[The role of TNF-α/TNFR1 inhibiting autophagy of M1-type Kupffer cells in liver injury in trichloroethylene-sensitized mice].

Objective: To detect the expression levels of M1-type polarization and autophagy-related indicators in the liver of trichloroethylene (TCE) -sensitized mice, and to explore the role of liver tumor necrosis factor-α (TNF-α) and tumor necrosis factor receptor 1 (TNFR1) in regulating M1-type Kupffer cells autophagy in liver injury in TCE-sensitized mice. Methods: In November 2019, according to simple random grouping, 45 SPF grade BALB/c female mice (6-8 weeks old) were divided into 4 groups: blank control group (n=5) , solvent control group (n=5) , TCE treatment group (n=18) , TCE+R7050 (inhibitor) treatment group (n=17) . Transdermally sensitized mice, 24 h after the last challenge, the mice were divided into TCE sensitized group and TCE non-sensitized group according to the skin reaction score. The livers of mice were harvested, and the pathological changes of the livers were observed under light and electron microscopes. Western blotting was used to detect the expressions of TNF-α, TNFR1 and autophagy-related indexes. The expression of inducible nitric oxide synthase (iNOS) , a marker of M1-type Kupffer cells, was detected by immunohistochemistry, and the occurrence of autophagy in M1-type Kupffer cells was detected by immunofluorescence double-labeling method. Results: The sensitization rate of TCE treatment group was 38.9% (7/18) , and TCE+R7050 treatment group was 35.3% (6/17) , with no significant difference between the two groups (P=1.000) . Compared with the blank control group, mice in the TCE sensitized group had abnormal liver ocytes, obvious liver injury, reduced mitochondria and broken endoplasmic reticulum. Western blotting results showed that the expressions of TNF-α and TNFR1 protein in the liver of the mice in the TCE sensitized group increased, the expression of iNOS protein in M1-type Kupffer cells increased, and the expressions of autophagic microtubule-associated protein 1 light-chain 3 (LC3B) and Beclin1 protein were decreased (P<0.05) . The results of immunohistochemistry showed that iNOS was not significantly expressed in the blank control group and solvent control group, and a small amount of expression was found in the TCE non-sensitized group, the positive staining area was obvious in TCE sensitized group, and the expression of iNOS was significantly increased (P<0.05) . Immunofluorescence results showed that the iNOS protein levels in the blank control group, solvent control group and TCE non-sensitized group were lower, and only partially colocalized with P62; the colocalization of iNOS with P62 in the TCE sensitized group was significantly increased. Conclusion: TNF-α/TNFR1 signaling pathway may promote liver injury in TCE-sensitized mice by inhibiting autophagy of M1-type Kupffer cells.

[The role of ROS/TXNIP/NLRP3 pathway in the skin injury of trichloroethylene sensitized mice].

Objective: To explore the mechanism of reactive oxygen species/thioredoxin-interacting protein/nucleotide-binding oligomerization domain-like receptor 3 (ROS/TXNIP/NLRP3) pathway in the skin injury of trichloroethylene (TCE) sensitized mice. Methods: In August 2020, 40 female BALB/c mice were randomly divided into control group (n=5) , solvent control group (n=5) , TCE treatment group (n=15) and TCE+(2-(2, 2, 6, 6-Tetrameyhylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl) triphenylphosphonium chloride (Mito TEMPO) treatment group (n=15) . The TCE sensitization model was established. Mice in the TCE treatment group and TCE+Mito TEMPO treatment group were divided into the sensitized positive group and the sensitized negative group according to the skin erythema and edema reactions on the back of the mice 24 h after the last stimulation. The mice were sacrificed 72 h after the last stimulation, the back skin of the mice was taken, and the skin lesions were observed. Immunohistochemistry (IHC) was used to detect the expression level of NLRP3, and the Western Blot was performed to detect the expression levels of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC) , cysteinyl aspartate specific proteinase 1 (Caspase 1) , Interleukin-1ß (IL-1ß) and TXNIP proteins in the skin of the mice, the reactive oxygen species (ROS) kit was used to detect the level of intracellular ROS in the back skin tissue. Results: The sensitization rates of TCE treatment group and TCE+Mito TEMPO treatment group were 40.0% (6/15) and 33.3% (5/15) , respectively, and there was no significant difference between the two groups (P>0.05) . The back skin of the mice in the TCE sensitized positive group was thickened and infiltrated by a large number of inflammatory cells. The number of mitochondria in the epidermis cells was significantly reduced, the mitochondrial crest disappeared and vacuolar degeneration occurred. TCE+Mito TEMPO sensitized positive group had less damage, more mitochondria and relatively normal cell structure. Compared with the solvent control group and corresponding sensitized negative groups, the expression levels of NLRP3, ASC, Caspase 1, IL-1ß, TXNIP proteins and the content of ROS in the TCE sensitized positive group and TCE+Mito TEMPO sensitized positive group were significantly increased (P<0.05) . Compared with TCE sensitized positive group, the expression levels of NLRP3, ASC, Caspase 1, IL-1ß, TXNIP proteins and the content of ROS in the TCE+Mito TEMPO sensitized positive group were significantly decreased (P<0.05) . Conclusion: ROS/TXNIP/NLRP3 pathway was activated and then encouraged the release of IL-1ß, finally aggravated the TCE-induced skin injury.

