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Three-section landslides are renowned for their immense size, concealed development process, and devastating impact. This study conducted physical model tests to simulate one special geological structure called a three-section-within landslide. The failure process and precursory characteristics of the tested samples were meticulously analyzed using video imagery, micro-seismic (MS) signals, and acoustic emission (AE) signals, with a focus on event activity, intensity, and frequency. A novel classification method based on AE waveform characteristics was proposed, categorizing AE signals into burst signals and continuous signals. The findings reveal distinct differences in the evolution of these signals. Burst signals appeared exclusively during the crack propagation and failure stages. During these stages, the cumulative AE hits of burst signals increased gradually, with amplitude rising and then declining. High-amplitude burst signals were predominantly distributed in the middle- and high-frequency bands. In contrast, cumulative AE hits of continuous signals escalated rapidly, with amplitude monotonously increasing, and high-amplitude continuous signals were primarily distributed in the low-frequency band. The emergence of burst signals and high-frequency AE signals indicated the generation of microcracks, serving as early-warning indicators. Notably, the early-warning points of AE signals were detected earlier than those of video imagery and MS signals. Furthermore, the early-warning point of burst signals occurred earlier than those of continuous signals, and the early-warning point of the classification method preceded that of overall AE signals.

Abstract Background Constipation has been hypothesized to be associated with the increased risk of wheezing or asthma. However, the relation remains a subject of debate. We conducted this meta-analysis to assess whether constipation influences the risk of wheezing/asthma. Methods PubMed, Embase, and Web of Science were systematically searched for studies published between 1955 and January 2022. Two reviewers independently extracted data and assessed the quality of each study. Results were pooled using fixed-effects models or random-effects models as appropriate. Results In total, 3 original articles with 178,661 participants, which met the criteria, were included in this meta-analysis. Constipation was associated with an increased risk of wheezing/asthma in later life (RR = 2.02, 95% CI = 1.24–3.29, P

Background: Minimal manifestation status (MMS) is an important landmark in the treatment of myasthenia gravis (MG), and predictors of MMS induction have rarely been identified in previous studies. Objective: The objective of this study is to evaluate the clinical factors associated with MMS induction among patients with MG. Design: This two-step retrospective cohort study with a single center investigated the factors that may be associated with MMS induction and retested these predictors in a test cohort. Methods: A total of 388 diagnosed MG patients who visited Xiangya Hospital between 1 July 2015 and 1 July 2019 were involved. We performed detailed chart reviews and recorded all cases achieving MMS. Demographics and clinical characteristics were also collected and their relationships to achieving MMS were investigated. Results: MMS was achieved in 124 patients (50.2%), and the median time to achieve MMS was 26 months. Several factors were found to be associated with MMS induction in exploring cohort, including muscle-specific tyrosine-protein kinase receptor (MuSK) antibody positivity (adjusted hazard ratio, HR = 4.333, 95% confidence interval, CI: 1.862–10.082), isolated ocular involvement (adjusted HR = 1.95, 95% CI: 1.284–2.961), and low baseline quantitative myasthenia gravis score (QMG score; adjusted HR = 2.022, 95% CI: 1.086–3.764). These factors were then retested in the test cohort. Isolated ocular involvement or low baseline QMG scores were factors found to be beneficial for MMS induction were confirmed. Conclusion: Isolated ocular involvement and low baseline QMG score are predictors of MMS induction in MG patients.

Abstract Background Helios is important for functional and phenotype stability of regulatory T cells (Tregs). However, the role of Helios in autoimmune diseases and its regulation remains unclear. This study aimed to investigate the role of Helios+ Tregs in myasthenia gravis (MG) and glucocorticoid-induced tumor necrosis factor receptor (GITR) and its ligand (GITRL) in the modulation of Helios. Method Multicolor flow cytometry was performed to analyze Helios+ Tregs in peripheral blood from MG patients and healthy donors (HDs). Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of soluble GITRL/GITR in plasma. Tregs were isolated via magnetic separation and treated with recombinant GITRL and GITR-Fc. Membrane GITRL on Tregs and expression of Helios and other markers (FOXP3, CD25, CD39, CTLA-4, PD-L1 and IL-10) involved in immunosuppressive activity were determined by flow cytometry. Result Both Helios+ Tregs and soluble GITR were decreased in generalized MG (GMG) patients (n = 14), compared with HDs (n = 14) and ocular MG (OMG) patients (n = 16). Helios+ Tregs possessed greater immunosuppressive capacity compared to Helios− Tregs. Further analysis indicates soluble GITR was negatively correlated with quantitative MG score and promoted Helios expression and enhanced function of Tregs independently of membrane GITRL. Conclusion This work demonstrates abnormal changes in Helios+ Tregs and soluble GITR in MG, as well as direct regulation of Helios by GITR in the context of Tregs. This work provides new insight into the role of GITR in the regulatory pathway of Helios and pathogenesis of MG.

