RESUMEN

Spatial proteomics is a multidimensional technique that studies the spatial distribution and function of proteins within cells or tissues across both spatial and temporal dimensions. This field multidimensionally reveals the complex structure of the human proteome, including the characteristics of protein spatial distribution, dynamic protein translocation, and protein interaction networks. Recently, as a crucial method for studying protein spatial localization, spatial proteomics has been applied in the clinical investigation of various diseases. This review summarizes the fundamental concepts and characteristics of tissue-level spatial proteomics, its research progress in common human diseases such as cancer, neurological disorders, cardiovascular diseases, autoimmune diseases, and anticipates its future development trends. The aim is to highlight the significant impact of spatial proteomics on understanding disease pathogenesis, advancing diagnostic methods, and developing potential therapeutic targets in clinical research.

RESUMEN

BACKGROUND: Gestational age (GEAA) estimated by newborn DNA methylation (GAmAge) is associated with maternal prenatal exposures and immediate birth outcomes. However, the association of GAmAge with long-term overweight or obesity (OWO) trajectories is yet to be determined. METHODS: GAmAge was calculated for 831 children from a US predominantly urban, low-income, multi-ethnic birth cohort based on cord blood DNA methylation profile using Illumina EPIC array. Repeated anthropometric measurements aligned with pediatric primary care schedule allowed us to calculate body-mass-index percentiles (BMIPCT) at specific age and to define long-term weight trajectories from birth to 18 years. RESULTS: GAmAge was associated with BMIPCT trajectories, defined by 4 groups: stable (consistent OWO: "early OWO"; constant normal weight: "NW") or non-stable (OWO by year 1 of follow-up: "late OWO"; OWO by year 6 of follow-up: "NW to very late OWO"). GAmAge differentiated between the group with consistently normal BMIPCT pattern and the non-stable groups with late and very late OWO development. Such differentiation was observed in the age periods of birth to 1year, 3years, 6years, 10years, and 14years (p < 0.05 for all). The findings persisted after adjusting for GEAA, maternal smoking, delivery method, and child's sex in multivariate models. Birth weight was a mediator for the GAmAge effect on OWO status for specific groups at multiple age periods. CONCLUSIONS: GAmAge is associated with BMIPCT trajectories from birth to age 18 years, independent of GEAA and birth weight. If further confirmed, GAmAge may serve as an early biomarker for predicting BMI trajectory to inform early risk assessment and prevention of OWO. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03228875).

Asunto(s)

Cohorte de Nacimiento , Metilación de ADN , Humanos , Recién Nacido , Femenino , Masculino , Adolescente , Niño , Lactante , Boston , Preescolar , Edad Gestacional , Índice de Masa Corporal , Trayectoria del Peso Corporal , Peso al Nacer , Sobrepeso/genética , Estudios de Cohortes

RESUMEN

Antibiotic residues have been found in several aquatic ecosystems as a result of the widespread use of antibiotics in recent years, which poses a major risk to both human health and the environment. At present, photocatalytic degradation is the most effective and environmentally friendly method. Titanium silicon molecular sieve (TS-1) has been widely used as an industrial catalyst, but its photocatalytic application in wastewater treatment is limited due to its small pores and few active sites. In this paper, we report a method for preparing multistage porous TS-1 with a high specific surface area by alkali treatment. In the photocatalytic removal of CIP (ciprofloxacin) antibiotic wastewater experiments, the alkali-treated catalyst showed better performance in terms of interfacial charge transfer efficiency, which was 2.3 times higher than that of TS-1 synthesized by the conventional method, and it was found to maintain better catalytic performance in the actual water source. In addition, this research studied the effects of solution pH, contaminant concentration, and catalyst dosage on CIP degradation, while liquid chromatography-mass spectrometry (LC-MS) was used to identify intermediates in the degradation process and infer possible degradation pathways and the toxicity of CIP, and its degradation product was also analyzed using ECOSAR 2.2 software, and most of the intermediates were found to be nontoxic and nonharmful. Finally, a 3:5:1 artificial neural network model was established based on the experiments, and the relative importance of the influence of experimental conditions on the degradation rate was determined. The above results confirmed the feasibility and applicability of photocatalytic treatment of wastewater containing antibiotics using visible light excitation alkali post-treatment TS-1, which provided technical support and a theoretical basis for the photocatalytic treatment of wastewater containing antibiotics.