[Research progress on the immunological pathogenesis of occupational medicamentosa-like dermatitis due to trichloroethylene].

Occupational exposure to trichloroethylene can induce a series of immune diseases which include systemic rash, multiple system and organ damage, which are defined as occupational medicamentosa-like dermatitis due to trichloroethylene (OMLDT) . This article reviews the research progress of the role of T cell immunity, humoral immunity and complement system in the immunological pathogenesis of OMLDT to provide theoretical basis for the diagnosis and treatment of OMLDT.

[The role of epigenetic effect in the trichloroethylene toxicity].

Trichloroethylene (TCE) is a commonly used organic solvent in industry and it was classified as a Group I carcinogen by IARC, with immunotoxicity, hepatotoxicity, kidney toxicity and neurotoxicity. Increasing evidence suggests that TCE-induced autoimmune diseases and cancer are involved in epigenetic modifications. This paper summarized the mechanism of DNA methylation, histone modification and microRNA in toxicity of TCE according to the newly published articles, so as to provide new ideas for further revealing the mechanism of TCE exposure affecting health.

[Cathepsin L mediates glomerular endothelial cell injury by cleavaging complement C3 in trichloroethylene-sensitized mice].

Objective: To observe the expressions of complement 3 (C3) and endothelial cell injury-associated proteins before and after cathepsin L (CTSL) blockade in renal injury of trichloroethylene (TCE) -sensitized mice. Methods: In June 2018, 41 SPF female BALB/c mice were divided respectively into blank control group (n=5) , vehicle control group (n=5) , TCE group (n=15) and TCE+CTSLi group (n=16) to establish trichloroethylene-sensitized mice model by pretreating the mice with intraperitoneal injection of CTSL inhibitor (CTSLi) and using TCE for the first and last challenge. According to the skin sensitization score, the mice were divided into positive group and negative group. 72 hours after the last challenge, the renal function indexes of the mice were detected, the pathological changes of mice kidneys were observed, and the glomerular C3 and endothelial cell damage-related proteins [vascular cell adhesion molecule 1 (VCAM-1) , tight junction protein 5 (Claudin-5) and Syndecan-1] expression levels were detected. Results: The sensitization rates of mice in TCE group and TCE+CTSLi group were 53.3% (8/15) and 50.0% (8/16) , respectively, and there was no significant difference between the two groups (P>0.05) . Compared with vehicle control group and the corresponding TCE negative group, the serum creatinine (CRE) and blood urea nitrogen (BUN) levels of mice in the TCE positive group was increased, while the TCE positive group were higher than the TCE+CTSLi positive group (P<0.05) . Pathological examination showed obvious vacuolar degeneration and cellular edema in the mice kidney of the TCE positive group. In the TCE+CTSLi positive group, the above pathological damage was significantly improved. Immunohistochemical results showed that the expression of glomerular C3 fragment and VCAM-1 in TCE positive group were significantly higher than that of the vehicle control and TCE negative group (P<0.05) , while TCE+CTSLi positive group was significantly lower than that of TCE positive group (P<0.05) . Western blot test results showed that the relative expression levels of Claudin-5 and Syndecan-1 protein in the mice glomeruli of TCE positive group were significantly lower than those in the vehicle control group and TCE negative group (P<0.05) . Compared with the TCE positive group, the Claudin-5 protein was increased in the kidney of the TCE+CTSLi positive group, but the difference was not statistically significant (P>0.05) , while the Syndecan-1 protein was significantly increased in the TCE+CTSLi positive group (P<0.05) . Conclusion: CTSL may mediate the glomerular structural damage by cutting complement C3, activating the complement system, damaging endothelial cell structural protein Syndecan-1 and overexpressing adhesion molecule VCAM-1 in TCE-sensitized mice. Inhibiting the expression of CTSL may be an effective way to protect the glomerular integrity of structure and function in pharmacology.

