T cell differentiation protein 2 facilitates cell proliferation by enhancing mTOR-mediated ribosome biogenesis in non-small cell lung cancer.

Dysregulation of T cell differentiation protein 2 (MAL2) has been observed in multiple cancers, but its exact role in lung cancer is poorly understood. Here we report a role of MAL2 in accelerating cell proliferation in non-small cell lung cancer (NSCLC). MAL2 expression enhances cell proliferation in both cell and nude mouse models. Mechanistically, overexpression of MAL2 results in the hyper-activation of the MAPK/mTOR signaling pathway in NSCLC cells which leads to active ribosome biogenesis. Importantly, pharmacological inhibition of mTOR or MEK lowered the abundance of PCNA, a marker of tumor cell proliferation, and subsequently suppressed ribosome biogenesis, cell growth and xenograft growth in mouse model. MAL2 upregulation in clinical tumors is also linked to worse prognosis. Overall our data reveal that MAL2 is a potential diagnostic biomarker and targeting the MAL2/MAPK/mTOR signaling pathway may improve therapeutic strategy and efficacy for this subset of NSCLC patients.

Reproductive tract microbiota of women in childbearing age shifts upon gynecological infections and menstrual cycle.

BACKGROUND: This study was undertaken to discover whether the vaginal microbe of women at childbearing age is different among groups defined by urogenital tract infections, childbearing history and menstrual cycle, respectively. RESULTS: This was a multiple case-control study of women at childbearing age who were assigned to case or control groups according to their states of urogenital tract infections. The participants were also grouped by childbearing history and menstrual cycle. Vaginal swabs were collected and stored at - 70 °C until assayed. The V3-V4 region of 16S rRNA gene was amplified using PCR and sequenced on the Illumina MiSeq platform. We tested the hypothesis of whether the relative abundance of microbial species in vaginal microbiota was varied with urogenital tract infections, childbearing history and menstrual cycle. The vaginal microbial richness (Alpha diversity measured by PD_whole tree) was decreased in normal women (without reproductive tract infections) than in those with bacterial vaginosis (BV), and decreased in pregnant women than in other groups of non-pregnancy. Similarly, women from groups of normal and in pregnancy had lower beta diversity on measure of unweighted_unifrac distance in comparison to those of infected and non-pregnant. The top 10 genus relative abundance, especially Lactobacillus, which was the most dominant genus with the relative abundance of 71.55% among all samples, did not differ significantly between groups of childbearing history and menstrual cycle analyzed by ANOVA and nonparametric kruskal_wallis. Lactobacillus iners and Lactobacillus helveticus have the most abundance, totally account for 97.92% relative abundance of genus Lactobacillus. We also found that a higher L.helveticus/L.iners ratio is more likely to present in normal women than in the infected and in pregnant than in non-pregnant, although these comparisons lack statistical significance. CONCLUSIONS: The relative abundance of dominant bacterial taxa in vaginal microbial communities of women at childbearing age were not different among groups of childbearing history and menstrual cycle. Women from groups of in pregnancy and without reproductive tract infections had lower alpha and beta diversity. The composition of the main lactobacillus species may shift upon phases of a menstrual cycle and the status of reproductive tract infections.

Epigallocatechin-3-gallate prevents inflammation and diabetes -Induced glucose tolerance through inhibition of NLRP3 inflammasome activation.

Epigallocatechin-3-gallate (EGCG), the primary polyphenol component of green tea, has been shown to inhibit both oxidation and inflammation. However, the exact mechanism through which EGCG exhibits anti-inflammatory effects remains unclear. In this study, we assessed the potential pathways by which EGCG regulates NLRP3 inflammasome activity in vitro. We found that EGCG inhibits caspase-1 activation and IL-1ß secretion by suppressing NLRP3 inflammasome activation in mouse bone marrow-derived macrophages (BMDMs). EGCG was also observed to block NLRP3-mediated ASC speckle formation and to alleviate pyroptosis in BMDMs. In addition, EGCG treatment could improve high-fat diet (HFD)-induced glucose tolerance and prevent NLRP3 inflammasome-dependent inflammation in a mouse model of HFD-induced type 2 diabetes (T2D). Taken together, our results show that EGCG is a general inhibitor of NLRP3 inflammasome activation and administration of EGCG in T2D mice could improve glucose tolerance in vivo.

