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1.
Phytomedicine ; 80: 153372, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33113505

RESUMO

BACKGROUND: Feiyangchangweiyan capsule (FYC) is a traditional Chinese medicine formulation used in the clinical treatment of acute and chronic gastroenteritis and bacterial dysentery. However, the effect of FYC on ulcerative colitis (UC) and the mechanism thereof remains unknown. PURPOSE: To investigate the protective effect of FYC on UC mice induced by dextran sulfate sodium and illustrate the potential mechanism of this effect. METHODS: Here, we established a model of UC mice by dextran sulfate sodium and administered with FYC. The disease activity index (DAI), colon length, myeloperoxidase (MPO) content in serum, pathological structure and ultrastructural changes, and inflammatory cell infiltration of colon tissue were evaluated. Transcriptome and 16S rDNA sequencing were employed to illuminate the mechanism of FYC in the protection of UC mice. RESULTS: FYC significantly alleviates the pathological damage and the infiltration of inflammatory cells in colon tissue of dextran sulfate sodium induced UC mice, rescues shortened colon length, reduces DAI score, MPO content in serum, and pro-inflammatory factors including IL-1ß, IL-6, CCL11, MCP-1 and MIP-2, and increases anti-inflammatory factors such as IL-10. Transcriptomics revealed that Oncostatin M (OSM) and its receptor (OSMR) are the critical pathway for UC treatment by FYC. OSM and OSMR increased in UC mice compared to control mice, and decreased with FYC, which was verified via measurement of OSM and OSMR mRNA and protein levels. Furthermore, we observed that FYC modulates intestinal microbiome composition (e.g., the proportion of Barnesiella/Proteobacteria) by affecting the inflammatory factors. CONCLUSION: FYC exerts an effect on UC by inhibiting the OSM/OSMR pathway and regulating inflammatory factors to improve the intestinal flora.

2.
Biomaterials ; 264: 120451, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33069133

RESUMO

Photothermal therapy (PTT) has been widely used in cancer treatment in recent years. However, it is difficult to completely eliminate tumors by single PTT, and the effects of single dose of PTT frequency on the therapeutic outcome of PTT and the multiple PTT-induced immune response in cancer therapy also remain unclear. Here, water-soluble Ag2S nanoparticles (NPs) with optimal particle size (~15 nm) were synthesized and used as the PTT agents. The in vitro and in vivo results demonstrated that Ag2S NPs had good photothermal conversion in response to the irradiation of an 808 nm laser, and the results indicated that the NPs have potential as contrast agents for photoacoustic imaging as well as good biocompatibility. The in vivo results further revealed that the frequency of the Ag2S NP-mediated PTT affected the cancer therapeutic outcome. The increase of frequency efficiently reduced the primary tumor recurrence and alleviated metastasis. The present study suggested that the mechanism involves multiple PTT cycles inhibiting the proliferation of primary tumor cells and stimulating the systematic immune response in the mouse breast cancer model. Therefore, frequency optimization in photothermal ablation may provide a promising strategy to enhance the therapeutic outcome in cancer therapy.

3.
Biomater Sci ; 8(23): 6611-6624, 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33231577

RESUMO

The tendon-to-bone healing after trauma is usually slow and weak, and the repair site is easily disrupted during early mobilization exercise. bFGF and VEGFA gene therapy may hold promise in augmenting the tendon-to-bone healing process through enhancing cell proliferation and angiogenesis. This study is conducted to determine the effects of nanoparticle-mediated co-delivery of bFGF and VEGFA genes to the tendon-to-bone repair interface on the healing strength and biological responses in a chicken model. The PLGA nanoparticle/pEGFP-bFGF + pEGFP-VEGFA plasmid complexes were prepared and were characterized in vitro and in vivo. The nanoparticle/plasmid complexes can effectively transfer bFGF and VEGFA genes to the tendon-to-bone interface. Nanoparticle-mediated co-delivery of bFGF and VEGFA genes significantly improved the tendon-to-bone healing in terms of healing strengths and histology in a chicken flexor tendon repair model. Our results suggest a new biological approach to accelerate the tendon-to-bone healing.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33197036

