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1.
J Transl Med ; 22(1): 559, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38863033

RESUMEN

BACKGROUND: Exploration of adaptive evolutionary changes at the genetic level in vaginal microbial communities during different stages of cervical cancer remains limited. This study aimed to elucidate the mutational profile of the vaginal microbiota throughout the progression of cervical disease and subsequently establish diagnostic models. METHODS: This study utilized a metagenomic dataset consisting of 151 subjects classified into four categories: invasive cervical cancer (CC) (n = 42), cervical intraepithelial neoplasia (CIN) (n = 43), HPV-infected (HPVi) patients without cervical lesions (n = 34), and healthy controls (n = 32). The analysis focused on changes in microbiome abundance and extracted information on genetic variation. Consequently, comprehensive multimodal microbial signatures associated with CC, encompassing taxonomic alterations, mutation signatures, and enriched metabolic functional pathways, were identified. Diagnostic models for predicting CC were established considering gene characteristics based on single nucleotide variants (SNVs). RESULTS: In this study, we screened and analyzed the abundances of 18 key microbial strains during CC progression. Additionally, 71,6358 non-redundant mutations were identified, predominantly consisting of SNVs that were further annotated into 25,773 genes. Altered abundances of SNVs and mutation types were observed across the four groups. Specifically, there were 9847 SNVs in the HPV-infected group and 14,892 in the CC group. Furthermore, two distinct mutation signatures corresponding to the benign and malignant groups were identified. The enriched metabolic pathways showed limited similarity with only two overlapping pathways among the four groups. HPVi patients exhibited active nucleotide biosynthesis, whereas patients with CC demonstrated a significantly higher abundance of signaling and cellular-associated protein families. In contrast, healthy controls showed a distinct enrichment in sugar metabolism. Moreover, biomarkers based on microbial SNV abundance displayed stronger diagnostic capability (cc.AUC = 0.87) than the species-level biomarkers (cc.AUC = 0.78). Ultimately, the integration of multimodal biomarkers demonstrated optimal performance for accurately identifying different cervical statuses (cc.AUC = 0.86), with an acceptable performance (AUC = 0.79) in the external testing set. CONCLUSIONS: The vaginal microbiome exhibits specific SNV evolution in conjunction with the progression of CC, and serves as a specific biomarker for distinguishing between different statuses of cervical disease.


Asunto(s)
Microbiota , Neoplasias del Cuello Uterino , Vagina , Humanos , Femenino , Neoplasias del Cuello Uterino/microbiología , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/genética , Vagina/microbiología , Microbiota/genética , Mutación/genética , Persona de Mediana Edad , Adulto , Polimorfismo de Nucleótido Simple/genética , Estudios de Casos y Controles , Progresión de la Enfermedad
2.
BMC Med Educ ; 24(1): 290, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38491487

RESUMEN

BACKGROUND: To compare the value and efficiency of the three-dimensional (3D) heads-up surgical system and traditional microscopic (TM) system in teaching and learning vitreoretinal surgeries. METHODS: Twenty ophthalmologists and scrub nurses were recruited as teachers, and 45 junior ophthalmology residents and trainee doctors, trainee nurses, and medical students were recruited as observers. Each teacher and observer were assigned to both a 3D-assisted and TM-assisted vitreoretinal surgery and then asked to complete satisfaction questionnaires for both surgical systems at the end of each surgery. RESULTS: The 3D heads-up surgical system was rated significantly higher in most of the subscales and overall satisfaction score by both teachers and observers (P < 0.05). However, ratings for instrument adjustment were significantly higher in the TM group compared to the 3D group for junior ophthalmology residents and trainee doctors (6.1 ± 1.7 vs. 8.8 ± 1.1, P < 0.001). CONCLUSIONS: The 3D heads-up surgical system has great didactical value in the medical education of vitreoretinal surgeries, but it is important to consider the specific needs of different learners when choosing between the two systems. TRIAL REGISTRATION: Not applicable.


