BACKGROUND: Depression among older adults is an important public health issue, and air and noise pollution have been found to contribute to exacerbation of depressive symptoms. This study examined the association of exposure to air and noise pollutants with clinically-newly-diagnosed depressive disorder. The mediating role of individual pro-inflammatory markers was explored. METHODS: We linked National Health Insurance claim data with 2998 healthy community-dwellers aged 55 and above who participated in the Healthy Aging Longitudinal Study between 2009 and 2013. Newly diagnosed depressive disorder was identified using diagnostic codes from the medical claim data. Pollutants were estimated using nationwide land use regression, including PM_2.5 and PM₁₀, carbon monoxide, ozone, nitrogen dioxide, sulfur dioxide, and road traffic noise. Cox proportional hazard models were employed to examine the association between pollutants and newly developed depressive disorders. The mediating effect of serum pro-inflammatory biomarkers on the relationship was examined. RESULTS: Among the 2998 participants, 209 had newly diagnosed depressive disorders. In adjusted Cox proportional hazard models, one interquartile range increase in PM_2.5 (8.53 µg/m³) was associated with a 17.5% increased hazard of developing depressive disorders. Other air pollutants and road traffic noise were not linearly associated with depressive disorder incidence. Levels of serum tumor necrosis factor receptor 1 mediated the relationship between PM_2.5 and survival time to newly onset depressive disorder. CONCLUSION PM_2.5 is related to an increased risk of newly developed depressive disorder among middle-aged and older adults, and the association is partially mediated by the pro-inflammatory marker TNF-R1.
Humans ; Particulate Matter/analysis* ; Male ; Female ; Middle Aged ; Longitudinal Studies ; Aged ; Incidence ; Air Pollutants/analysis* ; Environmental Exposure/adverse effects* ; Taiwan/epidemiology* ; Receptors, Tumor Necrosis Factor, Type I/blood* ; Proportional Hazards Models ; Biomarkers/blood* ; Depression/epidemiology* ; Aged, 80 and over ; Depressive Disorder/chemically induced* ; Risk Factors ; Air Pollution/adverse effects*

OBJECTIVE: To observe the therapeutic effect of acupuncture on cancer-related fatigue (CRF) and to explore its possible mechanism. METHODS: A total of 80 patients with CRF were randomized into an observation group and a control group, and finally 67 patients completed the trial (36 patients in the observation group, 31 patients in the control group). Patients in the control group were treated with conventional chemoradiotherapy and symptomatic treatment, while no particular anti-fatigue intervention was adopted. On the basis of treatment in the control group, acupuncture was applied at Baihui (GV 20), Guanyuan (CV 4), Qihai (CV 6), Fengchi (GB 20), Zusanli (ST 36), Sanyinjiao (SP 6) in the observation group, once a day, 5 times as one course, with 2 days interval between each course, totally 4 courses were required. Before and after treatment, scores of functional assessment of cancer therapy-fatigue (FACT-F) in Chinese and McGill quality of life questionnaire (MQOL), serum levels of C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α) and soluble TNF receptor-1 (sTNF-R1) were observed in the two groups. RESULTS: ①Compared before treatment, the FACT-F score was decreased after treatment in the observation group (<0.05), while there was no significant difference in the control group (<0.05). The change of the FACT-F score in the observation group was larger than that in the control group (<0.05). ②In the observation group, scores of physiological and psychological dimension were decreased (<0.05), score of social support dimension was increased after the treatment (<0.05). The score changes of physiological, psychological and social support dimension in the observation group were larger than those in the control group (all <0.05). ③After treatment, the serum levels of IL-6, TNF-α and sTNF-R1 were decreased in the observation group (<0.05), while the serum levels of CPR and IL-6 were increased in the control group (<0.05). The serum levels of CPR, IL-6 and TNF-α in the observation were lower than those in the control group (<0.05). CONCLUSION ①Acupuncture can improve the related symptoms of depression, weakness and headache in patients with CRF, strengthen their cognition of the support from society and family, and boost the confidence in curing the disease. ②Acupuncture can effectively down-regulate serum levels of the relative inflammatory factors, which may be its possible mechanism on treating CRF.
Acupuncture Points ; Acupuncture Therapy ; Biomarkers ; blood ; C-Reactive Protein ; analysis ; Fatigue ; etiology ; therapy ; Humans ; Interleukin-6 ; blood ; Neoplasms ; complications ; therapy ; Quality of Life ; Receptors, Tumor Necrosis Factor, Type I ; blood ; Tumor Necrosis Factor-alpha ; blood