RESUMO

Maternal hyperglycemia potentially inhibits the development of the fetal heart by suppressing cardiomyocyte proliferation and promoting apoptosis. Different studies have indicated that miRNAs are key regulators of cardiomyocyte proliferation, differentiation, and apoptosis and play a protective role in a variety of cardiovascular diseases. However, the biological function of miRNA-23a in hyperglycemia-related cardiomyocyte injury is not fully understood. The present study investigated the effect of miRNA-23a-3p on cell proliferation and apoptosis in a myocardial injury model induced by high glucose. H9c2 cardiomyocytes were exposed to high glucose to establish an in vitro myocardial injury model and then transfected with miRNA-23a-3p mimics. After miRNA-23a-3p transfection, lens-free microscopy was used to dynamically monitor cell numbers and confluence and calculate the cell cycle duration. CCK-8 and EdU incorporation assays were performed to detect cell proliferation. Flow cytometry was used to measured cell apoptosis. Upregulation of miRNA-23a-3p significantly alleviated high glucose-induced cell apoptosis and cell proliferation inhibition (p < 0.01 and p < 0.0001, respectively). The cell cycle of the miRNA-23a-3p mimics group was significantly shorter than that of the negative control group (p < 0.01). The expression of cell cycle-activating and apoptosis inhibition-associated factors Ccna2, Ccne1, and Bcl-2 was downregulated by high glucose and upregulated by miRNA-23a-3p overexpression in high glucose-injured H9c2 cells. miRNA-23a-3p mimics transfection before high glucose treatment had a significantly greater benefit than transfection after high glucose treatment (p < 0.0001), and the rescue effect of miRNA-23a-3p increased as the concentration increased. This study suggests that miRNA-23a-3p exerted a dose- and time-dependent protective effect on high glucose-induced H9c2 cardiomyocyte injury.

5.
Genome Biol ; 21(1): 269, 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33143730

RESUMO

BACKGROUND: Long noncoding enhancer RNAs (lnc-eRNAs) are a subset of stable eRNAs identified from annotated lncRNAs. They might act as enhancer activity-related therapeutic targets in cancer. However, the underlying mechanism of epigenetic activation and their function in cancer initiation and progression remain largely unknown. RESULTS: We identify a set of lncRNAs as lnc-eRNAs according to the epigenetic signatures of enhancers. We show that these lnc-eRNAs are broadly activated in MLL-rearranged leukemia (MLL leukemia), an aggressive leukemia caused by a chromosomal translocation, through a mechanism by which the HOXA cluster initiates enhancer activity, and the epigenetic reader BRD4 cooperates with the coregulator MLL fusion oncoprotein to induce transcriptional activation. To demonstrate the functional roles of lnc-eRNAs, two newly identified lnc-eRNAs transcribed from the SEELA eRNA cluster (SEELA), SEELA1 and SEELA2, are chosen for further studies. The results show that SEELA mediated cis-activated transcription of the nearby oncogene Serine incorporate 2 (SERINC2) by directly binding to the K31 amino acid (aa) of histone H4. Chromatin-bound SEELA strengthens the interaction between chromatin and histone modifiers to promote histone recognition and oncogene transcription. Further studies show that the SEELA-SERINC2 axis regulated aspects of cancer metabolism, such as sphingolipid synthesis, to affect leukemia progression. CONCLUSIONS: This study shows that lnc-eRNAs are epigenetically activated by cancer-initiating oncoproteins and uncovers a cis-activating mechanism of oncogene transcription control based on lnc-eRNA-mediated epigenetic regulation of enhancer activity, providing insights into the critical roles of lnc-eRNAs in cancer initiation and progression.

