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2.
Cardiovasc Diabetol ; 23(1): 188, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38824550

RESUMEN

BACKGROUNDS: Insulin resistance (IR) plays a vital role in the pathogenesis of the metabolic dysfunction-associated steatotic liver disease (MASLD). However, it remains unclear whether triglyceride-glucose (TyG) related parameters, which serve as useful biomarkers to assess IR, have prognostic effects on mortality outcomes of MASLD. METHODS: Participants in the National Health and Nutrition Examination Survey (NHANES) database from 1999 to 2018 years were included. TyG and its related parameters [TyG-waist circumference (TyG-WC) and TyG-waist to height ratio (TyG-WHtR)] were calculated. Kaplan-Meier curves, Cox regression analysis, and restricted cubic splines (RCS) were conducted to evaluate the association between TyG-related indices with the all-cause and cardiovascular mortality of adults with MASLD. The concordance index (C-index) was used to evaluate the prediction accuracy of TyG-related indices. RESULTS: A total of 8208 adults (4209 men and 3999 women, median age 49.00 years) with MASLD were included in this study. Multivariate-adjusted Cox regression analysis revealed that high quartile levels of TyG-related indices were significantly associated with the all-cause mortality of participants with MASLD [TyGadjusted hazard ratio (aHR) = 1.25, 95% confidence interval (CI) 1.05-1.50, P = 0.014; TyG-WCaHR for all-cause mortality = 1.28, 95% CI 1.07-1.52, P = 0.006; TyG-WHtRaHR for all-cause mortality = 1.50, 95% CI 1.25-1.80, P < 0.001; TyG-WCaHR for cardiovascular mortality = 1.81, 95% CI 1.28-2.55, P = 0.001; TyG-WHtRaHR for cardiovascular mortality = 2.22, 95% CI 1.55-3.17, P < 0.001]. The C-index of TyG-related indices for predicting all-cause mortality was 0.563 for the TyG index, 0.579 for the TyG-WC index, and 0.585 for the TyG-WHtR index, respectively. Regarding cardiovascular mortality, the C-index was 0.561 for the TyG index, 0.607 for the TyG-WC index, and 0.615 for the TyG-WHtR index, respectively. Nonlinear trends were observed between TyG and TyG-WC indices with all-cause mortality of MASLD (P < 0.001 and = 0.012, respectively). A non-linear relationship was observed between the TyG index and cardiovascular mortality of MASLD (P = 0.025). Subgroup analysis suggested that adults aged < 65 years old and those without comorbidities were more sensitive to the mortality prediction of TyG-related indices. CONCLUSION: Findings of this study highlight the predictive value of TyG-related indices, especially the TyG-WHtR index, in the mortality outcomes of adults with MASLD. TyG-related indices would be surrogate biomarkers for the clinical management of MASLD.


Asunto(s)
Biomarcadores , Glucemia , Enfermedades Cardiovasculares , Causas de Muerte , Resistencia a la Insulina , Encuestas Nutricionales , Triglicéridos , Humanos , Femenino , Masculino , Persona de Mediana Edad , Triglicéridos/sangre , Pronóstico , Medición de Riesgo , Biomarcadores/sangre , Estados Unidos/epidemiología , Glucemia/metabolismo , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/diagnóstico , Adulto , Factores de Tiempo , Bases de Datos Factuales , Anciano , Factores de Riesgo , Enfermedad del Hígado Graso no Alcohólico/mortalidad , Enfermedad del Hígado Graso no Alcohólico/sangre , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Estudios Transversales , Valor Predictivo de las Pruebas , Estudios Retrospectivos
3.
Ecotoxicol Environ Saf ; 280: 116531, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38852465