BACKGROUND/AIMS: Our aim was to assess whether short-term treatment with soluble tumor necrosis factor (TNF) receptor affects circulating markers of bone metabolism in rheumatoid arthritis (RA) patients. METHODS: Thirty-three active RA patients, treated with oral disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids for > 6 months, were administered etanercept for 12 weeks. Serum levels of bone metabolism markers were compared among patients treated with DMARDs at baseline and after etanercept treatment, normal controls and naive RA patients not previously treated with DMARDs (both age- and gender-matched). RESULTS: Bone-specific alkaline phosphatase (BSALP) and serum c-telopeptide (CTX)-1 levels were lower in RA patients treated with DMARDs than in DMARD-naive RA patients. After 12 weeks of etanercept treatment, serum CTX-1 and sclerostin levels increased. In patients whose DAS28 improved, the sclerostin level increased from 1.67 +/- 2.12 pg/mL at baseline to 2.51 +/- 3.03 pg/mL, which was statistically significant (p = 0.021). Increases in sclerostin levels after etanercept treatment were positively correlated with those of serum CTX-1 (r = 0.775), as were those of BSALP (r = 0.755). CONCLUSIONS: RA patients treated with DMARDs showed depressed bone metabolism compared to naive RA patients. Increases in serum CTX-1 and sclerostin levels after short-term etanercept treatment suggest reconstitution of bone metabolism homeostasis.
Adult ; Alkaline Phosphatase/blood ; Arthritis, Rheumatoid/blood/diagnosis/*drug therapy ; Biological Markers/blood ; Bone Morphogenetic Proteins/blood ; Bone Remodeling/*drug effects ; Collagen Type I/blood ; Female ; Genetic Markers ; Homeostasis ; Humans ; Immunoglobulin G/*administration & dosage ; Immunosuppressive Agents/*administration & dosage ; Inflammation Mediators/blood ; Male ; Middle Aged ; Peptides/blood ; Receptors, Tumor Necrosis Factor/*administration & dosage ; Time Factors ; Treatment Outcome ; Tumor Necrosis Factor-alpha/antagonists & inhibitors

Interleukin-1 receptor antagonist (IL-1ra), tumor necrosis factor soluble receptors (sTNF-R) type I and II, and regulated upon activation, normal T-cell expressed and secreted (RANTES) play an important role in the modulation of primary glomerulonephritis (GN) course. The aim of the study was to assess whether pre-treatment measurements of IL-1ra, sTNF-R, and RANTES assessed conjointly may be useful as predicting factors in patients with GN. In 84 patients (45 males and 39 female) serum concentration (pg/mL) and urinary excretion (pg/mgCr) of cytokines were measured. After 12 months of therapy with steroids and cyclophosphamide the patients were divided into two subgroups: Responders (R) and Non-Responders (NR) according to the treatment results. The urinary IL-1ra, TNF-RI and RII were significantly higher in R than NR (1,732 vs 646 with P < 0.001, 13.1 vs 6.3 with P = 0.005, and 33.6 vs 14.4 with P = 0.012). The urinary RANTES excretion was increased in NR (79.6 vs 28.5; P < 0.001). The multivariable analysis showed that if conjointly assessed, only urinary IL-1ra, TNF-R I and R II, RANTES with 85% probability pointed the feature remission (R). In conclusion, the urinary excretion of IL-1ra, TNF-R I and R II, and RANTES examined conjointly are effective in predicting favorable response to immunosuppressive treatment in patients with GN.
Adult ; Cyclophosphamide/therapeutic use ; Female ; Glomerulonephritis/drug therapy/*metabolism/pathology ; Humans ; Immunosuppressive Agents/therapeutic use ; Interleukin 1 Receptor Antagonist Protein/*analysis/blood/urine ; Lymphocyte Activation ; Male ; Middle Aged ; Multivariate Analysis ; Predictive Value of Tests ; Receptors, Tumor Necrosis Factor, Type I/*analysis/blood/urine ; Receptors, Tumor Necrosis Factor, Type II/*analysis/blood/urine ; Steroids/therapeutic use ; T-Lymphocytes/immunology/metabolism