Asunto(s)

Redes Neurales de la Computación , Titanio , Catálisis/efectos de la radiación , Titanio/química , Titanio/efectos de la radiación , Porosidad , Antibacterianos/química , Silicio/química , Contaminantes Químicos del Agua/química , Procesos Fotoquímicos , Ciprofloxacina/química , Aguas Residuales/química , Fotólisis/efectos de la radiación

RESUMEN

BACKGROUND: Gestational DNA methylation age (GAmAge) has been developed and validated in European ancestry samples. Its applicability to other ethnicities and associations with fetal stress and newborn phenotypes such as inflammation markers are still to be determined. This study aims to examine the applicability of GAmAge developed from cord blood samples of European decedents to a racially diverse birth cohort, and associations with newborn phenotypes. METHODS: GAmAge based on 176 CpGs (Haftorn GAmAge) was calculated for 940 children from a US predominantly urban, low-income, multiethnic birth cohort. Cord blood DNA methylation was profiled by Illumina EPIC array. Newborn phenotypes included anthropometric measurements and, for a subset of newborns (N = 194), twenty-seven cord blood inflammatory markers (sandwich immunoassays). RESULTS: GAmAge had a stronger correlation with GEAA in boys (r = 0.89, 95% confidence interval (CI) [0.87,0.91]) compared with girls (r = 0.83, 95% CI [0.80,0.86]), and was stronger among extremely preterm to very preterm babies (r = 0.91, 95% CI [0.81,0.96]), compared with moderate (r = 0.48, 95% CI [0.34,0.60]) and term babies (r = 0.58, 95% CI [0.53,0.63]). Among White newborns (N = 51), the correlation between GAmAge vs. GEAA was slightly stronger (r = 0.89, 95% CI [0.82,0.94]) compared with Black/African American newborns (N = 668; r = 0.87, 95% CI [0.85,0.89]) or Hispanic (N = 221; r = 0.79, 95% CI [0.74,0.84]). Adjusting for GEAA and sex, GAmAge was associated with anthropometric measurements, cord blood brain-derived neurotrophic factor (BDNF), and monocyte chemoattractant protein-1 (MCP-1) (p < 0.05 for all). CONCLUSIONS: GAmAge estimation is robust across different populations and racial/ethnic subgroups. GAmAge may be utilized as a proxy for GEAA and for assessing fetus development, indicated by inflammatory state and birth outcomes.

Asunto(s)

Metilación de ADN , Sangre Fetal , Desarrollo Fetal , Edad Gestacional , Humanos , Femenino , Masculino , Metilación de ADN/genética , Recién Nacido , Embarazo , Desarrollo Fetal/genética , Sangre Fetal/química , Boston , Cohorte de Nacimiento , Adulto , Biomarcadores/sangre , Población Blanca/genética , Islas de CpG/genética , Epigénesis Genética , Resultado del Embarazo/genética

RESUMEN

BACKGROUND: The impact of methylation gestational age (GAmAge; a biomarker of fetal maturity) at birth on childhood blood pressure (BP) trajectories is unknown. METHODS: This cohort study included 500 boys and 440 girls with data on cord blood DNA methylation and BP at 3 to 15 years of age. Systolic BP (SBP) and diastolic BP percentiles were calculated based on clinical guidelines. Time-series K-means clustering identified 4 distinct SBP and diastolic BP percentile trajectories: high-steady, high-decrease, normal-increase, and normal-steady. GAmAge was estimated using an existing pediatric epigenetic clock. Extrinsic age acceleration was calculated as residuals of associations between GAmAge and chronological gestational age. Intrinsic age acceleration was calculated using the same method adjusting for cord blood cell compositions. RESULTS: Extrinsic age acceleration and intrinsic age acceleration were inversely associated with repeated measures of BP percentiles. Significant inverse associations were observed between extrinsic age acceleration and SBP percentiles in boys (ß=-2.02; P=0.02) but not in girls (ß=-0.49; P=0.58). Both extrinsic age acceleration and intrinsic age acceleration were inversely associated with SBP percentiles in girls born preterm (<37 weeks; ßEAA=-2.95; ßIAA=-3.00; P<0.05). Compared with the normal-steady SBP trajectory, significant inverse associations were observed between intrinsic age acceleration and high-steady, high-decrease, and normal-increase SBP trajectories in boys (odds ratio, 0.73-0.81; P<0.03), and significant positive associations were observed for high-decrease and normal-increase SBP trajectories in girls (odds ratio, 1.26-1.38; P<0.01). Significant sex differences were observed (Psex-interaction<2×10-16). CONCLUSIONS: GAmAge acceleration at birth was inversely associated with child BP, and such association was more pronounced in boys than in girls. Our findings may shed new light on the developmental origins of high BP and sex differences in cardiovascular risk.

