Regulations of Citrus Pectin Oligosaccharide on Cholesterol Metabolism: Insights from Integrative Analysis of Gut Microbiota and Metabolites.

(1) Background: Recently, academic studies are demonstrating that the cholesterol-lowering effects of pectin oligosaccharides (POSs) are correlated to intestinal flora. However, the mechanisms of POS on cholesterol metabolisms are limited, and the observations of intestinal flora are lacking integrative analyses. (2) Aim and methods: To reveal the regulatory mechanisms of POS on cholesterol metabolism via an integrative analysis of the gut microbiota, the changes in gut microbiota structure and metabolite composition after POS addition were investigated using Illumina MiSeq sequencing and non-targeted metabolomics through in vitro gut microbiota fermentation. (3) Results: The composition of fecal gut flora was adjusted positively by POS. POS increased the abundances of the cholesterol-related bacterial groups Bacteroidetes, Bifidobacterium and Lactobacillus, while it decreased conditional pathogenic Escherichia coli and Enterococcus, showing good prebiotic activities. POS changed the composition of gut microbiota fermentation metabolites (P24), causing significant changes in 221 species of fermentation metabolites in a non-targeted metabolomics analysis and promoting the production of short-chain fatty acids. The abundances of four types of cholesterol metabolism-related metabolites (adenosine monophosphate, cyclic adenosine monophosphate, guanosine and butyrate) were significantly higher in the P24 group than those in the control group without POS addition. (4) Conclusion: The abovementioned results may explain the hypocholesterolemic effects of POS and promotion effects on cholesterol efflux of P24. These findings indicated that the potential regulatory mechanisms of citrus POS on cholesterol metabolism are modulated by cholesterol-related gut microbiota and specific metabolites.

Brachial-ankle pulse wave velocity increasing with heart rate accelerates.

Pulse wave velocity (PWV) indicates the degree of vascular stiffness. This study aimed to explore the association between heart rate (HR) and brachial-ankle (ba)-PWV in patients with pacemaker implantation. This retrospective observational study included patients who underwent permanent pacemaker implantation at the Second Hospital of Hebei Medical University between December 2018 and December 2021. All patients were pacemaker-dependent, and the ba-PWV values were collected during HR setted from 60 to 100 bpm. A total of 68 patients (34 males, aged 65.97 ± 9.90 years) were included in this study. There were significant difference of ba-PWV and diastolic blood pressure (DBP) among different HR (both P < 0.001). After adjusted systolic blood pressure (SBP), DBP, age, and sex, the generalized estimating equation showed ba-PWV was independently associated with HR, with increased HR showed higher coefficient: 70 bpm: ß = 42.26 (95% CI: 15.34-69.18, P = 0.002), 80 bpm: ß = 84.16 (95% CI: 52.48-115.84, P < 0.001), 90 bpm: ß = 129.27 (95% CI: 52.48-115.84, P < 0.001), and 100 bpm: 186.31 (95% CI: 137.02-235.59, P < 0.001). The results demonstrate that changes in HR may affect the ba-PWV, the ba-PWV values tend to be higher when HR accelerates.

Integrin beta 3-overexpressing mesenchymal stromal cells display enhanced homing and can reduce atherosclerotic plaque.

BACKGROUND: Umbilical cord (UC) mesenchymal stem cell (MSC) transplantation is a potential therapeutic intervention for atherosclerotic vascular disease. Integrin beta 3 (ITGB3) promotes cell migration in several cell types. However, whether ITGB-modified MSCs can migrate to plaque sites in vivo and play an anti-atherosclerotic role remains unclear. AIM: To investigate whether ITGB3-overexpressing MSCs (MSCsITGB3) would exhibit improved homing efficacy in atherosclerosis. METHODS: UC MSCs were isolated and expanded. Lentiviral vectors encoding ITGB3 or green fluorescent protein (GFP) as control were transfected into MSCs. Sixty male apolipoprotein E-/- mice were acquired from Beijing Vital River Lab Animal Technology Co., Ltd and fed with a high-fat diet (HFD) for 12 wk to induce the formation of atherosclerotic lesions. These HFD-fed mice were randomly separated into three clusters. GFP-labeled MSCs (MSCsGFP) or MSCsITGB3 were transplanted into the mice intravenously via the tail vein. Immunofluorescence staining, Oil red O staining, histological analyses, western blotting, enzyme-linked immunosorbent assay, and quantitative real-time polymerase chain reaction were used for the analyses. RESULTS: ITGB3 modified MSCs successfully differentiated into the "osteocyte" and "adipocyte" phenotypes and were characterized by positive expression (> 91.3%) of CD29, CD73, and CD105 and negative expression (< 1.35%) of CD34 and Human Leukocyte Antigen-DR. In a transwell assay, MSCsITGB3 showed significantly faster migration than MSCsGFP. ITGB3 overexpression had no effects on MSC viability, differentiation, and secretion. Immunofluorescence staining revealed that ITGB3 overexpression substantially enhanced the homing of MSCs to plaque sites. Oil red O staining and histological analyses further confirmed the therapeutic effects of MSCsITGB3, significantly reducing the plaque area. Enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction revealed that MSCITGB3 transplantation considerably decreased the inflammatory response in pathological tissues by improving the dynamic equilibrium of pro- and anti-inflammatory cytokines. CONCLUSION: These results showed that ITGB3 overexpression enhanced the MSC homing ability, providing a potential approach for MSC delivery to plaque sites, thereby optimizing their therapeutic effects.

