In a biological microenvironment, free fatty acids (FFA) as ubiquitous biological molecules might interact with nanoparticles (NPs) and consequently change the toxicological responses. However, whether the chemical structures of FFA could influence their interactions with NPs remain unknown. This study investigated the interactions between ZnO NPs and saturated or unsaturated FFA (complexed to BSA), namely stearic acid (SA, C18:0), oleic acid (OA, C18:1), and α-linolenic acid (ALA, C18:3). It was shown that BSA, SA, OA, and ALA increased the atomic force microscope (AFM) heights as well the polydispersity index (PDI) of ZnO NPs. BSA modestly protected THP-1 macrophages from ZnO NP exposure, whereas OA and ALA led to relatively less cyto-protective effects of BSA. Moreover, only co-exposure to ZnO NPs and SA significantly promoted the release of interleukin-8. BSA, SA, OA, and ALA equally changed intracellular ROS and Zn ions associated with ZnO exposure, but co-exposure to ZnO NPs and OA/ALA particularly activated the expression of endoplasmic reticulum stress-apoptosis genes. In combination, these results showed that FFA could influence the colloidal aspects and toxicological signaling pathway of ZnO NPs, which is dependent on the number of unsaturated bonds of FFA. 相似文献
Introduction: The rising prevalence of musculoskeletal pathologies in developed countries has caused a dramatic impact on social welfare. Amidst these musculoskeletal pathologies is Rheumatoid arthritis (RA), a chronic systemic autoimmune disease that mostly affects the synovium. RA metabolic-associated alterations, including distorted adipokine production, enhance RA inflammatory environment. Among the altered adipokines, visfatin is particularly involved in RA inflammation and catabolism and stands out as an essential enzyme linked to critical cell features.
Areas covered: We discuss the potential mechanism supporting the contribution of visfatin to RA and the association between RA and obesity. We discuss the repurposing of cancer-tested drugs to inhibit visfatin in the context of RA. Additionally, we address the possibility of combining these drugs with current RA therapy. Finally, we explore the future of visfatin as an RA biomarker or therapeutic target.
Expert opinion: Inhibition of visfatin has become an interesting therapeutic approach for RA pathology. Such a feat has already been attained in oncology using small molecule inhibitors, which suggest that a similar course of action would be worth pursuing in the RA context. Visfatin will become an important biomarker and therapeutic target for RA. 相似文献
ObjectiveRetinol-binding protein 4 (RBP4), systemic inflammation and insulin resistance (IR) are linked, yet the determinants of RBP4 and its impact on IR in rheumatoid arthritis (RA) are incompletely understood. The aim of this study was to explore the prevalence of IR in RA and investigate whether the serum levels of RBP4 were associated with IR in patients with RA.MethodsIn this study, 403 individuals with newly diagnosed and untreated RA were consecutively recruited. We calculated the Disease Activity Score assessed using 28-joint counts for swelling and tenderness (DAS28). Levels of serum RBP4, interleukin-6 (IL-6) and tumor necrosis factor (TNF) α were tested. IR was defined as Homeostasis model assessment for insulin resistance (HOMA-IR) index greater than or equal 2.40.ResultsIn those 403 patients, 68 (16.9%) were male and the median age was 43 years (IQR: 36–52). There was an evidently positive correlation between increased serum levels of RBP4 and increasing severity of RA (DAS28) (r = 0.403, P < 0.001). Furthermore, a modest positive correlation between levels of serum RBP4 and HOMA-IR score (r = 0.251; P < 0.0001) was found. Eighty-five patients (21.1%) in patients with RA were defined as IR (HOMA-IR ≥ 2.40), which was significantly higher than in normal cases (4.7%). In the patients with IR, serum levels of RBP4 were higher when compared with those in patients free-IR P < 0.001. The IR distribution across the quartiles of RBP4 ranged between 5.0% (first quartile) to 39.0% (fourth quartile), P for trend < 0.001. For each 1unit increase of RBP4, the unadjusted and adjusted risk of IR increased by 8% (OR: 1.08; 95% CI: 1.05–1.11, P < 0.001) and 5% (1.05; 1.02–1.09, P = 0.001), respectively. When RBP4 was added to the model containing established significant risk factors, AUROC (standard error) was increased from 0.768 (0.025) to 0.807(0.021). A significant difference in the AUC between the established risk factors alone and the addition of RBP4 was observed (difference, 0.039[0.004]; P = 0.02).ConclusionElevated serum levels of RBP4 were associated with increased risk of IR and might be useful in identifying RA at risk for IR and/or impaired glucose tolerance for early prevention strategies, especially in obese and women patients 相似文献
Inflammation and infections have been associated with prostate cancer progression. We assessed whether elevated serum cytokines or T. vaginalis seropositivity at the time of diagnosis was associated with higher grade or lethal prostate cancer.
Patients and Methods
Men with localized or metastatic prostate cancer were included in this study. Cytokine serum levels including interleukin (IL)-1α, IL-1β, IL-2, IL-6, IL-8, monocyte chemotactic protein 1 (CCL-2), tumor necrosis factor α, and growth-regulated oncogene α (CXCL-1) using a multiplex enzyme-linked immunosorbent assay and T. vaginalis serology were measured in blood samples at diagnosis.
