The LncRNA AK018453 regulates TRAP1/Smad signaling in IL-17-activated astrocytes: A potential role in EAE pathogenesis.

The pro-inflammatory cytokine interleukin 17 (IL-17), that is mainly produced by Th17 cells, has been recognized as a key regulator in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). Reactive astrocytes stimulated by proinflammatory cytokines including IL-17 are involved in blood brain barrier destruction, inflammatory cells infiltration and spinal cord injury. However, the role of long non-coding RNAs (lncRNAs) induced by IL-17 in the pathogenesis of MS and EAE remains unknown. Herein, we found that an IL-17-induced lncRNA AK018453 promoted TGF-ß receptor-associated protein 1 (TRAP1) expression and Smad-dependent signaling in mouse primary astrocytes. Knockdown of AK018453 significantly suppressed astrocytosis, attenuated the phosphorylation of Smad2/3, reduced NF-κB p65 and CBP/P300 binding to the TRAP1 promoter, and diminished pro-inflammatory cytokine production in the IL-17-treated astrocytes. AK018453 knockdown in astrocytes by a lentiviral vector in vivo dramatically inhibited inflammation and prevented the mice from demyelination in the spinal cord during the progression of EAE. Together, these results suggest that AK018453 regulates IL-17-dependent inflammatory response in reactive astrocytes and potentially promotes the pathogenesis of EAE via the TRAP1/Smad pathway. Targeting this pathway may have a therapeutic potential for intervening inflammatory demyelinating diseases.

Research on Very Volatile Organic Compounds and Odors from Veneered Medium Density Fiberboard Coated with Water-Based Lacquers.

Very volatile organic compounds (VVOCs) are a group of important odor pollutants affecting indoor air quality that have been shown to be harmful to human health. A 15 L environmental chamber, combined with multi-bed tube was used to collect gases. Fifteen very volatile organic compounds (VVOCs), including 12 odor compounds, were identified from veneered medium density fiberboard coated with water-based lacquer (WB-MDF) using gas chromatography-mass spectrometry/olfactometry (GC-MS/O). The total very volatile organic compound (TVVOC) and total odor intensity (TOI) showed a decreasing trend over time, reaching equilibrium on day 28. TVVOC showed an overall slow-fast-slow emission profile, from day 3 to day 7, with a maximum decay rate of 29.7%. TOI showed the greatest rate of decline from day 1 to day 3, at approximately 12%. Alkane and alcohol VVOCs were the more abundant compounds, accounting for at least 60% and even up to 80% of the total. The major odor impression was fruity, with a highest odor rating of 6.6, followed by sweet, with an odor rating of 6.1. Although the odor impression changed from sweet to fruity over time, it seemed pleasant overall. The odor contributors were mainly alkanes, alcohols, esters, and ethers, which had relatively high odor intensities. The main odor-contributing substances were dichloromethane, ethanol, ethyl acetate, 2-methylacrylic acid methyl ester, and tetrahydrofuran. When WB-MDF is used for furniture or other decorative materials, it is strongly recommended that it be stored under ventilation for at least 28 days and the adoption of substitute solvents of lacquers, modified adhesives, and low-odor wood raw materials is recommended. These possible initiatives would contribute to the aim of building an environmentally friendly indoor environment.

IL-9-triggered lncRNA Gm13568 regulates Notch1 in astrocytes through interaction with CBP/P300: contribute to the pathogenesis of experimental autoimmune encephalomyelitis.

BACKGROUND: Interleukin 9 (IL-9), produced mainly by T helper 9 (Th9) cells, has been recognized as an important regulator in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Astrocytes respond to IL-9 and reactive astrocytes always associate with blood-brain barrier damage, immune cell infiltration, and spinal injury in MS and EAE. Several long non-coding RNAs (lncRNAs) with aberrant expression have been identified in the pathogenesis of MS. Here, we examined the effects of lncRNA Gm13568 (a co-upregulated lncRNA both in EAE mice and in mouse primary astrocytes activated by IL-9) on the activation of astrocytes and the process of EAE. METHODS: In vitro, shRNA-recombinant lentivirus with glial fibrillary acidic protein (GFAP) promoter were performed to determine the relative gene expression and proinflammatory cytokines production in IL-9 treated-astrocytes using Western blot, real-time PCR, and Cytometric Bead Array, respectively. RIP and ChIP assays were analyzed for the mechanism of lncRNA Gm13568 regulating gene expression. Immunofluorescence assays was performed to measure the protein expression in astrocytes. In vivo, H&E staining and LFB staining were applied to detect the inflammatory cells infiltrations and the medullary sheath damage in spinal cords of EAE mice infected by the recombinant lentivirus. Results were analyzed by one-way ANOVA or Student's t test, as appropriate. RESULTS: Knockdown of the endogenous lncRNA Gm13568 remarkably inhibits the Notch1 expression, astrocytosis, and the phosphorylation of signal transducer and activator of transcription 3 (p-STAT3) as well as the production of inflammatory cytokines and chemokines (IL-6, TNF-α, IP-10) in IL-9-activated astrocytes, in which Gm13568 associates with the transcriptional co-activators CBP/P300 which are enriched in the promoter of Notch1 genes. More importantly, inhibiting Gm13568 with lentiviral vector in astrocytes ameliorates significantly inflammation and demyelination in EAE mice, therefore delaying the EAE process. CONCLUSIONS: These findings uncover that Gm13568 regulates the production of inflammatory cytokines in active astrocytes and affects the pathogenesis of EAE through the Notch1/STAT3 pathway. LncRNA Gm13568 may be a promising target for treating MS and demyelinating diseases.

