reached on the benefits of surgical drainage. However, catheter-related blockage and retrograde infection remain bottleneck problems in the treatment process. To this end, with Huashan Hospital, Fudan University, as the main inventors, a drainage tube dredging umbrella and anti-retrograde infection kit have been designed and applied for the national utility model patent (patent number: ZL 2023 2 1300036.2). The main body of the kit consists of a catheter dredging umbrella, drainage tube, and drainage bag. Several isolation layers are installed in the drainage bag to form a maze structure and a reflux valve is added, thereby increasing the distance and resistance of liquid reflux, greatly reducing the possibility of liquid reflux entering the drainage tube, so as to reduce the risk of retrograde infection through physical means. When the drainage tube is blocked, the drainage tube and joint tube of the drainage bag can be separated, the unblocking umbrella can be inserted into the blockage through the guide wire, the cannula can be inserted along the guide wire, the guide wire is pulled to release the dredging umbrella in the contraction state, and the dredging umbrella can be pulled back in the expansion state until the blockage is removed from the drainage tube. The operating procedure is standardized and simple. While preventing retrograde infection (anti-retrograde infection kit), the catheter dredging umbrella could effectively address the issue of catheter blockage. It has certain clinical promotion and application value.
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Objective To investigate the clinical characteristics and risk factors of thyroid dysfunction(TD)in malignant tumor patients treated with immune checkpoint inhibitors(ICIs).Methods A total of 157 cancer patients who were hospitalized and received ICIs treatment in the First People's Hospital of Yunnan Province from January 2019 to June 2022 were collected and divided into the normal thyroid function group and abnormal thyroid function group based on whether TD had occurred.Fifty-eight patients with the normal thyroid function and 58 patients with the abnormal thyroid function were selected,and 58 healthy adults who underwent the physical examination in our hospital were randomly selected as the control group.The baseline data on the gender,age,tumor and ICIs type,history of surgery before medication,history of radiotherapy and chemotherapy,and the related indicators of liver and kidney function,blood lipids,thyroid hormone levels and so on were collected.The relevant indicators of the three groups were statistically analyzed,and the normal thyroid function group and abnormal thyroid function group were compared to evaluate the clinical characteristics and related risk factors of TD caused by ICIs.Results 1.Among 157 patients treated with ICIs,58 cases(36.9%)had thyroid dysfunction,including 39 cases of hypothyroidism(including subclinical hypothyroidism),9 cases of hyperthyroidism(including subclinical hyperthyroidism),and 10 cases of pure related antibody abnormality.2.The analysis of the data of the normal thyroid function group,the abnormal thyroid function group and the control group showed that the age,thyroid stimulating hormone(TSH),and thyroid function of the three groups were significantly different.TSH)baseline level,free triiodothyronine(FT3)baseline level and aspartate transaminase(AST)baseline level were statistically different(P<0.05).There were significant differences in TSH baseline and radiotherapy history between the normal thyroid function group and the abnormal thyroid function group(P<0.05);Multivariate analysis showed that the radiotherapy history(OR=7.291,95% CI= 1.579-33.663,P<.05),baseline TSH level(OR=3.917,95% CI= 1.697-9.038,P<0.05)were the independent risk factors for thyroid dysfunction in cancer patients after ICIs treatment.Conclusion Hypothyroidism is the most common type of TD caused by ICIs in cancer patients.The baseline TSH level and the history of radiotherapy are the independent risk factors for thyroid dysfunction.
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Background/Aims@#This study aims to investigate the effect of a fermented rice drink with Lactiplantibacillus plantarum JSA22 on symptoms, blood tests, microbiomes, and fecal metabolites in patients with irritable bowel syndrome (IBS) who were overweight. @*Methods@#Sixty overweight (body mass index ≥ 23 kg/m2 ) patients aged between 20 and 65 with IBS were enrolled. Patients were divided into 2 groups and administered either a fermented rice drink or an nonfermented rice drink for a month. The symptom questionnaire, blood samples, and stool samples for microbiome and metabolite were collected before and after the month of rice drink administration.The primary efficacy variable was the subject’s global assessment of IBS symptoms. @*Results@#In both groups, global IBS symptoms, including abdominal pain, bowel habit, urgency, and abdominal distension, improved significantly (P < 0.01). The abdominal bloating was more significantly improved in the fermented rice drink group than in the nonfermented rice drink group (P < 0.05). Significant changes were not observed in metabolic syndrome-related blood tests or fecal metabolites in either group. However, microbiome analysis showed significant differences in genus levels before and after consuming fermented rice drink, such as in Blautia in stool (P = 0.020) and Prevotella (P = 0.017) and Oribacterium (P = 0.018) in saliva. @*Conclusions@#The fermented rice drink with L. plantarum JSA22 showed a beneficial effect in reducing abdominal distension in IBS patients. Bacteria that reduce visceral fat accumulation increased in the stool and saliva of patients who consumed fermented rice drinks.