Differentially expressed proteins identified by TMT proteomics analysis in children with verrucous epidermal naevi.

BACKGROUND: Verrucous epidermal naevi (VEN) are benign skin tumours, considered keratinocytic epidermal naevi, that appear at birth or early childhood. VEN may display a range of appearances, depending on patient age. Although the number of studies regarding VEN is increasing, the exact mechanism of VEN is still unknown. OBJECTIVES: The aim of this study was to analyse the changes in the expression of protein factors in lesions of VEN children by TMT labelling-based quantitative proteomics. METHODS: A total of 8 children with VEN (5 for experiment and 3 for validation) and 8 healthy children (5 for experiment and 3 for validation) presented to the Department of Dermatology, the First Affiliated Hospital of Anhui Medical University, Boao Super Hospital, between January 2019 and November 2019. The lesions and lesion-adjacent tissues from children with VEN and naevus-adjacent normal skin tissues from children with pigmented naevi were defined as the VEN group, VENC group and C group, respectively. We performed a proteomics analysis to screen for differentially expressed proteins in the lesions of these individuals. We further performed Western blotting to validate the relative expression levels of nine targeted proteins in the validation group. RESULTS: According to the proteomics results, a total of 4970 proteins were identified, and 4770 proteins were quantified. Among these proteins, 586 proteins were up- or downregulated at least 1.3-fold with a P-value < 0.05 (upregulated: 399, downregulated: 187) in lesions between the VEN group and the C group. These proteins played important roles in multiple biological functions, such as cornification, epidermal cell differentiation and neutrophil activation, and formed a complicated protein-protein interaction network. Of the 586 up- or downregulated proteins, nine were selected for further validation. According to Western blotting analysis results, the relative expression levels of Involucrin, NDUFA4, Loricrin, Keratin type II cytoskeletal 6A (Cytokeratin 6A), BRAF, Filaggrin, S100A7 and Desmocollin-3 were significantly upregulated in VEN children and may be associated with skin barrier dysfunction, epidermal cell overgrowth and differentiation, inflammation and immune and oxidative phosphorylation, which are involved in the pathogenesis of VEN. CONCLUSIONS: According to TMT-based proteomics and Western blotting results, we identified eight noteworthy proteins, Involucrin, NDUFA4, Loricrin, Keratin type II cytoskeletal 6A, BRAF, Filaggrin, S100A7 and Desmocollin-3, that were upregulated in the lesions of VEN children and may be associated with the pathogenesis of VEN. Our findings provide new starting points for identifying precise pathogenic mechanisms or therapeutic targets for VEN.

CircABCB10 promotes the proliferation and migration of lung cancer cells through down-regulating microRNA-217 expression.

OBJECTIVE: We aimed at studying the role and molecular mechanism of circular RNA circABCB10 in the progression of lung cancer (LCa). PATIENTS AND METHODS: We collected LCa tissues using quantitative real-time polymerase chain reaction (qRT-PCR) technology to determine circABCB10 expression and performed survival analysis based on the clinical data of LCa patients. At the same time, the specific effects of circABCB10 on the biological function of LCa cell lines were determined by certain cell function experiments, including cell counting kit-8 (CCK-8) test, plate cloning experiment, transwell and cell wound healing assays. The downstream key gene microRNA-217 of circABCB10 was predicted through bioinformatics analysis and the potential regulation between them was confirmed by luciferase assay. microRNA-217 was knocked down in LCa cell lines to verify its important role in the progression of LCa. RESULTS: CircABCB10 showed abnormally high expression in LCa tissues and cell lines and was related to the poor prognosis of patients. In vitro cell experiments demonstrated that knocking down circABCB10 remarkably suppressed the proliferation and migration ability of LCa cells. In addition, circABCB10 can specifically bind to microRNA-217 and negatively regulate its expression of microRNA-217 in LCa cells. Finally, cell functional experiments showed that microRNA-217 is a key downstream gene that mediates the regulation of circABCB10 on LCa cell function. CONCLUSIONS: CircABCB10, abnormally highly expressed in LCa tissues, is able to induce the malignant progression of this cancer.