CD109 regulates the inflammatory response and is required for the pathogenesis of rheumatoid arthritis.

OBJECTIVE: The aim of this study was to investigate the role of CD109 in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLSs) and to evaluate its potential as a therapeutic target. METHODS: CD109 expression was examined in synovial tissues and FLSs from RA patients and collagen-induced arthritis (CIA) model mice. CD109-deficient mice were developed to evaluate the severity of CIA. Small interfering RNAs and a neutralising antibody against CD109 (anti-CD109) were designed for functional or treatment studies in RA FLSs and CIA. RESULTS: CD109 was found to be abundantly expressed in the synovial tissues from RA patients and CIA mice. CD109 expression in RA FLSs was upregulated by inflammatory stimuli, such as interleukin-1ß and tumour necrosis factor-α. Silencing of CD109 or anti-CD109 treatment reduced proinflammatory factor production, cell migration, invasion, chemoattractive potential and osteoclast differentiation, thereby reducing the deleterious inflammatory response of RA FLSs in vitro. Mice lacking CD109 were protected against arthritis in the CIA model. Anti-CD109 treatment prevented the onset and ameliorated the severity of CIA lesions. CONCLUSION: Our study uncovers an antiarthritic role for CD109 and suggests that CD109 inhibition might serve as a promising novel therapeutic strategy for RA.

Emerging role of HOX genes and their related long noncoding RNAs in lung cancer.

The transcription factor homeobox (Hox) proteins are the master regulator for the embryonic development. Studies have identified new functions for HOX in the regulation of metabolism and other primary cellular processes in humans. Their dysregulation has been observed in a variety of cancers and accumulating evidence has revealed the crucial role of HOX in cancer progression, metastasis, and resistance to therapy. HOX-related long non-coding RNAs (lncRNAs) became the most attracting lncRNAs recently that play critical role in gene regulation and chromatin dynamics in cancers. In this review, we explore the roles of HOX and their related lncRNAs in lung cancer, indicating HOX genes as potential therapeutic targets in lung cancer.

Long non-coding RNA HOXD-AS1 in cancer.

Cancer is one of the leading causes of death worldwide with a high risk of incidence and mortality. Long non-coding RNAs (lncRNAs) have been shown to participate in various biological processes, including tumorigenesis and progression. The HOXD-AS1 (also known as HAGLR and Mdgt) gene is located between the HOXD1 and HOXD3 genes in the HOXD cluster and has been reported to play a critical role in the development and progression of cancers. This review summarizes the current knowledge on the biological functions and mechanisms of HOXD-AS1 in different human cancers, including bladder, cervical, colorectal, gastric, ovarian, and prostate cancers, glioma, hepatocellular carcinoma, melanoma, osteosarcoma, and non-small cell lung cancer. The aberrant expression of HOXD-AS1 in these cancers was related with clinical features of patients with cancers. HOXD-AS1 regulates the growth, invasion, and migration of tumor cells through different underlying mechanisms. In conclusion, HOXD-AS1 may be considered as a promising diagnostic/prognostic biomarker or a novel therapeutic target for cancers.

Deubiquitinase USP48 promotes ATRA-induced granulocytic differentiation of acute promyelocytic leukemia cells.

All-trans retinoic acid (ATRA) has been used for the treatment of acute promyelocytic leukemia (APL). However, its molecular mechanisms of action are unclear. Ubiquitin-specific protease 48 (USP48) is a deubiquitinase enzyme that can post-translationally remove ubiquitin molecules from substrates. In the present study, the role of USP48 in ATRA-induced differentiation of APL cells was studied. The expression of USP48 decreased following ATRA treatment. Functionally, overexpression of USP48 using electroporation-mediated delivery inhibited the proliferation of APL cells and promoted ATRA-mediated differentiation. The inverse observations were made upon siRNA-mediated knockdown of USP48. Furthermore, the expression of USP48 was increased in the nucleus upon ATRA exposure for ≤24 h, suggesting that USP48 was translocated into the nucleus. Interestingly, regulation of p65, a substrate of USP48, did not contribute to the downstream mechanism of ATRA-induced differentiation of APL cells. In addition, upstream mechanistic studies demonstrated that the expression of USP48 was regulated by microRNA-301a-3p. In conclusion, the present study highlights the function of USP48 in the ATRA-induced granulocytic differentiation of APL cells and provides a theoretical basis for identifying novel targets for differentiation therapy of APL.