Objective Early life bronchiolitis has been hypothesised to be associated with the subsequent risk of persistent wheezing or asthma. However, the link remains controversial. The objective of our study was to evaluate the association between bronchiolitis before 2 years of age and the late-onset wheezing/asthma.Design Systematic review and meta-analysis.Methods PubMed, Embase and Web of Science databases were systematically searched for studies published between 1955 and January 2020. Meanwhile, we also checked through the reference lists of relevant articles to see whether these references included reports of other studies that might be eligible for the review. Cohort and case–control studies assessing the association between early-life bronchiolitis and late-onset wheezing/asthma were included in this meta-analysis. Data were extracted by two independent reviewers. Results were pooled using a random-effects model or fixed-effects model according to the heterogeneity among studies.Results 32 original articles with 292 844 participants, which met the criteria, were included in this meta-analysis. Bronchiolitis before 2 years of age was associated with an increased risk of subsequent wheezing/asthma (relative risk=2.46, 95% CI 2.14 to 2.82, p

Human umbilical-cord mesenchymal stem cells (hUCMSCs) are a safe and convenient source of MSCs and have shown beneficial effects in neonatal infection and sepsis animal models. However, the factors leading to improved outcomes are still unclear. The aim of this study was to investigate the antibacterial effect and regulation of antimicrobial resistance of hUCMSCs. We separated imipenem-resistant Pseudomonas aeruginosa (PA) from neonates and incubated it with hUCMSCs as well as their culture medium. Assessment of direct inhibition of bacterial growth was done by counting CFUs. The concentration of antibacterial peptides in the culture medium of hUCMSCs was measured. Standard PA was inoculated with a sub-inhibitory concentration of imipenem with and without hUCMSC conditioned medium and antimicrobial peptides. The sensitivity to imipenem was detected until PA showed resistance to imipenem. Outer membrane protein (OprD2) mRNA expression in PA before and after the induction of imipenem resistance was analysed. We found that HUCMSCs possessed direct antimicrobial properties against bacteria and could alleviate antibiotic resistance via reserving OprD2 expression in PA.

Odorant-binding proteins (OBPs) play a key role in the olfactory system and are essential for mating and oviposition host selection. Tirathaba rufivena, a serious lepidopterous insect pest of the palm area in recent years, has threatened cultivations of Areca catechu in Hainan. Female-biased odorant-binding protein 4 of T. rufivena (TrufOBP4) expression was hypothesized to participate in the process of oviposition host recognition and localization. In this study, we cloned and analyzed the cDNA sequence of TrufOBP4. The predicted mature protein TrufOBP4 is a small, soluble, secretory protein and belongs to a classic OBP subfamily. Fluorescence binding assay results showed that TrufOBP4 had high binding abilities with the host plant volatiles, octyl methoxycinnamate, dibutyl phthalate, myristic acid and palmitic acid. These four components tend to dock in the same binding pocket based on the molecular docking result. The interactions and contributions of key amino acid residues were also characterized. This research provides evidence that TrufOBP4 might participate in the chemoreception of volatile compounds from inflorescences of A. catechu and can contribute to the integrated management of T. rufivena.

Perinatal nicotine exposure downregulated angiotensin II type 2 receptor (AT2R) in the developing brain and increased brain vulnerability to hypoxic–ischemic injury in male neonatal rats. We tested the hypothesis that site-specific CpG methylation at AT2R gene promoter contributes to the increased vulnerability of brain injury in the neonate. Nicotine was administered to pregnant rats from day 4 of gestation to day 10 after birth. Brain hypoxic–ischemic injury was induced in day 10 male pups. CpG methylation at AT2R promoter was determined in the brain by quantitative methylation-specific PCR. Nicotine exposure significantly increased the methylation of a single CpG−52 locus near the TATA-box at AT2R promoter. Electrophoretic mobility shift assay indicated that the methylation of CpG−52 significantly decreased the binding affinity of TATA-binding protein (TBP). Chromatin immunoprecipitation assay further demonstrated an increase in the binding of a methyl-binding protein and a decrease in TBP binding to AT2R promoter in vivo in neonatal brains of nicotine-treated animals. This resulted in AT2R gene repression in the brain. Intracerebroventricular administration of a demethylating agent 5-aza-2′-deoxycytidine abrogated the enhanced methylation of CpG−52, rescued the TBP binding, and restored AT2R gene expression. Of importance, 5-aza-2′-deoxycytidine reversed the nicotine-increased vulnerability of brain hypoxic–ischemic injury in the neonate. The finding provides mechanistic evidence of increased promoter methylation and resultant AT2R gene repression in the developing brain linking perinatal stress and a pathophysiological consequence of heightened vulnerability of brain hypoxic–ischemic encephalopathy in the neonate.