[Effect of complement C5a on the expression of MCP-1 and NGAL in immune kidney injury of trichloroethylene sensitized mice].

Objective: To explore the possible role of C5a in the pathogenesis of renal injury in TCE- sensitized mice, to analyze the impact of expression of neutrophil gelatinase-associated lipocalin (NGAL) and monocyte chemotactic protein-1 (MCP-1) in the presence or absence of C5a receptor antagonist (C5aRA) pretreatment. Methods: A total of 50 female specific pathogens free(SPF) BALB/c mice were randomly divided into blank control group (n=5) , solvent control group (n=5) , TCE group (n=20) , and TCE+C5aRA group (n= 20) . After one week for adaptive feeding, a mouse model of TCE-induced skin sensitization was established by treating with 50% TCE and 30% TCE in turn. The mice in solvent control group accept same reagents without TCE and the mice in blank control group underwent nothing. In TCE +C5aRA group, except for the TCE solution treatment, mice were intraperitoneally injected with 0.5 mg/kg C5aRA solution at the time of challenge. And the skin erythema and edema reaction were scored 24 h after the last challenge. The mice were divided into sensitization positive group and sensitization negative group according to the scoring result. The mice were aseptically sacrificed 72 h after the last challenge to obtain the kidneys. The structural damage of kidney was observed after histopathological staining. The levels of NGAL and MCP-1 mRNA and proteins were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) , respectively. Results: The sensitization rate of mice in TCE group and TCE+C5aRA group was 45.0% (9/20) and 40.0% (8/20) , respectively. No skin lesions was found in the mice of blank control group and solvent control group. The results of histopathological staining showed that the TCE sensitization positive mice showed renal tubular dilatation, vacuolar degeneration of renal tubular epithelial cells, and infiltration of interstitial cells. The pathological damage of the kidney in TCE sensitization positive group was mild, and no inflammatory cell infiltration was seen. The data of qRT-PCR showed that the expression levels of NGAL and MCP-1 mRNA in the TCE sensitization positive group were significantly increased than in solvent control group and TCE sensitization negative group (P<0.05) , while the levels of NGAL and MCP-1 mRNA in TCE+C5aRA sensitization positive group were decreased than TCE sensitization positive group (P <0.05) . The results of IHC showed that the expression levels of NGAL and MCP-1 in TCE protein sensitization positive group were significantly higher than those in solvent control group and TCE sensitization negative group (P<0.05) . After C5aRA pretreatment, the expression levels of NGAL and MCP-1 protein were decreased than the mice in TCE sensitization positive group (P<0.05) . Conclusion: The regulation of C5a on the expression of MCP-1 and NGAL may participate in TCE- induced mice kidney damage, and pharmacological inhibition of C5a seems to be an effective way to protect the kidney injury in TCE-sensitized mice.

Longitudinal changes in prostate volume in a community-based cohort study of middle-aged and elderly men in rural China.

BACKGROUND: Prostate volume (PV) and its change rate are important for the progression of prostate disease, but studies on their estimates are inconsistent. OBJECTIVES: To investigate whether age, prostate-specific antigen (PSA), and other specific characteristics are associated with PV and its change rate. MATERIALS AND METHODS: A community-based cohort study was conducted in a rural area of China among male residents aged 40-80 years. PV was estimated at baseline and at 4 years of follow-up by trans-abdominal ultrasound. Annual PV change rate (PVCR) was calculated as change in volume divided by time interval. Baseline characteristics, including age, serum PSA, and hormones, were evaluated. And their relationships with PV or PVCR were assessed with Pearson correlation and multivariate linear regression analyses. RESULTS: Totally, 462 participants completed the follow-up with baseline PV (PV0 ) of 15.6 ± 5.5 ml. PV0 was highly correlated with age and PSA in pairwise correlations (Pearson r = 0.35 and 0.34, respectively, p < 0.01). Multivariate linear regression showed similar associations that PV0 tended to increase with age and PSA. The average PVCR was 0.7 ± 1.8 ml/year. In pairwise correlations, PVCR was inversely correlated with PV0 and positively correlated with PSA, while it was not significantly related to baseline age. Linear regression of PVCR on age and PSA in groups classified by PV0 quartile showed that age was not a significant estimator of PVCR, whereas PSA was. In each PV0 group, PVCR tended to increase with PSA. DISCUSSION AND CONCLUSION: PV was positively associated with age and PSA, and it tended to grow faster in men with smaller baseline PV and higher PSA. PSA can be a valuable parameter for estimating both the size and the growth speed of prostate. Although age is associated with prostate enlargement, it does not appear to be related to the longitudinal change rate of PV.