Prognostic role of microRNA-155 in patients with leukemia: A meta-analysis.

BACKGROUND: Recent studies have shown that microRNA-155 (miR-155) is correlated with clinical outcomes of leukemia. This meta-analysis explores to evaluate the prognostic value of miR-155 for survival in patients with leukemia. METHODS: Eligible studies were searched from PubMed and EMBASE databases. Hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for overall survival (OS), disease-free survival, event-free survival, progression-free survival and treatment-free survival were extracted, if available. Pooled HRs and 95% CIs were used to study any correlation between miR-155 and survival. RESULTS: 11 studies from 10 articles containing 1718 leukemia patients were included. Data showed that the pooled HR for OS was 1.67 (95% CI: 1.44-1.95, P < 0.01). Subgroup analyses for OS showed that the pooled HRs and their 95% CIs were 1.68, 1.41-2.00 (P < 0.01) and 1.73, 1.25-2.41 (P < 0.01) for acute myeloid leukemia and chronic lymphoblastic leukemia, respectively. Furthermore, there was no significant heterogeneity or publication bias among the enrolled datasets. CONCLUSION: We conclude that high miR-155 expression was associated with shorter OS for leukemia patients, and that miR-155 might be a promising prognostic biomarker for this patient population.

Empty-nest-related psychological distress is associated with progression of brain white matter lesions and cognitive impairment in the elderly.

This study evaluated the association between empty-nest-related psychological distress and the progression of white matter lesions (WMLs) and cognitive impairment in 219 elderly subjects aged 60 years or over. Psychological distress was assessed using the University of California at Los Angeles Loneliness Scale (UCLA-LS) and Geriatric Depression Scale (GDS) Short-Form. Cognitive function was evaluated using the MMSE and MoCA. White matter hyperintensities (WMH) were assessed using magnetic resonance imaging. After 5.2-year follow-up, the reductions in MMSE and MoCA scores and the increases in periventricular (P)WMH, deep (D)WMH, and total WMH volumes in the empty-nest elderly were greater than those in the non-empty-nest elderly (P < 0.05). The reduced MMSE and MoCA scores and increased volumes of PWMH and total WMH in the empty-nest elderly living alone were greater than those in the empty-nest elderly living with a spouse (P < 0.05). UCLA-LS and GDS scores were significantly and independently associated with reduced MMSE and MoCA scores and the increased volumes of PWMH, DWMH, and total WMH. The results indicate that empty-nest-related psychological distress is associated with progression of WMLs and cognitive impairment in the elderly.

An increased duplication of ZRS region that caused more than one supernumerary digits preaxial polydactyly in a large Chinese family.

Preaxial polydactyly (PPD) is inherited in an autosomal dominant fashion and characterized by the presence of one or more supernumerary digits on the thumb side. It had been identified that point mutation or genomic duplications of the long-range limb-specific cis-regulator - zone of polarizing activity regulatory sequence (ZRS) cause PPD or other limb deformities such as syndactyly type IV (SD4) and Triphalangeal thumb-polysyndactyly syndrome (TPTPS). Most previously reported cases involved with no more than one extra finger; however, the role of the point mutation or genomic duplications of ZRS in the case of more than one redundant finger polydactyly remains unclear. In this article, we reported a family case of more than one redundant finger polydactyly on the thumb side for bilateral hands with a pedigree chart of the family. Results of quantitative PCR (qPCR) and sequence analysis suggested that the relative copy number (RCN) of ZRS but not point mutation (including insertion and deletion) was involved in all affected individuals.

Identification of vaginal bacteria diversity and it's association with clinically diagnosed bacterial vaginosis by denaturing gradient gel electrophoresis and correspondence analysis.