RESUMEN

BACKGROUND: Depression in late life has been associated with reduced quality of life and increased mortality. Whether the chronic fine particular matter (PM2.5) and its components exposure are contributed to the older depression symptoms remains unclear. METHOD: Middle-aged and older adults (>45 years) were selected from the China Health and Retirement Longitudinal Study during the four waves of interviews. The concentrations of PM2.5 and its major constituents were calculated using near real-time data at a spatial resolution of 10 km during the study period. The depressive symptom was evaluated by the Depression Center for Epidemiologic Studies Depression (CES-D)-10 score. The fix-effect model was applied to evaluate the association between PM2.5 and its major constituents with depressive symptoms. Three three-step methods were used to explore the modification role of sleep duration against the depressive symptoms caused by PM2.5 exposure. RESULTS: In our study, a total of 52,683 observations of 16,681 middle-aged and older adults were assessed. Each interquartile range (IQR) level of PM2.5 concentration exposure was longitudinally associated with a 2.6 % (95 % confidence interval [CI]: 1.3 %, 4.0 %) increase in the depression CES-D-10 score. Regarding the major components of PM2.5, OM, NO3-, and NH4+ showed the leading toxicity effects, which could increase the depression CES-D-10 score by 2.2 % (95 %CI: 1.0 %, 3.4 %), 2.2 % (0.6 %, 3.9 %), and 2.0 % (95 %CI: 0.6 %, 3.4 %) correspondingly. Besides, males were more susceptible to the worse depressive symptoms caused by PM2.5 and its major components exposure than female subpopulations. Shortened sleep duration might be the mediator of PM2.5-associated depressive symptoms. CONCLUSION: Our results suggest that long-term exposure to PM2.5 and its major components were associated with an increased risk for depressive symptoms in middle-aged and older adults. Reducing the leading components of PM2.5 may cost-effectively alleviate the disease burden of depression and promote healthy longevity in heavy pollutant countries.


Asunto(s)
Contaminantes Atmosféricos , Depresión , Exposición a Riesgos Ambientales , Material Particulado , Humanos , Material Particulado/análisis , Masculino , Persona de Mediana Edad , Femenino , Depresión/epidemiología , Depresión/psicología , Anciano , China/epidemiología , Contaminantes Atmosféricos/análisis , Estudios Longitudinales , Exposición a Riesgos Ambientales/estadística & datos numéricos , Estudios de Cohortes , Contaminación del Aire/efectos adversos , Contaminación del Aire/estadística & datos numéricos
4.
Int J Surg ; 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38874488

RESUMEN

BACKGROUND: Limited studies have explored the joint effect of physical activity (PA) and dietary quality (DQ) on the mortality outcomes of the cancer population. We aim to investigate the separate and joint prognostic effect of PA and DQ on the survival of US cancer survivors. METHODS: Data of cancer survivors (n=3,007, representing 22 million cancer survivors) were from the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2018. PA was assessed using the self-reported Global Physical Activity Questionnaire (GPAQ) and DQ was evaluated through the Health Eating Index-2015 (HEI-2015). Kaplan-Meier (KM) curves and the Cox proportional hazard model were used to evaluate the associations between separate and joint prognostic effects of PA and DQ with mortality outcomes among cancer survivors. RESULTS: In the joint analyses, cancer survivors with sufficiently active PA (≥600 MET-min/week) and qualified DQ (≥60) presented reduced risks of all-cause mortality (HR 0.45, 95% CI 0.35-0.59) as compared with each lifestyle intervention separately. Meanwhile, the joint effects of either insufficiently or sufficiently active PA (>0 MET-min/week) and qualified DQ (≥60) were associated with lower risks for cancer (HR 0.60, 95% CI 0.40-0.90) and non-cancer mortality (HR 0.43, 95% CI 0.32-0.59). CONCLUSIONS: Our study highlights the combination of active PA and qualified DQ was strongly associated with reduced mortality risk of cancer survivors. Our findings might help to refine the lifestyle intervention recommendations for this population.

5.
Breast Cancer Res Treat ; 206(1): 45-56, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38616207

RESUMEN

PURPOSE: The significance of postmastectomy radiotherapy (PMRT) in breast cancer patients who initially have clinically node-positive (cN +) status but achieve downstaging to ypN0 following neoadjuvant chemotherapy (NAC) remains uncertain. This study aims to assess the impact of PMRT in this patient subset. METHODS: Patients were enrolled from West China Hospital, Sichuan University from 2008 to 2019. Overall survival (OS), Locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and breast cancer-specific survival (BCSS) were estimated using the Kaplan-Meier method and assessed with the log-rank test. The impact of PMRT was further analyzed by the Cox proportional hazards model. Propensity score matching (PSM) was performed to reduce the selection bias. RESULTS: Of the 333 eligible patients, 189 (56.8%) received PMRT, and 144 (43.2%) did not. At a median follow-up period of 71 months, the five-year LRFS, DMFS, BCSS, and OS rates were 99.1%, 93.4%, 96.4%, and 94.3% for the entire cohort, respectively. Additionally, the 5-year LRFS, DMFS, BCSS, and OS rates were 98.9%, 93.8%, 96.7%, and 94.5% with PMRT and 99.2%, 91.3%, 94.9%, and 92.0% without PMRT, respectively (all p-values not statistically significant). After multivariate analysis, PMRT was not a significant risk factor for any of the endpoints. When further stratified by stage, PMRT did not show any survival benefit for patients with stage II-III diseases. CONCLUSION: In the context of comprehensive treatments, PMRT might be exempted in ypN0 breast cancer patients. Further large-scale, randomized controlled studies are required to investigate the significance of PMRT in this patient subset.