Asunto(s)

Presión Sanguínea , Metilación de ADN , Epigénesis Genética , Edad Gestacional , Humanos , Femenino , Masculino , Niño , Presión Sanguínea/fisiología , Presión Sanguínea/genética , Preescolar , Estudios Prospectivos , Recién Nacido , Adolescente , Cohorte de Nacimiento , Sangre Fetal/metabolismo , Hipertensión/genética , Hipertensión/fisiopatología , Hipertensión/epidemiología

RESUMEN

The elevated levels of antibiotic resistance genes (ARGs) in livestock manure represent a significant threat to both the environment and human health. Composting has been recognized as an effective strategy to mitigate the abundance of ARGs in manure. However, notable rebounds in ARGs abundance have been observed during this process. This study explored the changes in ARGs abundance and the underlying influencing factors during the composting of carnivore (chicken and pig) and herbivore (sheep and cow) manures, along with mushroom residues. The findings revealed that the total relative abundance of ARGs increased by 6.96 and 10.94 folds in chicken and pig manure composts, respectively, whereas it decreased by a remarkable 91.72% and 98.37% in sheep and cow manure composts. Nitrogen content emerged as the primary physicochemical factors governing the abundance of ARGs in chicken and pig manure composts. Conversely, carbon content played a pivotal role in determining ARGs abundance in chicken and pig manure composts. Furthermore, the presence of dominant hosts, such as Corynebacterium, Bacillus, and Clostridium, along with emerging bacteria like Thermobifida, Saccharomonospora, and Actinomadura, contributed significantly to the enrichment of total ARGs, including tetG, tetO, tetX, and sul2, in chicken and pig manure composts. The coexistence of these genes with mobile genetic elements and a plethora of host bacteria, coupled with their high abundance, renders them particularly high-risk ARGs. On the other hand, the observed decrease in the abundance of total ARGs in sheep and cow manure composts can be attributed to the decline in the population of host bacteria, specifically Atopostipes, Psychrobacter, and Corynebacterium. Collectively, these results provide crucial insights into the management of ARGs risks and offer essential theoretical support for enhancing the safe utilization of organic fertilizer in agriculture.

Asunto(s)

Pollos , Compostaje , Farmacorresistencia Microbiana , Estiércol , Estiércol/microbiología , Animales , Farmacorresistencia Microbiana/genética , Porcinos , Ovinos , Herbivoria , Bovinos , Antibacterianos/análisis , Microbiología del Suelo , Genes Bacterianos , Bacterias/genética , Nitrógeno/análisis

RESUMEN

AIM OF THE STUDY: Cholestasis induces severe liver injury and subsequent liver fibrosis. However, a comprehensive understanding of the relationships between liver fibrosis and cholestasis-induced changes in metabolites in the gut and fibrotic liver tissue and in the gut microbiota is insufficient. METHODS: Common bile duct ligation (BDL) was employed to establish a cholestatic liver fibrosis model in mice for 26 days. Fibrotic liver tissue and the gut contents were collected. Untargeted metabolomics was conducted for the determination of metabolites in the gut contents and liver tissues. Metagenomics was adopted to explore the gut microbiota. RESULTS: The metabolites in the gut contents and liver tissues between normal and cholestatic liver fibrosis mice were highly distinct. Beta-alanine metabolism and glutathione metabolism were downregulated in the gut of the BDL group. Galactose metabolism, biosynthesis of unsaturated fatty acids, and ABC transporters were upregulated in the gut and downregulated in the liver of the BDL group. Arginine biosynthesis, taurine and hypotaurine metabolism, arginine and proline metabolism, and primary bile acid biosynthesis were downregulated in the gut and upregulated in the liver of the BDL group. Metagenomic analysis revealed that the alpha diversity of the microbiota in the BDL group decreased. The altered structure of the gut microbiota in the BDL group led to the hypofunction of important metabolic pathways (such as folate biosynthesis, histidine metabolism, thiamine metabolism, biotin metabolism, and phenylalanine, tyrosine and tryptophan biosynthesis) and enzymes (such as NADH, DNA helicase, and DNA-directed DNA polymerase). Correlation analyses indicated that certain gut microbes were associated with gut and liver metabolites. CONCLUSIONS: Untargeted metabolomics and metagenomics provided comprehensive information on gut and liver metabolism and gut microbiota in mice with cholestatic liver fibrosis. Therefore, significantly altered bacteria and metabolites may help provide some targets against cholestatic liver fibrosis in the future.