Bacterial vaginosis (BV) is a common complex associated with numerous adverse health outcomes, affecting women of different ages throughout the world. The etiology of BV remains poorly understood due to the difficulty of establishing a molecular genetic criterion to recognize the vaginal microbiota of BV-positive women from that of the normal women. We used techniques of broad-range PCR-DGGE and gel imaging analysis system cooperated with 16S rRNA gene sequencing and statistical analysis to investigate the community structure of the healthy and BV-affected vaginal microbial ecosystems. The community of vaginal bacteria detected in subjects with BV was far more luxuriant and diverse than in subjects without BV. The mean number of microbial species in 128 BV-positive women was nearly two times greater than in 68 subjects without BV(4.05±1.96 versus 2.59±1.14). Our sequencing efforts yielded many novel phylotypes (198 of our sequences represented 59 species), including several novel BV-associated bacteria (BVAB) and many belonging to opportunistic infections, which remain inexplicable for their roles in determining the health condition of vaginal microflora. This study identifies Algoriphagus aquatilis, Atopobium vaginae, Burkholderia fungorum, Megasphaera genomosp species as indicators to BV and subjects with BV harbor particularly taxon-rich and diverse bacterial communities. Maybe Bifidobacterium, Staphylococcus or even more alien species are commensal creatures in normal vaginal microbiota.

Excessive visit-to-visit glycemic variability independently deteriorates the progression of endothelial and renal dysfunction in patients with type 2 diabetes mellitus.

BACKGROUND: Glycemic variability (GV) creates challenges to glycemic control and may be an independent marker for unfavorable outcome in management of patients with diabetes. This study was designed to investigate the effect of excessive visit-to-visit GV on the progression of endothelial and renal dysfunction in patients with type 2 diabetes mellitus (T2DM). METHODS: Two hundred and thirty nine patients with T2DM, who were recruited from outpatient, completed 48-month follow-up visit. Visit-to-visit GV was calculated by the standard deviation (SD) and coefficient of variation (CV) of serially measured HbA1c and fasting plasma glucose (FPG). Endothelial and renal function was assessed at baseline and end of follow-up. RESULTS: At end of follow-up, brachial flow-mediated dilation (FMD), nitric oxide (NO), creatinine-based estimated glomeruar filtration rate (eGFR-Cr), and cystatin C-based estimated glomeruar filtration rate (eGFR-Cys C) increased, and endothelin-1 and urine albumin/creatinine ratio (ACR) declined as compared with baseline in overall (P < 0.05). The increment of FMD, NO, eGFR-Cr, and eGFR-Cys C and the decrement of endothelin-1 and ACR in first tertile group were significantly greater than those in third tertile group classified by tertile of either SD of HbA1c or SD of FPG. Change percentage of FMD, NO, eGFR-Cr, and eGFR-Cys C were positively, and change percentage of endothelin-1 and ACR were negatively correlated with SDs of HbA1c and FPG, and CVs of HbA1c FPG (P < 0.01, respectively). After adjusted for mean HbA1c, mean FPG, baseline demographic, and clinical characteristics, SD of HbA1c and SD of FPG were always statistically correlated with change percentage of FMD, NO, endothelin-1, ACR, eGFR-Cr, and eGFR-Cys C. CONCLUSION: Excessive visit-to-visit GV independently deteriorates the progression of endothelial and renal dysfunction in patients with T2DM.

Low carotid artery wall shear stress is independently associated with brain white-matter hyperintensities and cognitive impairment in older patients.

BACKGROUND & AIMS: Brain white-matter lesions and cognitive impairment are increasing because of the increasing number of patients aged ≥80 y. Wall shear stress (WSS) plays a pivotal role as a fluid mechanical mediator in vascular reactivity and atherosclerosis. In this study, we investigated the associations among common carotid artery (CCA) WSS, white-matter lesions, and cognitive impairment in patients aged ≥80 y METHODS: We enrolled 384 patients aged ≥80 y. All subjects had CCA-WSS, brain white-matter hyperintensities (WMH), and Mini-Mental State Examination (MMSE) assessments and were divided into three groups using tertiles of mean and peak CCA-WSS. RESULTS: For groups classified by the tertile of mean CCA-WSS, WMH, and WMH fraction were decreased; the MMSE score increased from low to high in the respective groups. Differences in WMH, WMH fraction, and the MMSE score were significant between any two groups (all adjusted p < 0.001). Groups classified by the tertile of peak CCA-WSS had the same pattern. Mean and peak CCA-WSS were significantly and inversely correlated with WMH (r = -0.575 and -0.570, respectively; p < 0.001) and WMH fraction (r = -0.574 and -0.569, respectively; p < 0.001) but positively correlated with the MMSE score (r = 0.390 and 0.278, respectively; p < 0.001). Multiple linear backward stepwise regression indicated the mean and peak CCA-WSS were significantly and independently associated with WMH, WMH fraction, and the MMSE score (all adjusted p < 0.001). CONCLUSION: Carotid artery WSS was independently associated with brain white-matter lesions and cognitive impairment in patients aged ≥80 y.