Asunto(s)
Neoplasias de la Mama , Mastectomía , Terapia Neoadyuvante , Estadificación de Neoplasias , Humanos , Femenino , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/radioterapia , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Adulto , Anciano , Estudios Retrospectivos , Radioterapia Adyuvante/métodos , Quimioterapia Adyuvante/métodos , Metástasis Linfática , Recurrencia Local de Neoplasia/patología
6.
Cardiovasc Diabetol ; 23(1): 134, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38658993

RESUMEN

BACKGROUND: Triglyceride-glucose (TyG) index has been determined to play a role in the onset of metabolic syndrome (MetS). Whether the TyG index and TyG with the combination of obesity indicators are associated with the clinical outcomes of the MetS population remains unknown. METHOD: Participants were extracted from multiple cycles of the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2018 years. Three indicators were constructed including TyG index, TyG combining with waist circumference (TyG-WC), and TyG combining with waist-to-height ratio (TyG-WHtR). The MetS was defined according to the National Cholesterol Education Program (NCPE) Adult Treatment Panel III. Kaplan-Meier (KM) curves, restricted cubic splines (RCS), and the Cox proportional hazard model were used to evaluate the associations between TyG-related indices and mortality of the MetS population. The sensitive analyses were performed to check the robustness of the main findings. RESULTS: There were 10,734 participants with MetS included in this study, with 5,570 females and 5,164 males. The median age of the study population was 59 years old. The multivariate Cox regression analyses showed high levels of TyG-related indices were significantly associated with the all-cause mortality of MetS population [TyG index: adjustedhazard ratio (aHR): 1.36, 95%confidence interval (CI): 1.18-1.56, p < 0.001; TyG-WHtR index: aHR = 1.29, 95%CI: 1.13-1.47, p < 0.001]. Meanwhile, the TyG-WC and TyG-WHtR index were associated with cardiovascular mortality of the MetS population (TyG-WC: aHR = 1.45, 95%CI: 1.13-1.85, p = 0.004; TyG-WHtR: aHR = 1.50 95%CI: 1.17-1.92, p = 0.002). Three TyG-related indices showed consistent significant correlations with diabetes mortality (TyG: aHR = 4.06, 95%CI: 2.81-5.87, p < 0.001; TyG-WC: aHR = 2.55, 95%CI: 1.82-3.58, p < 0.001; TyG-WHtR: aHR = 2.53 95%CI: 1.81-3.54, p < 0.001). The RCS curves showed a non-linear trend between TyG and TyG-WC indices with all-cause mortality (p for nonlinearity = 0.004 and 0.001, respectively). The sensitive analyses supported the positive correlations between TyG-related indices with mortality of the MetS population. CONCLUSION: Our study highlights the clinical value of TyG-related indices in predicting the survival of the MetS population. TyG-related indices would be the surrogate biomarkers for the follow-up of the MetS population.


Asunto(s)
Biomarcadores , Glucemia , Causas de Muerte , Síndrome Metabólico , Encuestas Nutricionales , Triglicéridos , Circunferencia de la Cintura , Humanos , Síndrome Metabólico/sangre , Síndrome Metabólico/mortalidad , Síndrome Metabólico/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Triglicéridos/sangre , Glucemia/metabolismo , Medición de Riesgo , Biomarcadores/sangre , Anciano , Pronóstico , Adulto , Factores de Tiempo , Estados Unidos/epidemiología , Relación Cintura-Estatura , Valor Predictivo de las Pruebas , Factores de Riesgo , Factores de Riesgo Cardiometabólico , Estudios Transversales
7.
Curr Probl Cancer ; 48: 101060, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38211418