Asunto(s)

Colestasis , Microbioma Gastrointestinal , Cirrosis Hepática , Hígado , Animales , Colestasis/metabolismo , Colestasis/patología , Colestasis/microbiología , Cirrosis Hepática/metabolismo , Cirrosis Hepática/microbiología , Cirrosis Hepática/patología , Ratones , Hígado/metabolismo , Hígado/patología , Masculino , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Metabolómica

RESUMEN

Obesity is a modifiable predisposition factor for postmenopausal breast cancer. This suggests a localized, reciprocal interaction between breast cancer cells and the surrounding mammary white adipose tissue. To investigate how breast cancer cells alter the composition and function of adipose tissue, we screened the secretomes of 10 human breast cancer cell lines for the ability to modulate the differentiation of adipocyte stem and progenitor cells. The screen identified an adipogenic modulator, zinc-alpha-2-glycoprotein (ZAG/AZGP1) that is secreted by triple-negative breast cancer (TNBC) cells. TNBC-secreted ZAG inhibits adipogenesis and instead induces the expression of fibrotic genes. Accordingly, depletion of ZAG in TNBC cells attenuates fibrosis in white adipose tissue and inhibits tumor growth. Further, high expression of ZAG is linked to poor prognosis in patients with TNBC but not in patients with other clinical subtypes of breast cancer. Our findings suggest a role of TNBC-secreted ZAG in promoting the transdifferentiation of adipocyte stem and progenitor cells into cancer-associated fibroblasts to support tumorigenesis. SIGNIFICANCE: Functional screening of breast cancer secretomes revealed that triple-negative breast cancer promotes fibrosis in the adipose tissue microenvironment by secreting zinc-alpha-2-glycoprotein and promoting the transdifferentiation of adipocyte stem cells into myofibroblasts.

Asunto(s)

Fibrosis , Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/metabolismo , Femenino , Ratones , Fibrosis/metabolismo , Fibrosis/patología , Animales , Línea Celular Tumoral , Adipogénesis , Adipocitos/metabolismo , Adipocitos/patología , Zn-alfa-2-Glicoproteína , Microambiente Tumoral , Proteínas de Plasma Seminal/metabolismo , Proteínas de Plasma Seminal/genética , Tejido Adiposo Blanco/metabolismo , Tejido Adiposo Blanco/patología

RESUMEN

Environmentally persistent free radicals (EPFRs) can pose exposure risks by inducing the generation of reactive oxygen species. As a new class of pollutants, EPFRs have been frequently detected in atmospheric particulate matters. In this study, the seasonal variations and sources of EPFRs in a severe cold region in Northeastern China were comprehensively investigated, especially for the high pollution events. The geomean concentration of EPFRs in the total suspended particle was 6.58 × 1013 spins/m3 and the mean level in winter was one order of magnitude higher than summer and autumn. The correlation network analysis showed that EPFRs had significantly positive correlation with carbon component, K+ and PAHs, indicating that EPFRs were primarily emitted from combustion and pyrolysis process. The source appointment by the Positive Matrix Factorization (PMF) model indicated that the dominant sources in the heating season were coal combustion (48.4%), vehicle emission (23.1%) and biomass burning (19.4%), while the top three sources in the non-heating season were others (41.4%), coal combustion (23.7%) and vehicle emissions (21.2%). It was found that the high EPFRs in cold season can be ascribed to the extensive use of fossil fuel for heating demand; while the high EPFRs occurred in early spring were caused by the large-scale opening combustion of biomass. In summary, this study provided important basic information for better understanding the pollution characteristics of EPFRs, which suggested that the implementation of energy transformation and straw utilization was benefit for the control of EPFRs in severe cold region.

Asunto(s)

Contaminantes Atmosféricos , Carbón Mineral , Monitoreo del Ambiente , Estaciones del Año , Contaminantes Atmosféricos/análisis , Carbón Mineral/análisis , China , Radicales Libres/análisis , Biomasa , Material Particulado/análisis , Ciudades , Contaminación del Aire/análisis

