Age-associated declined function of endothelial progenitor cells and its correlation with plasma IL-18 or IL-23 concentrations in patients with ST-segment elevation myocardial infarction.

Background: ST-segment elevation myocardial infarction (STEMI) persists to be prevalent in the elderly with a dismal prognosis. The capacity of endothelial progenitor cells (EPCs) is reduced with aging. Nevertheless, the influence of aging on the functionality of EPCs in STEMI is not fully understood. Method: This study enrolled 20 younger STEMI patients and 21 older STEMI patients. We assessed the Thrombolysis in Myocardial Infarction (TIMI) and Global Registry of Acute Coronary Events Risk (GRACE) scores in two groups. Then, we detected EPC migration, proliferation, adhesion, and plasma interleukin (IL)-18 and IL-23 concentrations in two groups. In addition, we analyzed the interconnection between age, EPC function, plasma IL-18 and IL-23 concentrations, and GRACE or TIMI scores in STEMI patients. Result: GRACE and TIMI scores in older STEMI patients were higher than in younger STEMI patients, whereas EPC function declined. GRACE and TIMI scores were found to have an inverse relationship with the EPC function. In older STEMI patients, plasma concentrations of IL-18 and IL-23 increased. Plasma IL-18 and IL-23 concentrations were adversely connected to EPC capacity and positively related to GRACE and TIMI scores. Moreover, age was positively correlated with plasma IL-18 or IL-23 concentrations, as well as GRACE or TIMI scores. However, age was adversely correlated with EPC function. Conclusion: In patients with STEMI, aging results in declined EPC function, which may be associated with inflammatory cytokines. The current investigation may offer new perception about mechanism and therapeutic targets of aging STEMI.

Association Between Ultraprocessed Foods Consumption and Leucocyte Telomere Length: A Cross-Sectional Study of UK Biobank.

BACKGROUND: □ OBJECTIVES: This study aimed to investigate the association between consumption of ultraprocessed foods and leucocyte telomere length (LTL). METHODS: This cross-sectional study utilized data from the UK Biobank, including a total of 64,690 participants. LTL was measured using qPCR with natural logarithmic conversion and z-score normalization. Dietary data were collected through a 24-h recall questionnaire from 2009 to 2010. Ultraprocessed foods (UPFs) were identified using the NOVA food classification as either a continuous or a categorical variable. Multiple linear regression models were employed to analyze the association between UPF consumption and LTL. RESULTS: The included participants had an average age of 56.26 y, of whom 55.2% were female. After adjusting for demographic and health-related variables, LTL exhibited a decrease of 0.005 (95% CI: -0.007, -0.002) with 1 UPF serving increase. Compared with participants consuming ≤3.5 servings/d, those consuming 3.5 to <6 servings showed a shortening of LTL by 0.025 (95% CI: -0.046, -0.003). Participants consuming 6 to ≤8 servings/d and >8 servings/d had LTL shortening of 0.032 (95% CI: -0.054, -0.011) and 0.037 (95% CI: -0.060, -0.014), respectively (P for trend = 0.002). Subgroup analyses by UPF subclasses revealed that the consumption of ready-to-eat/heated food (ß: -0.010; 95% CI: -0.016, -0.004), beans and potatoes (ß: -0.027; 95% CI: -0.043, -0.012), animal-based products (ß: -0.012; 95% CI: -0.020, -0.005), artificial sugar (ß: -0.014; 95% CI:-0.025,-0.003), and beverages (ß: -0.005; 95% CI: -0.009, -0.001) showed negative associations with LTL. Conversely, breakfast cereals (ß: 0.022; 95% CI: 0.006, 0.038) and vegetarian alternatives (ß: 0.056; 95% CI:0.026,0.085) showed positive correlations with LTL. CONCLUSIONS: Our study found that a higher consumption of total UPF was associated with a shorter LTL. However, some UPFs may be associated with longer LTL, depending on their nutritional composition.

