Toxicity of ZnO nanoparticles (NPs) to THP-1 macrophages: interactions with saturated or unsaturated free fatty acids

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.     

Qualitative evidence for Resilience,Stress, and Ethnicity (RiSE): A program to address race-based stress among Black women at risk for cardiovascular disease

ObjectiveGrowing evidence demonstrates that perceived discrimination and racism are significant contributing factors to psychological distress, low-grade chronic inflammation, and cardiovascular health disparities among minorities, particularly among Black women. Despite this evidence, there are no evidence-based complementary therapy interventions available to ameliorate chronic stress associated with racism and discrimination. The purpose of this study was to examine the feasibility and effectiveness of a novel, 8-week, group-based stress reduction program, Resilience, Stress and Ethnicity (RiSE), designed to help Black women at risk for cardiovascular disease (CVD) develop effective coping skills for dealing with chronic stress uniquely associated with being a minority.MethodsWe conducted two semi-structured focus groups with Black women (N = 22) following their participation in the 8-week RiSE program. We analyzed the data using constant comparative qualitative methods.ResultsAttrition rate was low (13%) with all participants attending at least 6 of the 8 classes. Participants reported high levels of satisfaction with the program and the majority (81%) reported practicing the skills that they learned in real-life stressful situations. In describing the participants’ response to the program, four key categories emerged from the data: (1) Increasing awareness of stressors associated with perceived discrimination and racism; (2) Coping with race-based stressors; (3) Coping with other sources of stress; and (4) Increasing sense of empowerment and emotion regulation.ConclusionsFindings suggest that RiSE is feasible and effective in helping Black women at risk for CVD cope with chronic stress associated with being a minority. Given evidence that perceived discrimination and racism are underlying factors in many inflammatory-based chronic diseases, this research may have broader implications for reducing health disparities across a wide-spectrum of chronic illnesses in which women minorities are disproportionately affected.     

Damage-associated molecular pattern (DAMP) activation in melanoma: investigation of the immunogenic activity of 15-deoxy, Δ12,14 prostamide J2

Metastatic melanoma is the most deadly skin neoplasm in the United States. Outcomes for this lethal disease have improved dramatically due to the use of both targeted and immunostimulatory drugs. Immunogenic cell death (ICD) has emerged as another approach for initiating antitumor immunity. ICD is triggered by tumor cells that display damage-associated molecular patterns (DAMPs). These DAMP molecules recruit and activate dendritic cells (DCs) that present tumor-specific antigens to T cells which eliminate neoplastic cells. Interestingly, the expression of DAMP molecules occurs in an endoplasmic reticulum (ER) stress-dependent manner. We have previously shown that ER stress was required for the cytotoxic activity of the endocannabinoid metabolite, 15-deoxy, Δ^12,14 prostamide J₂ (15dPMJ₂). As such, the current study investigates whether 15dPMJ₂ induces DAMP signaling in melanoma. In B16F10 cells, 15dPMJ₂ caused a significant increase in the cell surface expression of calreticulin (CRT), the release of ATP and the secretion of high-mobility group box 1 (HMGB1), three molecules that serve as surrogate markers of ICD. 15dPMJ₂ also stimulated the cell surface expression of the DAMP molecules, heat shock protein 70 (Hsp70) and Hsp90. In addition, the display of CRT and ATP was increased by 15dPMJ₂ to a greater extent in tumorigenic compared to non-tumorigenic melanocytes. Consistent with this finding, the activation of bone marrow-derived DCs was upregulated in co-cultures with 15dPMJ₂-treated tumor compared to non-tumor melanocytes. Moreover, 15dPMJ₂-mediated DAMP exposure and DC activation required the electrophilic cyclopentenone double bond within the structure of 15dPMJ₂ and the ER stress pathway. These results demonstrate that 15dPMJ₂ is a tumor-selective inducer of DAMP signaling in melanoma.     

Anti-inflammatory and anti-oxidant effects of aloe vera in rats with non-alcoholic steatohepatitis

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.     

真菌性、细菌性和病毒性肺炎的若干凝血指标变化分析

探讨真菌性、细菌性和病毒性肺炎的若干凝血指标差异性研究。方法 回顾性分析2017 年7 月～2019 年11 月本院肺炎患者128 例与同期门诊健康体检者50 例，分析患者血浆纤维蛋白原（FIB）、凝血酶原时间（PT）和活化部分凝血酶时间（APTT）的水平。结果 三类肺炎组与对照组在FIB、PT 和APTT 水平比较，差异均有统计学意义（P＜0.01）；FIB、PT 水平与病原感染呈正相关，APTT 与病原感染呈负相关。结论FIB、PT、APTT 可以间接提示肺炎感染病原体类型，具有临床意义。