Excessive variability in systolic blood pressure that is self-measured at home exacerbates the progression of brain white matter lesions and cognitive impairment in the oldest old.

To investigate the effects of variability in self-measured systolic blood pressure at home on the progression of cognitive impairment and white matter lesions in the oldest old. Between April 2009 and October 2009, 248 oldest old aged 80 years or older were eligibly enrolled from geriatric practices and community-dwelling areas of Shandong, China. Self-measured blood pressure at home (HBP) was measured for 7 consecutive days at the baseline, and the Mini-Mental State Examination (MMSE) score and brain white matter hyperintensities (WMH) were assessed at the baseline and during the final follow-up visit. Variability in systolic HBP was evaluated using coefficient of variation (CV) in serial daily systolic HBP measurements of the last 6 consecutive days. After an average of 2.3 years of follow-up visits, 232 oldest old were included in and 16 were excluded from the analysis. The MMSE score declined -4.76 (interquartile ranges: -10.71, -0.83) %, the periventricular WMH, deep WMH, total WMH and WMH fraction increased 16.46 (s.d.: 6.72)%, 10.05 (s.d.: 6.40)%, 14.69 (s.d.: 6.07)% and 15.95 (s.d.: 6.32)%, respectively, in the total oldest old. A declined percentage of the MMSE score and increased percentages of the periventricular WMH, deep WMH, total WMH and WMH fraction in the high group divided by tertile of the CV of the systolic HBP at baseline were greater than those in the low group (P<0.05). The significant differences were retained after adjusting for covariates, including the MMSE score, periventricular WMH, deep WMH and WMH fraction at the baseline (P<0.05). Excessive variability in self-measured systolic HBP exacerbates the progression of cognitive impairment and brain white matter lesions in the oldest old.

Visit-to-visit variability in systolic blood pressure: correlated with the changes of arterial stiffness and myocardial perfusion in on-treated hypertensive patients.

BACKGROUND: Visit-to-visit variability in blood pressure (BP) was demonstrated to correlate with cardiovascular events independent of mean BP. The goal of the present study was to investigate the correlation of visit-to-visit BP variability with artery stiffness and myocardial perfusion in on-treated hypertensive patients. METHODS: BP was measured in 271 hypertensive patients at every visit over the course of the antihypertensive treatment, and the standard deviation (SD), coefficient of variation (CV), maximum, and minimum in serial BP were calculated. Non-invasive pulse wave analysis was performed in all patients. RESULTS: Compared with baseline, carotid-femoral pulse wave velocity (cfPWV), aortic augmentation index (Aix) and Aix adjusted to a "standard heart rate" of 75 beats/min (Aix@HR75) were markedly declined, and sub-endocardial viability ratio (SEVR) was obviously increased in each group (p < 0.001). The changes of cfPWV, SEVR, Aix and Aix@HR75 in patients with lower SD of systolic blood pressure (SBP) were significantly greater than those in patients with higher SD of SBP. And the changes were statistically correlated with both SD and CV of serial SBP during follow-up, even after adjusted for mean SBP and mean diastolic blood pressure (DBP). CONCLUSION: Visit-to-visit SBP variability is independently correlated with changes of artery stiffness and myocardial perfusion in on-treated hypertensive patients.

Effect of Selenium-Enriched Garlic Oil against Cytotoxicity Induced by OX-LDL in Endothelial Cells.

