Prevalence and risk factors of depression and anxiety symptoms in intensive care unit patients with cardiovascular disease: A cross-sectional study.

AIMS: To investigate the prevalence of anxiety and depression symptoms in intensive care unit (ICU) patients with cardiovascular disease (CVD) and to explore which elements are risk factors for the development of anxiety and depression symptoms. DESIGN: A cross-sectional study. METHODS: A total of 1028 ICU patients with CVD were enrolled in this cross-sectional study. Logistic regression was used to assess risk factors and associations between anxiety and depression symptoms, and mediation analysis was used to explore the effect of risk factors on the association between anxiety and depression symptoms. Reporting of the study followed the STROBE checklist. RESULTS: The results showed that among ICU patients with CVD, 38.1% had anxiety symptoms, 28.7% had depression symptoms and 19.3% had both anxiety and depression symptoms, and there was a significant association between anxiety and depression symptoms. We also identified female gender, hypertension, hyperlipidemia and cardiac function class IV as independent risk factors for anxiety and depression symptoms. Importantly, these factors also mediated the association between anxiety and depression symptoms, emphasising their role in the psychological well-being of this patient group. CONCLUSION: ICU patients with CVD were prone to anxiety and depression symptoms. Female gender, hypertension, hyperlipidemia and cardiac function class IV were identified as independent risk factors that also served as mediators in the relationship between anxiety and depression symptoms. Especially, cardiac function class IV emerged as a critical factor in this association. RELEVANCE TO CLINICAL PRACTICE: It is imperative for critical care professionals to recognize the elevated risk of depression and anxiety among ICU patients with severe CVD, especially those with cardiac function class IV, hypertension, hyperlipidemia and females. Proactive and supportive measures are essential for this vulnerable group during their ICU stay to safeguard their mental health and prevent negative outcomes. PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution.

Accumulation of Ag(0) Single Atoms at Water/Mineral Interfaces during Sunlight-Induced Reduction of Ionic Ag by Phenolic DOM.

Silver (Ag) undergoes a complex and dynamic Ag+/Ag0 cycle under environmental conditions. The Ag+ → Ag nanoparticles (AgNPs) transformation due to the combined actions of sunlight, O2, and dissolved organic matter has been a well-known environmental phenomenon. In this study, we indicate that this process may be accompanied by a pronounced accumulation of Ag(0) single atoms (Ag-SAs) on the minerals' surfaces. According to spherical aberration-corrected scanning transmission electron microscopy and high-energy-resolution X-ray adsorption fine structure analyses, humic acid (HA) and phenol (PhOH) can induce Ag-SAs accumulation, whereas oxalic acid causes only AgNPs deposition. Ag-SAs account for more than 20 wt % of total Ag(0) on the γ-Al2O3 surfaces during HA- and PhOH-mediated photolysis processes. HA also causes Ag-SAs to accumulate on two other prevalent soil minerals, SiO2 and Fe2O3, and the fractions of Ag-SAs are about 15 wt %. Our mechanism studies suggest that a phenolic molecule acts as a reducing agent of Ag+ and a stabilizer of Ag-SAs, protecting Ag-SAs against autocatalytic nucleation.

Effects of cereal bran consumption on cardiometabolic risk factors: A systematic review and meta-analysis.