RESUMEN

BACKGROUND: Treatment delays have frequently been observed in cancer patients. Whether the treatment delays would impair the survival of patients with nasopharyngeal carcinoma (NPC) is still unclear. METHODS: The data were derived from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015. Patients were divided into groups of timely treatment (<1 month), intermediate delay (1 and 2 months), and long delay (3-6 months). The influence of different treatment delay intervals on long-term survival was evaluated by multivariate Cox regression analysis. RESULTS: In total, 2,048 patients with NPC were included in our study. There were 551 patients in the early stage (I, II stage: 26.9 %) and 1,497 patients in the advanced stage (III, IV stage: 73.1 %). No significant difference in overall survival (OS) or cancer-specific survival (CSS) was observed among the groups with various treatment delay intervals (p = 0.48 in OS and p = 0.43 in CSS, respectively). However, upon adjusting for covariates, a significantly improved OS probability emerged in patients with intermediate treatment delays compared to those who received timely interventions in both the entire study population (adjustedHazard Ratio (aHR)=0.86, 95 % CI: 0.74-0.99, p = 0.043) and the subgroup with advanced stage (aHR=0.85, 95 % CI: 0.72-1.00, p = 0.049). Regarding the CSS probability, similar associations were also observed in the entire study population (aHR=0.84, 95 % CI: 0.71-0.98, p = 0.030) as well as the advanced-stage patients (aHR=0.83, 95 % CI: 0.70-0.99, p =  0.038). CONCLUSIONS: Our results revealed that treatment delays are not associated with worse survival of NPC patients. Tumor-specific characteristics and subsequent treatment modalities play more pivotal roles in the prognosis of NPC.


Asunto(s)
Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/patología , Estudios de Cohortes , Estadificación de Neoplasias , Pronóstico , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/terapia
8.
BMC Genom Data ; 25(1): 12, 2024 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-38297216

RESUMEN

Listeriosis caused by Listeria monocytogenes often poses a significant threat to vulnerable populations. Dairy products have been implicated in outbreaks of listeriosis worldwide. In Ethiopia, studies have identified Listeria spp. and L. monocytogenes in various dairy products, but the genetic diversity and phylogenetic relationships of these bacteria remain largely unknown in the low- and middle-income countries. Therefore, we conducted whole-genome sequencing on 15 L. monocytogenes and 55 L. innocua isolates obtained from different levels of the dairy supply chains across three regions in Ethiopia. Genomes were assembled and used for MLST genotyping and single nucleotide polymorphism (SNP) analysis to infer phylogenetic relationships. We identified a total of 3 L. monocytogenes (i.e., 2, 145, and 18) and 12 L. innocua (i.e., 1489, 1619, 603, 537, 1010, 3186, 492, 3007, 1087, 474, 1008, and 637) MLST sequence types among the studied isolates. Some of these sequence types showed region-specific occurrence, while others were broadly distributed across regions. Through high-quality SNP analysis, we found that among 13 L. monocytogenes identified as ST 2, 11 of them were highly similar with low genetic variation, differing by only 1 to 10 SNPs, suggesting potential selection in the dairy food supply chain. The L. innocua isolates also exhibited low intra-ST genetic variation with only 0-10 SNP differences, except for the ST 1619, which displayed a greater diversity.


Asunto(s)
Listeria monocytogenes , Listeria , Listeriosis , Humanos , Animales , Listeria monocytogenes/genética , Leche , Tipificación de Secuencias Multilocus , Etiopía/epidemiología , Filogenia , Listeria/genética , Listeriosis/epidemiología , Listeriosis/microbiología , Genómica
9.
Front Oncol ; 13: 1239636, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38152364