6.
Org Lett ; 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33170722

RESUMO

The first Lewis acid and chiral Brønsted acid cooperatively catalyzed asymmetric cascade ring opening/aza-Piancatelli rearrangement reaction of furyl-substituted donor-acceptor cyclopropanes is achieved, enabling the construction of functionalized aminocyclopentenones bearing α-quaternary carbon stereocenters in high yields with excellent enantio- and diastereoselectivities under remarkably low catalyst loading of 0.2-1.2 mol %.

7.
Biomark Med ; 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33174759

RESUMO

Aim: To evaluate the clinical value of plasma D-dimer/fibrinogen ratio (DFR) in patients hospitalized for heart failure (HF). Methods: Clinical data of 235 patients were retrospectively analyzed. Kaplan-Meier method and Cox regression analysis were used to identify significant prognosticators. Results: The Kaplan-Meier analysis showed that a higher DFR level was significantly associated with an increase in the end point outcomes, including HF readmission, thrombotic events and death (log-rank test: p < 0.001). The multivariate Cox regression analysis showed that the high tertile of DFR was significantly associated with the study end points (HR: 2.18; 95% CI: 1.31-3.62; p = 0.003), compared with the low tertile. Conclusion: DFR is a reliable prognostic indicator for patients hospitalized for HF.

8.
Physiol Behav ; : 113266, 2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33246000

RESUMO

Temperature is known to impact taste perception, but its reported effect on sweet taste perception in humans is inconsistent. Here, we assess whether thermal taste phenotype alters the temperature modulation of the brains' response to sweet samples and sweetness perception. Participants (n = 24 balanced for thermal tasters (TT) and thermal non-tasters (TnT), 25 ± 7 years (mean ± SD), 10 males) underwent a thermal taste phenotyping session to study responses to cooling and warming of the tongue using a thermode. In a separate session, functional Magnetic Resonance Images (fMRI) were collected during sweet samples (87 mM sucrose) delivery at two temperatures ('cold' (5 ± 2°C) and 'ambient' (20 ± 2°C)) and the perceived sweetness intensity rated. In the phenotyping session, TTs had heightened perceptual temperature sensitivity to cooling and warming of the tongue using a thermode compared to TnTs. Although there was no significant effect during the fMRI session, the fMRI response to the 'cold sweet' sample across all participants was significantly increased in anterior insula/frontal operculum and mid-insula compared to the 'ambient sweet' sample, likely to reflect the perceptual difference to temperature rather than taste perception. TTs showed significantly increased fMRI activation patterns compared with TnTs and an interaction effect between thermal taster status and sample temperature, with TTs showing selectively greater cortical responses to 'cold sweet' samples compared to TnTs in somatosensory regions (SI and SII). The increase in cortical activation in somatosensory cortices to the 'cold sweet' stimulus correlated with perceptual ratings of temperature sensitivity to the thermode. The results highlight the importance of investigating the effects of thermal taster phenotype across a range of temperatures representing the reality of consumer consumption to beverages.

9.
J Pharm Sci ; 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33166581

RESUMO

Prostate cancer is the most common malignant tumor with bone metastasis, and there is still no ideal treatment for bone metastasis of prostate cancer. In this study, a pH and GSH dual sensitive calcium phosphate-polymer hybrid nanoparticle (DTX@Cap/HP) was prepared to co-deliver zoledronate (ZOL) and docetaxel (DTX) to treat bone metastasis of prostate cancer. DTX@Cap/HP exhibited high bone binding affinity and released more DTX and ZOL in acidic and high GSH concentration environment. A large amount of DTX@Cap/HP was uptaken by PC-3 cell in acidic medium than that in neutral medium. DTX@Cap/HP obviously reduced PC-3 cell proliferation and bone lesion in in-vitro 3D model of bone metastases of prostate cancer. Besides, DTX@Cap/HP also exhibited stronger anti bone metastases of prostate cancer activity in vivo as compared with the same dose of DTX + ZOL, which resulted from the co-delivery of DTX and ZOL to bone metastases of prostate cancer by DTX@Cap/HP and the synergistic effects of DTX and ZOL. DTX@Cap/HP has great potential in the treatment of bone metastases of prostate cancer.