Asunto(s)
Educación Médica , Cirugía Vitreorretiniana , Humanos , Cirugía Vitreorretiniana/métodos , Estudios Prospectivos , Aprendizaje , Encuestas y Cuestionarios
3.
Ecotoxicol Environ Saf ; 263: 115208, 2023 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-37413945

RESUMEN

Taiwan had the high incidence of chronic kidney disease (CKD) worldwide. Our objective was to examine associations between daily exposure of phthalates and melamine, two common nephrotoxins, and kidney damage risk in a well-established nationwide cohort. Study subjects were from Taiwan Biobank (TWB) with existing data of questionnaire and biochemical examinations. Average daily intake (ADI) levels of melamine and seven parental phthalates, including DEHP (di-2-ethylhexylphthalate), DiBP (Dibutyl phthalate), DnBP (Di-n-butyl phthalate), BBzP (Butyl benzyl phthalate), DEP (Diethyl phthalate), and DMP (Dimethyl phthalate) were estimated using a creatinine excretion-based model from urine melamine and 10 phthalate metabolites. Urine microalbumin to creatinine ratio (ACR) was used to represent for the outcome of kidney damage. Two statistical strategies were used: First, a weighted quantile sum (WQS) regression model to select the most important exposure variables of ADI levels of phthalates and melamine associated with ACR; Second, to examine effects of those most important exposure variables on ACR in multivariable linear regression models. In total, 1153 eligible adults were left for analyses. Of them, 591 (51.3%) and 562 (48.7%) were men and women, respectively, with a median age of 49 years old. By WQS, a significant and positive association was found between ADI of melamine and phthalates and ACR (ß = 0.14, p = 0.002). ADI levels of melamine had the highest weight (0.57), followed by DEHP (0.13). Next, examining the two most important exposures in association with ACR, we found that the higher the melamine and DEHP intakes, the higher the ACR levels were found. An interaction effect was also found between melamine and DEHP intakes on urine ACR (p = 0.015). This result was more prominent in men (p = 0.008) than in women (p = 0.651). Environmental co-exposure of melamine and DEHP can potentially affect ACR in the community-dwelling Taiwanese adult population.


Asunto(s)
Dietilhexil Ftalato , Contaminantes Ambientales , Ácidos Ftálicos , Masculino , Humanos , Adulto , Femenino , Persona de Mediana Edad , Dietilhexil Ftalato/toxicidad , Contaminantes Ambientales/análisis , Taiwán/epidemiología , Creatinina , Bancos de Muestras Biológicas , Ácidos Ftálicos/análisis , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/análisis , Dibutil Ftalato , Riñón/metabolismo
4.
Environ Res ; 215(Pt 1): 114187, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36037918

RESUMEN

Environmental exposures to mixtures of toxic chemicals have potential interaction effects that may lead to hazard index values exceeding one. However, current regulation levels, such as tolerable daily intake (TDI), are mostly based on experimental studies conducted with a single chemical compound. In this study, we assessed the relationships between melamine and di-(2-ethylhexyl) phthalate (DEHP) exposure and their coexposure with the early renal injury markers N-acetyl -D-glucosaminidase (NAG), albumin/creatinine ratio (ACR), and microalbuminuria in 1236 pregnant women. Various generalized linear models with interaction terms and Bayesian kernel machine regression models were used for the (co-)exposure response associations. We derived the benchmark dose (BMD) and the corresponding one-sided 95% confidence bound BMDL based on the estimated (covariate-adjusted) average daily intake of melamine and DEHP metabolites measured in spot urine of the women collected during the third trimester. Given a benchmark response of 0.1, the BMDL level of melamine (DEHP) exposure on NAG (ACR, microalbuminuria) was 2.67 (11.20, 4.45) µg/kg_bw/day, and it decreased to as low as 1.46 (3.83, 2.73) µg/kg_bw/day when considering coexposure to DEHP (melamine) up to the 90th percentile. Both the exposure threshold levels of melamine and DEHP for early renal injuries in pregnant women were several-fold to one order lower than the current recommended TDIs by the WHO and the US FDA and EPA and were even lower considering coexposure. Because of concurrent exposures in real-world environments, more stringent regulation levels are recommended in susceptible populations, such as pregnant women, due to potential synergistic mixture effects.


