The chemokine CXCL8, also known as the neutrophil chemotactic factor, plays a crucial role in mediating inflammatory responses and managing cellular immune reactions during viral infections. Porcine ...reproductive and respiratory syndrome virus (PRRSV) primarily infects pulmonary alveolar macrophages (PAMs), leading to acute pulmonary infections. In this study, we explored a novel long non-coding RNA (lncRNA), termed lnc-CAST, situated within the Cxcl8 gene locus. This lncRNA was found to be highly expressed in porcine macrophages. We observed that both lnc-CAST and CXCL8 were significantly upregulated in PAMs following PRRSV infection, and after treatments with lipopolysaccharide (LPS) or lipoteichoic acid (LTA). Furthermore, we noticed a concurrent upregulation of lnc-CAST and CXCL8 expression in lungs of PRRSV-infected pigs. We then determined that lnc-CAST positively influenced CXCL8 expression in PAMs. Overexpression of lnc-CAST led to an increase in CXCL8 production, which in turn enhanced the migration of epithelial cells and the recruitment of neutrophils. Conversely, inhibiting lnc-CAST expression resulted in reduced CXCL8 production in PAMs, leading to decreased migration levels of epithelial cells and neutrophils. From a mechanistic perspective, we found that lnc-CAST, localized in the nucleus, facilitated the enrichment of histone H3K27ac in CXCL8 promoter region, thereby stimulating CXCL8 transcription in a cis-regulatory manner. In conclusion, our study underscores the pivotal critical role of lnc-CAST in regulating CXCL8 production, offering valuable insights into chemokine regulation and lung damage during PRRSV infection.
Healthy lifestyle and screening represent 2 major approaches to colorectal cancer (CRC) prevention. It remains unknown whether the CRC-preventive benefit of healthy lifestyle differs by endoscopic ...screening status, and how the combination of healthy lifestyle with endoscopic screening can improve CRC prevention.
We assessed lifestyle and endoscopic screening biennially among 75,873 women (Nurses' Health Study, 1988 to 2014) and 42,875 men (Health Professionals Follow-up Study, 1988 to 2014). We defined a healthy lifestyle score based on body mass index, smoking, physical activity, alcohol consumption, and diet. We calculated hazard ratios (HRs) and population-attributable risks (PARs) for CRC incidence and mortality in relation to healthy lifestyle score according to endoscopic screening. Participants' mean age (standard deviation) at baseline was 54 (8) years. During a median of 26 years (2,827,088 person-years) follow-up, we documented 2,836 incident CRC cases and 1,013 CRC deaths. We found a similar association between healthy lifestyle score and lower CRC incidence among individuals with and without endoscopic screening, with the multivariable HR per one-unit increment of 0.85 (95% CI, 0.80 to 0.90) and 0.85 (95% CI, 0.81 to 0.88), respectively (P-interaction = 0.99). The fraction of CRC cases that might be prevented (PAR) by endoscopic screening alone was 32% (95% CI, 31% to 33%) and increased to 61% (95% CI, 42% to 75%) when combined with healthy lifestyle (score = 5). The corresponding PAR (95% CI) increased from 15% (13% to 16%) to 51% (17% to 74%) for proximal colon cancer and from 47% (45% to 50%) to 75% (61% to 84%) for distal CRC. Results were similar for CRC mortality. A limitation of our study is that our study participants are all health professionals and predominantly whites, which may not be representative of the general population.
Our study suggests that healthy lifestyle is associated with lower CRC incidence and mortality independent of endoscopic screening. An integration of healthy lifestyle with endoscopic screening may substantially enhance prevention for CRC, particularly for proximal colon cancer, compared to endoscopic screening alone.
The increasing concern for the ecological risks of microplastics (MPs) as carriers of hydrophobic organic contaminants is evident. Di-butyl phthalate (DBP) is extensively utilized as an additive in ...plastic products, and both DBP and MPs are widespread in the environment. However, the combined toxicity of these substances remains uncertain. In this study, zebrafish embryos were employed to assess the toxic effects of polyethylene terephthalate (PET, MPs) and DBP, with a focus on the DBP toxicities influenced by PET. The embryonic chorion was partially covered by PET particles, and PET led to a delayed hatching of zebrafish embryos without inducing death or teratogenesis. On the other hand, exposure to DBP considerably inhibited the hatching of embryos, leading to severe lethal and teratogenic effects. The most common phenotypes induced by DBP exposure were delayed yolk sac absorption and pericardial edema. The mortality increased in co-treatment with 100 particles/mL PET and 2 mg/L DBP at 24 hpf and 48 hpf. The malformation phenotype, bent notochord, and delayed yolk sac absorption became more severe in 1 mg/L DBP exposition with the co-exposure of 100 particles/mL PET at 72 hpf. PET might act as a carrier that enhances the bioavailability of ambient DBP.
Context:
Compelling evidence suggests that the beneficial effects of weight-loss diet interventions on improvement of cardiometabolic risk factors may be partly through modulating secretion of ...adiponectin from adipose tissue.