The association of sleep duration and leukocyte telomere length in middle-aged and young-old adults: A cross-sectional study of UK Biobank.

BACKGROUND: The relationships between sleep duration and aging-associated diseases are intricate. Leukocyte telomere length (LTL) is a biomarker of aging, while the association of sleep duration and LTL is unclear. METHODS: The 310,091 study participants from UK Biobank were enrolled in this cross-sectional study. Restricted cubic splines (RCS) analysis was firstly performed to assess the nonlinear relationship between sleep duration and LTL. Sleep duration was then categorized into three groups: <7 h (short sleep duration), 7-8 h (reference group), and >8 h (long sleep duration) and multiple linear regression was applied to analyze the association of short sleep and long sleep duration with LTL. We further performed subgroup analyses stratified by sex, age, chronotype and snoring. RESULTS: RCS showed an inverted J-shaped relationship between sleep duration and LTL. Compared with the reference group, the inverse association of long sleep duration and LTL was statistically significant in fully-adjusted model (P = 0.001). Subgroup analyses showed that this association was more apparent in people over 50 years (51-60 y: P = 0.002; >60 y: P = 0.005), in men (P = 0.022), and in people preferred evening chronotype (P = 0.001). CONCLUSION: Compared with participants sleeping 7-8 h, those sleep longer than 8 h had shorter LTL in middle-aged and young-old adults. The negative association between long sleep duration and LTL was more apparent in older people, in men, and in people preferred evening chronotype.

Mannan-binding lectin exacerbates the severity of psoriasis by promoting plasmacytoid dendritic cell differentiation via the signal transducer and activator of transcription 3-interferon regulatory factor 8 axis.

Psoriasis is a chronic inflammatory skin disease mediated by host immune responses. Plasmacytoid dendritic cells (pDC) and interferon (IFN)-α secreted by pDC are involved in the initiation of psoriasis. Mannan-binding lectin (MBL), a vital component of the complement pathway, plays a critical role in innate immune defense and the inflammatory response. Our previous study found that MBL could exacerbate skin inflammation in psoriatic mice, but the effect of MBL on pDC remains unstudied. Herein, we revealed that the circulating level of MBL was elevated in patients with psoriasis compared with the healthy controls. Moreover, the MBL level was positively correlated with disease severity, relative inflammatory cytokine levels, and peripheral blood (PB) pDC frequency in psoriasis. An in vitro study determined that the MBL protein could promote the differentiation of human pDC and upregulate the production of relative inflammatory cytokines and chemokines. Additionally, MBL-deficient (MBL-/- ) mice exhibited decreased accumulation of pDC in lymph nodes, spleens, and skin lesions with reduced secretion of pDC-related cytokines compared with wild-type (WT) mice in the preliminary stage of psoriasis induced by imiquimod. Notably, the differentiation of pDC from bone marrow (BM) cells derived from MBL-/- mice was weakened compared with that from WT mice upon Fms-like tyrosine kinase 3 ligand (Flt3L) incubation. Mechanistic research indicated that the signal transducer and activator of transcription 3 (STAT3)-interferon regulatory factor 8 (IRF8) axis was responsible for MBL-modulated pDC differentiation. In summary, these results suggest that MBL exacerbates the severity of psoriasis by enhancing pDC differentiation and pDC-related cytokine secretion via the STAT3-IRF8 axis, thus providing a new target for psoriasis treatment.

Analysis of posttraumatic stress disorder in children with road traffic injury in Wenzhou, China.

OBJECTIVE: Road traffic accidents are the leading health threat to children and cause significant long-term mental health problems. This study aimed to characterize posttraumatic stress disorder (PTSD) in children suffering from road traffic injuries (RTIs) in Wenzhou, China. METHODS: We conducted a retrospective study of 537 children (aged 1 to 13 years old) with RTIs. The epidemiological features, PTSD incidence, clinical manifestation, and risk factors were analyzed based on a customized PTSD risk factor questionnaire. The outcome factors were also evaluated by means of the logistic regression method. RESULTS: The PTSD incidence was 24.77% in children with RTIs. The incidence of PTSD was related to the personality, family environment, and family care of the children. It was found that early psychological intervention and reasonable family care from the family might promote physical and mental welfare as well as contribute to the development of more effective treatments to prevent PTSD. CONCLUSION: For susceptible children, in addition to dealing with the somatic injury, psychological intervention and family care should be carried out as early as possible.