Asunto(s)
Dietilhexil Ftalato , Contaminantes Ambientales , Ácidos Ftálicos , Albúminas , Albuminuria/inducido químicamente , Teorema de Bayes , Benchmarking , Biomarcadores/orina , Creatinina , Dietilhexil Ftalato/toxicidad , Exposición a Riesgos Ambientales/análisis , Contaminantes Ambientales/orina , Femenino , Hexosaminidasas , Humanos , Riñón/metabolismo , Ácidos Ftálicos/orina , Embarazo , Mujeres Embarazadas , Triazinas
5.
Ecotoxicol Environ Saf ; 225: 112756, 2021 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-34507040

RESUMEN

Exposure to melamine, which is ubiquitous in daily life, is linked to adverse kidney outcomes. The melamine tolerable daily intake in humans is based on the no-observed-effect-level (NOEL) established in a single-toxicant murine model. However, humans are often simultaneously exposed to multiple environmental nephrotoxicants. The NOEL of melamine during coexposure with other toxicants needs to be evaluated. Oxalate is a potentially nephrotoxic terminal metabolite, and hyperoxaluria is reportedly associated with chronic kidney disease. We explored whether these two potential nephrotoxicants can interact and enhance kidney injury. We established a Sprague-Dawley rat model of coexposure to the melamine NOEL (63 mg/kg/day) and 2% hydroxy-L-proline (HLP, an oxalate precursor) in drinking water to simulate human environmental melamine exposure. Melamine/oxalate coexposure increased proximal tubular cell mitochondrial reactive oxygen species levels, lipid peroxidation and oxidative DNA damage. The degrees of mitochondrial damage, tubular cell apoptosis, tubular atrophy, and interstitial fibrosis were elevated in coexposed rat kidneys. The evidence indicated that exposure to the melamine NOEL can cause renal tubular injury via oxidative stress and that this effect may be enhanced via interaction of melamine with other environmental factors, such as oxalate. Thus, melamine risk assessment and toxicity prevention should be conducted carefully in different susceptible populations.


Asunto(s)
Oxalatos , Estrés Oxidativo , Animales , Riñón , Ratones , Ratas , Ratas Sprague-Dawley , Triazinas
6.
Environ Res ; 181: 108902, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31785779

RESUMEN

BACKGROUND: Phthalic acid esters are established as endocrine disruptors. The study aimed to evaluate the association between urinary phthalate metabolites and prostate cancer occurrence. METHODS: The study was based on the Taiwan Community-Based Cancer Screening Program, which was set up in 1991-1992 and followed periodically. By 2010, 80 incident prostate cancer cases were identified in the 12,020 men. For each case, 2 controls were randomly selected, matched by age (±3 years), urine collection date (±3 months), and residential township. Frequently used phthalate metabolites from the urine samples were quantified by liquid chromatography/electrospray ionization tandem mass spectrometry. Logistic regression was conducted to assess the association between the exposure levels and prostate cancer occurrence. RESULTS: Exposure to di (2-ethylhexyl), butyl-benzyl and di-isobutyl phthalates (DEHP, BBzP, DiBP) was positively associated with prostate cancer in men with waist circumference (WC) ≥90 cm but not in the leans. Odds ratio for the DEHP metabolite summary score (upper tertile compared to the rest) and prostate cancer were 7.76 (95% CI = 1.95-30.9) for WC ≥ 90 cm. CONCLUSIONS: DEHP, BBzP, and DiBP exposure were associated with prostate cancer occurrence in abdominally obese men. The main limitation remains the lack of mechanistic experiments and comparable toxicological data.