Objective. To detect the effect of selenium-enriched garlic oil (Se-garlic oil) against cytotoxicity induced by ox-LDL in endothelial cells. Methods. Se-garlic oil was extracted by organic solvent extraction. High performance liquid chromatography (HPLC) was used to detect the content of allicin in the Se-garlic oil. Hydride generation atomic fluorescence spectrometry (HG-AFS) was used to detect the content of Se in the Se-garlic oil. ECV-304 cells were separated into five groups (blank, ox-LDL, and low-, medium-, and high-dose Se-garlic oil). Methyl thiazolyl tetrazolium (MTT) assay was used to detect the cytoactivity of each cell group after culturing for 24, 48, and 72 hours. Flow cytometry (FCM) stained with annexin V-FITC/PI was used to detect the apoptosis of the cells from the blank, Se-garlic oil, ox-LDL, and Se-garlic oil + ox-ldl groups after 48 hours of incubation. Results. The amount of allicin in Se-garlic oil was 142.66 mg/ml, while, in Se, it was 198 mg/kg. When ox-LDL was added to low-, medium-, and high-dose Se-garlic oil, the cell viability rates of ECV-304 cells treated in the three groups were all higher, while the apoptosis rates were significantly lower than those of the ox-LDL group (P < 0.05). However, there was no significant difference between the apoptosis rates of the blank, Se-garlic oil, and Se-garlic oil + ox-LDL groups (P > 0.05). Conclusion. Se-garlic oil could inhibit the cytotoxic effect induced by ox-LDL in endothelial cells.

Reversion of P-glycoprotein-mediated multidrug resistance by diallyl trisulfide in a human osteosarcoma cell line.

Diallyl trisulfide (DATS), the main sulfuric compound in garlic, has been shown to have antitumor effects. The present study aimed to ascertain whether DATS reverses the drug resistance of human osteosarcoma cells in vitro and to investigate its potential mechanisms. Human osteosarcoma U2-OS cells were treated with different concentrations of DATS. Cell proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, while P-glycoprotein (P-gp) expression and the proportion of apoptotic cells were measured by flow cytometry. Morphological changes were observed under an optical microscope. Νuclear factor-κB (NF-κB) and inhibitor of NF-κB (IκB) activities were measured by PCR and western blot analysis. Results showed that the proliferation of U2-OS cells treated with different concentrations of DATS was significantly decreased in a concentration- and time-dependent manner. DATS increased the toxic effect of adriamycin on U2-OS cells. Moreover, P-gp expression was decreased and the apoptosis rate was increased in a concentration-dependent manner following treatment of DATS. Additionally, NF-κB activity was inhibited by DATS while expression of IκB was increased. Our data clearly suggest that DATS has significant anticancer effects on human osteosarcoma cells. The potential mechanisms include reducing the multidrug resistance and inducing apoptosis. NF-κB suppression may be involved in DATS-induced inhibition of cell proliferation.

Treatment with telmisartan/rosuvastatin combination has a beneficial synergistic effect on ameliorating Th17/Treg functional imbalance in hypertensive patients with carotid atherosclerosis.

OBJECTIVES: To explore synergistic effect between angiotensin II receptor blockers (ARBs) and statins on Th17/Treg functional imbalance in hypertensive patients with carotid atherosclerosis. METHODS: This study was a 2 × 2 factorial randomized, prospective, double-blind, placebo-controlled trial. One hundred and fifty nine hypertensive patients with carotid atherosclerosis were randomized to the administration of control group, telmisartan group, rosuvastatin group, and combination group (telmisartan plus rosuvastatin) base on hydrochlorothiazide treatment. Carotid ultrasonography, parameters of Th17/Treg functional axis, interleukin (IL)-1ß, IL-2, interferon (IFN)-γ, hypersensitive C-reactive protein (hsCRP), monocyte chemotactic protein (MCP)-1 were evaluated. RESULTS: Blood pressure level markedly reduced in four groups. There was significantly synergistic effect of combination of telmisartan with rosuvastatin on reducing carotid imtima-media thickness (IMT), Th17 cells frequency, IL-17, IL-6, IL-23, tumor necrosis factor (TNF)-α, expression of retinoic acid receptor-related orphan receptor (ROR)γt mRNA, Th17/Treg ratio, IL-1ß, IL-2, IFN-γ, hsCRP, and MCP-1, and increasing Treg cells frequency, IL-10, transforming growth factor(TGF)-ß1, and expression of forkhead/winged helix transcription factor (Foxp3) mRNA (all P<0.05). Change rate of IMT statistical positively related to descent rates of Th17 cells frequency, IL-17, IL-6, IL-23, TNF-α, expression of RORγt mRNA, Th17/Treg ratio, IL-1ß, IL-2, IFN-γ, hsCRP, and MCP-1, and negatively related to increased rates of Treg frequency, IL-10, TGF-ß1, and expression of Foxp3 mRNA, respectively (all P<0.05). CONCLUSION: There is a synergistic effect of combination of telmisartan with rosuvastatin on ameliorating Th17/Treg functional imbalance in hypertensive patients with carotid atherosclerosis.