RESUMEN

INTRODUCTION: Regorafenib remains the standard and widely used second-line strategy for advanced hepatocellular carcinoma (HCC). There is still a lack of large-scale multicenter real-world evidence concerning the concurrent use of regorafenib with immune checkpoint inhibitors (ICI). This study aims to evaluate whether combining regorafenib with ICI provides greater clinical benefit than regorafenib monotherapy as second-line therapy for advanced HCC under real-world circumstances. PATIENTS AND METHODS: The study included 208 patients from five medical facilities. One hundred forty-three patients received regorafenib plus ICI combination therapy, while 65 patients received regorafenib monotherapy. Propensity score matching (PSM) analysis was employed. RESULTS: The regorafenib plus ICI group demonstrated significantly higher objective response rate (24.3% vs. 10.3%, after PSM, p = 0.030) and disease control rate (79.4% vs. 50.0%, after PSM, p < 0.001) compared to the regorafenib monotherapy group based on mRECIST criteria. Median progression-free survival (7.9 vs. 3.2 months, after PSM, p < 0.001) and overall survival (25.6 vs. 16.4 months, p = 0.010, after PSM) were also considerably longer in the regorafenib plus ICI group. The incidence of Grades 3-4 treatment-related adverse events (TRAEs) was marginally greater in the regorafenib plus ICI group than in the regorafenib group (23.8% vs. 20.0%, p = 0.546). Notably, there were no instances of treatment-related mortality or emergence of new TRAEs in any treatment group. CONCLUSION: The combination of regorafenib and ICI shows potential as a viable second-line treatment for advanced HCC, exhibiting favorable efficacy while maintaining a tolerable safety profile in contrast to regorafenib monotherapy.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Hepatocelular , Neoplasias Hepáticas , Compuestos de Fenilurea , Piridinas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patología , Piridinas/uso terapéutico , Compuestos de Fenilurea/uso terapéutico , Compuestos de Fenilurea/administración & dosificación , Compuestos de Fenilurea/efectos adversos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patología , Femenino , Masculino , Persona de Mediana Edad , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Estudios Retrospectivos , Adulto , Inmunoterapia/métodos

RESUMEN

Background: Due to a lack of related research, we aimed to determine the effectiveness of a pharmacist-led medication reconciliation intervention in China. Methods: We conducted a multicentre, prospective, open-label, assessor-blinded, cluster, nonrandomised controlled study at six county-level hospitals, with hospital wards serving as the clusters. We included patients discharged from the sampled hospitals who were aged ≥60 years; had ≥1 studied diagnoses; and were prescribed with ≥3 medications at discharge. Patients in the intervention group received a pharmacist-led medication reconciliation intervention and those in the control group received standard care. We assessed the incidence of medication discrepancies at discharge, patients' medication adherence, and health care utilisation within 30 days after discharge. Results: There were 429 patients in the intervention group (mean age = 72.5 years, standard deviation (SD) = 7.0) and 526 patients in the control group (mean age = 73.6 years, SD = 7.1). Of the 1632 medication discrepancies identified at discharge, fewer occurred in the intervention group (1.9 per patient on average) than the control group (2.6 per patient on average).The intervention significantly reduced the incidence of medication discrepancy by 9.6% (95% confidence interval (CI) = -15.6, -3.6, P = 0.002) and improved patients' medication adherence, with an absolute decrease in the mean adherence score of 2.5 (95% CI = -2.8, -2.2, P < 0.001). There was no significant difference in readmission rates between the intervention and control groups. Conclusions: Pharmacist-led medication reconciliation at discharge from Chinese county-level hospitals reduced medication discrepancies and improved patients' adherence among patients aged 60 years or above, though no impact on readmission after discharge was observed. Registration: ChiCTR2100045668.

Asunto(s)

Conciliación de Medicamentos , Farmacéuticos , Humanos , Anciano , Estudios Prospectivos , Hospitales de Condado , Cumplimiento de la Medicación

RESUMEN

Maize plastid terminal oxidase1 (ZmPTOX1) plays a pivotal role in seed development by upholding redox balance within seed plastids. This study focuses on characterizing the white kernel mutant 3735 (wk3735) mutant, which yields pale-yellow seeds characterized by heightened protein but reduced carotenoid levels, along with delayed germination compared to wild-type (WT) seeds. We successfully cloned and identified the target gene ZmPTOX1, responsible for encoding maize PTOX-a versatile plastoquinol oxidase and redox sensor located in plastid membranes. While PTOX's established role involves regulating redox states and participating in carotenoid metabolism in Arabidopsis leaves and tomato fruits, our investigation marks the first exploration of its function in storage organs lacking a photosynthetic system. Through our research, we validated the existence of plastid-localized ZmPTOX1, existing as a homomultimer, and established its interaction with ferredoxin-NADP+ oxidoreductase 1 (ZmFNR1), a crucial component of the electron transport chain (ETC). This interaction contributes to the maintenance of redox equilibrium within plastids. Our findings indicate a propensity for excessive accumulation of reactive oxygen species (ROS) in wk3735 seeds. Beyond its known role in carotenoids' antioxidant properties, ZmPTOX1 also impacts ROS homeostasis owing to its oxidizing function. Altogether, our results underscore the critical involvement of ZmPTOX1 in governing seed development and germination by preserving redox balance within the seed plastids.