Asunto(s)
Dietilhexil Ftalato , Contaminantes Ambientales , Ácidos Ftálicos , Neoplasias de la Próstata/epidemiología , Estudios de Casos y Controles , Exposición a Riesgos Ambientales , Humanos , Masculino , Taiwán/epidemiología
7.
Ecotoxicol Environ Saf ; 200: 110741, 2020 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-32497990

RESUMEN

Environmental exposure to melamine has been associated with early renal injury in urolithiasis patients even when urinary concentrations of melamine are low. The aim of this study was to derive a benchmark dose (BMD) for melamine for urolithiasis patients. To do this, one-spot urine sample from 309 participants was obtained to measure urinary melamine and N-acetyl ß-D-glucosaminidase (NAG), an early renal damage biomarker. The participants were then classified into four exposure groups based on the outcomes of melamine tableware usage questionnaire. A beta distribution of urinary excretion fraction for each group was assumed to estimate their average daily intakes (AvDIs) of melamine. The BMD and the corresponding one-sided 95% lower bound (BMDL) was then derived based on Bayesian model averaging of alternative regression models between the participants' NAG levels and their estimated AvDIs, adjusting for age, gender, and other covariates. Bayesian Markov chain Monte Carlo simulations were used for all the estimates. With a benchmark response of 0.10, the simulated BMDL of 4.89 µg/kg-bw/day for melamine exposure threshold was much lower than the WHO's current recommended tolerable daily intake of 200 µg/kg_bw/day and the US FDA's 63 µg/kg_bw/day. The current regulation level of melamine might not safeguard urolithiasis patients from further deterioration of renal function.


Asunto(s)
Calcio , Riñón/efectos de los fármacos , Triazinas/toxicidad , Triazinas/orina , Urolitiasis/orina , Acetilglucosaminidasa/orina , Adulto , Anciano , Teorema de Bayes , Biomarcadores/orina , Exposición a Riesgos Ambientales , Femenino , Humanos , Riñón/fisiopatología , Masculino , Cadenas de Markov , Persona de Mediana Edad , Método de Montecarlo , Probabilidad , Urolitiasis/fisiopatología
8.
ACS Omega ; 9(15): 17667-17680, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38645334

RESUMEN

We present a general scheme for converting coarse-grained models into Dissipative Particle Dynamics (DPD) models. We build the corresponding DPD models by analogy with the de novo DPD coarse-graining scheme suggested by Groot and Warren (J. Chem. Phys., 1997). Electrostatic interactions between charged DPD particles are represented though the addition of a long-range Slater Coulomb potential as suggested by González-Melchor et al. (J. Chem. Phys., 2006). The construction is illustrated by converting MARTINI models for various proteins into a DPD representation, but it not restricted to the usual potential form in the MARTINI model-viz., Lennard-Jones potentials. We further extended the DPD scheme away from the typical use of homogeneous particle sizes, therefore faithfully representing the variations in the particle sizes seen in the underlying MARTINI model. The accuracy of the resulting construction of our generalized DPD models with respect to several structural observables has been benchmarked favorably against all-atom and MARTINI models for a selected set of peptides and proteins, and variations in the scales of the coarse-graining of the water solvent.

9.
Biomaterials ; 311: 122681, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38944968

RESUMEN

Cell-laden bioprinting is a promising biofabrication strategy for regenerating bioactive transplants to address organ donor shortages. However, there has been little success in reproducing transplantable artificial organs with multiple distinctive cell types and physiologically relevant architecture. In this study, an omnidirectional printing embedded network (OPEN) is presented as a support medium for embedded 3D printing. The medium is state-of-the-art due to its one-step preparation, fast removal, and versatile ink compatibility. To test the feasibility of OPEN, exceptional primary mouse hepatocytes (PMHs) and endothelial cell line-C166, were used to print hepatospheroid-encapsulated-artificial livers (HEALs) with vein structures following predesigned anatomy-based printing paths in OPEN. PMHs self-organized into hepatocyte spheroids within the ink matrix, whereas the entire cross-linked structure remained intact for a minimum of ten days of cultivation. Cultivated HEALs maintained mature hepatic functions and marker gene expression at a higher level than conventional 2D and 3D conditions in vitro. HEALs with C166-laden vein structures promoted endogenous neovascularization in vivo compared with hepatospheroid-only liver prints within two weeks of transplantation. Collectively, the proposed platform enables the manufacture of bioactive tissues or organs resembling anatomical architecture, and has broad implications for liver function replacement in clinical applications.