AIMS: Cardiovascular disease is a prevalent worldwide disease, and cardiometabolic risk factors (CMRFs) include hyperlipidemia, hypertension, diabetes, and adiposity. Healthy diets are the critical factor in controlling these CMRFs risks, especially cereal bran which contains many beneficial substances. However, there are still contradictions in the indicators of improving CMRFs by bran from different grain sources or even the same grain source. Therefore, this study aimed to investigate the effects of cereal bran consumption on CMRFs. DATA SYNTHESIS: Eligible randomized controlled studies were searched in PubMed, Embase, Scopus, the Cochrane Library and Web of Science until February 2023. The random-effects model was used to calculate overall effect sizes of weighted mean difference (WMD) and 95% confidence interval (CI). Finally, 22 studies were included in the present meta-analysis. Compared to the control, cereal bran consumption had no significant effect on high-density lipoprotein cholesterol, triglycerides, waist circumference, and body mass index, but could reduce systolic blood pressure (WMD: -1.59; 95% CI: -2.45 to -0.72), diastolic blood pressure (WMD: -1.96; 95% CI: -3.89 to -0.04), total cholesterol (WMD: -0.19; 95% CI: -0.34 to -0.04), low-density lipoprotein cholesterol (WMD: -0.21; 95% CI: -0.38 to -0.04), and fasting blood glucose (WMD: -0.13; 95% CI: -0.24 to -0.01). Additionally, oat bran can lower blood lipids in individuals with lipid diseases and blood pressure in obese or hypertensive patients. CONCLUSIONS: Cereal bran could significantly reduce blood pressure, total cholesterol, low-density lipoprotein cholesterol, and fasting blood glucose in individuals with CMRFs, and oat bran had the most obvious effect.

Research trends in hypertension associated with obstructive sleep apnea: a bibliometric analysis.

OBJECTIVES: The purpose of this study was to systematically analyze the studies of hypertension associated with obstructive sleep apnea to assess the current status and hot spots in this field. METHODS: We searched the Web of Science Core Collection for publications related to hypertension associated with obstructive sleep apnea published before July 3, 2021. Bibliometric analyses and science mappings were carried out using the CiteSpace 5.8.R1 and Microsoft Office Excel 2019. CiteSpace 5.8.R1 was used to visualize the distribution of research fields, analyze co-occurring keywords and burst terms to detect trends and frontiers, and identify leading collaborations among countries, authors, and institutions. Microsoft Office Excel 2019 was used to make bar graphs, histograms and line graphs. RESULTS: According to the search strategy, a total of 7263 published articles and reviews were retrieved. The research on hypertension associated with obstructive sleep apnea has been developing quickly at present. Sleep and Breathing was the most productive journal. The USA was a major producing country and Harvard Medical School was the most productive institution in this field. In the field of hypertension associated with obstructive sleep apnea, the main research hotspots were continuous positive airway pressure, cardiovascular disease, and obesity. CONCLUSIONS: The present study provides a new perspective for the study of hypertension associated with obstructive sleep apnea and valuable information for researchers to find potential partners and cooperative institutions, hot issues and research frontiers.

Effect of nanoparticles on gouty arthritis: a systematic review and meta-analysis.

OBJECTIVE: The purpose of this study was to explore the effects of nanoparticles on gouty arthritis, and to provide evidence for the preclinical application of nanoparticles in gouty arthritis and ideas for nanomedicine improvement for nanoparticle researchers. METHODS: Five databases including the Cochrane Library, PubMed, Scopus, Web of Science, and Embase were searched for eligible studies until April 2022. The quality of the selected studies was assessed by SYRCLE's risk of bias (RoB) tool, and the random-effects model was used to calculate the overall effect sizes of weighted mean differences (WMD). RESULTS: Ten studies met the inclusion criteria. Results showed that nanoparticles were effective in reducing uric acid levels (WMD: -4.91; 95% confidence interval (CI): - 5.41 to - 4.41; p < 0.001), but were not better than allopurinol (WMD: -0.20; 95% CI: - 0.42 to 0.02; p = 0.099). It was worth noting that the nanoparticles were safer than allopurinol. Subgroup analyses indicated that nanoparticle encapsulated substance, animal species, nanoparticle dosage, animal quantity, and animal gender were all sources of heterogeneity. CONCLUSION: The nanoparticles are safe medications for gouty arthritis which can effectively reduce uric acid levels in rodents. Although the results are still uncertain, it is expected to have certain clinical application value. The nanoparticles may be the preclinical medications for gouty arthritis in the future.

Effects of virtual reality on the treatment of amblyopia in children: A systematic review and meta-analysis.