RESUMEN

Purpose: To evaluate the efficacy and safety of 3D-printed tissue compensations in breast cancer patients receiving breast reconstruction and postmastectomy radiotherapy (PMRT). Methods and materials: We enrolled patients with breast cancer receiving breast reconstruction and PMRT. The dose distribution of target and skin, conformability, and dose limit of organs at risk (OARs) were collected to evaluate the efficacy of the 3D-printed bolus. Radiation Therapy Oncology Group (RTOG) radiation injury classification was used to evaluated the skin toxicities. Results: A total of 30 patients diagnosed between October 2019 to July 2021 were included for analysis. Among all the patients, the 3D-printed bolus could ensure the dose coverage of planning target volume (PTV) [homogeneity index (HI) 0.12 (range: 0.08-0.18)], and the mean doses of D99%, D98%, D95%, D50%, D2% and Dmean were 4606.29cGy, 4797.04cGy, 4943.32cGy, 5216.07cGy, 5236.10cGy, 5440.28cGy and 5462.10cGy, respectively. The bolus demonstrated an excellent conformability, and the mean air gaps between the bolus and the chest wall in five quadrants were 0.04cm, 0.18cm, 0.04cm, 0.04cm and 0.07cm, respectively. In addition, the bolus had acceptable dosage limit of OARs [ipsilateral lung: Dmean 1198.68 cGy, V5 46.10%, V20 21.66%, V30 16.31%); heart: Dmean 395.40 cGy, V30 1.02%, V40 0.22%; spinal cord planning risk volume (PRV): Dmax 1634 cGy] and skin toxicity (grade 1, 76.0%; grade 2, 21.0%; grade 3, 3.3%). Conclusion: The 3D-printed bolus offers advantages in terms of dose uniformity and controllable skin toxicities in patients receiving breast reconstruction and PMRT. Further research is needed to comprehensively evaluate the effectiveness of the 3Dprinted bolus in this patient subset.

10.
Front Immunol ; 14: 1289356, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37908362

RESUMEN

Background: The hepatoprotective effect of interleukin 22 (IL-22) has been reported in several models of liver injuries, including alcohol-associated liver disease (ALD). However, the intestinal role of IL-22 in alcoholic hepatitis remains to be elucidated. Methods: Intestinal IL-22 levels were measured in mice fed with alcohol for 8 weeks. IL-22 was then administered to alcohol-fed mice to test its protective effects on alleviating alcoholic hepatitis, focusing on intestinal protection. Acute IL-22 treatment was conducted in mice to further explore the link between IL-22 and the induction of antimicrobial peptide (AMP). Intestinal epithelial cell-specific knockout of signal transducer and activator of transcription 3 (STAT3) mice were generated and used for organoid study to explore its role in IL-22-mediated AMP expression and gut barrier integrity. Results: After alcohol feeding for 8 weeks, the intestinal levels of IL-22 were significantly reduced in mice. IL-22 treatment to alcohol-fed mice mitigated liver injury as indicated by normalized serum transaminase levels, improved liver histology, reduced lipid accumulation, and attenuated inflammation. In the intestine, alcohol-reduced Reg3γ and α-defensins levels were reversed by IL-22 treatment. IL-22 also improved gut barrier integrity and decreased endotoxemia in alcohol-fed mice. While alcohol feeding significantly reduced Akkermansia, IL-22 administration dramatically expanded this commensal bacterium in mice. Regardless of alcohol, acute IL-22 treatment induced a fast and robust induction of intestinal AMPs and STAT3 activation. By using in vitro cultured intestinal organoids isolated from WT mice and mice deficient in intestinal epithelial-STAT3, we further demonstrated that STAT3 is required for IL-22-mediated AMP expression. In addition, IL-22 also regulates intestinal epithelium differentiation as indicated by direct regulation of sodium-hydrogen exchanger 3 via STAT3. Conclusion: Our study suggests that IL-22 not only targets the liver but also benefits the intestine in many aspects. The intestinal effects of IL-22 include regulating AMP expression, microbiota, and gut barrier function that is pivotal in ameliorating alcohol induced translocation of gut-derived bacterial pathogens and liver inflammation.


Asunto(s)
Antiinfecciosos , Hepatitis Alcohólica , Hepatopatías Alcohólicas , Microbiota , Ratones , Animales , Hepatitis Alcohólica/prevención & control , Simbiosis , Interleucinas , Hepatopatías Alcohólicas/prevención & control , Etanol , Inflamación , Bacterias , Interleucina-22
11.
JMIR Public Health Surveill ; 9: e47110, 2023 07 18.
Artículo en Inglés | MEDLINE | ID: mdl-37463020