10.
Biomaterials ; 311: 122691, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38996673

RESUMEN

Acoustic holography (AH), a promising approach for cell patterning, emerges as a powerful tool for constructing novel invitro 3D models that mimic organs and cancers features. However, understanding changes in cell function post-AH remains limited. Furthermore, replicating complex physiological and pathological processes solely with cell lines proves challenging. Here, we employed acoustical holographic lattice to assemble primary hepatocytes directly isolated from mice into a cell cluster matrix to construct a liver-shaped tissue sample. For the first time, we evaluated the liver functions of AH-patterned primary hepatocytes. The patterned model exhibited large numbers of self-assembled spheroids and superior multifarious core hepatocyte functions compared to cells in 2D and traditional 3D culture models. AH offers a robust protocol for long-term in vitro culture of primary cells, underscoring its potential for future applications in disease pathogenesis research, drug testing, and organ replacement therapy.

11.
Adv Sci (Weinh) ; 11(2): e2304460, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37973557

RESUMEN

Methods accurately predicting the responses of colorectal cancer (CRC) and colorectal cancer liver metastasis (CRLM) to personalized chemotherapy remain limited due to tumor heterogeneity. This study introduces an innovative patient-derived CRC and CRLM tumor model for preclinical investigation, utilizing 3d-bioprinting (3DP) technology. Efficient construction of homogeneous in vitro 3D models of CRC/CRLM is achieved through the application of patient-derived primary tumor cells and 3D bioprinting with bioink. Genomic and histological analyses affirm that the CRC/CRLM 3DP tumor models effectively retain parental tumor biomarkers and mutation profiles. In vitro tests evaluating chemotherapeutic drug sensitivities reveal substantial tumor heterogeneity in chemotherapy responses within the 3DP CRC/CRLM models. Furthermore, a robust correlation is evident between the drug response in the CRLM 3DP model and the clinical outcomes of neoadjuvant chemotherapy. These findings imply a significant potential for the application of patient-derived 3DP cancer models in precision chemotherapy prediction and preclinical research for CRC/CRLM.


Asunto(s)
Bioimpresión , Neoplasias Colorrectales , Neoplasias Hepáticas , Humanos , Neoplasias Colorrectales/patología , Pronóstico , Neoplasias Hepáticas/genética
12.
Risk Anal ; 33(11): 1958-68, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23755826

RESUMEN

To date, the variant Creutzfeldt-Jakob disease (vCJD) risk assessments that have been performed have primarily focused on predicting future vCJD cases in the United Kingdom, which underwent a bovine spongiform encephalopathy (BSE) epidemic between 1980 and 1996. Surveillance of potential BSE cases was also used to assess vCJD risk, especially in other BSE-prevalent EU countries. However, little is known about the vCJD risk for uninfected individuals who accidentally consume BSE-contaminated meat products in or imported from a country with prevalent BSE. In this article, taking into account the biological mechanism of abnormal prion PrP(res) aggregation in the brain, the probability of exposure, and the expected amount of ingested infectivity, we establish a stochastic mean exponential growth model of lifetime exposure through dietary intake. Given the findings that BSE agents behave similarly in humans and macaques, we obtained parameter estimates from experimental macaque data. We then estimated the accumulation of abnormal prions to assess lifetime risk of developing clinical signs of vCJD. Based on the observed number of vCJD cases and the estimated number of exposed individuals during the BSE epidemic period from 1980 to 1996 in the United Kingdom, an exposure threshold hypothesis is proposed. Given the age-specific risk of infection, the hypothesis explains the observations very well from an extreme-value distribution fitting of the estimated BSE infectivity exposure. The current BSE statistics in the United Kingdom are provided as an example.