Chronic hypoxia during gestation has profound adverse effects on the adaptation of uteroplacental circulation in pregnancy. Yet, the underlying mechanisms are not fully understood. The present study tested the hypothesis that enhanced production of reactive oxygen species (ROS) in uterine arteries plays a critical role in the maladaptation of uterine circulation associated with chronic hypoxia. Uterine arteries were isolated from nonpregnant and near-term pregnant sheep maintained at sea level (~300 m) or exposed to high-altitude (3801 m) hypoxia for 110 days. Hypoxia significantly increased ROS production in uterine arteries of pregnant, but not nonpregnant, sheep. This was associated with a significant increase in NADPH oxidase (Nox) 2, but not Nox1 or Nox4, protein abundance and total Nox activity in uterine arteries of pregnant animals. Chronic hypoxia significantly increased pressure-dependent uterine arterial myogenic tone in pregnant sheep, which was abrogated by a Nox inhibitor apocynin. Additionally, the hypoxia-induced increase in myogenic reactivity of uterine arteries to phorbol 12,13-dibutyrate in pregnant sheep was blocked by apocynin and tempol. In consistence with the myogenic responses, the hypoxia-mediated down-regulation of BKCa channel activity in uterine arteries of pregnant animals was reversed by apocynin. The findings suggest that heightened oxidative stress in uterine arteries plays a key role in suppressing the BKCa channel activity, resulting in increased myogenic reactivity and maladaptation of uteroplacental circulation caused by chronic hypoxia during gestation.

Catalytic stimulation of cAMP-dependent protein kinase (cAPK) induced by cAMP can take place without holoenzyme dissociation. C subunits and cAMP-bound R square can be separated with a mild force. Morphochemical and biochemical studies suggest that cAPK can dissociate its units in vivo.

The complex H2(di o-aminophenyl etioporphyrin) (DPE) can undergo condensation with the addition of nicotinoyl chloride HCl in triethylamine to produce (H2 DPE)-(py)2 in 76% yield. Insertion of Ni(II) and Cu(II) in the binucleating porphyrin core results in the formation of mononuclear complexes having a free pyridine binding site. Moreover, the introduction of another metal group via M'(DMSO)2Cl2 reactions in the mononuclear complex, leads to the formation of the dinuclear (M- DPE)-(py)2M'Cl2, wherein M represents Pd, Pt and Zn.

Aim: The purpose of the present study was to explore the function and mechanism of tensin 1 (TNS1) in non-small cell lung cancer (NSCLC) progression. Methods: The expression of TNS1 in NSCLC cells and tissues was assessed by RT-PCR and Western blot. Besides, Kaplan-Meier survival analysis was recruited to explore the association between TNS1 and NSCLC. Cell growth was analyzed by MTT and flow cytometry assay, while cell metastasis was determined by wound healing and transwell assays. The targeting relationship between TNS1 and miR-152 was assessed by luciferase activity assays. And Western blot was employed to determine the expression of related proteins of Akt/mTOR/RhoA pathway. Results: TNS1 level was boosted in NSCLC cells and tissues, related to the prognosis of NSCLC patients. Furthermore, it was proved that TNS1 promoted the growth and metastasis of NSCLC cells via Akt/mTOR/RhoA pathway. And miR-152 targeted TNS1 to affect the progression of NSCLC. Conclusion: miR-152/TNS1 axis inhibits the progression of NSCLC by Akt/mTOR/RhoA pathway. [ABSTRACT FROM AUTHOR]

Gestational hypoxia inhibits large conductance Ca2+-activated K+ (BKCa) channel expression and function in uterine arterial adaptation to pregnancy. Given the findings that microRNA-210 (miR-210) is increased in hypoxia during gestation and preeclampsia, the present study sought to investigate the role of miR-210 in the regulation of BKCa channel adaptation in the uterine artery. Gestational hypoxia significantly increased uterine vascular resistance and blood pressure in pregnant sheep and upregulated miR-210 in uterine arteries. MiR-210 bound to ovine ten-eleven translocation methylcytosine dioxygenase 1 mRNA 3' untranslated region and decreased ten-eleven translocation methylcytosine dioxygenase 1 mRNA and protein abundance in uterine arteries of pregnant sheep, as well as abrogated steroid hormone-induced upregulation of ten-eleven translocation methylcytosine dioxygenase 1 expression in uterine arteries of nonpregnant animals. In accordance, miR-210 blocked pregnancy- and steroid hormone-induced upregulation of BKCa channel β1 subunit expression in uterine arteries. Functionally, miR-210 suppressed BKCa channel current density in uterine arterial myocytes of pregnant sheep and inhibited steroid hormone-induced increases in BKCa channel currents in uterine arteries of nonpregnant animals. Blockade of endogenous miR-210 inhibited hypoxia-induced suppression of BKCa channel activity. In addition, miR-210 decreased BKCa channel-mediated relaxations and increased pressure-dependent myogenic tone of uterine arteries. Together, the results demonstrate that miR-210 plays an important role in the downregulation of ten-eleven translocation methylcytosine dioxygenase 1 and repression of BKCa channel function in uterine arteries, revealing a novel mechanism of epigenetic regulation in the maladaptation of uterine hemodynamics in gestational hypoxia and preeclampsia. [ABSTRACT FROM AUTHOR]