[A multicenter clinical study on 1 138 cases of invasive pneumococcal disease in children from 2012 to 2017].

Objective: To explore the clinical features, the serotype distribution and drug resistance of the isolates in patient with invasive pneumococcal disease (IPD). Methods: By retrieving the laboratory information system in 18 children's hospitals from 2012 to 2017, the children with IPD were enrolled. Streptococcus pneumoniae (Spn) must be isolated from the sterile sites (blood, cerebrospinal fluid, hydrothorax and joint effusion etc.). The clinical characteristics, serotype, drug resistance, treatment and prognosis were reviewed and analyzed. According to the telephone follow up results, the patients were divided into death group and recovered group. The index as an independent risk factor of mortality was demonstrated by multivariate logistic regression analysis. Results: There were 1 138 children with IPD, including 684 male and 454 female. The proportion of male to female was 1.5∶1. The age ranged from one day to 16 years. The median age was 1 year 3 month. The majority was under 5 years of age (89.3%, n= 1 016), especially under 2 years of age (61.9%, n=704). In all cases, 88.2% (n=1 004) were community acquired infection. The infections included meningitis (n=446, 39.2%), pneumonia with bacteremia (n=339, 29.8%), and bacteremia without focus (n=232, 20.4%). Underlying diseases were found in 242 cases (21.3%). Co-infections were determined in 62 cases (5.4%) with mycoplasma, 27 cases (2.4%) with adenovirus and 34 cases with influenza virus (3.0%). The penicillin insensitivity (PNSP) rates in meningitis and non-meningitis isolates were 69.5% (276/397) and 35.9% (221/615), respectively. There were 81 strains serotyped, in which 93.8% (76/81) were covered by 13-valent protein-polysaccharide conjugate vaccine (PCV13). In the 965 patients who were followed up by phone call, 156 cases (16.2%) were confirmed dead. The independent risk factors for the death were under 2 years of age (OR=2.143, 95%CI 1.284-3.577, P=0.004), meningitis (OR=3.066, 95%CI 1.852-5.074, P<0.01), underlying disease (OR=4.801, 95%CI 2.953-7.804, P<0.01), septic shock(OR=3.542, 95%CI 1.829-6.859, P<0.01), disseminated intravascular coagulation (DIC) (OR=4.150, 95%CI 1.468-11.733, P=0.007), multiple organ failure (OR=12.693, 95%CI 6.623-24.325, P<0.01) and complications of central nervous system (OR=1.975, 95%CI 1.144-3.410, P=0.015). Conclusions: Most children with IPD were under 5 years of age, having underlying diseases and acquired the infection in community. The independent risk factors for death were under two years old, meningitis, underlying diseases and multiple organ failure. The problem of drug resistance was severe. The universal immunization of PCV13 would be effective to prevent IPD in Chinese children.

The involvement of miR-155 in blood pressure regulation in pregnant hypertension rat via targeting FOXO3a.

OBJECTIVE: Pathogenesis factor of pregnant hypertension is still unclear and lacks of effective treatment. MiR-155 is a recently discovered miRNA molecule with differential expression in pregnant hypertension, which participates in the disease regulation. As a downstream target gene of miR-155, FOXO3a is correlated with blood pressure regulation. We investigated the regulatory role and mechanism of miR-155 in pregnant hypertension. MATERIALS AND METHODS: We established a pregnant hypertension rat model, on which miR-155 inhibitor or FOXO3a siRNA was applied, followed by HE staining, 24 h urea protein, blood pressure and serum creatine assay to evaluate disease severity. RESULTS: MiR-155 expression was significantly elevated in model rats, accompanied by a reduction of the FOXO3a level. MiR-155 inhibitor suppressed miR-155 expression, increased FOXO3a level and placental tissue morphology by HE staining, and depressed blood pressure as well as serum creatine level. Downregulation of FOXO3a by specific siRNA resulted in opposite effects. These results illustrated the miR-155 mediated FOXO3a expression in pregnant hypertension. CONCLUSIONS: The inhibition of miR-155 improves the damage of pregnant hypertension via the upregulation of FOXO3a, which provides academic leads for the future therapy of pregnant hypertension.