Analysis of Results of Continuous Invasive Arterial Blood Pressure Monitoring in Postoperative Patients.

Objective: In patients with postoperative circulatory instability, the exploration of invasive arterial blood pressure (IABP) monitoring is of great significance because it can provide real-time cardiovascular function information and help medical staff to better assess and manage the patient's circulatory status. To explore the value of IABP monitoring for patients with postoperative circulatory instability in the postanesthesia care unit (PACU). Methods: From January to December 2021, 160 postoperative patients with circulatory instability were randomly divided into a control group and a study group (80 patients in each group). A random number sequence is generated through a random number table, and random numbers are distributed to different patients to achieve random grouping. SPSS was used for data processing and statistical analysis, t test was used for continuous variables, chi-square test was used for count data, and the significance level was P < .05.We compared various parameters, such as systolic blood pressure (SBP), PACU observation time, arterial partial pressure of oxygen (PaO2), total hospitalization time, heart rate (HR), arterial partial pressure of carbon dioxide (PaCO2), re-intubation rate, mean arterial pressure (MAP), adverse events, and blood oxygen saturation (SaO2), between the two groups. Flow cytometry was used to analyze changes in immune lymphocyte subsets in the patient's peripheral blood. Results: During the postoperative observation period, there were no significant differences in SBP, PaCO2, HR, SaO2, MAP, and PaO2 between the two groups (P > .05)The study group showed higher SBP, SaO2, MAP, and PaO2, and lower HR and PaCO2 compared to the control group (P < .05). The study group also had shorter PACU observation time, total hospitalization time, and a lower re-intubation rate compared to the control group (P < .05). There was no significant difference in the overall incidence of adverse events between the two groups (7.50% vs 3.75%) (P > .05). The study group showed significantly higher proportions of lymphocytes, CD3+ T cells, CD3+ CD4+ T cells, and CD3+ CD4+/CD3+ CD8+ ratio compared to the control group (P < .05). This change may reflect the patients with a positive response of the immune system, help to resist disease progress and infection. Conclusion: IABP monitoring can continuously, dynamically and accurately collect arterial blood pressure data of patients with postoperative circulatory instability, contributing to the recovery of immune competence in patients to help formulate the best clinical treatment and intervention plan. The dynamic and accurate arterial blood pressure data collection provided by IABP monitoring contributes not only to immune competence recovery but also to overall patient management and treatment planning.

Effect of long-term nursing intervention on quality of life and social support of patients with coronary heart disease after percutaneous coronary intervention.

OBJECTIVE: To assess the effect of long-term nursing intervention on the quality of life and social support of patients after percutaneous coronary intervention (PCI). METHODS: A randomised controlled trial was designed. A total of 60 patients with coronary heart disease treated with PCI were randomly divided into the control group and the intervention group. The patients in the control group received routine nursing care, while the patients in the intervention group received long-term nursing intervention. The Simplified Quality of Life Scale-Quality of Life Scale, the Coronary Heart Disease Self-Management Scale, and the Social Support Rating Scale were used to collect and analyse the data. RESULTS: After the intervention, the scores for quality of life, social support and self-management in the intervention group were higher than those in the control group, and the differences were statistically significant (p < 0.05). CONCLUSION: Long-term nursing intervention can improve the quality of life and sense of social support of patients with coronary heart disease after PCI.