Asunto(s)

Germinación , Homeostasis , Oxidación-Reducción , Proteínas de Plantas , Plastidios , Semillas , Zea mays , Semillas/crecimiento & desarrollo , Semillas/genética , Semillas/metabolismo , Germinación/genética , Plastidios/metabolismo , Plastidios/genética , Plastidios/enzimología , Zea mays/genética , Zea mays/crecimiento & desarrollo , Zea mays/metabolismo , Zea mays/enzimología , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Oxidorreductasas/metabolismo , Oxidorreductasas/genética , Regulación de la Expresión Génica de las Plantas , Carotenoides/metabolismo

RESUMEN

AIM: Occurrence of anastomotic biliary stricture (AS) remains an essential issue following hepatobiliary surgeries, and percutaneous transhepatic cholangioscopy (PTCS) has great therapeutic significance in handling refractory AS for patients with altered gastrointestinal anatomy after cholangio-jejunostomy. This present study aimed to investigate feasibility of PTCS procedures in AS patients for therapeutic indications. MATERIALS AND METHODS: This study was a single-center, retrospective cohort study with a total number of 124 consecutive patients who received therapeutic PTCS due to AS. Clinical success rate, required number, and adverse events of therapeutic PTCS procedures as well as patients survival state were reviewed. RESULTS: These 124 patients previously underwent choledochojejunostomy or hepatico-jejunostomy, and there was post-surgical altered gastrointestinal anatomy. Overall, 366 therapeutic PTCS procedures were performed for these patients through applying rigid choledochoscope, and the median time of PTCS procedures was 3 (1-11). Among these patients, there were 34 cases (27.32%) accompanied by biliary strictures and 100 cases (80.65%) were also combined with biliary calculi. After therapeutic PTCS, most patients presented with relieved clinical manifestations and improved liver functions. The median time of follow-up was 26 months (2-86 months), and AS was successfully managed through PTCS procedures in 104 patients (83.87%). During the follow-up period, adverse events occurred in 81 cases (65.32%), most of which were tackled through supportive treatment. CONCLUSION: PTCS was a feasible, safe and effective therapeutic modality for refractory AS, which may be a promising alternative approach in clinical cases where the gastrointestinal anatomy was changed after cholangio-jejunostomy.

Asunto(s)

Anastomosis Quirúrgica , Colestasis , Humanos , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Adulto , Constricción Patológica/cirugía , Constricción Patológica/diagnóstico por imagen , Colestasis/cirugía , Colestasis/diagnóstico por imagen , Colestasis/etiología , Anastomosis Quirúrgica/efectos adversos , Estudios de Factibilidad , Endoscopía del Sistema Digestivo/métodos , Resultado del Tratamiento , Complicaciones Posoperatorias/diagnóstico por imagen

RESUMEN

Obesity is a predisposition factor for breast cancer, suggesting a localized, reciprocal interaction between breast cancer cells and the surrounding mammary white adipose tissue. To investigate how breast cancer cells alter the composition and function of adipose tissue, we screened the secretomes of ten human breast cancer cell lines for the ability to modulate the differentiation of adipocyte stem and progenitor cells (ASPC). The screen identified a key adipogenic modulator, Zinc Alpha-2-Glycoprotein (ZAG/AZGP1), secreted by triple-negative breast cancer (TNBC) cells. TNBC-secreted ZAG inhibits adipogenesis and instead induces the expression of fibrotic genes. Accordingly, depletion of ZAG in TNBC cells attenuates fibrosis in white adipose tissue and inhibits tumor growth. Further, high expression of ZAG in TNBC patients, but not other clinical subtypes of breast cancer, is linked to poor prognosis. Our findings suggest a role of TNBC-secreted ZAG in promoting the transdifferentiation of ASPCs into cancer-associated fibroblasts to support tumorigenesis.

RESUMEN

BACKGROUND: There are increasing numbers of metabolomic studies in food allergy (FA) and asthma, which, however, are predominantly limited by cross-sectional designs, small sample size, and being conducted in European populations. OBJECTIVE: We sought to identify metabolites unique to and shared by children with FA and/or asthma in a racially diverse prospective birth cohort, the Boston Birth Cohort. METHODS: Mass spectrometry-based untargeted metabolomic profiling was performed using venous plasma collected in early childhood (n = 811). FA was diagnosed according to clinical symptoms consistent with an acute hypersensitivity reaction at food ingestion and food specific-IgE > 0.35 kU/L. Asthma was defined on the basis of physician diagnosis. Generalized estimating equations were applied to analyze metabolomic associations with FA and asthma, adjusting for potential confounders. RESULTS: During a mean ± standard deviation follow-up of 11.8 ± 5.2 years from birth, 78 children developed FA and 171 developed asthma. Androgenic and pregnenolone steroids were significantly associated with a lower risk of FA, especially for egg allergy. N,N,N-trimethyl-5-aminovalerate (odds ratio [OR] = 0.65, 95% confidence interval [CI] = 0.48-0.87), and 1-oleoyl-2-arachidonoyl-sn-glycero-3-phosphoinositol (OR = 0.77; 95% CI = 0.66-0.90) were inversely associated with FA risk. Orotidine (OR = 4.73; 95% CI = 2.2-10.2) and 4-cholesten-3-one (OR = 0.52; 95% CI = 0.35-0.77) were the top 2 metabolites associated with risk of asthma, although they had no association with FA. In comparison, children with both FA and asthma exhibited an altered metabolomic profile that aligned with that of FA, including altered levels of lipids and steroids. CONCLUSION: In this US multiethnic prospective birth cohort, unique and shared alterations in plasma metabolites during early childhood were associated with risk of developing FA and/or asthma. These findings await further validation.