10.
Cell Tissue Res ; 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33245416

RESUMO

Vascular smooth muscle cell (VSMC) phenotypic switching is a hallmark of vascular remodeling that contributes to atherosclerotic diseases. MicroRNA 4463 (miR-4463) has been implicated in the development of arteriosclerosis obliterans, whereas the underlying mechanisms in VSMCs have not been fully addressed. In this study, we assessed whether miR-4463 is involved in the phenotypic switching process in VSMCs. Oxidized low-density lipoprotein (Ox-LDL, 50 mg/L) was used to simulate the oxidative stress condition, and miR-4463 expression in VSMCs was detected by a quantitative polymerase chain reaction. To determine the effect of Ox-LDL-mediated regulation of miR-4463 on the phenotypic switching of VSMCs, cell counting kit-8, cell migration assays, and cytoskeleton test were performed. After using specific antagonists of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK), the relationship between miR-4463 and its downstream signaling proteins was explored. Ox-LDL induced oxidative stress to promote VSMC transformation from contraction to secretion, which clearly decreased the level of miR-4463. Then, downregulated miR-4463 enhanced the migration and phenotypic transformation of VSMCs and activated the phosphorylation of JNK and ERK; these effects were increased after Ox-LDL induction. As expected, inhibiting the two signaling proteins blocked the effect of the miR-4463 inhibitor combined with Ox-LDL. In addition, inhibition of miR-4463 led to the upregulation of basic fibroblast growth factor (bFGF) expression. The results of this study demonstrate that miR-4463 is a novel regulator of VSMC function in hypoxic conditions and modulates VSMC phenotypic switching via the JNK and ERK signaling pathways; bFGF may be the target gene of miR-4463.

11.
Theranostics ; 10(26): 12144-12157, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33204334

RESUMO

Rationale: Capillaries are composed of endothelial cells and the surrounding mural cells, pericytes. Microvascular repair after injury involves not only the proliferation of endothelial cells but also pericyte-based vessel stabilization. Exogenous bone marrow derived-putative endothelial progenitor cells (b-pEPCs) have the potential for vascular repair; however, their effect on vascular structure stabilization and pericyte-related pathobiological outcomes in the injured kidney has not been fully examined. Methods: We applied ischemia-reperfusion (IR) to induce renal vascular injury and renal fibrosis in mice. Platelet-derived growth factor receptor ß (PDGFR-ß)-DTR-positive mice were generated to deplete pericytes, and exogenous b-pEPCs and the PDGFR-ß ligand, PDGF chain B (PDGF-BB), were employed to explore the relationship among b-pEPCs, pericytes, vascular repair, and early renal fibrosis. Results: Administration of b-pEPCs reduced IR-induced pericyte-endothelial detachment, pericyte proliferation, and myofibroblast transition via a paracrine mode, which preserved not only vascular stabilization but also ameliorated IR-initiated renal fibrosis. PDGF-BB upregulated the expression of PDGFR-ß, exacerbated vascular abnormality, and pericyte-myofibroblast transition, which were ameliorated by b-pEPCs administration. The exogenous b-pEPCs and their culture medium (CM) induced vascular injury protection, and renal fibrosis was blocked by selective deletion of pericytes. Conclusion: Exogenous b-pEPCs directly protect against IR-induced vascular injury and prevent renal fibrosis by inhibiting the activation of PDGFR-ß-positive pericytes.

12.
Artigo em Inglês | MEDLINE | ID: mdl-33165141

RESUMO

Hydrogen sulfide (H2S), generally known as a new gas signal molecule after nitric oxide (NO) and carbon monoxide (CO), in the last few decades has been found as an important endogenous gasotransmitter, playing a significant role in the cardiovascular system both pathologically and physiologically. In recent years, there is growing evidence that H2S provides myocardial protection against myocardial ischemia-reperfusion injury (MIRI), which resulted in an ongoing focus on the possible mechanisms of action accounting for the H2S cardioprotective effect. At present, lots of mechanisms of action have been verified through in vitro and in vivo models of ischemia-reperfusion (I/R) injury, such as S-sulfhydrated modification, anti-apoptosis, effects on miRNA, bidirectional effect on autophagy, anti-oxidant stress, or interaction with NO and CO. With advances in understanding of the molecular pathogenesis of MIRI and pharmacology studies, the design, the development and the pharmacological characterization of H2S-donor drugs have been made great important progress. This review summarizes the latest research progress on the role of H2S in MIRI, systematically explains the molecular mechanism of H2S affecting MIRI, and provides a new idea for the formulation of a myocardial protection strategy in the future.