Asunto(s)
Síndrome de Creutzfeldt-Jakob/etiología , Encefalopatía Espongiforme Bovina/transmisión , Productos de la Carne/efectos adversos , Animales , Bovinos , Síndrome de Creutzfeldt-Jakob/epidemiología , Encefalopatía Espongiforme Bovina/epidemiología , Humanos , Incidencia , Productos de la Carne/virología , Modelos Teóricos , Factores de Riesgo , Reino Unido/epidemiología
13.
Biomater Adv ; 152: 213499, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37295133

RESUMEN

Three-dimensional (3D) bioprinting is a promising technology for fabricating complex tissue constructs with biomimetic biological functions and stable mechanical properties. In this review, the characteristics of different bioprinting technologies and materials are compared, and development in strategies for bioprinting normal and diseased hepatic tissue are summarized. In particular, features of bioprinting and other bio-fabrication strategies, such as organoids and spheroids are compared to demonstrate the strengths and weaknesses of 3D printing technology. Directions and suggestions, such as vascularization and primary human hepatocyte culture, are provided for the future development of 3D bioprinting.


Asunto(s)
Bioimpresión , Ingeniería de Tejidos , Humanos , Ingeniería de Tejidos/métodos , Organoides , Impresión Tridimensional , Hígado , Bioimpresión/métodos
14.
Int J Chron Obstruct Pulmon Dis ; 18: 1655-1664, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37551392

RESUMEN

Purpose: Inhaled medication adherence is an important issue for patients with chronic obstructive pulmonary disease (COPD) because adhering to inhaled medications could substantially improve their health. However, patients with COPD may not be always adhere to the prescribed inhaled medications. Therefore, understanding the underlying reasons for patients with COPD adhering to inhaled medications is important. The present study used Theory of Planned Behavior (TPB) as a theoretical framework to develop the Intention of Inhaled Medication Adherence Scale (IMAS) and assess its psychometric properties. Patients and Methods: After reviewing papers using the TPB to design psychometric scales and the TPB scale development guidelines, 28 items were generated for expert evaluation. Eight experts reported that the 28 items all had good content validity (content validity index ranged from 0.88 to 1.00 at item-level; and from 0.981 to 0.987 at scale-level) comprising four factors. Following initial development, 235 patients with COPD (mean age 73.12 years; 93.6% males) completed the IMAS via interview with a respiratory therapist and a research assistant. The four-factor structure of the IMAS was evaluated using confirmatory factor analysis (CFA). Results: Nine IMAS items were removed because of low factor loadings or offending estimates. The 19-item IMAS was confirmed as having a four-factor structure supported by the CFA results (comparative fit index=1.00; Tucker-Lewis index=1.00; root mean square error of approximation=0.00; standardized root mean square residual=0.06). Conclusion: The 19-item IMAS had satisfactory psychometric properties in construct validity. The 19-item IMAS is an instrument that could help healthcare providers understand potential factors associated with adherence to inhaled medications among people with COPD.


Asunto(s)
Enfermedad Pulmonar Obstructiva Crónica , Masculino , Humanos , Anciano , Femenino , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Intención , Teoría del Comportamiento Planificado , Encuestas y Cuestionarios , Reproducibilidad de los Resultados , Cumplimiento de la Medicación , Psicometría
15.
Clin Transl Med ; 13(7): e1331, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37462602