Asunto(s)

Asma , Hipersensibilidad a los Alimentos , Metabolómica , Humanos , Asma/sangre , Asma/epidemiología , Hipersensibilidad a los Alimentos/sangre , Hipersensibilidad a los Alimentos/epidemiología , Femenino , Masculino , Niño , Estudios Prospectivos , Preescolar , Cohorte de Nacimiento , Metaboloma , Boston/epidemiología , Lactante , Adolescente

RESUMEN

BACKGROUND: IL-33/ST2 signaling plays crucial roles in the development and progression of various human malignancies. However, its significance in intrahepatic cholangiocarcinoma (ICC) still remains unclear. OBJECTIVE: This study aimed to investigate the expression of IL-33/ST2 signaling and its correlations with macrophage heterogeneity and ICC patients' clinicopathologic features. METHODS: The expression of different phenotype macrophage markers and IL-33/ST2 signalingrelated markers was detected. The correlation between L-33/ST2 signaling and different phenotype macrophage markers as well as ICC patients' clinicopathologic data was evaluated. RESULTS: Massive heterogeneous cancer cells and PAS-positive cells were observed in tumor tissues. CD68-positive cells accumulated in tumor tissues and expression of both M1 phenotype markers and M2 phenotype macrophage markers was higher in tumor samples than para-carcinoma samples. However, M2 phenotype macrophages represented the dominant macrophage population in ICC tissues. Plasma levels of IL-33, ST2, and MIF were evidently enhanced in ICC patients compared to healthy controls. IL-33/ST2 signaling-related markers exhibited a massive increase in tumor samples than para-carcinoma samples. IL-33 and ST2 expression in ICC tissues was positively associated with M1 and M2 phenotype macrophages. Plasma levels of IL-33, ST2, and MIF were correlated with the diameter of tumor lesions, lymph node metastasis, TNM stage, and tumor differentiation degree. Multivariate analysis demonstrated IL-33 expression to exhibit a correlation with the diameter of tumor lesions, lymph node metastasis, and TNM stage. Additionally, there was a relationship observed between ST2, MIF expression, and diameter of tumor lesions plus TNM stage. CONCLUSION: IL-33/ST2 signaling exhibited a positive relationship with macrophage heterogeneity in ICC tissues, and upregulated levels of IL-33, ST2, and MIF were associated with aggressive clinicopathologic characteristics. These findings may provide promising diagnostic biomarkers and potential therapeutic strategies for ICC patients targeting IL-33/ST2 signaling.

Asunto(s)

Neoplasias de los Conductos Biliares , Colangiocarcinoma , Proteína 1 Similar al Receptor de Interleucina-1 , Interleucina-33 , Macrófagos , Transducción de Señal , Humanos , Interleucina-33/metabolismo , Colangiocarcinoma/patología , Colangiocarcinoma/metabolismo , Proteína 1 Similar al Receptor de Interleucina-1/metabolismo , Masculino , Femenino , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/metabolismo , Macrófagos/metabolismo , Macrófagos/patología , Persona de Mediana Edad , Factores Inhibidores de la Migración de Macrófagos/metabolismo , Anciano , Oxidorreductasas Intramoleculares/metabolismo , Biomarcadores de Tumor/metabolismo