Preliminary mechanism on the methylation modification of Dkk-1 and Dkk-3 in hepatocellular carcinoma.

Wnt/ß-catenin signaling pathway, having a crucial role in regulating diverse cellular processes, can be a new therapeutic target in cancer. To investigate the role of Dkk-1 (Dickkopf-1) and Dkk-3 in tumors and cirrhoses of the liver tissue in hepatocellular carcinoma (HCC), tissues from 38 patients with HCC resections including 5 patients who underwent hemangioma surgery of adjacent tumor tissues at the same time were obtained. Tissues were divided into three groups (nonfibrosis, cirrhosis, and carcinoma) through hematoxylin-eosin (HE) staining. Methylation-specific polymerase chain reaction (PCR) (MSP) measured the methylation status, and reverse transcription-PCR tested the messenger RNA (mRNA) levels, and immunohistochemical analysis provided levels of protein expression. The methylation detection rate of Dkk-1 and Dkk-3 was the highest (P < 0.05) and the mRNA levels of Dkk-1 and Dkk-3 were the lowest (P < 0.05) in the carcinoma tissues. The mRNA levels of ß-catenin were significantly higher in the carcinoma tissue than the other tissues (P < 0.05). The expression of Dkk-1 and Dkk-3 was significantly higher in the carcinoma tissues than the other tissues (P < 0.05); but the ß-catenin expression was the highest (P < 0.05). Compared with the control, the mRNA levels of ß-catenin in the Dkk-1 and Dkk-3 silencing cells increased 5.34 (P < 0.05) and 3.5 times (P > 0.05). After the interference of 5-aza-2'-deoxycytidine, the mRNA levels of Dkk-1 and Dkk-3 significantly increased 58.9 and 59.3 times (P < 0.0001), and the mRNA levels of ß-catenin decreased 6.02 times (P < 0.05). In the process of HCC, the abnormal activity of Wnt/ß-catenin signaling may be associated with the methylation of Dkk-1 and Dkk-3.

Reference intervals and factors contributing to serum glycated albumin levels in West China.

BACKGROUND: In diabetic patients, non-enzymatically glycated albumin (GA), Amadori adducts, has been suggested as an ideal biomarker of short-term glycemic control. OBJECTIVE: To describe the reference intervals of serum GA and identify factors associated with serum GA, including age, gender, hemoglobin A1C (HbA1c) levels, fasting blood glucose (FPG) levels, total glycerin (TG) levels, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), systolic pressure (SBP) and diastolic pressure (DBP). METHODS: This study enrolled 1,296 healthy participants aged between 18 to 84 years of age attending physical tests in West China. Serum GA, blood glucose, blood lipid, and HbA1c levels were tested with commercially available reagents on automated clinical chemistry analyzers. RESULTS: In the West China population, the levels of serum GA concentrations were 11.6% (95% CI, 11.4 - 11.7) for overall population and 11.3% (95% CI, 11.1 - 11.4) and 11.9% (95% CI, 11.8 - 12.0) for males and females, respectively. In contrast, in a multiple model, gender (beta = 0.127), age (beta = 0.125), and HbAlc (beta = 0.177) were positively correlated with GA whilst body mass index (BMI) (beta = -0.197) and TG (beta = -0.153) were negatively correlated with GA. CONCLUSIONS: The reference intervals of GA were partitioned into five categories by age and gender; 8.7 - 13.7% for subjects aged 18 to 29 including both male and female, 8.1 - 13.7% for 30 to 49 years old males, 9.4 - 14.2% for 30 - 49 years old females, 9.1 - 14.9% for male and female subjects aged 50 - 59 and 9.6 - 15.7% for the male and female subjects over the age of 60 years.

Demethylation of lignin with mild conditions and preparation of green adhesives to reduce formaldehyde emissions and health risks.