The large-conductance Ca2+-activated K+ (BKCa) channel is of critical importance in pregnancy-mediated increase in uterine artery vasodilation and blood flow. The present study tested the hypothesis that active DNA demethylation plays a key role in pregnancy-induced reprogramming and upregulation of BKCa channel β1 subunit (BKβ1) in uterine arteries. Uterine arteries were isolated from nonpregnant and near-term pregnant sheep. Pregnancy significantly increased the expression of ten-eleven translocation methylcytosine dioxygenase 1 (TET1) in uterine arteries. A half-palindromic estrogen response element was identified at the TET1 promoter, and estrogen treatment increased TET1 promoter activity and TET1 expression in uterine arteries. In accordance, pregnancy and steroid hormone treatment resulted in demethylation of BKβ1 promoter by increasing 5-hydroxymethylcytosine and decreasing 5-methylcytosine at the CpG in the Sp1-380 binding site that is of critical importance in the regulation of the promoter activity and BKβ1 expression. Inhibition of TET1 with fumarate significantly decreased BKβ1 expression in uterine arteries of pregnant animals and blocked steroid hormone-induced upregulation of BKβ1. Functionally, fumarate treatment inhibited pregnancy and steroid hormone-induced increases in BKCa channel current density and BKCa channel-mediated relaxations. In addition, fumarate blocked pregnancy and steroid hormone-induced decrease in pressure-dependent myogenic tone of the uterine artery. The results demonstrate a novel mechanism of estrogen-mediated active DNA demethylation in reprogramming of BKCa channel expression and function in the adaption of uterine circulation during pregnancy. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. The results of the present study demonstrate that high expression of microRNA (miR)-137 and low expression of steroid receptor coactivator-3 (SRC3) had a significant negative correlation in 40 NSCLC tissue samples. In addition, cell colony formation and proliferation was significantly reduced in miR-137-transfected A549 and NCI-H838 cells compared with scramble-transfected NSCLC cell lines. miR-137 was identified to induce G1/S cell cycle arrest and dysregulate the mRNA expression of cell cycle-associated proteins (proliferating cell nuclear antigen, cyclin E, cyclin A1, cyclin A2 and p21) in NSCLC cells. Notably, miR-137 could significantly suppress SRC3 3' untranslated region (UTR) luciferase-reporter activity, an effect that was not detectable when the putative 3'-UTR target-site was mutated, further clarifying the molecular mechanisms underlying the role of miR-137 in NSCLC. In conclusion, the results of the present study suggest that miR-137 suppresses NSCLC cell proliferation by partially targeting SRC3. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the effects of human papillomavirus (HPV) infection on the gynecological disease of vaginitis and to demonstrate how the small interfering RNA (siRNA) method may be used for HPV prevention in the clinic. Human vaginal epithelial cells were transfected with HPV-11 L1 expression vector and siRNA-HPV-11 L1 vectors and a control group was transfected with scrambled siRNA. Cell proliferation in each group was analyzed using the MTT assay and the expression of apoptosis-associated proteins was measured by western blot analysis. Compared with the control group, HPV-11 L1 mRNA and protein levels were significantly increased following transfection with the HPV-11 L1 expression vector in cells (P<0.05), but this result was significantly reversed by silencing of HPV-11 L1 (P<0.05). In addition, cell proliferation in the HPV-11 group was lower than that in the control group; however, cell proliferation was signifi- cantly increased in cells transfected with silenced L1 compared with that in the control group (P<0.05). Furthermore, silencing of HPV-11 L1 significantly decreased caspase-3 and caspase-9 expressions in cells, whereas the expression was increased in the HPV-11 L1 group (P<0.05). The present study suggested that siRNA-mediated silencing of HPV-11 L1 may have potential therapeutic applications for treating gynecological diseases associated with HPV-11 infection. [ABSTRACT FROM AUTHOR]

Previous in vivo study demonstrated that chronic hypoxia during gestation was associated with estrogen receptor-α (ER-α) gene repression in ovine uterine arteries. Yet, it remains undetermined whether hypoxia had a direct effect and if DNA methylation played a causal role in hypoxia-mediated ER-α gene repression. Thus, this study tested the hypothesis that prolonged hypoxia has a direct effect and increases promoter methylation resulting in ER-α gene repression and inhibition of estrogen-mediated adaptation of uterine vascular tone. Uterine arteries isolated from nonpregnant and pregnant sheep were treated ex vivo with 21.0% O2 and 10.5% O2 for 48 hours. Hypoxia significantly increased ER-α promoter methylation at both specificity protein-1 and upstream stimulatory factor binding sites, decreased specificity protein-1 and upstream stimulatory factor binding to the promoter, and suppressed ER-α expression in uterine arteries of pregnant animals. Of importance, the effects of hypoxia were blocked by a methylation inhibitor 5-aza-2'-deoxycytidine. In addition, hypoxia abrogated steroid hormone-mediated increase in ER-α expression and inhibited the hormoneinduced increase in large-conductance Ca2+-activated K+ channel activity and decrease in myogenic tone in uterine arteries of nonpregnant animals, which were reversed by 5-aza-2'-deoxycytidine. The results provide novel evidence of a direct effect of hypoxia on heightened promoter methylation that plays a causal role in ER-α gene repression and ablation of steroid hormone-mediated adaptation of uterine arterial large conductance Ca2+-activated K+ channel activity and myogenic tone in pregnancy. [ABSTRACT FROM AUTHOR]