RESUMEN

Blurry scenarios, such as light reflections and water ripples, often affect the clarity and signal-to-noise ratio of fish images, posing significant challenges for traditional deep learning models in accurately recognizing fish species. Firstly, deep learning models rely on a large amount of labeled data. However, it is often difficult to label data in blurry scenarios. Secondly, existing deep learning models need to be more effective for the processing of bad, blurry, and otherwise inadequate images, which is an essential reason for their low recognition rate. A method based on the diffusion model and attention mechanism for fish image recognition in blurry scenarios, DiffusionFR, is proposed to solve these problems and improve the performance of species recognition of fish images in blurry scenarios. This paper presents the selection and application of this correcting technique. In the method, DiffusionFR, a two-stage diffusion network model, TSD, is designed to deblur bad, blurry, and otherwise inadequate fish scene pictures to restore clarity, and a learnable attention module, LAM, is intended to improve the accuracy of fish recognition. In addition, a new dataset of fish images in blurry scenarios, BlurryFish, was constructed and used to validate the effectiveness of DiffusionFR, combining bad, blurry, and otherwise inadequate images from the publicly available dataset Fish4Knowledge. The experimental results demonstrate that DiffusionFR achieves outstanding performance on various datasets. On the original dataset, DiffusionFR achieved the highest training accuracy of 97.55%, as well as a Top-1 accuracy test score of 92.02% and a Top-5 accuracy test score of 95.17%. Furthermore, on nine datasets with light reflection noise, the mean values of training accuracy reached a peak at 96.50%, while the mean values of the Top-1 accuracy test and Top-5 accuracy test were at their highest at 90.96% and 94.12%, respectively. Similarly, on three datasets with water ripple noise, the mean values of training accuracy reached a peak at 95.00%, while the mean values of the Top-1 accuracy test and Top-5 accuracy test were at their highest at 89.54% and 92.73%, respectively. These results demonstrate that the method showcases superior accuracy and enhanced robustness in handling original datasets and datasets with light reflection and water ripple noise.

RESUMEN

BACKGROUND: The presence of gallstones in both the gallbladder and bile ducts is referred to as cholelithiasis. The prevalence of cholecystolithiasis and bile duct stones differs. Observational and Mendelian randomization (MR) studies have elucidated the significant contributing role of numerous fatty acids (FAs) in the development of cholelithiasis. Despite numerous studies about cholelithiasis, evidence on the relationship between serum FA levels and cholecystolithiasis, as well as bile duct stones with or without inflammation, remains insufficient. METHODS: A two-sample MR study was designed to clarify the impact of serum FA levels on various bile duct inflammatory diseases. The summary statistics of single nucleotide polymorphisms (SNPs) associated with fatty acids were obtained from the UK Biobank (UKB) and included data from 114,999 participants. The researchers obtained GWAS summary statistics for cholecystolithiasis and bile duct stones in 463,010 and 361,194 European participants, including cases with and without inflammation. No sample overlap between the exposure and outcome was verified through the "mr-lap" package. The SNPs were screened to identify instrumental variables (IVs). Cochran's Q test was applied for heterogeneity assessment. Inverse variance weighting (IVW) (fixed effects or random effects), MR-Egger regression and weighted median methods were used for MR. Multivariable MR was applied to determine the direct effect of each exposure on the outcome. A false discovery rate (FDR) was applied to adjust for multiple testing correction based on the Benjamini-Hochberg method. Finally, the FinnGen Consortium was used to validate some results. RESULTS: The overall concentration of polyunsaturated fatty acids (PUFAs) in the serum was negatively associated with the risk of calculus of the gallbladder with acute cholecystitis (IVW, OR = 0.996, P = 0.038, CI 0.992-0.999; weighted median, OR = 0.995, P = 0.025, CI 0.991-0.999). The percentage of PUFAs to total monounsaturated fatty acids(MUFAs) (IVW, OR = 0.998, P = 0.045, CI 0.997-0.999) and the percentage of PUFAs to total FAs (IVW, OR = 0.997, P = 0.025, CI 0.995-0.999) had a protective role against cholecystitis. The percentage of PUFAs to total FAs had a protective role against calculus of the gallbladder without cholecystitis (IVW, OR = 0.995, P = 0.026, CI 0.990-0.999; MR Egger, OR = 0.99, P = 0.03, CI 0.982-0.998; weighted median, OR = 0.991, P = 5.41e-06, CI 0.988-0.995). Conversely, the percentage of MUFAs to total FAs increased the risk for cholecystitis (IVW, OR = 1.001, P = 0.034, CI 1.0001-1.002). However, there were no causal effects of the above exposures on the outcomes through multivariable MR and multiple testing correction. Finally, the causal effects of the above exposures on cholecystitis were validated in the FinnGen Consortium, which suggested that the percentage of PUFAs to total FAs (IVW, OR = 0.744, P = 0.021, CI 0.579-0.957) had a protective role against cholecystitis. CONCLUSION: These Mendelian randomization findings suggested that more attention should be focused on people who have low serum PUFA levels, which may have a potential role in the occurrence of calculus of the gallbladder or cholecystitis rather than calculus of the bile duct without cholangitis or cholecystitis.

Asunto(s)

Sistema Biliar , Colecistitis , Cálculos Biliares , Humanos , Cálculos Biliares/genética , Ácidos Grasos , Análisis de la Aleatorización Mendeliana , Inflamación/genética , Colecistitis/genética