Reducing Visit-To-Visit Variability in Systolic Blood Pressure for Improving the Progression of Carotid Atherosclerosis and Endothelial Dysfunction in Patients with Hypertension Management.

BACKGROUND: Visit-to-visit variability (VVV) in blood pressure (BP) creates challenges to hypertension control and was independent associated with increased all-cause mortality in hypertensive patients. The major goal of the present study was to investigate the association of VVV in systolic (S)BP with progression of carotid atherosclerosis and en-dothelial dysfunction in on-treated hypertensive patients. METHODS: Overall, 356 hypertensive patients were enrolled and completed the trial. Clinic BP was measured at baseline and at 3 monthly thereafter. Carotid artery ultrasound and endothelial function were evaluated at baseline and annually follow-up visit. VVV in BP was assessed by standard deviation (SD) and coefficient of variation (CV) of serial follow-up BP measurements. The patients were divided into low, middle, and high group by tertile of SD in SBP. RESULTS: Decrease percentage of maximum intima-media thickness (IMT) and stiffness index ß and increase percentage of brachial flow-mediated dilation (FMD) and nitric oxide (NO) in lower groups were significant greater than in higher groups (P < 0.05). Change percentage of stiffness index ß and endothelin-1 positively, and change percentage of FMD and NO negatively correlated with SD, CV, maximum, and delta of SBP (P < 0.05). SD and CV of SBP were risk factors for change percentage of IMT, stiffness index ß, FMD, NO, and endothelin-1 independently of other influential factors, such as age, and mean SBP. CONCLUSION: Excessive VVV in SBP maybe increase carotid atherosclerosis and impair endothelial function in on-treated hypertensive patients. Reducing VVV in SBP is benefit for patients with hypertension management.

Day-by-day variability in self-measured blood pressure at home: effects on carotid artery atherosclerosis, brachial flow-mediated dilation, and endothelin-1 in normotensive and mild-moderate hypertensive individuals.

OBJECTIVE: To investigate variability in self-measured home blood pressure (HBP) and its effects on carotid artery atherosclerosis and endothelial function in normotensive and mild-moderate hypertensive individuals. MATERIALS AND METHODS: This is a cross-sectional study. HBP monitoring over 7 consecutive days, carotid artery ultrasound, and brachial artery flow-mediated dilation (FMD) were performed in 314 normotensive, prehypertensive, and mild-moderate hypertensive volunteers. Variability in HBP was assessed by the SDs of the daily BP average of the last 6 consecutive days. The plasma endothelin-1 (ET-1) level was tested using an enzyme-linked immunosorbent assay. RESULTS: The tendency of SD of systolic HBP increased significantly from the normotension to the moderate hypertension group. SD of systolic HBP was significantly correlated with carotid intima-media thickness (IMT) (r=0.569, P<0.001), stiffness parameter ß (r=0.447, P<0.001), FMD (r=-0.636, P<0.001), and ET-1 (r=0.649, P<0.001). SD of diastolic HBP was also correlated with carotid IMT, stiffness parameter ß, FMD, and ET-1, but the strength of the correlation was weaker than SD of systolic HBP (all P<0.001). After adjustment of all covariants, SD of systolic HBP was always significantly associated with carotid IMT, stiffness parameter ß, FMD, and ET-1. CONCLUSION: Day-by-day variability in HBP increased with increasing BP level. This was significantly associated with carotid artery atherosclerosis and endothelial function in normotensive and mild-moderate hypertensive individuals. Day-by-day variability in HBP may serve as an important prognostic factor for atherosclerosis and endothelial dysfunction.