RESUMEN

BACKGROUND: Young breast cancer patients are more likely to develop aggressive tumor characteristics and a worse prognosis than older women, and different races and ethnicities have distinct epidemiologies and prognoses. However, few studies have evaluated the clinical biological features and relapse patterns in different age strata of young women in Asia. OBJECTIVE: We aimed to explore survival differences and the hazard function in young Chinese patients with breast cancer (BC) by age. METHODS: The patients were enrolled from West China Hospital, Sichuan University. The chi-squared test, a Kaplan-Meier analysis, a log-rank test, a Cox multivariate hazards regression model, and a hazard function were applied for data analysis. Locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), breast cancer-specific survival (BCSS), and overall survival (OS) were defined as end points. RESULTS: We included 1928 young BC patients diagnosed between 2008 and 2019. Patients aged 18 to 25, 26 to 30, 31 to 35, and 36 to 40 years accounted for 2.7% (n=53), 11.8% (n=228), 27.7% (n=535), and 57.7% (n=1112) of the patients, respectively. The diagnosis of young BC significantly increased from 2008 to 2019. Five-year LRFS, DMFS, BCSS, and OS for the entire population were 98.3%, 93.4%, 94.4%, and 94%, respectively. Patients aged 18 to 25 years had significantly poorer 5-year LRFS (P<.001), 5-year DMFS (P<.001), 5-year BCSS (P=.04), and 5-year OS (P=.04) than those aged 31 to 35, 26 to 30, and 36 to 40 years. The hazard curves for recurrence and metastasis for the whole cohort continuously increased over the years, while the BC mortality risk peaked at 2 to 3 years and then slowly decreased. When stratified by age, the annualized hazard function for recurrence, metastasis, and BC mortality in different age strata showed significantly different trends, especially for BC mortality. CONCLUSIONS: The annual diagnosis of young BC seemed to increase in Chinese patients, and the distinct age strata of young BC patients did not differ in survival outcome or failure pattern. Our results might provide strategies for personalized management of young BC.


Asunto(s)
Neoplasias de la Mama , Femenino , Humanos , Neoplasias de la Mama/diagnóstico , Pueblos del Este de Asia , Pronóstico , Modelos de Riesgos Proporcionales , Adolescente , Adulto Joven , Adulto , Análisis de Supervivencia
14.
Front Pharmacol ; 14: 1109580, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37153802

RESUMEN

Background: Statin use for cancer prevention has raised wide attention but the conclusions are still controversial. Whether statins use have exact causal effects on cancer prevention remains unclear. Methods: Based on the Genome-Wide Association Studies (GWAS) datasets from the large prospective UK Biobank and other consortium databases, two-sample mendelian randomization (MR) analysis was conducted to explore the causal effects of statins use on varied site-specific cancer risks. Five MR methods were applied to investigate the causality. The stability, heterogeneity, and pleiotropy of MR results were also evaluated. Results: The atorvastatin use could increase the risk of colorectal cancer (odd ratio (OR) = 1.041, p = 0.035 by fixed-effects inverse variance weighted (IVW) method (IVWFE), OR = 1.086, p = 0.005 by weighted median; OR = 1.101, p = 0.048 by weighted mode, respectively). According to the weighted median and weighted mode, atorvastatin could modestly decrease the risk of liver cell cancer (OR = 0.989, p = 0.049, and OR = 0.984, p = 0.004, respectively) and head and neck cancer (OR = 0.972, p = 0.020). Besides, rosuvastatin use could reduce the bile duct cancer risk by 5.2% via IVWEF method (OR = 0.948, p = 0.031). No significant causality was determined in simvastatin use and pan-cancers via the IVWFE or multiplicative random-effects IVW (IVWMRE) method if applicable (p > 0.05). There was no horizontal pleiotropy observed in the MR analysis and the leave-one-out analysis proved the stability of the results. Conclusion: The causalities between statin use and cancer risk were only observed in colorectal cancer and bile duct cancer in the European ancestry population. Future works are warranted to provide more robust evidence for supporting statin repurposing for cancer prevention.

15.
Front Immunol ; 14: 1141956, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36936956

RESUMEN

The evidence for chronic hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC) occurrence is well established. The hepatocyte epithelium carcinogenesis caused by HBV has been investigated and reviewed in depth. Nevertheless, recent findings from preclinical and observational studies suggested that chronic HBV infection is equally important in extrahepatic cancer occurrence and survival, specifically gastrointestinal system-derived cancers. Immune microenvironment changes (immune-suppressive cytokine infiltration), epigenetic modification (N6-methyladenosine), molecular signaling pathways (PI3K-Akt and Wnt), and serum biomarkers such as hepatitis B virus X (HBx) protein are potential underlying mechanisms in chronic HBV infection-induced extrahepatic cancers. This narrative review aimed to comprehensively summarize the most recent advances in evaluating the association between chronic HBV infection and extrahepatic cancer risk and explore the potential underlying molecular mechanisms in the carcinogenesis induction of extrahepatic cancers in chronic HBV conditions.