Extra green light induced ZnO ultraviolet lasing enhancement assisted by Au surface plasmons.

We observed the dramatic enhancement of the intrinsic spontaneous and stimulated emission as well as the ensuing suppression of defect-related green emission in Au-decorated ZnO microrods. A series of spectral experiments and theoretical analysis demonstrated an electron transfer assisted process by surface plasmon (SP) resonant coupling between the Au nanoparticles and ZnO. The mechanism indicates an approach to enhance the UV emission of ZnO through an extra excitation of visible light similar to that for the defect emission of ZnO. Based on the coupling mechanism, the externally enhanced ultraviolet lasing was further improved from 1.5 to 2.8-fold by adjusting the pumping power of the green light intensity in the Au/ZnO hybrid cavity. This research not only further confirms the SPR-assisted electron transfer process but also offers an approach to improve the intrinsic UV emission even for heavily-defected ZnO through visible light excitation via a nonlinear process.

[Role of complement regulatory protein CD55 in the liver immune injury of trichloroethylene-sensitized mice].

Objective: To explore the expression of CD55 in liver tissue of trichloroethylene-sensitized mice and discuss the role of CD55 in the liver immune injury of trichloroethylene-sensitized mice. Methods: 6-8 weeks specific pathogen free female BALB/c were randomly divided into blank control group, solvent control group and TCE treatment group to establish BALB/c mice sensitized model. According to mouse skin sensitization reaction score, TCE treatment mice were divided into sensitized and non-sensitized group at 24 h after the last challenge. At 48 h after the last challenge, the blood and aseptic livers were collected. The level of serum ALT was tested by automatic biochemical analyzer and pathology of the liver was observed. C5b-9 deposition was studied by immunohistochemistry (IHC) . CD55 protein expression level in liver tissue was studied by immunohistochemistry and Western blotting. The expression of CD55 mRNA in liver tissue was detected by qRT-PCR. Results: Liver function test result showed level of serum ALT in TCE sensitized group was significantly higher than solvent control group and TCE non-sensitized group (P<0.05) . There was ballooning degeneration and necrosis of liver cells in TCE sensitized group. IHC demonstrated that TCE sensitized group had obviously increased content of C5b-9 but had reduced content of CD55 compared with solvent control group and TCE non-sensitized group (P<0.05) . Western blotting also showed that TCE sensitized group had lower expression of CD55 than solvent control group and TCE non-sensitized group (P<0.05) . qRT-PCR showed that CD55 mRNA expression level in liver tissue of TCE sensitized group was apparently lower than solvent control group and TCE non-sensitized group (P<0.05) . Conclusion: Complement activation may be involved in TCE-induced liver injury, and the expression change of complement regulatory protein CD55 may play essential role in the process.

[The effect of complement C3a receptor antagonist in the kidney immune injury in trichloroethylene-sensitized mice].

Objective: To explore the effect of complement C3 a-C3a receptor in the kidney immune inju-ry in trichloroethylene-sensitized mice by using C3a receptor specific antagonist C3aRA and discuss the patho-genesis of kidney injury in occupational dermatitis medicamentosa-like of trichloroethylene (ODMLT) . Methods: 42 female 6~8 weeks old BALB/c mice of specific pathogen free were randomly divided into blank control group (5) , solvent control group (5) , TCE treatment group (16) and TCE+C3aRA treatment group (16) . The TCE treat-ment group and TCE+C3aRA treatment group were further divided into the sensitized group and the non-sensi-tized group according to the skin sensitization test score. Renal function was detected by biochemical detection kit; expression of C3aR in kidney tissue was detected by qPCR; expression of IL-1ß and TNF-α protein were de-tected by immunohistochemical. Results: Compared with solvent control group and corresponding non-sensitized group, CRE and BUN in TCE sensitized group and TCE + C3aRA sensitized group were significantly increased (P<0.05) . Compared with TCE sensitized group, CRE and BUN in TCE+C3aRA sensitized group were signifi-cantly decreased (P<0.05) . Compared with solvent control group and TCE non-sensitized group, the expression level of C3aR gene in kidney tissue in TCE sensitized group was significantly increased (P<0.05) . There was a large number of IL-1ß and TNF-α protein expression in kidney tissue in TCE sensitized group and TCE+C3aRA sensitized group. Compared with the TCE sensitized group, the expression level of IL-1ß and TNF-α protein in kidney tissue in TCE+C3aRA sensitized group was significantly decreased (P<0.05) . Conclusion: C3a-C3aR may be involved in the kidney immune injury in TCE sensitized mice, C3aRA has a protective effect on the kid-ney immune injury in TCE sensitized mice.