Treponemal antibody in CSF and cellular immunity in peripheral blood of syphilitic patients with persisting positive rapid plasma regain.

The ratio of patients with RPR constant positive more than 2 years despite receiving standard syphilis treatment has been reported to be 11.54%~31.3%. The current interpretations on this phenomenon are cellular immune function restrained and the existence of neurosyphilis or asymptomatic neurosyphilis. We conducted this study to detect the treponemal antibody in cerebrospinal fluid (CSF) and lymphocyte subsets in peripheral blood of syphilis patients with persisting RPR positive more than 2 years without neurologic signs, and then explore their relationship. In this study, Treponemal antibody in CSF of 46 syphilitic with HIV negative were measured by syphilis serum test and compared with that of 5 neurosyphilis. Lymphocyte subsets were measured by flow cytometry (FCM) and compared with that of 30 healthy controls. We observed that treponemal antibody in CSF was detected not only in 12 cases (25.21%) of 46 treated patients, but also in 5 neurosyphilis. The ratio of lymphocyte subsets revealed that CD3+, CD4+ T cells and natural killer (NK) cells showed no significant differences between the patient and healthy controls (P>0.05), while CD8+ T cells in patients were significant higher than that in healthy controls (P<0.001). Lymphocyte subsets showed no significant differences between the patients with treponemal antibody positive and negative in CSF (P>0.05). In conclusion, the treponemal antibody in CSF of treated patients suggests that part of them were asymptomatic neurosyphilis and with cellular immunodifeciency. And there is no significant relationship between asymptomatic neurosyphilis and cellular immunodeficiency in peripheral blood.

A correlation study of the expression of resistin and glycometabolism in muscle tissue after traumatic brain injury in rats.

OBJECTIVE: To investigate the expression pattern of resistin (RSTN) in skeletal muscle tissue and its influence on glycometabolism in rats with traumatic brain injury (TBI). METHODS: Seventy-eight SD rats were randomly divided into traumatic group (n=36), RSTN group (n=36) and sham operation group (n=6). Fluid percussion TBI model was developed in traumatic and RSTN groups and the latter received additional 1 mg RSTN antibody treatment for each rat. At respectively 12 h, 24 h, 72 h, 1 w, 2 w, and 4 w after operation, venous blood was collected and the right hind leg skeletal muscle tissue was sampled. We used real-time PCR to determine mRNA expression of RSTN in skeletal muscles, western blot to determine RSTN protein expression and ELISA to assess serum insulin as well as fasting blood glucose (FBG) levels. Calculation of the quantitative insulin sensitivity check index (Q value) was also conducted. The above mentioned indicators and their correction were statistically analyzed. RESULTS: Compared with sham operation group, the RSTN expression in the skeletal muscle as well as serum insulin and FBG levels revealed significant elevation (P<0.05), and reduced Q value (P<0.05) in traumatic group. Single factor linear correlation analysis showed a significant negative correlation between RSTN expression and Q values (P<0.001) in traumatic group. CONCLUSION: The expression of RSTN has been greatly increased in the muscular tissue of TBI rats and it was closely related to the index of glycometabolism. RSTN may play an important role in the process of insulin resistance after TBI.

Activation of coagulation, anti-coagulation, fibrinolysis and the complement system in patients with urticaria.