Small-conductance Ca2+-activated K (SKCa,) channels are crucial in regulating vascular tone and blood pressure. The present study tested the hypothesis that SKCa channels play an important role in uterine vascular adaptation in pregnancy, which is inhibited by chronic hypoxia during gestation. Uterine arteries were isolated from nonpregnant and near-term pregnant sheep maintained at sea level (≈300 m) or exposed to high-altitude (3801 m) hypoxia for 110 day Immunohistochemistry revealed the presence of SKCa channels type 2 (SK2) and type 3 (SK3) in both smooth muscles and endothelium of uterine arteries. The expression of SK2 and SK3 channels was significantly increased during pregnancy, which was inhibited by chronic hypoxia. In normoxic animals, both SKCa channel opener NS309 and a large-conductance These relaxations were inhibited by selective SKCa, and BKCa channel blockers, respectively. NS309-induced relaxation (BKCa,) channel opener NS 1619 relaxed norepinephrine-contracted uterine arteries in pregnant but not nonpregnant sheep. These relaxations were inhibited by selective SKCa and BKCa channel blockers, respectively. NS309-induced relaxation was largely endothelium-independent. In high-altitude hypoxic animals, neither NS 1691 nor NS309 produced significant relaxation of uterine arteries in either nonpregnant or pregnant sheep. Similarly, the role of SKCa channels in regulating the myogenic reactivity of uterine arteries in pregnant animals was abrogated by chronic hypoxia. Accordingly, the enhanced SKCa channel activity in uterine arterial myocytes of pregnant animals was ablated by chronic hypoxia. The findings suggest a novel mechanism of SKc, channels in regulating myogenic adaptation of uterine arteries in pregnancy and in the maladaptation of uteroplacental circulation caused by chronic hypoxia during gestation. [ABSTRACT FROM AUTHOR]

Perinatal nicotine exposure caused a sex-dependent heightened vascular response to angiotensin II (Ang II) and increased blood pressure in adult male but not in female rat offspring. The present study tested the hypothesis that estrogen normalizes perinatal nicotine--induced hypertensive response to Ang II in female offspring. Nicotine was administered to pregnant rats via subcutaneous osmotic minipumps from day 4 of gestation to day 10 after birth. Ovariectomy and 17β-estradiol replacement were performed on 8-week-old female offspring. At 5 months of age, Ang II-induced blood pressure responses were not changed by nicotine treatment in the sham groups. In contrast, nicotine significantly enhanced Ang II--induced blood pressure responses as compared with saline control in the ovariectomy groups, which was associated with increased Ang II--induced vascular contractions. These heightened responses were abrogated by 17β-estradiol replacement. In addition, nicotine enhanced Ang II receptor type I, NADPH (nicotinamide adenine dinucleotide phosphate) oxidase type 2 protein expressions, and reactive oxygen species production of aortas as compared with saline control in the ovariectomy groups. Antioxidative agents, both apocynin and tempol, inhibited Ang II--induced vascular contraction and eliminated the differences of contractions between nicotine-treated and control ovariectomy rats. These findings support a key role of estrogen in the sex difference of perinatal nicotine--induced programming of vascular dysfunction, and suggest that estrogen may counteract heightened reactive oxygen species production, leading to protection of females from development programming of hypertensive phenotype in adulthood. [ABSTRACT FROM AUTHOR]

This article discusses a study which determined whether hypoxia causes epigenetic repression of the estrogen receptor-α gene in uterine arteries via heightened promoter methylation. The results showed evidence of hypoxia causing heightened promotor methylation and resultant estrogen receptor-α gene repression in uterine. New insights of molecular mechanisms linking gestational hypoxia to aberrant uteroplacental circulation and increased risk of preeclampsia are also described.