Effect of C1q/TNF-Related Protein 9 on Coronary Artery Calcification: An Observational Study.

Coronary artery calcification (CAC) increases the risk of acute coronary syndrome. This study examined the correlation between C1q/TNF-related protein 9 (CTRP9) and CAC and explored CTRP9 as a biomarker for prognosis. We divided 275 patients with coronary heart disease into four groups. In order to balance the baseline confounding factors, propensity score matching (PSM) was performed to match CAC patients with non-CAC patients in a 1:1 ratio. Optical coherence tomography (OCT) calcification scoring was performed in 126 patients with CAC. Moreover, 140 patients who underwent OCT were followed-up for 9 months for analysis of the correlation between CTRP9 levels and clinical prognosis. Based on OCT calcification scores, 126 patients with CAC were divided into the 0-2 and 3-4 groups. Plasma CTRP9 levels were significantly lower in the type 2 diabetes mellitus (T2DM), CAC and CAC with T2DM groups than in the control group. CTRP9 played roles as a protective factor and potential predictor in CAC severity. The AUC of the OCT calcification score 3-4 group predicted by the plasma CTRP9 level was 0.766. During the follow-up period, the cumulative event-free survival rate was significantly lower in the low-level CTRP9 (L-CTRP9) group than in the high-level (H-CTRP9) group, and the incidence of major endpoint events was significantly higher in the L-CTRP9 group than in the H-CTRP9 group. CTRP9 can be a valuable biomarker for CAC occurrence and severity and can predict patients' clinical prognosis.

Urine N-terminal pro-B-type natriuretic peptide and plasma proenkephalin are promising biomarkers for early diagnosis of cardiorenal syndrome type 1 in acute decompensated heart failure: a prospective, double-center, observational study in real-world.

BACKGROUND: Patients with acute decompensated heart failure (ADHF) show cardiorenal syndrome type 1 (CRS-1) are more likely to have a poor outcome. However, the current criteria often lead to delayed CRS-1 diagnosis. Therefore, we evaluated the predictive value of plasma proenkephalin (pPENK) and urine NT-proBNP (uNT-proBNP) for early diagnosis of CRS-1 and vulnerable-phase prognosis in ADHF patients. METHODS: The plasma NT-proBNP (pNT-proBNP), pPENK, and uNT-proBNP were measured in 121 ADHF patients on admission. The plasma neutrophil gelatinase-associated lipocalin (pNGAL) was chosen as the reference. Logistic regression was used to determine the predictors of CRS-1. The area under the receiver operating curves (ROCs) was calculated to assess the early diagnostic value of pNGAL, pPENK, and uNT-proBNP/uCr for CRS-1. To evaluate the prognostic risk of factors for the 90-d outcomes of all ADHF patients, the Cox regression was performed and the cumulative risk curve was plotted. RESULTS: We found that pPENK [OR 1.093 (95% CI 1.022-1.169), p = 0.010; AUROC = 0.899 (95% CI 0.831-0.946)] and uNT-proBNP/uCr ratio [OR 1.015 (95% CI 1.003-1.028), p = 0.012; AUROC = 0.934 (95% CI 0.874-0.971)] could independently predict the occurrence of CRS-1 in hospitalized patients with ADHF. The pPENK [HR 1.014 (95% CI 1.000-1.042), p = 0.044] and uNT-proBNP/uCr ration [HR 0.998 (95% CI 0.997-1.000), p = 0.045] were also independent predictors of the risk of HF readmission or all-cause death 90 d after discharge in ADHF patients. CONCLUSIONS: The newly found pPENK and noninvasive test of uNT-proBNP/uCr ratio (pg/nmol) on admission may be two promising novel predictive biomarkers for early diagnosis of CRS-1 occurrence and vulnerable-phase outcomes in ADHF patients.

DLEU2 modulates proliferation, migration and invasion of platelet-derived growth factor-BB (PDGF-BB)-induced vascular smooth muscle cells (VSMCs) via miR-212-5p/YWHAZ axis.