BACKGROUND: Recently released studies indicate that activation of blood coagulation may be involved in causing urticaria. OBJECTIVE: To evaluate whether or not anticoagulation, fibrinolysis and the complement system are also involved in the pathogenesis of urticaria. METHODS: Coagulant factors, anticoagulant factors, fibrinolytic markers and complement components were analysed in patients with acute urticaria (AU) and chronic urticaria (CU). Conclusion: The activation of coagulation, anti-coagulation, fibrinolysis and the complement system may be involved in the pathogenesis of urticaria. It also indicates that coagulation conditions in CU patients can recover after antihistamine treatment, but do not immediately return to normal levels directly after administration. RESULTS: Plasma levels of activated factor VII (FVIIa) were higher in AU patients (P <0.01) but not significantly different in CU patients (P >0.05), while levels of the thrombin-antithrombin complex (TAT) and prothrombin fragment 1+2 (F1+2) were significantly higher in CU patients (P <0.01). Levels of factor IX (FIX) and tissue factor (TF) were lower in CU patients (P <0.01). Plasma levels of tissue factor pathway inhibitor/activated factor X (TFPI/Xa) were higher in CU patients (P <0.01) but not significantly different in AU patients (P >0.05), whereas levels of thrombomodulin (TM) were lower in CU patients (P <0.01). Plasma levels of D-dimer in AU and CU patients and levels of high molecular weight kininogen (HMWK) in CU patients were increased significantly (P <0.01), while levels of tissue-type plasminogen activator (t-PA) were decreased (P <0.01). Plasma concentrations of C5a in CU patients were superior to those in healthy controls (P <0.01). Serum levels of C4 also increased (P <0.01). CONCLUSION: The activation of coagulation, anti-coagulation, fibrinolysis and the complement urticaria. It also indicates that coagulation conditions in CU patients can recover after antihistamine treatment, but do not immediately return to normal levels directly after administration.

An important role of matrix metalloproteinase-8 in angiogenesis in vitro and in vivo.

AIMS: Growing evidence suggests a close association of plaque angiogenesis with atherosclerotic plaque formation and progression, and an important role of matrix metalloproteinase (MMP) in angiogenesis and atherosclerosis. We attempted to investigate the functional involvements of MMP8 in angiogenesis. METHODS AND RESULTS: Knockdown of MMP8 in human umbilical vein endothelial cells (HuVECs) with MMP-8 shRNA lentivirus resulted in a decrease in in vitro capillary-like network formation, cell proliferation and migration, and impaired its capacity of in vivo angiogenesis. Less nuclear accumulation of ß-catenin and lower ß-catenin target gene expression levels was observed in the HuVECs expressing lower levels of endogenous MMP8. Knockdown of endogenous MMP8 in HuVECs down-regulated platelet/endothelial cell adhesion molecule-1 (PECAM-1) expression by converting less angiotensin I to II, which is an inducer for PECAM-1 gene expression. Aortic rings isolated from MMP8(-/-)/apoE(-/-) mice had less endothelial cell sprouting, and endothelial cells in MMP8(-/-)/apoE(-/-) mice had a lower ability to migrate into Matrigel plugs and less capacity of proliferation and angiogenesis. Moreover, immunohistochemical analyses revealed that MMP8 was expressed in microvessels within human atherosclerotic plaques and aneurysm. Finally, analyses of MMP8(-/-)/apoE(-/-) and MMP8(+/+)/apoE(-/-) mice fed a Western diet for 12 weeks showed that MMP8-deficient mice had small lesion size and less endothelial cells within atherosclerotic lesions. CONCLUSION: We demonstrated for the first time that MMP8 plays an important role in angiogenesis in vitro and in vivo. Our findings provide new insights into the molecular mechanisms of plaque angiogenesis and suggest that MMP8 is a potential therapeutic target of cardiovascular diseases.

Functional involvements of heterogeneous nuclear ribonucleoprotein A1 in smooth muscle differentiation from stem cells in vitro and in vivo.