Uterine vascular tone significantly decreases whereas uterine blood flow dramatically increases during pregnancy. However, the complete molecular mechanisms remain elusive. We hypothesized that increased Ca(2+)-activated K(+) (BK(Ca)) channel activity contributes to the decreased myogenic tone of uterine arteries in pregnancy. Resistance-sized uterine arteries were isolated from nonpregnant and near-term pregnant sheep. Electrophysiological studies revealed a greater whole-cell K(+) current density in pregnant compared with nonpregnant uterine arteries. Tetraethylammonium and iberiotoxin inhibited K(+) currents to the same extent in uterine arterial myocytes. The BK(Ca) channel current density was significantly increased in pregnant uterine arteries. In accordance, tetraethylammonium significantly increased pressure-induced myogenic tone in pregnant uterine arteries and abolished the difference in myogenic responses between pregnant and nonpregnant uterine arteries. Activation of protein kinase C produced a similar effect to tetraethylammonium by inhibiting BK(Ca) channel activity and increasing myogenic tone in pregnant uterine arteries. Chronic treatment of nonpregnant uterine arteries with physiologically relevant concentrations of 17β-estradiol and progesterone caused a significant increase in the BK(Ca) channel current density. Western blot analyses demonstrated a significant increase of the β1, but not α, subunit of BK(Ca) channels in pregnant uterine arteries. In accordance, steroid treatment of nonpregnant uterine arteries resulted in an upregulation of the β1, but not α, subunit expression. The results indicate that the steroid hormone-mediated upregulation of the β1 subunit and BK(Ca) channel activity may play a key role in attenuating myogenic tone of the uterine artery in pregnancy. [ABSTRACT FROM AUTHOR]

The article presents a study testing the hypothesis that the downregulation of actin polymerization plays a key role in reduced vascular tone of uterine arteries in the pregnant state. Uterine arteries were isolated from nonpregnant and near-term pregnant sheep. The results indicate a key role of actin polymerization in protein kinase C-induced myogenic contractions. This suggests a new mechanism of sex steroid hormone-mediated downregulation of actin polymerization underlying the decreased myogenic tone of uterine arteries in pregnancy.

Pregnancy is associated with a significant decrease in uterine vascular tone and an increase in uterine blood flow. The present study tested the hypothesis that estrogen and progesterone differentially regulate the extracellular signal-regulated kinase (ERK)1/2 and protein kinase C (PKC) signaling pathways in vascular smooth muscle, resulting in a decrease in uterine vascular myogenic tone in pregnancy. Uterine arteries were isolated from nonpregnant and near-term pregnant sheep. Chronic treatment (48 hours) of nonpregnant uterine arteries with 17beta-estradiol and progesterone caused a significant decrease in PKC-mediated contractions and pressure-induced myogenic tone. In accordance, treatment of near-term pregnant uterine arteries for 48 hours with ICI 182780 and RU 486 significantly increased PKC-induced contractions and myogenic tone. In contrast, acute treatment for 30 minutes had no effect on uterine artery contractility. An ERK1/2 inhibitor, PD098059, restored the chronic effect of steroids on PKC-mediated contractions in nonpregnant sheep. ERK1/2 protein and mRNA levels were greater in near-term pregnant as compared with nonpregnant uterine arteries. 17beta-Estradiol and progesterone increased ERK1/2 protein in nonpregnant sheep. In agreement, ICI 182780 and RU 486 caused significant decreases in ERK1/2 protein in near-term pregnant sheep. Western blot showed 6 PKC isozymes, alpha, beta(I), beta(II), delta, epsilon, and zeta, in the uterine arteries. 17beta-Estradiol and progesterone decreased the particulate:cytosolic ratios of PKCalpha, epsilon, and zeta, respectively, in nonpregnant sheep. ICI 182780 and RU 486 increased the ratios in near-term pregnant sheep. The results indicate a direct chronic effect of the steroid hormones in the upregulation of ERK1/2 expression and downregulation of the PKC signaling pathway, resulting in attenuated myogenic tone of the uterine artery in pregnancy. [ABSTRACT FROM AUTHOR]

The article presents a study which tested the hypothesis that prenatal cocaine exposure causes reprogramming of vascular reactivity, leading to an increased risk of hypertension in adult offspring. The researchers concluded that prenatal cocaine exposure programs vascular contractility via changes in endothelial nitric oxide (NO) synthase-regulated Calcium (Ca2+ sensitivity of myofilaments in the sex- and tissue-dependent manners in resistance arteries leading to an increased risk of hypertension in male offspring.

Epidemiological studies suggest that maternal cigarette smoking is associated with an increased risk of elevated blood pressure (BP) in postnatal life. The present study tested the hypothesis that prenatal nicotine exposure causes an increase in BP response to angiotensin II (Ang II) in adult offspring. Nicotine was administered to pregnant rats via subcutaneous osmotic minipumps throughout the gestation. BP and vascular responses to Ang II were measured in 5-month-old adult offspring. Prenatal nicotine had no effect on baseline BP but significantly increased Ang II-stimulated BP in male but not female offspring. The baroreflex sensitivity was significantly decreased in both male and female offspring. Prenatal nicotine significantly increased arterial media thickness in male but not female offspring. In male offspring, nicotine exposure significantly increased Ang II-induced contractions of aortas and mesenteric arteries. These responses were not affected by inhibition of endothelial NO synthase activity. Losartan blocked Ang II-induced contractions in both control and nicotine-treated animals. In contrast, PD123319 had no effect on Ang II-induced contractions in control but inhibited them in nicotine-treated animals. Nicotine significantly increased Ang II type 1 receptor but decreased Ang II type 2 receptor protein levels, resulting in a significant increase in the ratio of Ang II type 1 receptor/Ang II type 2 receptor in the aorta. Furthermore, the increased contractions of mesenteric arteries were mediated by increases in intracellular Ca(2+) concentrations and Ca(2+) sensitivity. These results suggest that prenatal nicotine exposure alters vascular function via changes in Ang II receptor-mediated signaling pathways in adult offspring in a gender-specific manner, which may lead to an increased risk of hypertension in male offspring. [ABSTRACT FROM AUTHOR]