Allergy is associated with reduced risk of glioma: A meta-analysis.

BACKGROUND: Increasing evidences suggest that allergy may reduce the risk of glioma, so it is necessary to perform an up-to-data literature search and investigate this relationship by meta-analysis. METHODS: We identified the included studies by searching PubMed and Web of Science and excluding irrelevant or ineligible articles. Nineteen studies from 15 articles, including 8435 cases and 118,719 controls, were selected for data extraction and synthesis. RESULTS: Pooled outcomes showed that there was an inverse association between allergy and risk of glioma (OR=0.64, 95% CI=0.52-0.78, P<0.001). Meanwhile, asthma and eczema would reduce the risk of glioma by 33% and 23% (OR=0.67, 95% CI=0.59-0.75, P<0.001; OR=0.77, 95% CI=0.68-0.86, P<0.001), respectively. Sensitivity analyses confirmed the stability of these findings. Besides, no publication biases were detected regarding all the investigations. CONCLUSIONS: Overall or specific allergy is protective against glioma. More prospective cohort studies or molecular laboratory experiments are warranted to elucidate the causation and key mechanism.

[Role of kallikrein kinin system activation in kidney injury induced by trichloroethylene sensitized mice].

OBJECTIVE: Through testing the expression of complement C3 fragment C3b and iC3b, C5b-9 as well as indexes of KKS before and after using kallikrein-kinin system inhibitor PKSI-527, observing the relevant between KKS and complement system, we preliminary study on the mechanism how KKS works on the renal injury of sensitized mice model induced by trichloroethylene. METHODS: Female BALB/c mice (6~8 weeks) were randomly divided into blank control group (5), TCE treated group (15), PKSI-527+TCE treated group (15). Mice were sensitized with TCE in the 1,3,7,10 days, the first and the last challenge were on day 17 and 19. 24h before every challenge, mice in PKSI-527+TCE group were treated with intraperitoneal injection of KKS inhibitor PKSI-527 inhibitor (50mg/kg). Mice were killed 72h after the last challenge. The function of kidney in mice were detected and kidney B1R, B2R expression were detected using real-time quantitative PCR, mice kidney complement C3 fragments C3b, iC3b and C5b-9 deposition were also detected by chemoimmunology. RESULTS: Compared with blank control group, all indexes expressions in the solvent control group have no significant change. Compared with the solvent control group, BUN、Cr level and B1R、B2R level have an significant increase (P< 0.05) in TCE sensitized group and PKSI-527+TCE sensitized group; There is a sharp decrease in PKSI-527+TCE sensitized group compared to TCE sensitized group(P< 0.05). CONCLUSION: The renal damage in the TCE sensitization mouse model may aggravated by upregulate complement system followed by the activation of kallikrein-kinin system.

N-acetylcysteine attenuates subcutaneous administration of bleomycin-induced skin fibrosis and oxidative stress in a mouse model of scleroderma.

BACKGROUND: Several lines of evidence suggest that the generation of reactive oxygen species (ROS) is of major importance in the pathogenesis of scleroderma, and thus antioxidant therapy may be useful for patients with an impaired oxidative defence mechanism. AIM: To examine the effect of N-acetylcysteine (NAC) on skin fibrosis and oxidative stress in a bleomycin (BLM)-induced mouse model of scleroderma. METHODS: We used this mouse model to evaluate the effect of NAC on skin fibrosis and oxidative stress. Skin fibrosis was evaluated by histopathological examination and hydroxyproline content. To measure lipid peroxidation, we used a thiobarbituric acid-reactive species, malondialdehyde (MDA). Oxidative protein damage (carbonyl content) and the activities of catalase (CAT) and superoxide dismutase (SOD) were determined to evaluate oxidative stress in the skin tissue. RESULTS: Treatment with NAC attenuated the skin fibrosis induced by BLM, significantly reducing the MDA and protein carbonyl content in these mice. SOD activity in BLM-only mice and BLM plus NAC-treated mice was increased compared with control mice. However, there was no significant difference in skin SOD activity of mice treated with both BLM and NAC compared with those treated with BLM only. In addition, CAT activity was not altered in the BLM plus NAC mice. CONCLUSIONS: NAC treatment attenuates skin fibrosis in a BLM-induced mouse model of scleroderma, and this is associated with diminished oxidative stress. The results suggest that NAC may be a potential therapeutic agent for patients with scleroderma.