RESUMEN

BACKGROUND: The dismal prognosis of hepatocellular carcinoma (HCC) is closely associated with characteristics of the tumour microenvironment (TME). Recent studies have confirmed the presence and potential influence of the microbiome in TME on cancer progression. Elucidating the relationship between microbes in the TME and cancer could provide valuable insights into novel diagnostic markers and therapeutic strategies for HCC and thus warrants a closer investigation of the role of intratumoural microbiome in the HCC TME. METHODS: We determined the presence of intratumoural microbiome using fluorescence in situ hybridisation, and explored the microbial community profiles in the HCC TME in paired tumour and adjacent normal tissues using 16S rDNA sequencing. Microbial signatures were characterised in the paired group, and their correlation with clinical characteristics was further investigated. We clustered the microbial signatures of tumour tissues by hepatotypes, and further analysis was performed to elucidate the independent prognostic value of the hepatotypes. RESULTS: This study revealed that microbial profiles and community networks differed notably between tumours and adjacent normal tissues. Proteobacteria and Actinobacteria were the most abundant phyla in the HCC TME. The TME microbial profiles also revealed heterogeneities between individuals and between multiple tumour lesions. Clustering of the microbial profiles into two hepatotypes revealed different microbial network patterns. Additionally, the hepatotypes were revealed to be independent prognostic factors in patients with resected HCC. CONCLUSIONS: Our study illuminates the microbial profiles in the TME of HCC and presents the hepatotype as a potential independent biomarker for the prognostic prediction of HCC after surgery.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Microbiota , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/genética , Pronóstico , Microbiota/genética , Microambiente Tumoral
16.
Cancers (Basel) ; 15(15)2023 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-37568641

RESUMEN

Esophageal cancers are globally the sixth deadliest malignancy, with limited curative options. The association of high serum elafin levels, a molecule produced by epithelial cells, with esophageal squamous cell carcinoma (ESCC) risk is established, but its link to poor ESCC prognosis remains unclear. To explore this question, we first used three-dimensional confocal imaging to create a model of the spatial distribution of elafin inside locoregional ESCC tissues. Then, after analyzing data obtained from whole-genome microarrays for ESCC cell lines and their more invasive sublines, we performed in vitro experiments using RNA sequencing to identify possible elafin-related pathways. Three-dimensional tissue imaging showed elafin distributed as an interweaved-like fibrous structure in the stroma of tissue obtained from patients with high serum levels of elafin and poorer prognoses. By contrast, the signal was confined inside or around the tumor nest in patients who had lower serum levels and better survival. The analysis of a TCGA dataset revealed that higher levels of elafin mRNA in stage I-IIIA ESCC patients were associated with shorter survival. The in vitro studies revealed that elafin promoted ESCC cell proliferation, migration, and invasion via the epithelial-mesenchymal transition pathway. Thus, elafin inhibition could potentially be used therapeutically to improve survival in patients with locoregional ESCC.

17.
J Clin Med ; 12(6)2023 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-36983169

RESUMEN

BACKGROUND: Short-term outcomes of laparoscopic hepatectomy of central-located liver lesions (LHCL) compared with traditional open hepatectomy of central-located liver lesions (OHCL) remain unclear. The aim of this study was to explore the safety and efficacy of LHCL. METHODS: A retrospective analysis was performed on 262 patients who underwent hepatectomies involving resections of liver segment II, IV or VIII from January 2015 to June 2021 in two institutions. Patients in the LHCL group were matched in a 1:2 ratio to patients in the OHCL group. RESULTS: After propensity score-matched (PSM) analysis, 61 patients remained in the LHCL group and 122 patients were in the OHCL group. What needs to be mentioned is that although not significant, patients in the OHCL group had increased lesion size (4.3 vs. 3.6 cm, p = 0.052), number (single/multiple, 84.8%/15.2% vs. 93.4%/6.6%, p = 0.097), and number of liver segments involved (one/two/three, 47.3%/42.0%/10.7% vs. 57.4%36.1%/10.7%, p = 0.393). To ensure surgical safety, fewer patients in the LHCL group underwent vascular exclusion than those in the OHCL group (p = 0.004). In addition, LHCL was associated with lower blood loss (p = 0.001) and transfusion requirement (p = 0.004). In terms of short-term outcomes, the LHCL group had significantly lower levels of peak ALT (p < 0.001), peak DBIL (p = 0.042), peak PT (p = 0.012), and higher levels of bottom ALB (p = 0.049). Moreover, the LHCL group demonstrated quicker postoperative recovery, which was represented by shorter time to first flatus, time to oral intake, time to drain off, and hospital stay (all p < 0.001). Importantly, the LHCL group had a significantly reduced occurrence of postoperative complications (p < 0.001) and similar R0 resection rates (p = 0.678) when compared to the OHCL group. CONCLUSION: LHCL is associated with increased safety and better perioperative outcomes and thus could be recommended for patients with central space-occupying liver lesions when appropriately selecting the surgical procedure according to the total tumor burden and carefully handled by experienced surgeons. From the experience of our center, LHCL could be performed to solitary lesion involving liver segment IV/V/VIII, <5 cm, with good safety and feasibility.