In six sheep, radiopaque markers were placed on the left ventricle (LV), the mitral annulus, the left atrium (LA), and the central edge of both mitral leaflets to investigate the effects of acute LV ischemia on atrial contraction, mitral annular area (MAA), and mitral regurgitation (MR). Animals were studied with biplane videofluoroscopy and transesophageal echocardiography before and during balloon occlusion of the left anterior descending (LAD), distal circumflex (dLCX), and proximal circumflex (pLCX) coronary arteries. MAA and LA area were calculated from the corresponding markers. LAD occlusion did not alter LA area reduction or presystolic MAA reduction, whereas dLCX occlusion resulted in a mild decrease in the former with no change in the latter. Neither occlusion resulted in MR. pLCX occlusion, however, significantly decreased LA area and presystolic MAA reduction and resulted in increased end-diastolic MAA, delayed valve closure from end diastole, and MR. Decreased atrial contractile function, as observed during acute posterolateral ischemia, is linked to diminished presystolic mitral annular reduction, a larger mitral annular size at end diastole, and MR. [ABSTRACT FROM AUTHOR]

Background and Objectives: To investigate the capacity of clinical nutrition services in secondary and tertiary hospitals in the Sichuan Province, China. Methods and Study Design: Convenience sampling was used. Equestionnaires were distributed to all eligible medical institutions in Sichuan through the official network of provincial and municipal clinical nutrition quality control centers. The data obtained were sorted in Microsoft Excel and analyzed by SPSS. Results: A total of 519 questionnaires were returned, of which 455 were valid. Only 228 hospitals were accessible to clinical nutrition services, of which 127 hospitals had independently set up clinical nutrition departments (CNDs). The ratio of clinical nutritionists to beds was 1:214. During the last decade, the rate of constructing new CNDs was maintained at approximately 5 units/year. A total of 72.4% of hospitals managed their clinical nutrition units as part of their medical technology departments. The specialist number ratio of senior, associate, intermediate and junior is approximately 1:4:8:10. There were 5 common charges for clinical nutrition. Conclusions: The sample representation was limited, and the capacity of clinical nutrition services may have been overestimated. Secondary and tertiary hospitals in Sichuan are currently in the second high tide of department establishment, with a positive trend of departmental affiliation standardization and a basic formation of a talent echelon. [ABSTRACT FROM AUTHOR]

Maternal cigarette smoking is the single most widespread prenatal insult. Smoking has long been associated with adverse pregnancy outcomes, both for the mother, her fetus, and newborn. The present study was designed to test the hypothesis that fetal and neonatal nicotine exposure has adverse effects on coronary vasculature development, resulting in changes in coronary blood flow in adult offspring. Nicotine (2.1mg/d) was administered to pregnant rats via subcutaneous osmotic minipumps throughout gestation and up to 10 days after delivery. Hearts were isolated from 3 month-old male and female offspring, and were subjected to 25-min of ischemia followed by 60-rain of reperfusion in a Langendorff preparation. Pulmonary artery effluent was collected as an index of coronary flow (ml/min/g heart wet weight). Nicotine significantly decreased coronary flow in female (10.4±0.8 vs. 7.1±0.7, P<0.05) but not in male (9.1±0.5 vs. 9.0±0.7, P>0.05) hearts at baseline. Ischemia and reperfusion decreased coronary flow in both male and female hearts, with higher coronary flow in female hearts. Nicotine treatment significantly decreased coronary flow during reperfusion up to 60 min in female, but not in male, hearts. The results suggest that prenatal nicotine exposure selectively decreases coronary flow in adult female offspring. (Supported in part by NIH grant S06GM073842 and TRDRP Award # 14FT-0075) [ABSTRACT FROM AUTHOR]