DLEU2 has been proved to act as an oncogene in a variety of cancers, but its role in cardiovascular diseases is dearth of research. Thus, this study mainly discussed the effect and possible mechanism of DLEU2 on platelet-derived growth factor-BB (PDGF-BB)-triggered vascular smooth muscle cell (VSMC) injury. To obtain authentic results, the expressions of target genes in atherosclerosis serum were determined by reverse transcription quantitative PCR (RT-qPCR) and the protein levels were evaluated by Western blot. PDGF-BB was used to simply simulate the biological characteristics of VSMCs in vitro. The effect of DLEU2 on the biological behavior of PDGF-BB-induced VSMCs was analyzed by gain- and loss-of-function assays. Bioinformatics analysis, dual luciferase reporter assay, and Pearson correlation method were conducted to determine the relationship between target genes. The role of DLEU2/miR-212-5p/ YWHAZ (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta) axis in PDGF-BB-induced VSMCs was verified by rescue experiments. As a result, DLEU2 and YWHAZ were up-regulated, and miR-212-5p was down-regulated in atherosclerosis serum. Overexpressed DLEU2 facilitated the biological behavior of PDGF-BB-induced VSMCs, whilst siDLEU2 did the opposite. Moreover, overexpressed DLEU2 promoted proliferating cell nuclear antigen (PCNA) expression but repressed α-smooth muscle actin (α-SMA) and Calponin expressions, while it also enhanced YWHAZ expression via suppressing miR-212-5p. MiR-212-5p mimic and siYWHAZ reversed the effects of overexpressed DLEU2 on above biological characteristics and protein expressions in PDGF-BB-induced VSMCs, while the regulatory effect of miR-212-5p mimic was partially offset by overexpressed YWHAZ. Collectively, DLEU2 modulates PDGF-BB-induced VSMC injury via miR-212-5p/YWHAZ axis in atherosclerosis.

Comparative Evaluation on the Bioaccessibility of Citrus Fruit Carotenoids In Vitro Based on Different Intake Patterns.

The intake pattern has a great impact on the bioaccessibility of carotenoids from citrus fruit. Here, we compared the bioaccessibility of carotenoids from fresh citrus fruit (FC), fresh citrus juice (FCJ), and not-from-concentrate citrus juice (NCJ) and analyzed the influencing factors. The results demonstrated that particle size, viscosity, and some active components of the samples during digestion are potential factors affecting the bioaccessibility of carotenoids. The total carotenoid bioaccessibility of NCJ (31.45 ± 2.58%) was significantly higher than that of FC (8.11 ± 0.43%) and FCJ (12.43 ± 0.49%). This work demonstrates that NCJ is an appropriate intake pattern to improve the bioaccessibility of carotenoids from citrus fruit. The findings also suggest that adjustment of food intake patterns is an effective way to improve the digestion and absorption of nutrients.

Physical optimization of cell proliferation and differentiation using spinner flask and microcarriers.

The traditional breeding industry has been increasingly saturated and caused environmental pollution, disease transmission, excessive resource use, and methane emission; however, it still cannot meet the needs of the growing population. To explore other alternatives, researchers focused on cell agriculture and cell-based meat, especially large-scale cell culture. As a prerequisite for production, large-scale culture technology has become an important bottleneck restricting cell-based meat industrialization. In this study, the single-factor variable method was adopted to examine the influence of Cytodex1 microcarrier pretreatment, spinner flask reaction vessel, cell culture medium, serum and cell incubation, and other influencing factors on large-scale cell cultures to identify the optimization parameters suitable for 3D culture environment. Collagen and 3D culture were also prospectively explored to promote myogenesis and cultivate tissue-like muscle fibers that contract spontaneously. This research lays a theoretical foundation and an exploratory practice for large-scale cell cultures and provides a study reference for the microenvironment of myoblast culture in vitro, a feasible direction for the cell therapy of muscular dystrophy, and prerequisites for the industrialized manufacturing of cell-based meat. Graphical summary: Research on large-scale myoblast culture using spinner flasks and microcarriers. For cell culture, the microcarriers were pretreated with UV and collagen. Cell seeding condition, spinner flask speed, resting time, and spinner flask culture microenvironment were then optimized. Finally, two culture systems were prepared: a culture system based on large-scale cell expansion and a culture system for myogenesis promotion and differentiation.

Assessing serum levels of SM22α as a new biomarker for patients with aortic aneurysm/dissection.

