Colorectal cancer cells with high metastatic potential drive metastasis by transmitting exosomal miR-20a-3p through modulating NF1/MAPK pathway.

Cancer cells exhibit heterogenous metastatic potential, and high metastatic subclones can enhance metastatic potential of low metastatic subclones by transmitting some factors. Exosomal miRNAs play a pivotal role in the crosstalk of heterogenous metastatic subclones. This study discovered that miR-20a-3p was upregulated in colorectal adenocarcinoma (CRA), correlated with metastasis, and potentially served as a prognostic indicator for CRA. miR-20a-3p could promote the proliferation, migration and invasion of CRA cells. Interestingly, high metastatic CRA cells could promote malignant phenotypes of low metastatic CRA cells by transmitting exosomal miR-20a-3p. Mechanically, miR-20a-3p could inhibit NF1, thereby activate the RAS-mediated mitogen-activated protein kinases (MAPK) signaling pathway to drive the metastasis of CRA. In summary, our study provided the evidence that colorectal cancer cells with high metastatic potential drive metastasis by transmitting exosomal miR-20a-3p through modulating NF1/MAPK pathway.

Higher oxidative balance score is associated with lower kidney stone disease in US adults: a population-based cross-sectional study.

PURPOSE: Oxidative balance stress (OBS) was an important indicator for assessing exposure to oxidative stress related to diet and lifestyle. The purpose of this study was to explore the relationship between OBS and kidney stone disease (KSD). METHODS: Secondary dataset analysis was performed by the study from six survey cycles (2007-2018) in the National Health and Nutrition Examination Survey (NHANES). OBS was the exposure factor and ever had kidney stone (yes or no) was the outcome. Weighted univariate or multivariate logistic regression models were used to estimate the associations. RESULTS: The prevalence of KSD among participants was 8.6%. OBS showed a significant negative correlation with KSD (OR: 0.98, 95% CI 0.96-0.999), 35% reduction in KSD in the highest OBS quartile compared to the lowest OBS quartile. Dietary OBS was significantly negatively correlated with KSD (OR: 0.98, 95% CI 0.96-0.9998), but not with lifestyle OBS. In addition, OBS had a negative correlation with KSD in females (OR: 0.97, 95% CI 0.94-0.996), non-diabetic participants (OR: 0.98, 95% CI 0.96-0.99), and hypertensive participants (OR: 0.96, 95% CI 0.93-0.99), but OBS was not observed to be associated with KSD in gout participants. Interestingly, this relationship existed in participants aged 30-60 years and a ratio of family income to poverty (PIR) of 1.3-3.5 (all P value < 0.05). CONCLUSION: Our study revealed that OBS was negative associated with KSD, and high OBS might be a protective factor in KSD. Targeting one of the components of OBS might be beneficial.

Antioxidant diet/lifestyle could mitigate the adverse impacts of urinary polycyclic aromatic hydrocarbons on lung function.

BACKGROUND: Extant research has demonstrated a correlation between exposure to polycyclic aromatic hydrocarbons (PAHs) and impaired lung function. The maintenance of an antioxidant-rich diet/lifestyle positively benefits pulmonary health. However, the potential ameliorative impact of an antioxidant-based diet/lifestyle on PAH-induced detrimental effects remains unclear. METHODS: The study drew upon cross-sectional data encompassing 1615 participants derived from the National Health and Nutrition Examination Survey 2007 to 2012. To gauge the maintenance of an antioxidant-rich diet/lifestyle, we employed Oxidative Balance Score (OBS) that incorporates sixteen nutrients and four lifestyle factors. Lung function was evaluated using percent-predicted Forced Vital Capacity (FVC), Forced Expiratory Volume 1st Second (FEV1), FEV1/FVC, and fractional exhaled nitric oxide (FENO). Our analytical approach entailed the utilization of weighted linear models. RESULTS: Our analysis unveiled interaction effects between urinary monohydroxy polycyclic aromatic hydrocarbons (OH-PAHs) and OBS concerning lung function. A one-unit increase in ∑OH-PAH (sum of eight OH-PAHs) was linked to a -0.75% reduction (95% CI: -1.28, -0.22) in FEV1/FVC. Individuals exhibiting low OBS displayed a marked decrease in FEV1/FVC (mean difference = -1.10%; 95% CI: -1.82, -0.39) for each unit increase in ∑OH-PAH, whereas no significant associations were discerned for those with medium or high OBS. Further stratification by gender yielded consistent results. The correlation between ∑OH-PAH and FENO proved statistically significant among participants with low OBS (P = 0.002) and medium OBS (P = 0.001), but non-significant for those with high OBS. Parallel findings emerged when examining percent-predicted FEV1 and FVC. CONCLUSIONS: In conclusion, our study underscores the existence of statistically significant interactions between OH-PAHs and the maintenance of an antioxidant-rich diet and lifestyle concerning lung function. These findings underscore the pivotal role of maintaining an antioxidant-based diet and lifestyle in mitigating the adverse impacts of PAH exposure on lung function.