PURPOSE: Our aim was to determine the effects of infliximab on bone mineral metabolism in rheumatoid arthritis (RA) patients and analyze the relationship between inflammatory markers of acute phase thought to play a major role in bone remodeling. MATERIALS AND METHODS: 36 patients with established RA were investigated. All patients underwent physical examination and blood and urinary analysis at baseline, 2 weeks, 14 weeks, 6 months and 12 months after the initiation of treatment. The serum levels of: tumor necrosis factor alpha (TNF-alpha), tumor necrosis factor alpha receptor 1 (TNFR1), TNFR2, interleukin 6 (IL-6), IL-17, IL-23 and markers of bone remodeling such as osteocalcin (BGP), deoxypyridynoline (Dpd), and N-telopeptide of type I collagen (NTx) were measured by ELISA. RESULTS: The results showed significant decrease of all the above cytokines levels in RA patients in comparison with those after 2 weeks of treatment. After 6 months, the markers of bone formation and resorption decreased compared to baseline values. We found positive correlation between the levels of NTx and the levels of IL-6, IL-17 and TNFR1, and between the levels of Dpd and IL-6 and Dpd and TNFR2, whereas negative correlation between BGP and IL-23. After 12 months the positive association was found at the BGP level and IL-6 as well as Dpd and the level of IL-6. We also observed a positive relation between Dpd and TNF-alpha and negative between BGP and TNFR1. CONCLUSION: We suggest that infliximab treatment may limit the risk of osteoporosis in RA patients.
Adult ; Aged ; Antibodies, Monoclonal/*therapeutic use ; Antirheumatic Agents/therapeutic use ; Arthritis, Rheumatoid/blood/complications/*drug therapy ; Biological Markers/metabolism ; Bone Remodeling/*drug effects ; Bone Resorption ; Cytokines/*metabolism ; Female ; *Gene Expression Regulation ; Humans ; Interleukin-17/metabolism ; Interleukin-6/metabolism ; Middle Aged ; Osteoporosis/complications/prevention & control ; Receptors, Tumor Necrosis Factor, Type I/metabolism

INTRODUCTIONRheumatoid arthritis (RA) is a chronic, deforming arthritis that can lead to disabilities and poor quality of life. Cytokines are protein mediators of inflammation and are produced as a result of the activation of various cellular reactions. They are the final mediators and/or regulators of the inflammatory process.

MATERIALS AND METHODSThe sera from 64 RA patients were assayed for both Th-1 and Th-2 related cytokines and soluble TNF-alpha receptors (IFN-gamma, TGF-beta, TNF-alpha, IL-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-18, sTNF-R1 and sTNFR2) using ELISA.

RESULTSThe pro-inflammatory cytokines (IL-1, IL-6, IL-8, IL-18 and TNF- alpha) were significantly elevated in RA patients, while TGF-beta, an immunomodulatory cytokine, was elevated in control individuals. When the RA patients were categorised as active or inactive based on DAS scores, similar cytokines profiles were observed in both RA sub-groups. However, assays of sTNF-R1 and sTNFR-2 were noted to be significantly elevated in inactive RA patients when compared to active patients.

CONCLUSIONOur findings indicate that local production of cytokine inhibitors is capable of diminishing disease activity and cytokine activity.

Adult ; Aged ; Arthritis, Rheumatoid ; blood ; pathology ; Cell Differentiation ; Cytokines ; blood ; Female ; Humans ; Male ; Middle Aged ; Receptors, Tumor Necrosis Factor, Type I ; chemistry ; Receptors, Tumor Necrosis Factor, Type II ; chemistry ; Transforming Growth Factor beta ; chemistry

OBJECTIVETo analyze the phenotypic and functional characteristics of endothelial (T3A) cells derived from human hepatocellular cell carcinoma.

METHODSEndothelial cells were isolated from human hepatocellular carcinoma specimens. The identification of T3A cells was performed by checking von Willebrand Factor (vWF), CD31, CD34 and Dil-Ac-LDL uptake. The cell surface fenestrations, a specific morphological feature of tumor derived EC, were investigated by scanning and transmission electron microscopy. The phenotypic characteristics of T3A cells were analyzed by fluorescence-activated cell sorter (FACS) and were further conformed by real-time PCR at transcription level. Furthermore, tumor necrosis factor alpha (TNFalpha)-induced cytotoxicity was evaluated by 3-(4, 5-dimethythiazolyl) -2, -diphenyl-2H-tetrazolium-bromide (MTT) assay; Matrix metalloproteinase secretion was detected by zymography; Angiogenic ability in vitro was analyzed by culturing T3A cells in three-dimensional Matrigel plug. Coagulant and fibrinolytic activities were detected by enzyme-linked immunosorbent assay (ELISA).