PROBLEM: Virtual reality technology has been used to treat amblyopia in children. However, it is unclear how virtual reality technology differs from conventional patching therapy in terms of effectiveness. ELIGIBILITY CRITERIA: Eligible randomized controlled studies were retrieved from PubMed, Embase, Scopus, the Cochrane Library, and Web of Science through February 2023. SAMPLE: Eight studies included 10 trials with 459 participants were included in the current meta-analysis. Two studies (Herbison et al., 2016; Huang et al., 2022) included two trials each. Thus, a total of ten trials were included in the current meta-analysis. RESULTS: Overall, virtual reality technology treatment significantly improved visual acuity by 0.07 log MAR (95% confidence interval [CI], -0.11 to -0.02; P < 0.001; I2 = 94.4%) compared with traditional patching therapy. In addition, subgroup analyses also revealed that treatment with virtual reality technology was more effective when the child was younger than seven years old, or when the duration of the intervention was no more than twenty hours. CONCLUSIONS: Virtual reality technology treatment showed significant effects in improving visual acuity in children who were seven years of age or younger with amblyopia. IMPLICATIONS: Virtual reality technology treatment is effective in treating amblyopia in children. Virtual reality therapy is also entertaining and popular among children and can be applied to the treatment of amblyopia in children in the future.

Loss of IP3R-BKCa Coupling Is Involved in Vascular Remodeling in Spontaneously Hypertensive Rats.

Mechanisms by which BKCa (large-conductance calcium-sensitive potassium) channels are involved in vascular remodeling in hypertension are not fully understood. Vascular smooth muscle cell (VSMC) proliferation and vascular morphology were compared between hypertensive and normotensive rats. BKCa channel activity, protein expression, and interaction with IP3R (inositol 1,4,5-trisphosphate receptor) were examined using patch clamp, Western blot analysis, and coimmunoprecipitation. On inside-out patches of VSMCs, the Ca2+-sensitivity and voltage-dependence of BKCa channels were similar between hypertensive and normotensive rats. In whole-cell patch clamp configuration, treatment of cells with the IP3R agonist, Adenophostin A (AdA), significantly increased BKCa channel currents in VSMCs of both strains of rats, suggesting IP3R-BKCa coupling; however, the AdA-induced increases in BKCa currents were attenuated in VSMCs of hypertensive rats, indicating possible IP3R-BKCa decoupling, causing BKCa dysfunction. Co-immunoprecipitation and Western blot analysis demonstrated that BKCa and IP3R proteins were associated together in VSMCs; however, the association of BKCa and IP3R proteins was dramatically reduced in VSMCs of hypertensive rats. Genetic disruption of IP3R-BKCa coupling using junctophilin-2 shRNA dramatically augmented Ang II-induced proliferation in VSMCs of normotensive rats. Subcutaneous infusion of NS1619, a BKCa opener, to reverse BKCa dysfunction caused by IP3R-BKCa decoupling significantly attenuated vascular hypertrophy in hypertensive rats. In summary, the data from this study demonstrate that loss of IP3R-BKCa coupling in VSMCs induces BKCa channel dysfunction, enhances VSMC proliferation, and thus, may contribute to vascular hypertrophy in hypertension.

The Efficient Synthesis and Anti-Fatigue Activity Evaluation of Macamides: The Unique Bioactive Compounds in Maca.

Macamides are a class of amide alkaloids that are only found in maca and are widely considered to be its bioactive marker compounds. More than thirty macamide monomers have been identified in recent years; however, it is difficult to obtain a single macamide monomer from the maca plant because of their similar structures and characteristics. We used the carbodiimide condensation method (CCM) to efficiently synthesize five typical macamides, including N-benzyl-hexadecanamide (NBH), N-benzyl-9Z,12Z,15Z-octadecenamide, N-(3-methoxybenzyl)-9Z,12Z-octadecenamide, N-benzyl-9Z,12Z-octadecenamide, and N-(3-methoxybenzyl)-9Z,12Z,15Z-octadecadienamide. All the synthesized macamides were purified by a one-step HPLC with a purity of more than 95%. NBH is the most abundant macamide monomer in natural maca, and it was selected to evaluate the anti-fatigue effects of macamides. The results indicated that NBH could enhance the endurance capacity of mice by increasing liver glycogen levels and decreasing blood urea nitrogen, lactate dehydrogenase, blood ammonia, and blood lactic acid levels. Macamides might be the active substances that give maca its anti-fatigue active function.