Higher oxidative balance score was associated with decreased risk of erectile dysfunction: a population-based study.

BACKGROUND: Erectile dysfunction (ED) is a prevalent condition that is thought to be significantly impacted by oxidative stress. The oxidative balance score (OBS) has been built to characterize the state of antioxidant/pro-oxidant balance. There is less known regarding the relationship of OBS with ED. METHODS: This study conducted cross-sectional analyses on 1860 males who participated in the National Health and Nutrition Examination Survey (NHANES) from 2001 to 2004. OBS was constructed by the 16 dietary components and 4 lifestyle factors. Self-reported ED was defined as men who indicated that they "never" or "sometimes" could achieve or keeping an erection adequate for satisfactory intercourse. Multivariate logistic regression models were applied to examine the association between OBS and the risk of ED. RESULTS: Among 1860 participants, the median OBS was 20 (IQR 15-26), and OBS was lower in males with ED vs. those without ED (P = 0.001). The results of our analyses indicated a negative correlation between OBS and ED among male subjects. Specifically, each one-unit increase in the continuous OBS was relate to 3% reduction in the odds of ED after full adjustment. Moreover, when extreme OBS quartiles were compared, the adjusted odds ratio (95% confidence interval) for the 4th OBS category was 0.53 (0.32 to 0.88) after full adjustment (P for trend < 0.05). There was also statistical significance in the relationships between dietary/lifestyle OBS with ED, and the association between lifestyle OBS and ED may be even tighter. For each unit increase in lifestyle OBS, the odds of ED decreased by 11% after full adjustment. CONCLUSION: Higher OBS was associated with reduced risk of ED in U.S. males. These findings suggested that adopting an antioxidant-rich diet and engaging in antioxidant-promoting lifestyle behaviors may contribute to a lower incidence of ED. These results provided recommendations for a comprehensive dietary and lifestyle antioxidants for ED patients.

Risk factors and predicting nomogram for the clinical deterioration of non-severe community-acquired pneumonia.

BACKGROUND: Currently, there remains insufficient focus on non-severe community-acquired pneumonia (CAP) patients who are at risk of clinical deterioration, and there is also a dearth of research on the related risk factors. Early recognition of hospitalized patients at risk of clinical deterioration will be beneficial for their clinical management. METHOD: A retrospective study was conducted in The First Affiliated Hospital of Wenzhou Medical University, China, spanning from January 1, 2018 to April 30, 2022, and involving a total of 1,632 non-severe CAP patients. Based on whether their condition worsened within 72 h of admission, patients were divided into a clinical deterioration group and a non-clinical deterioration group. Additionally, all patients were randomly assigned to a training set containing 75% of patients and a validation set containing 25% of patients. In the training set, risk factors for clinical deterioration in patients with non-severe CAP were identified by using LASSO regression analysis and multivariate logistic regression analysis. A nomogram was developed based on identified risk factors. The effectiveness of the nomogram in both the training and validation sets was assessed using Receiver Operating Characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). RESULTS: Age, body mass index (BMI), body temperature, cardiovascular comorbidity, respiratory rate, LDH level, lymphocyte count and D-dimer level were identified as risk factors associated with the clinical deterioration of non-severe CAP within 72 h of admission. The area under curve (AUC) value of the nomogram was 0.78 (95% CI: 0.74-0.82) in the training set and 0.75 (95% CI: 0.67-0.83) in the validation set. Furthermore, the calibration curves for both the training and validation sets indicated that the predicted probability of clinical deterioration aligned with the actual probability. Additionally, DCA revealed clinical utility for the nomogram at a specific threshold probability. CONCLUSION: The study successfully identified the risk factors linked to the clinical deterioration of non-severe CAP and constructed a nomogram for predicting the probability of deterioration. The nomogram demonstrated favorable predictive performance and has the potential to aid in the early identification and management of non-severe CAP patients at elevated risk of deterioration.