Objective:
To investigate the effects of long-term weight-loss diets with different compositions of macronutrients on longitudinal changes in circulating adiponectin concentrations and how such changes, if they exist, affect cardiometabolic risk.
Design, Setting, and Participants:
In the 2-year Preventing Overweight Using Novel Dietary Strategies trial, 811 overweight or obese adults were randomly assigned to 1 of 4 diets varying in macronutrient intakes. The current analysis was restricted to participants who had baseline adiponectin measurement (n = 768). Circulating concentrations of adiponectin and cardiometabolic outcomes were repeatedly measured at baseline, 6 months, and 2 years.
Main Outcome Measures:
Circulating concentrations of adiponectin and cardiometabolic risk factors.
Results:
Weight-loss diet interventions significantly increased circulating adiponectin concentrations over 2 years, similarly in 4 diet groups (P value for difference >.05). We found that the increase of adiponectin was significantly associated with reduction of waist circumference and low-density lipoprotein cholesterol, but associated with increase of high-density lipoprotein cholesterol (P < .001 for each), after adjusting for age, sex, ethnicity, follow-up time, diet group, baseline body mass index, baseline level of respective outcome trait, and concurrent weight change.
Conclusions:
Our findings indicate that long-term interventions by weight-loss diets varying in macronutrients similarly increase circulating adiponectin, which may particularly improve abdominal fat distribution and lipid metabolism independently of weight change.
“Long-term weight-loss diets varying in macronutrients similarly increased circulating adiponectin concentrations, which was related to an improvement of abdominal fatdistribution and lipid profile independently of weight change.”
The gut microbiome is increasingly recognized to play a role in cognition and dementia. Antibiotic use impacts the gut microbiome and has been linked with chronic disease. Despite these data, there ...is no evidence supporting an association between long-term antibiotic use in adults and cognitive function. We conducted a prospective population-based cohort study among 14,542 participants in the Nurses' Health Study II who completed a self-administered computerized neuropsychological test battery between 2014-2018. Multivariate linear regression models were used to assess if chronic antibiotic use in midlife was associated with cognitive impairment assessed later in life. Women who reported at least 2 months of antibiotic exposure in midlife (mean age 54.7, SD 4.6) had lower mean cognitive scores seven years later, after adjustment for age and educational attainment of the spouse and parent, with a mean difference of -0.11 standard units for the global composite score (Ptrend <0.0001), -0.13 for a composite score of psychomotor speed and attention (Ptrend <0.0001), and -0.10 for a composite score of learning and working memory (Ptrend <0.0001) compared with non-antibiotic users. These differences were not materially changed after multivariate adjustment for additional risk factors, including comorbid conditions. As a benchmark, the mean difference in score associated with each additional year of age was (-0.03) for global cognition, (-0.04) for psychomotor speed and attention, and (-0.03) for learning and working memory; thus the relation of antibiotic use to cognition was roughly equivalent to that found for three to four years of aging. Long-term antibiotic use in midlife is associated with small decreases in cognition assessed seven years later. These data underscore the importance of antibiotic stewardship, especially among aging populations.
In this paper, areas of soil disturbed by pipe jack construction are categorized and analyzed in detail. Mechanisms of soil disturbance are discussed and patterns of soil deformation are studied ...using random medium theory. Lateral deformations in deep soil, pore water pressures, stratified settlement, and earth pressures are investigated using measurements from an electrical transmission pipeline project in China. The measurements show that soil layer movement can be predicted by monitoring changes in pore water pressure, and the amplitude of soil disturbance transverse to the pipeline is larger than that above the pipeline in this project. The distributions of stress components in the direction of, and vertical to, the pipeline axis are studied by numerical simulation. It shows that the closer to the pipeline axis, the greater the additional stress, the faster the attenuation speed, and the smaller the range of influence. Relationships of positive propulsion, friction, and stratum loss with longitudinal and transverse surface deformations are also discussed. The ground displacement is a coupling of the three factors to the action of the soil. The surface transverse subsidence with a main influence range of about ±4 D (D is outer diameter of pipe jacking). The findings from this study can be used as technical foundation and reference for the construction of similar projects.
The etiopathogenesis of diverticulitis, among the most common gastrointestinal diagnoses, remains largely unknown. By leveraging stool collected within a large prospective cohort, we performed ...shotgun metagenomic sequencing and untargeted metabolomics profiling among 121 women diagnosed with diverticulitis requiring antibiotics or hospitalizations (cases), matched to 121 women without diverticulitis (controls) according to age and race. Overall microbial community structure and metabolomic profiles differed in diverticulitis cases compared to controls, including enrichment of pro-inflammatory Ruminococcus gnavus, 1,7-dimethyluric acid, and histidine-related metabolites, and depletion of butyrate-producing bacteria and anti-inflammatory ceramides. Through integrated multi-omic analysis, we detected covarying microbial and metabolic features, such as Bilophila wadsworthia and bile acids, specific to diverticulitis. Additionally, we observed that microbial composition modulated the protective association between a prudent fiber-rich diet and diverticulitis. Our findings offer insights into the perturbations in inflammation-related microbial and metabolic signatures associated with diverticulitis, supporting the potential of microbial-based diagnostics and therapeutic targets.