Transition-Metal-Free Cascade Approach for the Synthesis of Functionalized Biaryls by SNAr of Arylhydroxylamines with Arylsulfonium Salts.

We report a transition-metal-free protocol for the synthesis of functionalized biaryls through nucleophilic aromatic substitution (SNAr) of arylhydroxylamines to arylsulfonium salts. With this protocol, structurally diverse functionalized biaryls were obtained smoothly in moderate to good yields. Merits of this transformation include mild reaction conditions, broad substrate scope, great functional group tolerance, feasibility of a one-pot procedure, and ease of handing and scale-up.

Coordination Polymers from Biphenyl-Dicarboxylate Linkers: Synthesis, Structural Diversity, Interpenetration, and Catalytic Properties.

The present work explores two biphenyl-dicarboxylate linkers, 3,3'-dihydroxy-(1,1'-biphenyl)-4,4'-dicarboxylic (H4L1) and 4,4'-dihydroxy-(1,1'-biphenyl)-3,3'-dicarboxylic (H4L2) acids, in hydrothermal generation of nine new compounds formulated as [Co2(µ2-H2L1)2(phen)2(H2O)4] (1), [Mn2(µ4-H2L1)2(phen)2]n·4nH2O (2), [Zn(µ2-H2L1)(2,2'-bipy)(H2O)]n (3), [Cd(µ2-H2L1) (2,2'-bipy)(H2O)]n (4), [Mn2(µ2-H2L1)(µ4-H2L1)(µ2-4,4'-bipy)2]n·4nH2O (5), [Zn(µ2-H2L1)(µ2-4,4'-bipy)]n (6), [Zn(µ2-H2L2)(phen)]n (7), [Cd(µ3-H2L2)(phen)]n (8), and [Cu(µ2-H2L2) (µ2-4,4'-bipy)(H2O)]n (9). These coordination polymers (CPs) were generated by reacting a metal(II) chloride, a H4L1 or H4L2 linker, and a crystallization mediator such as 2,2'-bipy (2,2'-bipyridine), 4,4'-bipy (4,4'-bipyridine), or phen (1,10-phenanthroline). The structural types of 1-9 range from molecular dimers (1) to one-dimensional (3, 4, 7) and two-dimensional (8, 9) CPs as well as three-dimensional metal-organic frameworks (2, 5, 6). Their structural, topological, and interpenetration features were underlined, including an identification of unique two- and fivefold 3D + 3D interpenetrated nets in 5 and 6. Phase purity, thermal and luminescence behavior, as well as catalytic activity of the synthesized products were investigated. Particularly, a Zn(II)-based CP 3 acts as an effective and recyclable heterogeneous catalyst for Henry reaction between a model substrate (4-nitrobenzaldehyde) and nitroethane to give ß-nitro alcohol products. For this reaction, various parameters were optimized, followed by the investigation of the substrate scope. By reporting nine new compounds and their structural traits and functional properties, the present work further outspreads a family of CPs constructed from the biphenyl-dicarboxylate H4L1 and H4L2 linkers.

Coordination Polymers Constructed from an Adaptable Pyridine-Dicarboxylic Acid Linker: Assembly, Diversity of Structures, and Catalysis.