Asunto(s)
Carcinoma Hepatocelular , Hepatitis B Crónica , Hepatitis B , Neoplasias Hepáticas , Humanos , Virus de la Hepatitis B , Carcinoma Hepatocelular/patología , Hepatitis B Crónica/complicaciones , Neoplasias Hepáticas/patología , Fosfatidilinositol 3-Quinasas , Carcinogénesis , Microambiente Tumoral
16.
Hepatology ; 78(3): 896-910, 2023 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-36626632

RESUMEN

BACKGROUND AND AIMS: Alcohol-perturbed gut immune homeostasis is associated with the development of alcoholic liver disease (ALD). However, the role of intestinal dendritic cells (DCs) in ALD progression is still unknown. This study aimed to investigate the cellular and molecular mechanisms through which intestinal DCs respond to alcohol exposure and contribute to the pathogenesis of ALD. APPROACH AND RESULTS: After 8 weeks of alcohol consumption, the number of basic leucine zipper transcription factor ATF-like 3 ( Batf3 )-dependent conventional type 1 DCs (cDC1s) was dramatically decreased in the intestine but not the liver. cDC1 deficient Batf3 knockout mice along with wild-type mice were subjected to chronic-binge ethanol feeding to determine the role of intestinal cDC1s reduction in ALD. cDC1s deficiency exacerbated alcohol-induced gut barrier disruption, bacterial endotoxin translocation into the circulation, and liver injury. Adoptive transfer of cDC1s to alcohol-fed mice ameliorated alcohol-mediated gut barrier dysfunction and liver injury. Further studies revealed that intestinal cDC1s serve as a positive regulator of Akkermansia muciniphila ( A. muciniphila ). Oral administration of A. muciniphila markedly reversed alcoholic steatohepatitis in mice. Mechanistic studies revealed that cDC1s depletion exacerbated alcohol-downregulated intestinal antimicrobial peptides which play a crucial role in maintaining A. muciniphila abundance, by disrupting the IL-12-interferon gamma signaling pathway. Lastly, we identified that intestinal cDC1s were required for the protective role of Lactobacillus reuteri in alcoholic steatohepatitis. CONCLUSIONS: This study demonstrated that cDC1s protect alcohol-induced liver injury by maintaining A. muciniphila abundance in mice. Targeting cDC1s may serve as a promising therapeutic approach for treating ALD.


Asunto(s)
Hígado Graso Alcohólico , Hepatopatías Alcohólicas , Ratones , Animales , Hepatopatías Alcohólicas/prevención & control , Hepatopatías Alcohólicas/patología , Etanol , Verrucomicrobia , Células Dendríticas/metabolismo , Endotoxinas , Ratones Endogámicos C57BL
17.
Front Vet Sci ; 9: 1076906, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36578437

RESUMEN

The fermented feed has been used extensively as a growth promoter in agricultural animal production. However, the effects of fermented feed on swine gut microbiota are still largely unknown. The work presented here aimed to investigate the growth performance and gut microbiota of nursery pigs receiving the LPF diet (10% Lactobacillus plantarum and Pediococcus acidilactici co-fermented feed + basal diet) compared with pigs receiving the NC diet (basal diet). The data showed LPF diet numerically improved average daily gain and significantly increased fecal acetate, butyrate, and total short-chain fatty acid (SCFA) concentrations. Furthermore, gut microbiota structure and membership significantly changed in response to the addition of fermented feed in the diet. Gut microbiota results indicated that LPF treatment significantly enriched SCFA-producing bacteria such as Megasphaera, Roseburia, Faecalibacterium, Blautia, Selenomonas, Dialister, Acidaminococcus, Ruminococcus, and Bifidobacterium. Some of these bacteria also had anti-inflammatory and other beneficial functions. Overall, these findings suggested that Lactobacillus plantarum and Pediococcus acidilactici co-fermented feed benefited growth performance and established potential health impacts on the gut microbiota of nursery pigs.