Demethylated lignin (DL) was prepared in a NaOH/urea solution at room temperature, and the DL solution was directly substituted for phenol to prepare demethylated lignin phenol formaldehyde (DLPF). The 1H NMR results showed that the benzene ring's -OCH3 content dropped from 0.32 mmol/g to 0.18 mmol/g, whereas the functional group content of the phenolic hydroxyl group increased by 176.67 %, increasing the reactivity of DL. The bonding strength of 1.24 MPa and formaldehyde emission of 0.059 mg/m3 met the Chinese national standard with a 60 % replacement of DL with phenol. The volatile organic compound (VOC) emissions of DLPF and PF were simulated, with 25 types of VOCs were found in PF plywood and 14 types found in DLPF plywood. Terpene and aldehyde emissions from DLPF plywood rose, but total VOC emissions were 28.48 % less than those from PF. For carcinogenic risks (CR), both PF and DLPF showed ethylbenzene and naphthalene as carcinogenic VOCs, whereas DLPF had a lower total CR of 6.50 × 10-5. Both plywood had a noncarcinogenic risks of <1, which was within the permissible range to harm humans. In this study, the mild modification conditions of DL benefit its large-scale production, and DLPF effectively reduces the VOCs released from plywood in indoor environments, diminishing the health risks to humans.

Association between two single nucleotide polymorphisms at corresponding microRNA and schizophrenia in a Chinese population.

Numerous linkage and association studies have been performed to identify genetic predispositions to schizophrenic (SCZ) in different populations, but its genetic basis remains unclear. Some findings may provide a clue in understanding the association between abnormal immunity and SCZ. MicroRNA (miRNA) involves in regulating both schizophrenic and immunity as previous reported. And single nucleotide polymorphisms (SNPs) within miRNAs can change their characteristics, resulting in functional and/or phenotypic changes. So two SNPs (hsa-pre-mir-146a rs2910164 G>C and hsa-mir-499 rs3746444 T>C) at two miRNAs, were genotyped to demonstrate their association with susceptibility to SCZ. Polymorphisms were analyzed among 268 Chinese schizophrenic patients and 232 healthy controls by PCR-RFLP and validated by sequencing. No association was found between the two polymorphisms and SCZ either in cases or in controls. SCZ patients with family history showed significant increase of the G allele frequency of rs2910164 in comparison to those without (P = 0.018). The CC genotype frequency of rs3746444 was also higher in the patients having hallucinations than those without hallucinations (P = 0.012). In addition, patients carrying CC genotype of rs3746444 were more likely to be lack of motivation in comparison to normal controls (P = 0.042). Allele and genotype frequency of rs2910164 showed no significant difference between patients and normal subjects or between patients with and without clinical variables. Although patients carrying CC genotype of rs3746444 were found to be more likely to develop hallucination and individuals carrying C allele to lack motivation, there is lacking association between SCZ and the two SNPs at miRNAs, which may regulate immune response.

Candida albicans biofilms: antifungal resistance, immune evasion, and emerging therapeutic strategies.

Candida albicans is a fungal pathogen that can form biofilms on medical devices and host tissue, resulting in serious, life-threatening infections. These fungal biofilms are inherently resistant to traditional antifungal therapies and the host immune system; therefore, biofilm-associated infections are a huge clinical challenge. This review summarizes the most important insights into C. albicans biofilm-associated antifungal drug resistance mechanisms and immune evasion strategies. In addtion, this review also discusses the strategies for antifungal drug use to combat these processes, providing further evidence for novel drugs research and clinical therapies.

Effect of gender-related depression on heart rate variability during an autonomic nervous test.

Patients with depression have lower heart rate variability (HRV) compared with controls. However, studies have indicated HRV difference between male and female controls. The gender effect might be interactive with the depression effect on the HRV, resulting in a low accuracy of recognising the patients with depression from the controls. Our study explores the effect of gender-related depression on HRV. Four ANS tests including resting, deep breathing, Valsalva, and orthostatic test are employed as stimuli. HRV were collected from 182 subjects comprising 91 depressive patients (33 females/58 males) and 91 controls (33 females/58 males) in the four tests. Time and frequency domains and nonlinear parameters are employed to quantify HRV. Two-way ANOVA is applied to evaluate the effect of gender-related depression. Most HRV parameters of the patients significantly differ from those of the controls, but some parameters indicate different depression effect between the males and females in the deep breathing and Valsalva test. Some HRV parameters illustrate significant difference between the male and female controls. Therefore, the effect of depression on HRV of each gender should be investigated.

Hypnosis in the Treatment of Major Depression: An Analysis of Heart Rate Variability.

Hypnosis is an adjuvant treatment of major depression (MD). Heart rate variability (HRV) can assess the autonomic nervous system, which is associated with MD, and HRV is decreased in MD patients. There is a lack of research on HRV changes before, during, and after the use of hypnosis in MD patients. A total of 21 MD patients participated in this study, and 5-minute electrocardiograms were recorded before, during, and after hypnosis. Compared with the prehypnotic condition, HRV parameters significantly (p < .01) increased in the hypnotic and posthypnotic conditions. The results suggest that hypnosis treatment should bring some functional improvement to the autonomic nervous system. HRV is potentially a useful tool that quantifies the physiological impact of hypnosis treatment in MD patients.