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Non-alcoholic fatty liver disease (NAFLD) is associated with mutations in lipopolysaccharide-binding protein ( LBP), but the underlying epigenetic mechanisms remain understudied. Herein, LBP -/- rats with NAFLD were established and used to conduct integrative targeting-active enhancer histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation coupled with high-throughput and transcriptomic sequencing analysis to explore the potential epigenetic pathomechanisms of active enhancers of NAFLD exacerbation upon LBP deficiency. Notably, LBP -/- reduced the inflammatory response but markedly aggravated high-fat diet (HFD)-induced NAFLD in rats, with pronounced alterations in the histone acetylome and regulatory transcriptome. In total, 1â¯128 differential enhancer-target genes significantly enriched in cholesterol and fatty acid metabolism were identified between wild-type (WT) and LBP -/- NAFLD rats. Based on integrative analysis, CCAAT/enhancer-binding protein ß (C/EBPß) was identified as a pivotal transcription factor (TF) and contributor to dysregulated histone acetylome H3K27ac, and the lipid metabolism gene SCD was identified as a downstream effector exacerbating NAFLD. This study not only broadens our understanding of the essential role of LBP in the pathogenesis of NAFLD from an epigenetics perspective but also identifies key TF C/EBPß and functional gene SCD as potential regulators and therapeutic targets.
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Hepatopatia Gordurosa não Alcoólica , Animais , Ratos , Acetilação , Histonas/metabolismo , Lipídeos , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/veterinária , Estearoil-CoA Dessaturase/metabolismoRESUMO
Distiller's grains, byproducts of the brewing process, represent a valuable resource for extracting natural phenolic compounds due to their significant global production. This study presents the first evidence of the protective effects of Moutai distiller's grain polyphenol extract (MDGP) on dextran sulfate sodium (DSS)-induced colitis in mice. These protective effects manifest predominantly through the amelioration of general colitis indices and histopathological improvements. Utilizing liquid chromatography-high-resolution electrospray ionization mass spectrometry (LC-HR-ESI-MS), the main components of MDGP were identified as rutin, quercetin, naringenin, and dihydroquercetin. Moreover, a novel mechanism was elucidated by which rutin, the primary active component of MDGP, alleviates DSS-induced colitis. Assessment of intestinal barrier function, microbial sequencing, fecal transplantation, and antibiotic depletion experiments revealed that rutin suppresses the abundance of pathogenic bacteria (Helicobacter, Klebsiella, and Veillonella) while promoting the proliferation of beneficial bacteria (Ruminococcus_torques_group, Lachnoclostridium, and norank_f__Muribaculaceae). This modulation culminates in elevated butyric acid concentrations within short-chain fatty acids (SCFAs), amplified integrity of tight (ZO-1, occludin) and adherent (E-cadherin, ß-catenin) junctional complexes, fortified intestinal barrier function, and diminished intestinal inflammation.This investigation accentuates the innovative therapeutic potential of MDGP and its main active component, rutin, in assuaging DSS-induced intestinal inflammation and fortifying the intestinal barrier through a mechanism predominantly mediated by the intestinal microbiota. Such insights potentially elevate the prominence of distiller's grains in the realm of functional food development.
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Esophageal cancer (EC) has a high incidence and mortality rate and is emerging as one of the most common health problems globally. Owing to the lack of sensitive detection methods, uncontrollable rapid metastasis, and pervasive treatment resistance, EC is often diagnosed in advanced stages and is susceptible to local recurrence. Exosomes are important components of intercellular communication and the exosome-mediated crosstalk between the cancer and surrounding cells within the tumor microenvironment plays a crucial role in the metastasis, progression, and therapeutic resistance of EC. Considering the critical role of exosomes in tumor pathogenesis, this review focused on elucidating the impact of exosomes on EC metastasis and therapeutic resistance. Here, we summarized the relevant signaling pathways involved in these processes. In addition, we discussed the potential clinical applications of exosomes for the early diagnosis, prognosis, and treatment of EC.