BACKGROUND: Aortic aneurysm/dissection (AAD) is now encountered more often because of the increasing prevalence of atherosclerosis and hypertension in the population. Despite many therapeutic improvements, in particular timely and successful surgery, in-hospital mortality rates are still higher. Timely identification of patients at high risk will help improve the overall prognosis of AAD. Since early clinical and radiological signs are nonspecific, there is an urgent need for accurate biomarkers. Smooth muscle 22α (SM22α) is a potential marker for AAD because of its abundant expression in vascular smooth muscle, which is involved in development of AAD. METHODS: We prepared three different mouse models, including abdominal aortic aneurysm, neointimal hyperplasia and atherosclerosis. SM22α levels were assessed in serum and vascular tissue of the mice. Next, the relationships between serum SM22α level and vascular lesion were studied in mice. Finally, serum from 41 patients with AAD, 107 carotid artery stenosis (CAS) patients and 40 healthy volunteers were tested for SM22α. Serum levels of SM22α were measured using an enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared with the controls, serum SM22α levels were reduced in the models of aortic aneurysm, neointimal formation and atherosclerosis, and elevated in mice with ruptured aneurysm. Serum SM22α level was negatively correlated with apoptosis rate of vascular smooth muscle cells (VSMC), ratio of intima/ media (I/M) area and plaque size. Patients with AAD had significantly higher serum SM22α levels than patients with only CAS, or normal controls. CONCLUSION: Serum SM22α could be a potential predictive marker for AAD, and regulation of VSMC is a possible mechanism for the effects of SM22α.

Interrupted sleep by ambulatory blood pressure monitoring does not affect blood pressure.

BACKGROUND: For the past 20 years, many hypertension guidelines have strongly recommended the practical use of ambulatory blood pressure monitoring (ABPM) to the diagnosis and management of hypertension. However, whether different sleep conditions during ABPM will affect blood pressure (BP) fluctuations and lead to inaccurate measurement results is a concern of clinicians. METHOD: This was a prospective cohort study in the real-world setting. The participants were recruited between June 2018 and June 2019 in Hebei Province, China. There are three types of sleep during ABPM: undisturbed sleep, disturbed sleep and severely disturbed sleep. The people were divided into three groups according to their sleep types during ABPM. The primary outcome is 24-h mean BP, circadian rhythm of BP and variation coefficient of 24-h BP. Comparisons between groups are tested by Kruskal-Wallis H test. RESULTS: In total 1154 people completed the study. There was no significant difference in 24-h mean BP and circadian rhythm of BP among the three groups. There are statistically significant differences among the three groups in the variation coefficient of 24-h BP for the general population and noninsomnia population. There was no significant difference in mean BP, circadian rhythm of BP and variation coefficient of BP among the three groups for the insomnia people. CONCLUSION: Regardless of the insomniac or noninsomniac population, sleep conditions during ABPM do not affect BP value and BP rhythm. For noninsomniac people, the sleep situation during ABPM may affect the BP variation coefficient.

JMJD5 attenuates oxygen-glucose deprivation and reperfusion-induced injury in cardiomyocytes through regulation of HIF-1α-BNIP3.

Proteins in Jumonji family function as histone demethylases and participate in cardiac development. Jumonji domain containing 5 (JMJD5) is responsible for the embryonic development through removing methyl moieties from H3K36me2 histone, and has pro-proliferative effect on heart and eye development. However, the protective role of JMJD5 against oxygen-glucose deprivation and reperfusion (OGD/R)-induced injury in cardiomyocytes has not been fully understood. Firstly, myocardial ischemia/reperfusion (I/R) rat model was established by ligation of left coronary artery. OGD/R was performed in non-transfected H9C2 or H9C2 transfected with pcDNA-JMJD5 plasmid to induce cell cytotoxicity. Data from qRT-PCR and western blot showed that JMJD5 was reduced in the heart tissues of myocardial I/R rat model and OGD/R-induced H9C2. Secondly, JMJD5 over-expression attenuated OGD/R-induced decrease in cell viability and increase in lactate dehydrogenase secretion and cell apoptosis in H9C2. Mitophagy was promoted by pcDNA-mediated over-expression of JMJD5 with enhanced protein expression of LC3-I, LC3-II, Atg5, and Beclin 1. Thirdly, knockdown of JMJD5 aggravated OGD/R-induced decrease in hypoxia-inducible factor-1α (HIF-1α), whereas JMJD5 over-expression enhanced BNIP3 (Bcl-2/adenovirus E1B 19-kDa interacting protein) through upregulation of HIF-1α. Lastly, BNIP3 silencing promoted cell apoptosis, suppressed mitophagy, and attenuated the protective effects of JMJD5 over-expression against OGD/R-induced injury in H9C2. In conclusion, JMJD5 exerted protective effects against OGD/R-induced injury in cardiomyocytes through upregulation of HIF-1α-BNIP3.