18.
Nanoscale ; 14(26): 9516-9525, 2022 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-35758638

RESUMEN

Carbon dots (CDs) are emerging as the material of choice in a range of applications due to their excellent photoluminescence properties, ease of preparation from inexpensive precursors, and low toxicity. However, the precise nature of the mechanism for the fluorescence is still under debate, and several molecular fluorophores have been reported. In this work, a new blue fluorophore, 5-oxopyrrolidine-3-carboxylic acid, was discovered in carbon dots synthesized from the most commonly used precursors: citric acid and urea. The molecular product alone has demonstrated interesting aggregation-enhanced emission (AEE), making it unique compared to other fluorophores known to be generated in CDs. We propose that this molecular fluorophore is associated with a polymer backbone within the CDs, and its fluorescence behavior is largely dependent on intermolecular interactions with the polymers or other fluorophores. Thus, a new class of non-traditional fluorophores is now relevant to the consideration of the CD fluorescence mechanism, providing both an additional challenge to the community in resolving the mechanism and an opportunity for a greater range of CD design schemes and applications.

19.
Foods ; 11(19)2022 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-36230038

RESUMEN

The hydrolysis time is directly related to the flavor of the Maillard reaction, but existing proxy models cannot simulate and model the variation curves of vital volatile components. This study developed a predictive model for modelling and simulating key volatile compounds of Maillard reaction products (MRPs) derived from beef tallow residue hydrolysate. Results showed the degree of hydrolysis increased with hydrolysis time, and the most significant improvement in the roast flavor and overall acceptance was when hydrolyzing 4 h. Based on flavor dilution value and the relative odor activity value, nine key volatile components were identified, and 2-ethyl-3,5-dimethylpyrazine with roast flavor was the highest. Compared with Polynomial Curve Fitting (PCF) and Cubic Spline Interpolation (CSI), key volatile compounds of MRPs could be better modeled and simulated by the Curve Prediction Model (CPM). All results suggested that CPM could predict the changes in key volatile components produced by MRPs.

20.
Food Chem X ; 15: 100447, 2022 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-36211755

RESUMEN

The beef flavor of beef tallow residue was improved by enzymatic hydrolysis followed by the Maillard reaction, and the flavor could be predicted using an artificial neural network. Five beef tallow residue hydrolysates were prepared using different enzymes. The Flavourzyme and Papain (FP) hydrolysate had low molecular weight peptides and high degree of hydrolysis and free amino acid content. We identified 49 main compounds, including aldehydes, pyrazines, and furan. Furan and pyrazine were the dominant volatile compounds in the five beef tallow residue-derived Maillard reaction products (MRPs), and their profiles and levels in the FP MRPs were high. The FP MRPs had the best sensory characteristics. The artificial neural network analysis revealed that the multiple input single output model had a better performance than the single input single output model, and the prediction accuracy was>90%, indicating that the MRPs sensory evaluation scores could be accurately predicted.

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