4,4'-(Pyridine-3,5-diyl)dibenzoic acid (H2pdba) was explored as an adaptable linker for assembling a diversity of new manganese(II), cobalt(II/III), nickel(II), and copper(II) coordination polymers (CPs): [Mn(µ4-pdba)(H2O)]n (1), {[M(µ3-pdba)(phen)]·2H2O}n (M = Co (2), Ni (3)), {[Cu2(µ3-pdba)2(bipy)]·2H2O}n (4), {[Co(µ3-pdba)(bipy)]·2H2O}n (5), [Co2(µ3-pdba)(µ-Hbiim)2(Hbiim)]n (6), and [M(µ4-pdba)(py)]n (M = Co (7), Ni (8)). The CPs were hydrothermally synthesized using metal(II) chloride precursors, H2pdba, and different coligands functioning as crystallization mediators (phen: 1,10-phenanthroline; bipy: 2,2'-bipyridine, H2biim: 2,2'-biimidazole; py: pyridine). Structural networks of 1-8 range from two-dimensional (2D) metal-organic layers (1-3, 5-8) to three-dimensional (3D) metal-organic framework (MOF) (4) and disclose several types of topologies: sql (in 1), hcb (in 2, 3, 5), tfk (in 4), 3,5L66 (in 6), and SP 2-periodic net (6,3)Ia (in 7, 8). Apart from the characterization by standard methods, catalytic potential of the obtained CPs was also screened in the Knoevenagel condensation of benzaldehyde with propanedinitrile to give 2-benzylidenemalononitrile (model reaction). Several reaction parameters were optimized, and the substrate scope was explored, revealing the best catalytic performance for a 3D MOF 4. This catalyst is recyclable and can lead to substituted dinitrile products in up to 99% product yields. The present study widens the use of H2pdba as a still poorly studied linker toward designing novel functional coordination polymers.

Preventive effect of swim bladder hydrolysates on cyclophosphamide-induced ovarian injury in mice.

AIMS: This study aimed to prepare swim bladder hydrolysate (SBH) with Mn  < 4000 Da, and investigate its effects on cyclophosphamide (CTX)-mediated ovarian injury in mice. METHODS: Hydrolysates were prepared by heating extraction, enzymatic hydrolysis and ultrafiltration. Mn and distribution of SBH were analyzed via gel filtration chromatography and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Changes in the mouse oestrus cycle were determined by cytological examination. The number of follicles was examined using histopathology. Enzyme-linked immunosorbent assays (ELISAs) were used to determine the serum sex hormone levels. RESULTS: The Mn of SBH, prepared by heating extraction, enzymatic hydrolysis, ultrafiltration, and from different batches, was below 4000 Da, and the preparation process was stable. Compared with the control group, the low-, middle-, and high-dose SBH treatment groups showed different trends in oestrus duration, serum sex hormone levels, and the number of primordial and secondary follicles. The oestrus cycle duration of the high-dose SBH group was longer than that of the model group. The serum luteinizing hormone, follicle-stimulating hormone, and anti-Müllerian hormone levels in the middle-dose group were the closest to those of control group. The number of primordial and secondary follicles in the medium-dose group was significantly higher than that in the model group and closest to those of control group. CONCLUSION: After heating extraction, trypsin/Flavourzyme hydrolysis and ultrafiltration, a hydrolysate with Mn below 4000 Da could be prepared. We found that a moderate (400 mg/kg) SBH dose resulted in the greatest effect on ovarian injury remission in mice.

A Docosahexaenoic Acid Derivative (N-Benzyl Docosahexaenamide) as a Potential Therapeutic Candidate for Treatment of Ovarian Injury in the Mouse Model.

Commonly used clinical chemotherapy drugs, such as cyclophosphamide (CTX), may cause injury to the ovaries. Hormone therapies can reduce the ovarian injury risk; however, they do not achieve the desired effect and have obvious side effects. Therefore, it is necessary to find a potential therapeutic candidate for ovarian injury after chemotherapy. N-Benzyl docosahexaenamide (NB-DHA) is a docosahexaenoic acid derivative. It was recently identified as the specific macamide with a high degree of unsaturation in maca (Lepidium meyenii). In this study, the purified NB-DHA was administered intragastrically to the mice with CTX-induced ovarian injury at three dose levels. Blood and tissue samples were collected to assess the regulation of NB-DHA on ovarian function. The results indicated that NB-DHA was effective in improving the disorder of estrous cycle, and the CTX+NB-H group can be recovered to normal levels. NB-DHA also significantly increased the number of primordial follicles, especially in the CTX+NB-M and CTX+NB-H groups. Follicle-stimulating hormone and luteinizing hormone levels in all treatment groups and estradiol levels in the CTX+NB-H group returned to normal. mRNA expression of ovarian development-related genes was positive regulated. The proportion of granulosa cell apoptosis decreased significantly, especially in the CTX+NB-H group. The expression of anti-Müllerian hormone and follicle-stimulating hormone receptor significantly increased in ovarian tissues after NB-DHA treatment. NB-DHA may be a promising agent for treating ovarian injury.