13.
Sensors (Basel) ; 20(22)2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33182697

RESUMO

To realize the blind estimation of binary phase shift keying (BPSK) signal, this paper describe a new relational expression among the state of Duffing oscillator excited by BPSK signal, the pseudo-random code of BPSK signal, and the difference frequency between the to-be-detect signal and internal drive force signal of Duffing oscillator. Two output characteristics of Duffing oscillators excited by BPSK signals named implied periodicity and pilot frequency array synchronization are presented according to the different chaotic states of Duffing oscillator. Then two blind estimation methods for the carrier frequency and pseudo-random sequence of the BPSK signal are proposed based on these two characteristics, respectively. These methods are shown to have a significant effect on the parameter estimation of BPSK signals with no prior knowledge, even at very low signal-to-noise ratios (SNRs).

14.
Ann Palliat Med ; 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33183047

RESUMO

BACKGROUND: Septic pulmonary embolism (SPE) is attracting more attention as a special pulmonary sign in severe infection. We aimed to describe the clinical and imaging features of Klebsiella pneumoniae (K. pneumonia)-associated SPE in the emergency department. METHODS: Records of patients with primarily extrapulmonary infection of K. pneumoniae who were admitted to the emergency department between 2014 and 2019 were retrieved. The identifications of K. pneumoniaeassociated SPE were mainly dependent on the clinical manifestations, typical imaging findings, and presence of a primary source of K. pneumoniae infection. RESULTS: A total of 33 cases were identified as SPE with extrapulmonary K. pneumoniae infection. The main clinical manifestations were a febrile/fragile state (100%), respiratory symptoms (18.2%), and digestive symptoms (33.3%). Eight patients (24.2%) developed septic shock, 2 (6.0%) experienced respiratory failure, and 2 (6.0%) complicated endophthalmitis. The major source of infection was liver abscess (n=26, 78.8%), followed by septicemia (n=8, 24.2%), intestinal infection (n=3, 9.1%), and ascites (n=1, 3.0%). The computed tomography (CT) features included the following: peripheral wedge-shaped opacity (n=12, 36.4%), a feeding vessel sign (n=3, 9.1%), multiple nodular lesions (n=5, 15.2%), multifocal lung ill-infiltrations (n=15, 45.5%), patchy ground-glass opacities (n=6, 18.2%), focal consolidations (n=9, 27.3%), lung abscesses (n=4, 12.1%), and pleural effusion (n=21, 63.6%). Re-examination of lung HRCT conducted in 7 patients demonstrated imaging improvement after treatment. CONCLUSIONS: K. pneumonia-SPE presented special clinical and imaging characteristics, which bear similarities to the signs of pneumonia, but was potentially catastrophic. Identifying SPE in septic conditions is crucial to improving clinical outcomes.