Recent epidemiological studies have demonstrated that in utero exposure to maternal cigarette smoking is associated with cardiovascular diseases in offspring later in life. The present study tested the hypothesis that fetal and neonatal nicotine exposure increased heart susceptibility to ischemia/reperfusion (I/R) injury in adult offspring. Nicotine (2.1 mg/d) was administered to pregnant rats via subcutaneous osmotic minipumps throughout gestation and up to 10 days after delivery. Hearts were isolated from 3 month-old male and female offspring, and were subjected to 25-min of ischemia followed by 60-min of reperfusion in a Langendorff preparation. Cardiac functional parameters: heart rate, left ventricular developed pressure and end diastolic pressure, dP/dtmax, dP/dtmin, and left ventricular infarct size were measured. Pre-ischemic values of cardiac function were not significantly different between the control and nicotine-treated hearts in either male or female offspring. Prenatal nicotine exposure significantly increased I/R-induced infarct size in left ventricles, and significantly attenuated postischemic recovery of left ventricular function in both male and female offspring. However, the effect of nicotine was significantly more pronounced in females than males. The findings suggest that prenatal nicotine exposure causes a reprogramming of cardiac function resulting in an increase in heart susceptibility to I/R injury in adult offspring. In addition, the effect of nicotine shows a gender dichotomy with females being more susceptible than males. [ABSTRACT FROM AUTHOR]

Epidemiologic studies suggest that prenatal exposure to maternal cigarette smoking is associated with an increased risk of elevated blood pressure in postnatal life. The present study was designed to test the hypothesis that fetal and neonatal nicotine exposure increased vascular contractility in adult offspring. Nicotine was administered to pregnant rats via subcutaneous osmotic minipumps throughout gestation and up to 10 days after delivery. Aortas were isolated from 3 month-old male and female offspring. Nicotine significantly increased KCl- and NE-induced contractions in male, but not in female, arteries. Inhibition of eNOS with L-NNA significantly increased NE-induced contractions in control, but not in nicotine-treated, male arteries. In contrast, nicotine caused a significant increase in L-NNA-mediated potentiation of NE-induced contractions in female arteries. Nicotine had no effect on SNP-induced relaxations of aortas. However, it decreased endothelium-dependent relaxation induced by acetylcholine in male offspring, but increased it in females. There were no differences in eNOS protein levels in aortas between control and nicotine-treated animals. The results suggest that fetal and neonatal nicotine exposure alters vascular functions in adult offspring in a gender specific manner, which may lead to an increased risk of cardiovascular dysfunction in later life. [ABSTRACT FROM AUTHOR]

Studies in both humans and animals have demonstrated that nicotine impairs endothelium-dependent relaxation of arterioles. It has been suggested that plasma levels of nitric oxide are decreased following the infusion of nicotine. The present study tested the hypothesis that nicotine has direct effects on endothelial cells and causes decreases in intracellular Ca2+ concentrations and nitric oxide release. Bovine coronary artery endothelial cells at the fifth passage were cultured to 80% confluence. For the time course study, cells were treated with 10 µM nicotine from 5 min to 48 h. To determine the dose-response, cells were treated with 0.01 - 30 µM nicotine for 24 h. Intracellular Ca2+ concentrations were measured with cells loaded with fura-2. Nitric oxide in culture medium was measured by the chemiluminescence method. Short-term nicotine treatment up to 60 min showed no effect on intracellular Ca2+ concentrations and nitric oxide release. However, nicotine treatment for 24 h inhibited ATP-induced increases in intracellular Ca2+ concentrations and significantly decreased the maximal Ca2+ response from 187.4±13.2 to 115.0±7.3 nM. In accordance, nicotine treatment had no effect on nitric oxide release until 24 h. At 24 h treatment, nicotine (0.01 to 30 µM) produced dose-dependent decreases in nitric oxide release. The results suggest that chronic nicotine exposure decreases intracellular Ca2+ concentrations and nitric oxide release in cultured coronary artery endothelial cells. [ABSTRACT FROM AUTHOR]

Cigarette smoking increases coronary vascular resistance, impairs coronary flow-mediated dilation, and is a major risk factor for coronary heart disease. Out of over 4000 individual compounds contained in tobacco smoke, nicotine is one of the most important ones in related to coronary heart disease. The present study tested the hypothesis that prenatal nicotine exposure decreases coronary nitric oxide release in adult offspring. Nicotine (2.1 mg/d) was administered to pregnant rats via subcutaneous osmotic minipumps throughout gestation and up to 10 days after delivery. Hearts were isolated from 3 month-old male and female offspring, and were subjected to 25-rain of ischemia followed by 60-min of reperfusion in a Langendorff preparation. Nitric oxide (nmols/min/g heart wet weight) in coronary effluent was measured by the chemiluminescence method. Nicotine significantly decreased coronary nitric oxide release in male (4.9±0.8 vs. 2.8±0.4, P<0.05) but not in female (3.3±1.0 vs. 1.8±0.5, P>0.05) hearts at baseline. Ischemia and reperfusion decreased coronary nitric oxide release in both male and female hearts, with higher nitric oxide levels in male hearts. Nicotine treatment significantly decreased coronary nitric oxide release during reperfusion up to 60 min in male, but not in female, hearts. These findings suggest that prenatal nicotine exposure selectively decreases coronary nitric oxide release in adult male offspring, which may lead to a change in coronary blood flow. [ABSTRACT FROM AUTHOR]