Genome-Wide Analysis of the Oat (Avena sativa) HSP90 Gene Family Reveals Its Identification, Evolution, and Response to Abiotic Stress.

Oats (Avena sativa) are an important cereal crop and cool-season forage worldwide. Heat shock protein 90 (HSP90) is a protein ubiquitously expressed in response to heat stress in almost all plants. To date, the HSP90 gene family has not been comprehensively reported in oats. Herein, we have identified twenty HSP90 genes in oats and elucidated their evolutionary pathways and responses to five abiotic stresses. The gene structure and motif analyses demonstrated consistency across the phylogenetic tree branches, and the groups exhibited relative structural conservation. Additionally, we identified ten pairs of segmentally duplicated genes in oats. Interspecies synteny analysis and orthologous gene identification indicated that oats share a significant number of orthologous genes with their ancestral species; this implies that the expansion of the oat HSP90 gene family may have occurred through oat polyploidization and large fragment duplication. The analysis of cis-acting elements revealed their influential role in the expression pattern of HSP90 genes under abiotic stresses. Analysis of oat gene expression under high-temperature, salt, cadmium (Cd), polyethylene glycol (PEG), and abscisic acid (ABA) stresses demonstrated that most AsHSP90 genes were significantly up-regulated by heat stress, particularly AsHSP90-7, AsHSP90-8, and AsHSP90-9. This study offers new insights into the amplification and evolutionary processes of the AsHSP90 protein, as well as its potential role in response to abiotic stresses. Furthermore, it lays the groundwork for understanding oat adaptation to abiotic stress, contributing to research and applications in plant breeding.

3-methyladenine ameliorates acute lung injury by inhibiting oxidative damage and apoptosis.

Background: Acute lung injury (ALI) is a condition characterized by inflammation and oxidative damage. 3-methyladenine (3-MA) has great potential for regulating apoptosis, but its regulatory role in ALI is unknown. Methods: Lipopolysaccharide (LPS)-treated mice and tert-butyl hydroperoxide (TBHP)-treated bronchial epithelial cells were used to simulate in vivo and in vitro ALI models, respectively. In vivo, lung injury was assessed by histopathological analysis and lung injury scoring. The total cell count, protein content, and inflammatory factors in bronchoalveolar lavage fluid (BALF) were examined. The level of apoptosis in lung tissue was assessed through TUNEL staining. In the vitro ALI model, cell viability and levels of reactive oxygen species and apoptosis were assessed. Results: 3-MA pretreatment ameliorated lung injury, including intra-alveolar hemorrhage and inflammatory cell accumulation, both in vitro and in vivo. 3-MA pretreatment also decreased inflammatory factor levels in the BALF. 3-MA pretreatment alleviated oxidative damage, decreased reactive oxygen species levels, and attenuated morphological changes. TUNEL and Annexin V-FITC/PI staining revealed that pretreatment with 3-MA reduced the level of apoptosis. 3-MA pretreatment significantly decreased the expression of caspase-3 and Bax but increased the expression of Bcl-2 in ALI. Mechanistically, 3-MA pretreatment also affected the PKCα/NOX4 and Nrf2 pathways, which decreased the level of apoptosis in ALI. Conclusions: 3-MA pretreatment inhibited inflammation and oxidative damage in ALI and inhibited apoptosis to mitigate ALI in part by inhibiting the PKCα/NOX4 pathway and activating the Nrf2 pathway. Based on these results, 3-MA might be a viable medication to treat with ALI.

E3 ubiquitin ligase RNF128 attenuates colitis and colorectal tumorigenesis by triggering the degradation of IL-6 receptors.