Effect of inorganic nitrate supplementation on blood pressure in older adults: A systematic review and meta-analysis.

BACKGROUND: Previous clinical studies have shown controversial results regarding the effect of inorganic nitrate supplementation on blood pressure (BP) in older individuals. We performed this systematic review and meta-analysis to assess the effect of inorganic nitrate on BP in older adults. METHODS: Eligible studies were searched in Cochrane Library, PubMed, Scopus, Web of Science, and Embase. Randomized controlled trials which evaluated the effect of inorganic nitrate consumption on BP in older adults were recruited. The random-effect model was used to calculate the pooled effect sizes. RESULTS: 22 studies were included in this meta-analysis. Overall, inorganic nitrate consumption significantly reduced systolic blood pressure (SBP) by -3.90 mmHg (95% confidence interval: -5.23 to -2.57; P < 0.001) and diastolic blood pressure (DBP) by -2.62 mmHg (95% confidence interval: -3.86 to -1.37; P < 0.005) comparing with the control group. Subgroup analysis showed that the BP was significantly reduced when participants' age≥65, BMI>30, or baseline BP in prehypertension stage. And both SBP and DBP decreased significantly after acute nitrate supplementation of a single dose (<1 day) or more than 1-week. However, participants with hypertension at baseline were not associated with significant changes in both SBP and DBP. Subgroup analysis of measurement methods showed that only the resting BP group showed a significant reduction in SBP and DBP, compared with the 24-h ambulatory BP monitoring (ABPM) group and daily home BP measurement group. CONCLUSION: These results demonstrate that consuming inorganic nitrate can significantly reduce SBP and DBP in older adults, especially in whose age ≥ 65, BMI＞30, or baseline BP in prehypertension stage.

Exercise therapy in patients with constipation: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Exercise therapy has shown significant efficacy as a means of treating various intestinal diseases, but its role in the treatment of constipation is still unclear. The purpose of this study was thus to analyze the effects of exercise on constipation by means of a systematic review and meta-analysis. METHODS: PubMed, Web of Science, EMBASE, Cochrane Library and three Chinese databases [Wanfang Database, Chinese Biomedical Literature (CBM) and China National Knowledge Infrastructure (CNKI)] were searched for relevant studies published through June 2018. Eligible studies were selected in accordance with the PRISMA statement. The main results of interest were changes in gastrointestinal symptoms. RESULTS: A total of nine randomized controlled trials involving 680 participants were included. Eight studies involved aerobic exercise and only one study involved anaerobic exercise. The aerobic exercises included were Qigong, walking and physical movement. The results of this systematic review and meta-analysis indicated that exercise had significant benefits as a means of improving the symptoms of constipation patients [relative risk (RR) = 1.97; 95% CI: 1.19, 3.27; p = .009; I2=91.3%]. Subgroup analyses showed that aerobic exercise (RR = 2.42; 95% CI: 1.34, 4.36; p = .000; I2=88%) similarly had a positive effect on constipation. However, these results were associated with a high risk of bias. CONCLUSION: Our results suggest that exercise may be a feasible and effective treatment option for patients with constipation. However, due to methodological shortcomings, the real effect of this intervention cannot be definitively determined. Researchers should, therefore, design more rigorous studies in order to evaluate the effect of exercise on constipation.

Angiotensin-(1-7) attenuates angiotensin II-induced cardiac hypertrophy via a Sirt3-dependent mechanism.