15.
Med Sci Monit ; 26: e926815, 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33166272

RESUMO

BACKGROUND Cardiopulmonary resuscitation (CPR) is a topic of great scientific and clinical interest that has received much attention in the past decade. Our study aimed to predict the trends in CPR research activities and evaluate hot topics via bibliometric means, quantitatively and qualitatively. MATERIAL AND METHODS All data were collected from a search of the Web of Science Core Collection on May 12, 2020. Retrieved information was investigated with bibliometric analysis by CiteSpace and VOSviewer software and the Online Analysis Platform of Literature Metrology to analyze and predict the trends and hotspots in this field. RESULTS Our search returned a total of 9563 articles and reviews on CPR published from 2010 through 2019. The number of original research studies on CPR has been increasing annually. The journal Resuscitation published the greatest number of manuscripts involved CPR, and the leading country and institution with regard to contributions on CPR were the United States and the University of Pennsylvania. Keyword co-occurrence/co-citation-cluster analysis showed that the most popular terms associated with CPR occurred in the manner of cluster labels, such as therapeutic hypothermia and treatment recommendation, among others. In addition, palliative care, sepsis, extracorporeal membrane oxygenation, and brain injury were identified as new foci through burst detection analysis. CONCLUSIONS Our study showed that the scientific research focus on CPR is switching from traditional therapeutic treatments to a public health practice, with in-depth understanding and development of CPR-related techniques expanding over the past decade. These results demonstrate trends in the CPR research and detected the possible neo-foci for ensuing research.

16.
J Appl Microbiol ; 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33151560

RESUMO

AIMS: Acute hepatopancreatic necrosis disease (AHPND) caused by Vibrio parahaemolyticus has emerged as a severe bacterial disease of cultured shrimp. To identify the key virulence factors, two AHPND-causing V. parahaemolyticus (VpAHPND ) strains (123 and 137) and two non-VpAHPND strains (HZ56 and ATCC17082) were selected. METHODS AND RESULTS: Challenge tests showed that the four strains exhibited different virulence towards shrimp with cumulative mortalities at 48 hours post-infection (hpi) ranging from 10% to 92%. The expression of pirABVP in strain 123 and 137 was not significantly different. Genomic analysis revealed that the two VpAHPND strains contain a plasmid with the PirABVP toxins (pirABVP ) flanked by the insertion sequence (ISVal1) that has been identified in various locations of chromosomes in VpAHPND strains. The two VpAHPND strains possessed almost identical virulence factors, while ISVal1 disrupted three genes related to flagellar motility in strain 137. Phenotype assay showed that strain 123 possessed the highest growth rate and swimming motility, followed by strain 137, suggesting the disruption of essential genes mediated by ISVal1 significantly affected the virulence level. Transcriptome analysis of two VpAHPND strains (123 and 137) further suggested that virulence genes related to the capsule, flagella, and primary metabolism were highly expressed in strain 123. CONCLUSIONS: Here, for the first time, it is demonstrated that the virulence of VpAHPND is not only determined by the expression of pirABVP , but also is mediated by ISVal1 which affects the genes involved in flagellar motility and primary metabolism. SIGNIFICANCE AND IMPACT OF STUDY: The genomic and transcriptomic analysis of VpAHPND strains provides valuable information on the virulence factors affecting the pathogenicity of VpAHPND.

17.
FASEB J ; 34(12): 15822-15836, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33103304

RESUMO

Retinopathy of prematurity (ROP) is a vision-threatening disorder characterized with retinal vaso-obliteration in phase 1 and pathological neovascularization (NV) in phase 2. However, there has been no effective and safe treatment for ROP. Current management is mainly focused on the reduction of abnormal NV in phase 2, and anti-vascular endothelial growth factor (VEGF) therapy is the first-line treatment, yet, with great risks of late recurrence and systemic side effects. It has been reported that the severity of vaso-obliteration in phase 1 largely influences subsequent NV, suggesting that it may be a promising target to develop novel treatments for ROP. Here, we investigated the therapeutic potential and safety of early rapamycin intervention in treating phase 1 ROP and possible underlying mechanisms using the mouse model of oxygen-induced retinopathy (OIR). We found that intravitreal injection of rapamycin at postnatal day 7 (P7) significantly reduced retinal avascular area, increased vascular density, and reversed the suppression of deep capillaries development in phase 1 of OIR mice. Rapamycin treatment not only reduced vascular apoptosis, but also promoted proliferation and tip cell functions. Additionally, rapamycin did not interfere with normal retinal vascular development. Further investigation showed that Ang1/Tie2 pathway might be involved in rapamycin's vascular protection in phase 1 OIR retinas. Moreover, early rapamycin treatment at P7 had long-term protective effects of reducing retinal NV and avascular area, as well as enhancing vascular maturity in phase 2 of OIR mice. Together, our data suggest that rapamycin may be a safe and promising strategy for early intervention of ROP.