CTRP3 is a coronary artery calcification biomarker and protects against vascular calcification by inhibiting ß-catenin nuclear translocation to prevent vascular smooth muscle cell osteogenic differentiation.

BACKGROUND: Coronary artery calcification (CAC) is an important risk factor for cardiovascular events and has been shown to be correlated with serum adiponectin levels. However, it remains unknown whether C1 tumor necrosis factor-related protein 3 (CTRP3) (homologous to adiponectin) is associated with CAC, and whether CTRP3 affects the osteoblastic differentiation of vascular smooth muscle cells. Here, we analyzed the association between CTRP3 expression and CAC. METHODS: A case-control study was conducted involving 119 patients with coronary heart disease to identify the predictive value of CTRP3 for CAC. Additionally, mouse aortic smooth muscle cells transfected for ß-catenin overexpression were subjected to treatment with CTRP3 and the ß-catenin inhibitor JW74. The calcium content in smooth muscle cells was determined. Western blotting was performed to measure the expression levels of different osteoblastogenic proteins in vascular smooth muscle cells obtained from different treatment groups. RESULTS: The serum CTRP3 levels were significantly lower in patients with CAC than in those without CAC, and even lower in patients with both CAC and diabetes mellitus. CTRP3 played roles as a protective factor and potential predictor in CAC. CTRP3 inhibited the osteogenic differentiation of vascular smooth muscle cells induced under high glucose and lipid conditions by inhibiting the nuclear translocation of ß-catenin. CONCLUSIONS: CTRP3 may serve as a valuable screening biomarker and a novel therapeutic target in CAC, particularly in diabetes patients.

Performance of bone tracer for diagnosis and differentiation of transthyretin cardiac amyloidosis: a systematic review and meta-analysis.

PURPOSE: Bone tracers have been validated for many years in detecting transthyretin cardiac amyloidosis (TTR-CA). However, several new studies suggest conflicting results. Our study aimed to systematically evaluate the accuracy of bone radiotracers for diagnosis and differentiation of TTR-CA via a systematic review and meta-analysis. METHODS: We retrieved articles assessing the performance of bone tracer in diagnosing and differentiating TTR-CA from PubMed, the Cochrane Library, ScienceDirect, and DOAJ databases, dating up to 10 July 2020. The meta-analysis was conducted through Stata 16 software, and the risk of bias for the included studies was assessed by the QUADAS-2 tool. Moreover, we made a comprehensive review. RESULTS: Fourteen articles were included in the systematic review, and 9 in the meta-analysis. The pooled sensitivity was 0.97 (95% confidence interval [95% CI] 0.85-0.99) with heterogeneity (I2=73.5, 95% CI 55.6-91.2), and the specificity was 0.92 (95% CI 0.82-0.96) with heterogeneity (I2=42.0, 95% CI 0.0-86.9). The pooled positive and negative likelihood ratios were 11.49 (95% CI 5.07-26.0) and 0.03 (95% CI 0.01-0.18), respectively. The diagnostic odds ratio was 341 (95% CI 53-2194), and the area under the receiver operating characteristic curve was 0.96 (95% CI 0.94-0.97). CONCLUSION: The findings evidence that the bone radiotracer is a valuable noninvasive approach that provides high accuracy for diagnosing TTR-CA and plays a modest role in differentiating TTR-CA from immunoglobulin amyloid light-chain cardiac amyloidosis. 99mTc-HMDP may be more accurate than 99mTc-PYP, 99mTc-DPD, and 18F-NaF in the TTR-CA detecting process, and 18F-NaF is a promising bone tracer to diagnose and differentiate TTR-CA.

Characterization of Citrus Pectin Oligosaccharides and Their Microbial Metabolites as Modulators of Immunometabolism on Macrophages.