18.
Anal Chem ; 94(46): 15964-15970, 2022 11 22.
Artículo en Inglés | MEDLINE | ID: mdl-36346959

RESUMEN

Long-lived emissive nucleic acid probes are widely used in biochemical analysis due to their programmable structures, high signal-to-background ratio, and high sensitivity. Homogeneous detection based on long-lived emissive nucleic acid probes is often achieved through Förster resonance energy transfer (FRET), which suffers from the limitation of a narrow effective distance range. Herein, a new strategy of accessing nucleic acid hybridization-responsive luminescent probes is presented. The photoluminescence (PL) of a Lumi4-Tb complex internally modified with DNA is switched on by nucleic acid hybridization, after which the PL is increased up to 20 times. PL lifetime analysis revealed a possible mechanism of luminescence enhancement. Due to the flexibility of single-stranded nucleic acid chains, the bases and phosphate groups can coordinate with the Tb(III), which reduces the stability of the Tb complex and results in weak PL. After hybridization, the rigid double helix structure suppresses the coordination between Tb(III) and the bases or phosphate groups, causing luminescence enhancement. As the DNA sequence can be freely designed, an array of probes for different DNA or RNA targets can be created with the same Tb complex. Moreover, the novel probe design can afford pM detection limits of DNA or RNA without any nucleic acid amplification and exhibits great potential for nucleic acid detection in clinical diagnosis.


Asunto(s)
Luminiscencia , Ácidos Nucleicos , ARN , Hibridación de Ácido Nucleico/métodos , ADN/química , Sondas de Ácido Nucleico , Fosfatos
19.
Bioresour Technol ; 354: 127232, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35483532

RESUMEN

Anaerobic co-digestion (ACoD) of poultry litter (PL) and wheat straw (WS) in an anaerobic sequencing batch reactor (ASBR) for continuous bio-energy generation was started up for the first time by gradually increasing the organic loading rate (OLR). A steady-state was reached with a daily biogas production of (13.06 ± 0.21) L and methane content of (54.38 ± 0.53) %. The subsequent regular operation achieved a daily methane yield of (100.41-188.65) mL CH4/g VS added and a total chemical oxygen demand (tCOD) removal rate of (70.3-85.9) % in the effluent under different operating parameters. The overall microbial community became more uniform, and the dominant aceticlastic methanogen of Methanosaeta was enriched after the start-up. While the microbial community was largely stable in the overall structure since the regular operation. Therefore, the start-up of the ACoD of PL and WS was successful with stable and continuous methane production.


Asunto(s)
Microbiota , Triticum , Anaerobiosis , Animales , Biocombustibles , Reactores Biológicos , Digestión , Metano/análisis , Aves de Corral , Triticum/química
20.
Front Microbiol ; 13: 845621, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35387077

RESUMEN

Archaea are considered a "keystone" of the gut microbiome and are linked with the host's energy harvest and health. Although a few studies have investigated the gut archaea in pigs, especially piglets, little is known about the effects of weaning on archaeal structure and function. In this study, we explored the effects of weaning on the longitudinal changes of archaeal composition, diversity, and functional potential in pigs overtime by re-analyzing a recently published metagenomic dataset that included 176 fecal samples collected from commercial pigs on days 7, 14, 21, 28, 35, 70, and 140 after birth. Overall, the richness and diversity of archaeal species showed an increasing trend, and weaning significantly affected the richness of archaeal species. Methanobrevibacter A smithii significantly decreased and was replaced by Methanobrevibacter A sp900769095 within 2 weeks after weaning. For the functional potential, the richness of KEGG KOs increased over time. LEfSe analysis identified 18 KOs, including for example, ko04623 (cytosolic DNA-sensing pathway), ko00500 (starch and sucrose metabolism), and so on, significantly enriched in the weaning pigs, suggesting the involvement of archaea in the piglets' adaptation to the new diet after weaning. Correlation analysis based on Random Forest regression and Pearson correlation showed that archaeal species richness was significantly associated with pig bodyweight on both days 70 and 140. Methanobrevibacter A sp900769095 (R = 0.405, p = 0.040) and Methanobrevibacter A smithii (R = 0.535, p = 0.004) were positively linked with pigs' bodyweight on days 70 and 140, respectively. Our results revealed the dynamic changes of archaeal diversity and functions and demonstrated the effects of weaning on the gut archaea of pigs, suggesting archaea might play essential roles in swine nutrition, metabolism, and growth performance, especially during the critical weaning process.

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