The objectives of the present study were to investigate the effect of ANG-(1-7) on the development of cardiac hypertrophy and to identify the intracellular mechanism underlying this action of ANG-(1-7). Blood pressure and heart rate were recorded using radiotelemetry before and after chronic subcutaneous infusion of control (PBS), ANG II, ANG-(1-7), or ANG II + ANG-(1-7) for 4 wk in normotensive rats. Chronic administration of ANG-(1-7) did not affect either basal blood pressure or the ANG II-induced elevation in blood pressure. However, ANG-(1-7) significantly attenuated ANG II-induced cardiac hypertrophy and perivascular fibrosis in these rats. These effects of ANG-(1-7) were confirmed in cultured cardiomyocytes, in which ANG-(1-7) significantly attenuated ANG II-induced increases in cell size. This protective effect of ANG-(1-7) was significantly attenuated by pretreatment with A779 (a Mas receptor antagonist) or Mito-TEMPO (a mitochondria-targeting superoxide scavenger) as well as blockade of Sirt3 (a deacetylation-acting protein) by viral vector-mediated overexpression of sirtuin (Sirt)3 short hairpin (sh)RNA. Western blot analysis demonstrated that treatment with ANG-(1-7) dramatically increased Sirt3 expression. In addition, ANG-(1-7) attenuated the ANG II-induced increase in mitochondrial ROS generation, an effect that was abolished by A779 or Sirt3 shRNA. Moreover, ANG-(1-7) increased FoxO3a deacetylation and SOD2 expression, and these effects were blocked by Sirt3 shRNA. In summary, the protective effects of ANG-(1-7) on ANG II-induced cardiac hypertrophy and increased mitochondrial ROS production are mediated by elevated SOD2 expression via stimulation of Sirt3-dependent deacetylation of FoxO3a in cardiomyocytes. Thus, activation of the ANG-(1-7)/Sirt3 signaling pathway could be a novel therapeutic strategy in the management of cardiac hypertrophy and associated complications.NEW & NOTEWORTHY Chronic subcutaneous ANG-(1-7) has no effect on ANG II-induced elevations in blood pressure but significantly attenuates ANG II-induced cardiac hypertrophy and fibrosis by a mitochondrial ROS-dependent mechanism. This protective effect of ANG-(1-7) against the action of ANG II action is mediated by stimulation of sirtuin-3-mediated deacetylation of FoxO3a, which triggers SOD2 expression.

The Construction of Homochiral Lanthanide Quadruple-Stranded Helicates with Multiresponsive Sensing Properties toward Fluoride Anions.

A series of unique homochiral lanthanide tetranuclear quadruple-stranded helicates have been self-assembled controllably by using the intrinsic advantages of chiral bridging ligands, (S)-H2 L and (R)-H2 L, and lanthanide ions with high coordination numbers. The self-assembly process of these chiral helicates not only ensures the structural stability and quadruple-stranded feature of lanthanide cluster in the solid state and solution, but also achieves effective transfer and amplification of the chirality code from the ligand to a higher supramolecular level. Moreover, through using optical rotation, circular dichroism spectra analysis, and luminescence measurements, we demonstrate that these chiral lanthanide helicates could serve as sensitive and multi-responsive sensors to recognize and detect F- anions based on the change of chiral signal and NIR luminescence simultaneously, which represents a meaningful exploration for developing functional lanthanide-based polynuclear clusters.

ACE2/Ang-(1-7)/Mas axis stimulates vascular repair-relevant functions of CD34+ cells.