Fibroblast growth factor 21 (FGF21) is involved in the regulation of energy balance and adipose metabolism. Our previous genome-wide association study identified genetic variants in the FGF21 region ...associated with macronutrient intake preference. We investigated whether the FGF21 genotype modified effects of weight-loss diets varying in macronutrient intake on changes in adiposity in a 2-year randomized diet intervention trial.
We genotyped FGF21 rs838147 in 715 overweight or obese individuals who were assigned to one of four diets varying in macronutrient contents. A DEXA scan was performed to evaluate body composition.
We observed a significant interaction between the FGF21 genotype and carbohydrate/fat intake on 2-year changes in waist circumference (WC), percentage of total fat mass, and percentage of trunk fat (P = 0.049, P = 0.001, and P = 0.003 for interaction, respectively). In response to the low-carbohydrate/high-fat diet, carrying the carbohydrate intake-decreasing C allele of rs838147 was marginally associated with less reduction in WC (P = 0.08) and significantly associated with less reduction of total fat mass (P = 0.01) and trunk fat (P = 0.02). Opposite genetic associations with these outcomes were observed among the high-carbohydrate/low-fat diet group; carrying the C allele was associated with a greater reduction of WC, total body fat mass, and trunk fat.
Our data suggest that FGF21 genotypes may interact with dietary carbohydrate/fat intake on changes in central adiposity and body fat composition. A low-calorie, high-carbohydrate/low-fat diet was beneficial for overweight or obese individuals carrying the carbohydrate intake-decreasing allele of the FGF21 variant to improve body composition and abdominal obesity.
Abnormal angiogenesis is crucial for gallbladder cancer (GBC) tumor growth and invasion, highlighting the importance of elucidating the mechanisms underlying this process. LncRNA (long non-coding ...RNA) is widely involved in the malignancy of GBC. However, conclusive evidence confirming the correlation between lncRNAs and angiogenesis in GBC is lacking.
LncRNA sequencing was performed to identify the differentially expressed lncRNAs. RT-qPCR, western blot, FISH, and immunofluorescence were used to measure TRPM2-AS and NOTCH1 signaling pathway expression in vitro. Mouse xenograft and lung metastasis models were used to evaluate the biological function of TRPM2-AS during angiogenesis in vivo. EDU, transwell, and tube formation assays were used to detect the angiogenic ability of HUVECs. RIP, RAP, RNA pull-down, dual-luciferase reporter system, and mass spectrometry were used to confirm the interaction between TRPM2-AS, IGF2BP2, NUMB, and PABPC1.
TRPM2-AS was upregulated in GBC tissues and was closely related to angiogenesis and poor prognosis in patients with GBC. The high expression level and stability of TRPM2-AS benefited from m
A modification, which is recognized by IGF2BP2. In terms of exerting pro-angiogenic effects, TRPM2-AS loaded with exosomes transported from GBC cells to HUVECs enhanced PABPC1-mediated NUMB expression inhibition, ultimately promoting the activation of the NOTCH1 signaling pathway. PABPC1 inhibited NUMB mRNA expression through interacting with AGO2 and promoted miR-31-5p and miR-146a-5p-mediated the degradation of NUMB mRNA. The NOTCH signaling pathway inhibitor DAPT inhibited GBC tumor angiogenesis, and TRPM2-AS knockdown enhanced this effect.
TRPM2-AS is a novel and promising biomarker for GBC angiogenesis that promotes angiogenesis by facilitating the activation of the NOTCH1 signaling pathway. Targeting TRPM2-AS opens further opportunities for future GBC treatments.
Racial/ethnic minorities have been disproportionately impacted by COVID-19. The effects of COVID-19 on the long-term mental health of minorities remains unclear. To evaluate differences in odds of ...screening positive for depression and anxiety among various racial and ethnic groups during the latter phase of the COVID-19 pandemic, we performed a cross-sectional analysis of 691,473 participants nested within the prospective smartphone-based COVID Symptom Study in the United States (U.S.) and United Kingdom (U.K). from February 23, 2021 to June 9, 2021. In the U.S. (n=57,187), compared to White participants, the multivariable odds ratios (ORs) for screening positive for depression were 1·16 (95% CI: 1·02 to 1·31) for Black, 1·23 (1·11 to 1·36) for Hispanic, and 1·15 (1·02 to 1·30) for Asian participants, and 1·34 (1·13 to 1·59) for participants reporting more than one race/other even after accounting for personal factors such as prior history of a mental health disorder, COVID-19 infection status, and surrounding lockdown stringency. Rates of screening positive for anxiety were comparable. In the U.K. (n=643,286), racial/ethnic minorities had similarly elevated rates of positive screening for depression and anxiety. These disparities were not fully explained by changes in leisure time activities. Racial/ethnic minorities bore a disproportionate mental health burden during the COVID-19 pandemic. These differences will need to be considered as health care systems transition from prioritizing infection control to mitigating long-term consequences.
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