RESULTSThe isolated T3A cells exhibited classic "spindle-shape" morphology and monolayer growth and contact inhibition properties. Immunofluorescent staining showed that T3A cells expressed vWF, CD31, CD34, and uptake of Dil-Ac-LDL at a high level. The cell surface fenestrations were observed on T3A cells by scanning and transmission electron microscopy. By FACS and real-time PCR, T3A cells were found to express alphav3, alphavbeta5 and TNF receptor p75 at high levels, and TNF receptor p55 and ICAM-1 at low levels, as compared with those in human liver sinusoidal endothelial cells (LSEC). In response to TNFalpha, LSEC exhibited a dose-dependent cytotoxicity, while T3A cells were resistant. Gelatin zymography showed that MMP-2 activity was higher in T3A cells than that in LSEC. In a three-dimensional plug of Matrigel, T3A cells exhibited stronger angiogenic ability as compared with LSEC. In addition, T3A cells released more tissue factor (TF), tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1) and urine plasminogen activator (u-PA) than LSEC in response to TNFalpha.

CONCLUSIONTumor-derived endothelial cells are phenotypically and functionally different from those derived from normal liver tissue.

Antigens, CD34 ; metabolism ; Carcinoma, Hepatocellular ; genetics ; metabolism ; pathology ; Cell Proliferation ; drug effects ; Cell Shape ; Cells, Cultured ; Endothelial Cells ; metabolism ; pathology ; ultrastructure ; Gene Expression ; Humans ; Integrin alphaVbeta3 ; metabolism ; Integrins ; metabolism ; Intercellular Adhesion Molecule-1 ; metabolism ; Lipoproteins, LDL ; metabolism ; Liver Neoplasms ; genetics ; metabolism ; pathology ; Lung ; blood supply ; metabolism ; pathology ; Matrix Metalloproteinase 2 ; metabolism ; Microscopy, Electron, Scanning ; Neovascularization, Pathologic ; metabolism ; pathology ; Phenotype ; Plasminogen Activator Inhibitor 1 ; metabolism ; Platelet Endothelial Cell Adhesion Molecule-1 ; metabolism ; Receptors, Tumor Necrosis Factor, Type I ; metabolism ; Receptors, Vitronectin ; metabolism ; Tissue Plasminogen Activator ; metabolism ; Tumor Cells, Cultured ; Tumor Necrosis Factor Decoy Receptors ; metabolism ; Tumor Necrosis Factor-alpha ; pharmacology ; von Willebrand Factor ; metabolism

OBJECTIVETo investigate the expression of T cell early activation marker (CD(69)) on peripheral CD(4)(+) and CD(8)(+) lymphocytes and serum levels of soluble tumor necrosis factor receptor 1 and 2 (sTNF-R1 and sTNF-R2) in serum and bone marrow in patients with aplastic anemia (AA) and their pathophysiological significance.

METHODSIn vitro activation of T lymphocytes was carried out by whole blood cell culture containing PHA (20 micro g/ml). The CD(69) expressions on CD(4)(+) and CD(8)(+) lymphocytes at 0 h and 4 h after PHA exposure were analyzed by two-color flow cytometry. The levels of sTNF-R1 and sTNF-R2 in serum and bone marrow were measured by ELISA.

RESULTSThe CD(69) expression rates of CD(4)(+) and of CD(8)(+) cells in SAA patients were (8.96 +/- 7.23)% and (10.67 +/- 7.58)%, respectively, and that of CD(8)(+) cells in CAA patients was (7.36 +/- 5.49)% before PHA stimulation. The CD(69) expression rates of CD(4)(+) and of CD(8)(+) cells in SAA patients were (71.73 +/- 11.91)% and (61.74 +/- 13.44)% and in CAA (59.35 +/- 10.15)% and (48.78 +/- 8.25)% respectively, and were significantly elevated after PHA stimulation. CD(69) expression on CD(4)(+) cells was much higher than that on CD(8)(+) cells after stimulation. The levels of the two sTNF-R (sTNF-R1 and sTNF-R2) in peripheral blood and bone marrow of SAA patients were elevated and in the bone marrow of CAA patients were also increased. The serum levels of sTNF-R2 were positively related to the CD(69) expression rates of CD(8)(+) cells before PHA stimulation.

CONCLUSIONIncreased early activation and activated potentials of T lymphocytes, along with abnormally elevated immunologically active molecules might play a major role in the pathogenesis of AA.

Adolescent ; Adult ; Aged ; Anemia, Aplastic ; immunology ; Antigens, CD ; blood ; Antigens, Differentiation, T-Lymphocyte ; blood ; CD4-Positive T-Lymphocytes ; chemistry ; CD8-Positive T-Lymphocytes ; chemistry ; Child ; Female ; Humans ; Lectins, C-Type ; Male ; Middle Aged ; Receptors, Tumor Necrosis Factor ; blood ; Receptors, Tumor Necrosis Factor, Type I ; Receptors, Tumor Necrosis Factor, Type II