Protective effects of Ginkgo biloba leaf extracts on trichloroethylene-induced human keratinocyte cytotoxicity and apoptosis.

The objective of this study was to assess the protective effects of Ginkgo biloba leaf extracts (EGb) on trichloroethylene (TCE)-induced cytotoxicity and apoptosis in normal human epidermal keratinocytes (NHEK). Cytotoxicity was determined by neutral red uptake, and lipid peroxidation of the cells was assessed by malondialdehyde (MDA) and superoxide dismutase (SOD). Electron microscopy and flow cytometry were used to evaluate NHEK apoptosis. Treatment of NHEK with various concentrations of TCE caused a substantial decrease in cell viability. NR(50 )from the cytotoxicity assay was found to be 4.53 mM. TCE caused an increase in MDA, while an inhibition of SOD activity, in a concentration-dependent manner. Electron microscopic examination revealed typical morphologic changes of apoptosis in cells treated with TCE. Incubation of NHEK with TCE (0, 0.125, 0.5, 2.0 mM) for 4 h increased the proportion of apoptotic cells from control of 19.23% to nearly 44.35%. Pretreatment of EGb at 10-200 mg/l dose-dependently attenuated the cytotoxic effect of TCE, prevented TCE-induced elevation of lipid peroxidation and decline of antioxidant enzyme activities. Similar inhibition by EGb on TCE-mediated NHEK apoptosis was also observed. These results suggest that EGb can protect NHEK from TCE-induced cytotoxicity and apoptosis, which may be associated with the superoxide scavenging effect and enhancement of antioxidant enzyme activities.

The effect of mizolastine on expression of vascular endothelial cell growth factor, tumour necrosis factor-alpha and keratinocyte-derived chemokine in murine mast cells, compared with dexamethasone and loratadine.

It has been shown that many antihistamines may have anti-inflammatory activity in addition to being H1 antagonists. Mizolastine (MIZ), a novel antihistamine, might also have anti-angiogenesis properties. In this study, we investigated the influence of MIZ on proangiogenesis factors, vascular endothelial cell growth factor (VEGF), tumour necrosis factor (TNF)-alpha and keratinocyte-derived chemokine (KC) in murine mast cells by using ELISA and RT-PCR, as compared with dexamethasone (DEX) and loratadine (LOR). Our results show that MIZ is effective in the inhibition of KC, VEGF and TNF-alpha release induced by an IgE-dependent mechanism, in a time- and dose-dependent manner. The differences between the inhibitory effects of the three drugs on these proangiogenic factors were rather subtle. Semiquantitative analysis using RT-PCR showed that the three drugs significantly reduced VEGF165, VEGF120, TNF-alpha and KC mRNA expression. Statistical results revealed that the effect of DEX on VEGF165 mRNA was different from that of MIZ or LOR (P < 0.01) and the differences between the three drugs on VEGF120, TNF-alpha and KC mRNA were not statistically significant (P > 0.05). These findings raise the possibility that MIZ can mediate anti-angiogenesis activity and that the effect may depend not only on the inhibition on the levels of cytokine proteins but also at the mRNA level.

Glyceroglycolipids from Serratula strangulata.

The rhizomes of Serratula strangulata yielded three glyceroglycolipids, i.e. 1,2-di-O-(9Z,12Z,15Z-octadecatrienoyl)-3-O-(6-amine-6-deoxy-alpha-D-glucosyl)-glycerol, 1,2-di-O-(9Z,12Z,15Z-octadecatrienoyl)-3-O-(6-p-hydroxy-phenyl-propionamido-6-deoxy-alpha-D-glucosyl)-glycerol and 1,2-di-O-(9Z,12Z,15Z-octadecatrienoyl)-3-O-[alpha-D-glucose(1-6)-beta-D-allose]-glycerol, as well as a known sesquiterpene lactone and three known phytoecdysones. Their structures were elucidated on the basis of spectral data, especially by 2D NMR spectroscopic methods and chemical conversion. These compounds exhibited significant antibacterial and antitumor activities.