CD34(+) stem/progenitor cells have been identified as a promising cell population for the autologous cell-based therapies in patients with cardiovascular disease. The counter-regulatory axes of renin angiotensin system, angiotensin converting enzyme (ACE)/Ang II/angiotensin type 1 (AT1) receptor and ACE2/Ang-(1-7)/Mas receptor, play an important role in the cardiovascular repair. This study evaluated the expression and vascular repair-relevant functions of these two pathways in human CD34(+) cells. CD34(+) cells were isolated from peripheral blood mononuclear cells (MNCs), obtained from healthy volunteers. Expression of ACE, ACE2, AT1, and angiotensin type 2 and Mas receptors were determined. Effects of Ang II, Ang-(1-7), Norleu(3)-Ang-(1-7), and ACE2 activators, xanthenone (XNT) and diminazene aceturate (DIZE) on proliferation, migration, and adhesion of CD34(+) cells were evaluated. ACE2 and Mas were relatively highly expressed in CD34(+) cells compared with MNCs. Ang-(1-7) or its analog, Norleu(3)-Ang-(1-7), stimulated proliferation of CD34(+) cells that was associated with decrease in phosphatase and tensin homologue deleted on chromosome 10 levels and was inhibited by triciribin, an AKT inhibitor. Migration of CD34(+) cells was enhanced by Ang-(1-7) or Norleu(3)-Ang-(1-7) that was decreased by a Rho-kinase inhibitor, Y-27632. In the presence of Ang II, XNT or DIZE enhanced proliferation and migration that were blocked by DX-600, an ACE2 inhibitor. Treatment of MNCs with Ang II, before the isolation of CD34(+) cells, attenuated the proliferation and migration to stromal derived factor-1α. This attenuation was reversed by apocynin, an NADPH oxidase inhibitor. Adhesion of MNCs or CD34(+) cells to fibronectin was enhanced by Ang II and was unaffected by Ang-(1-7). This study suggests that ACE2/Ang-(1-7)/Mas pathway stimulates functions of CD34(+) cells that are cardiovascular protective, whereas Ang II attenuates these functions by acting on MNCs. These findings imply that activation of ACE2/Ang-(1-7)/Mas axis is a promising approach for enhancing reparative outcomes of cell-based therapies.

High salt-diet reduces SLC14A1 gene expression in the choroid plexus of Dahl salt sensitive rats.

Elevated Na(+) concentration ([Na(+)]) in the cerebrospinal fluid (CSF) contributes to the development of salt-sensitive hypertension. CSF is formed by the choroid plexus (CP) in cerebral ventricles, and [Na(+)] in CSF is controlled by transporters in CP. Here, we examined the effect of high salt diet on the expression of urea transporters (UTs) in the CP of Dahl S vs Dahl R rats using real time PCR. High salt intake (8%, for 2 weeks) did not alter the mRNA levels of UT-A (encoded by SLC14A2 gene) in the CP of either Dahl S or Dahl R rats. In contrast, the mRNA levels of UT-B (encoded by SLC14A1 gene) were significantly reduced in the CP of Dahl S rats on high salt diet as compared with Dahl R rats or Dahl S rats on normal salt diet. Reduced UT-B expression was associated with increased [Na(+)] in the CSF and elevated mean arterial pressure (MAP) in Dahl S rats treated with high salt diet, as measured by radiotelemetry. High salt diet-induced reduction in UT-B protein expression in the CP of Dahl S rats was confirmed by Western blot. Immunohistochemistry using UT-B specific antibodies demonstrated that UT-B protein was expressed on the epithelial cells in the CP. These data indicate that high salt diet induces elevations in CSF [Na(+)] and in MAP, both of which are associated with reduced UT-B expression in the CP of Dahl S rats, as compared with Dahl R rats. The results suggest that altered UT-B expression in the CP may contribute to an imbalance of water and electrolytes in the CSF of Dahl S rats on high salt diet, thereby leading to alterations in MAP.

Extrarenal phenotypes of the UT-B knockout mouse.

The urea transporter UT-B is expressed in multiple tissues including erythrocytes, kidney, brain, heart, liver, colon, bone marrow, spleen, lung, skeletal muscle, bladder, prostate, and testis in mammals. Phenotype analysis of UT-B-null mice has confirmed that UT-B deletion results in a urea-selective urine-concentrating defect (see Chap. 9 ). The functional significance of UT-B in extrarenal tissues studied in the UT-B-null mouse is discussed in this chapter. UT-B-null mice present depression-like behavior with urea accumulation and nitric oxide reduction in the hippocampus. UT-B deletion causes a cardiac conduction defect, and TNNT2 and ANP expression changes in the aged UT-B-null heart. UT-B also plays a very important role in protecting bladder urothelium from DNA damage and apoptosis by regulating the urea concentration in urothelial cells. UT-B functional deficiency results in urea accumulation in the testis and early maturation of the male reproductive system. These results show that UT-B is an indispensable transporter involved in maintaining physiological functions in different tissues.