INTRODUCTION: Intestinal immune dysregulation is strongly linked to the occurrence and formation of tumors. RING finger protein 128 (RNF128) has been identified to play distinct immunoregulatory functions in innate and adaptive systems. However, the physiological roles of RNF128 in intestinal inflammatory conditions such as colitis and colorectal cancer (CRC) remain controversial. OBJECTIVES: To elucidate the function and mechanism of RNF128 in colitis and CRC. METHODS: Animal models of dextran sodium sulfate (DSS)-induced colitis and azoxymethane (AOM)/DSS-induced CRC were established in WT and Rnf128-deficient mice and evaluated by histopathology. Co-immunoprecipitation and ubiquitination analyses were employed to investigate the role of RNF128 in IL-6-STAT3 signaling. RESULTS: RNF128 was significantly downregulated in clinical CRC tissues compared with paired peritumoral tissues. Rnf128-deficient mice were hypersusceptible to both colitis induced by DSS and CRC induced by AOM/DSS or APC mutation. Loss of RNF128 promoted the proliferation of CRC cells and STAT3 activation during the early transformative stage of carcinogenesis in vivo and in vitro when stimulated by IL-6. Mechanistically, RNF128 interacted with the IL-6 receptor α subunit (IL-6Rα) and membrane glycoprotein gp130 and mediated their lysosomal degradation in ligase activity-dependent manner. Through a series of point mutations in the IL-6 receptor, we identified that RNF128 promoted K48-linked polyubiquitination of IL-6Rα at K398/K401 and gp130 at K718/K816/K866. Additionally, blocking STAT3 activation effectively eradicated the inflammatory damage of Rnf128-deficient mice during the transformative stage of carcinogenesis. CONCLUSION: RNF128 attenuates colitis and colorectal tumorigenesis by inhibiting IL-6-STAT3 signaling, which sheds novel insights into the modulation of IL-6 receptors and the inflammation-to-cancer transition.

Oxidative balance score was negatively associated with the risk of metabolic syndrome, metabolic syndrome severity, and all-cause mortality of patients with metabolic syndrome.

Background: The oxidative balance score (OBS), an encompassing scoring mechanism for assessing oxidative stress, is formulated based on nutritional and lifestyle components. The emergence of metabolic syndrome (MetS) is intricately linked to oxidative stress. Nonetheless, the correlation between OBS and MetS displays variability within distinct cohorts. Objective: We worked on the relationships between OBS and the risk of MetS, MetS severity, and all-cause mortality of MetS patients. Methods: A total of 11,171 adult participants were collected from the U.S. National Health Examination Survey (NHANES) 2007-2018. Employing survey-weighted logistic models, we evaluated the relationship between OBS and MetS risk. Furthermore, survey-weighted linear models were utilized to investigate the connection between OBS and MetS severity. Among the participants, 3,621 individuals had their survival status recorded, allowing us to employ Cox proportional hazards regression models in order to ascertain the association between OBS and the all-cause mortality within the subset of individuals with MetS. The OBS (where a higher OBS signified an increased prevalence of anti- or pro-oxidant exposures) weighed the 20 factors, while the MetS severity score weighed the five factors. Results: After multivariable adjustment, individuals with elevated OBS were found to exhibit a decreased susceptibility to MetS [odds ratio (OR) 0.95; 95% CI 0.94-0.96]. The adjusted OR was 0.42 (95% CI 0.33-0.53) for MetS risk in the fourth OBS quartile compared with those in the first OBS quartile (P for trend < 0.001). A one-unit increase in OBS was linked to a 3% reduction in MetS severity score by 3% (mean difference, -0.03; 95% CI, -0.04 to -0.03). Moreover, increased OBS correlated with decreased hazard of all-cause mortality risk among MetS subjects (adjusted hazard ratio, 0.95; 95% CI, 0.93-0.98). These associations retained their strength even subsequent to the introduction of sensitivity analyses. There existed a statistically significant negative correlation between diet/lifestyle OBS and both MetS risk as well as MetS severity. Conclusions: An inverse correlation was observed between OBS and the susceptibility to MetS, MetS severity, and all-cause mortality of MetS patients. Health outcomes for MetS patients were positively related to antioxidant diets and lifestyles.