To investigate the functional involvements of heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) in smooth muscle cell (SMC) differentiation from stem cells, embryonic stem cells were cultivated on collagen IV-coated plates to allow for SMC differentiation. We found that hnRNPA1 gene and protein expression was upregulated significantly during differentiation and coexpressed with SMC differentiation markers in the stem cell-derived SMCs as well as embryonic SMCs of 12.5 days of mouse embryos. hnRNPA1 knockdown resulted in downregulation of smooth muscle markers and transcription factors, while enforced expression of hnRNPA1 enhanced the expression of these genes. Importantly, knockdown of hnRNPA1 also resulted in impairment of SMC differentiation in vivo. Moreover, we demonstrated that hnRNPA1 could transcriptionally regulate SMC gene expression through direct binding to promoters of Acta2 and Tagln genes using luciferase and chromatin immunoprecipitation assays. We further demonstrated that the binding sites for serum response factor (SRF), a well-investigated SMC transcription factor, within the promoter region of the Acta2 and Tagln genes were responsible for hnRNPA1-mediated Acta2 and Tagln gene expression using in vitro site-specific mutagenesis and luciferase activity analyses. Finally, we also demonstrated that hnRNPA1 upregulated the expression of SRF, myocyte-specific enhancer factor 2c (MEF2c), and myocardin through transcriptional activation and direct binding to promoters of the SRF, MEF2c, and Myocd genes. Our findings demonstrated that hnRNPA1 plays a functional role in SMC differentiation from stem cells in vitro and in vivo. This indicates that hnRNPA1 is a potential modulating target for deriving SMCs from stem cells and cardiovascular regenerative medicine.

Functional role of matrix metalloproteinase-8 in stem/progenitor cell migration and their recruitment into atherosclerotic lesions.

RATIONALE: Accumulating evidence indicates that stem/progenitor cells (SPCs) represent an important source of cells in atheromas and contribute to lesion formation and progression. OBJECTIVE: We investigated whether matrix metalloproteinase-8 (MMP8) played a role in SPC migration and their recruitment into atheromas. METHODS AND RESULTS: We found that SPCs in atheromas expressed MMP8 and that MMP8 knockout significantly reduced SPC numbers in atherosclerotic lesions in apolipoprotein E (ApoE)-deficient mice fed a Western diet. Further in vivo experiments showed that ApoE(-/-)/MMP8(-/-) mice injected with stem cells isolated from bone marrows of ApoE(-/-)/MMP8(-/-) mice had fewer SPCs in atheromas and smaller lesions than ApoE(-/-)/MMP8(-/-) mice injected with stem cells isolated from bone marrows of ApoE(-/-)/MMP8(+/+) mice. Ex vivo experiments showed that MMP8 deficiency inhibited the ability of SPCs to migrate from the arterial lumen and the adventitia into atherosclerotic lesions. In vitro assays indicated that MMP8 facilitated SPC migration across endothelial cells and through Matrigel or collagen I. We also found that MMP8 cleaved a-disintegrin-and-metalloproteinase-domain-10 and that MMP8 deficiency reduced mature a-disintegrin-and-metalloproteinase-domain-10 on SPCs. Knockdown of MMP8 or incubation with the a-disintegrin-and-metalloproteinase-domain-10 inhibitor GI254023X decreased E-cadherin shedding on SPCs. The decrease in migratory ability of SPCs with MMP8 knockdown was reduced by incubation of such cells with culture supernatant from SPCs without MMP8 knockdown, and this compensatory effect was abolished by an antibody against soluble E-cadherin. CONCLUSIONS: MMP8 plays an important role in SPC migration and their recruitment into atherosclerotic lesions.

ERCC1 polymorphisms and risk of adult glioma in a Chinese population: a hospital-based case-control study.

To examine the associations of two polymorphisms in excision repair cross-complementing rodent repair deficiency complementation group 1 (ERCC1) gene, C8092A (rs3212986) and T19007C (rs11615), with the risk of adult glioma, we performed a hospital-based case-control study with 257 new cases of glioma and 278 controls in Wenzhou, China. Results showed that polymorphisms C8092A and T19007C in ERCC1 gene were not associated with the risk of glioma in a Chinese population. Further studies in Chinese populations with larger sample sizes are still warranted.