Results
A total of 324 patients were identified at time of localized disease and 118 at time of metastatic disease. Of the 189 patients with localized disease and clinical follow-up data (median, 73 months), 28 developed lethal disease. There was no association between circulating cytokine levels above median concentrations nor T. vaginalis seropositivity and risk of intermediate- to high-risk or lethal prostate cancer.
Conclusion
Higher levels of serum cytokine levels and T. vaginalis seropositivity at diagnosis are not associated with high-grade or lethal prostate cancer and do not aid risk stratification of localized prostate cancer. 相似文献
Objective: The objective of this study was to gain greater insight into individuals’ quality of life (QOL) definitions, appraisals, and adaptations following spinal cord injury (SCI).
Design: A mixed-methods design, applying the Schwartz and Sprangers response shift (RS) model. RS is a cognitive process wherein, in response to a change in health status, individuals change internal standards, values, or conceptualization of QOL
Setting: Community-dwelling participants who receive medical treatment at a major Midwestern medical system and nearby Veterans’ Affairs hospital.
Participants: A purposive sample of participants with SCI (N?=?40) completed semi-structured interviews and accompanying quantitative measures.
Interventions: Not applicable.
Outcome Measures: Qualitative data were analyzed using content analysis to identify themes. Analysis of variance were performed to detect differences based on themes and QOL, well-being, and demographic and injury characteristics.
Results: Four RS themes were identified, capturing the range of participant perceptions of QOL. The themes ranged from complete RS, indicating active engagement in maintaining QOL, to awareness and comparisons redefining QOL, to a relative lack of RS. Average QOL ratings differed as a function of response shift themes. PROMIS Global Health, Anxiety, and Depression also differed as a function of RS themes.
Conclusion: The RS model contextualizes differences in QOL definitions, appraisals, and adaptations in a way standardized QOL measures alone do not. 相似文献
BACKGROUND Aloe vera exerts several biological activities, such as, anti-inflammatory, antioxidant, and antimicrobial effects. It was recently shown to reduce insulin resistance and triglyceride level. We hypothesized that aloe vera would have beneficial effects in alleviating non-alcoholic steatohepatitis(NASH) in rats.AIM To examine the therapeutic effects of aloe vera in NASH rats.METHODS All rats were randomly divided into 3 groups(n = 6 in each group). Rats in the control group were fed ad libitum with a standard diet for 8 wk. Rats in the NASH group were fed ad libitum with a high-fat high-fructose diet(HFHFD) for 8 wk. Rats in the aloe vera group were fed ad libitum with a HFHFD and aloe vera in dimethylsulfoxide(50 mg/kg) by gavage daily for 8 wk. Liver samples were collected at the end of the treatment period.RESULTS Hepatic malondialdehyde(MDA) levels increased significantly in the NASH group as compared with the control group(377 ± 77 nmol/mg vs 129 ± 51 nmol/mg protein, respectively, P 0.001). Glutathione(GSH) levels were significantly lower in the NASH group than the control group(9 ± 2 nmol/mg vs 24 ± 8 nmol/mg protein, respectively, P = 0.001). The expression of interleukin-18(IL-18), nuclear factor-kappa β, and caspase-3 increased, while peroxisome proliferator-activated receptor gamma decreased in the NASH group compared with the controls. Following aloe vera administration, MDA levels decreased(199 ± 35 nmol/mg protein) and GSH increased(18 ± 4 nmol/mg protein) markedly. Steatosis, hepatocyte ballooning, lobular inflammation and increased hepatocyte apoptosis were observed in the NASH group. Aloe vera treatment attenuated these changes in liver histology.CONCLUSION Aloe vera attenuated oxidative stress, hepatic inflammation and hepatocyte apoptosis, thus improving liver pathology in rats with NASH. 相似文献
Arsenic (As) and cadmium (Cd) have recently emerged as major health concerns owing to their strong association with diabetes mellitus (DM). We aimed to investigate the heavy metals exposure towards incidence of DM at various enzymatic and hormonal levels. Additionally, association of As and Cd with Zinc (Zn, essential metal) was also evaluated. Spot urine samples were collected to assess As, Cd and Zn through ICP-OES. Serum was analyzed by assay method for fasting blood glucose, liver and renal function biomarkers. ELISA was performed to investigate the impact of heavy metals on HbA1c, α-amylase, DPP-IV, IGF-1, leptin, GSH, MDA, SOD, HDL, FFA, TG and interleukin (IL)-6. Association of heavy metals with DM was measured by odds ratio (OR) and level of significance was assessed by Chi-squared test. Unpaired student's t-test was used to compare DM-associated risk factors in heavy metals-exposed and unexposed participants. As and Cd were detectable in 75.4% and 83% participants with mean concentration of 75.5 ppb and 54.5 ppb, respectively. For As exposure, OR in the third quartile was maximum ie 1.34 (95% CI, 0.80 to 2.23), however the result was not statistically significant (P > .05). For Cd exposure, OR in the fourth quartile was considerably high, 1.62 (95% CI, 1.00 to 2.61), with a significant probability value (P < .05). Urinary Cd was negatively associated with Zn. As and Cd exposure increases the incidence of DM in the general population. Impaired hormonal and enzymatic levels in diabetic and non-diabetic exposed participants reflect the multiple organ damage by heavy metal exposure. 相似文献