We characterized the structure of prepared citrus pectin oligosaccharides (POS) and investigated the immunometabolism-modulating effects of POS and their microbial metabolites on human macrophages. Both POS and metabolites activated immune responses and exhibited anti-inflammatory properties in the presence of lipopolysaccharide (LPS) via regulating expressions of inflammatory cytokines and nuclear factor-kappa B. Cholesterol efflux was also facilitated via increased gene expressions of the liver X receptor-α-adenosine triphosphate-binding cassette transporter (ABC) A1/ABCG1 pathway and suppressed cholesterol synthesis via suppressing expressions of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Microbial degradation prevented POS from attenuating palmitoyl-3-cysteine-serine-lysine-4-induced inflammation and promoting M2 polarization, but it is capable of inhibiting cholesterol uptake-related genes CD36 and SR-A. These findings indicate that immunometabolism-modulating effects of POS are not solely microbiota-dependent effects. Both POS and their microbial metabolites are potential immunometabolism modulators via different mechanisms.

PCAT-1 facilitates breast cancer progression via binding to RACK1 and enhancing oxygen-independent stability of HIF-1α.

Hypoxia induces a series of cellular adaptive responses that enable promotion of inflammation and cancer development. Hypoxia-inducible factor-1α (HIF-1α) is involved in the hypoxia response and cancer promotion, and it accumulates in hypoxia and is degraded under normoxic conditions. Here we identify prostate cancer associated transcript-1 (PCAT-1) as a hypoxia-inducible long non-coding RNA (lncRNA) that regulates HIF-1α stability, crucial for cancer progression. Extensive analyses of clinical data indicate that PCAT-1 is elevated in breast cancer patients and is associated with pathological grade, tumor size, and poor clinical outcomes. Through gain- and loss-of-function experiments, we find that PCAT-1 promotes hypoxia-associated breast cancer progression including growth, migration, invasion, colony formation, and metabolic regulation. Mechanistically, PCAT-1 directly interacts with the receptor of activated protein C kinase-1 (RACK1) protein and prevents RACK1 from binding to HIF-1α, thus protecting HIF-1α from RACK1-induced oxygen-independent degradation. These findings provide new insight into lncRNA-mediated mechanisms for HIF-1α stability and suggest a novel role of PCAT-1 as a potential therapeutic target for breast cancer.

The Effects of Renal Nerve Denervation on Blood Pressure and Target Organs in Different Hypertensive Rat Models.

BACKGROUND: Hypertension contributes to the progression of cardiac remodeling and renal damage. In turn, renal sympathetic hyperactivation showed elevated sympathetic nervous system activity and led to blood pressure increase in certain patients. The purpose of this study was to observe the effect of renal nerve denervation on blood pressure and target organ changes in two hypertensive rat models. METHODS: Hypertensive rats were randomly divided into a renal denervation (RDN) group and sham operation group. Wistar-Kyoto (WKY) rats of the same age were set as the baseline control group. In the secondary hypertension model, SD rats were randomly divided into five groups. Blood pressure and bodyweight were measured every week until they were euthanized. RESULTS: The two rat models underwent RDN at key timepoints. At these timepoints, the hearts and kidneys were collected for norepinephrine and angiotensin II measurements and histological analysis. CONCLUSION: RDN performed before development of hypertension showed a significant antihypertensive effect on the secondary hypertension model.

Analysis of factors affecting students going to school toilets in a rural primary school in China.

BACKGROUND: Several factors may affect students going to school toilets, but a few studies have analyzed the reasons for students using toilets. This study aimed to use a structural equation model to understand the factors that impacted children's toilet behavior. METHODS: This study was performed in 12 rural nonboarding primary schools (6 schools in the northern and 6 schools in the southern regions of China). All students of the third and sixth grades (761 students) were examined. A questionnaire on students' toilet behavior was used. The questionnaire included 33 perceptual items based on 5 factors: toilet facilities, cleanliness, hygiene practices, peer relationship, and experience. The questionnaire also covered the frequency of voiding and defecating by themselves. The exploratory factor analysis, confirmatory factor analysis, and pathway analysis were used to analyze the causes of students' toilet behavior. RESULTS: A statistically significant correlation coefficient of 0.300 indicated that cleanliness impacted the toilet frequency of students. The visual experience of the overall cleanliness of the toilet had the most significant impact on students' toilet behavior (path coefficient, 0.81). Washing facilities and convenient handwashing had the least impact on toilet use (path coefficient, 0.52). CONCLUSION: Cleanliness was the primary consideration for students' toilet use on campus. The visual experience of the overall cleanliness of toilets had the most significant impact when students used toilets. No pre-survey was conducted to test the reliability and validity of the questionnaire. Using self-reported data might be associated with potential recall errors.