18.
Herz ; 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33084909

RESUMO

OBJECTIVE: The aim of this study was to evaluate the prognostic value of a novel scoring system, based on D­dimer, total cholesterol, high-sensitivity cardiac troponin T (hs-cTnT), and serum albumin levels, in patients with heart failure. METHODS: A total of 221 patients diagnosed with heart failure between May 2016 to January 2020 were enrolled in this retrospective study. The prognostic significance of the biomarkers D­dimer, total cholesterol, hs-cTnT, and serum albumin was determined with univariate and multivariate Cox proportional hazard models. A novel prognostic score based on these predictors was established. The Kaplan-Meier method and log-rank test were used to compare the adverse outcomes of patients in different risk groups. RESULT: Results from univariate and multivariate analyses showed that high D­dimer, low serum albumin, high hs-cTnT, and low total cholesterol levels were independent prognostic factors for adverse outcomes (D-dimer >0.63 mg/l, HR = 1.84, 95% CI = 1.16-2.94, p = 0.010; serum albumin >34 g/l, HR = 0.67, 95% CI = 0.45-0.99, p = 0.046; hs-cTnT >24.06 pg/ml, HR = 1.65, 95% CI = 1.08-2.53, p = 0.020; total cholesterol >3.68 mmol/l, HR = 0.63, 95% CI = 0.43-0.92, p = 0.017). Moreover, all the patients were stratified into low-risk or high-risk group according to a scoring system based on these four markers. Kaplan-Meier analyses demonstrated that patients in the high-risk group were more prone to having adverse outcomes compared with patients in the low-risk group. CONCLUSION: D­dimer, total cholesterol, hs-cTnT, and serum albumin levels were independent prognostic factors in the setting of heart failure. A novel and comprehensive scoring system based on these biomarkers is an easily available and effective tool for predicting the adverse outcomes of patients with heart failure.

19.
Sci Rep ; 10(1): 17475, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-33060734

RESUMO

Observational studies have found associations between urinary sodium (UNa) with obesity, body shape and composition; but the findings may be biased by residual confounding. The objective of this two-sample Mendelian randomization (MR) study was to analyze their causal associations in both sex-combined and sex-specific models. Genome-wide association studies of UNa, body mass index (BMI), BMI-adjusted waist-to-hip ratio (WHR), body fat (BF) percentage and estimated glomerular filtration rate (eGFR) were identified. We initially extracted fifty SNPs associated with UNa at significance level of 5 × 10-8, but further removed those SNPs with potential horizontal pleiotropy. Univariable and multivariable MR with adjustment for eGFR were performed. Inverse-variance weighted MR was performed as the primary analysis, with MR-Egger methods as sensitivity analysis. The potential bidirectional association between BMI and UNa was investigated. All exposure and outcomes were continuous, and the effect measure was regression coefficients (beta) and their 95% confidence intervals (95% CI). The total sample size was up to 322 154. UNa was causally associated with increased BMI in both men [eGFR-adjusted beta 0.443 (0.163-0.724)] and women [0.594 (0.333-0.855)]. UNa caused BF percentage increase in men [0.622 (0.268-0.976)] and women [0.334 (0.007-0.662)]. UNa significantly elevated BMI-adjusted WHR in men [0.321 (0.094-0.548)], but not in women [0.170 (- 0.052 to 0.391)]. Additionally, we found that BMI causally increased UNa [0.043 (0.023-0.063)]. UNa increased BMI and BF percentage. Salt intake affects male body shape by increasing BMI-adjusted WHR, but showed no effects on female body shape. The bidirectional association between BMI and UNa suggested that salt reduction measures and weight reduction measures should be implemented simultaneously to break the vicious cycle and gain more health benefits.

20.
J Agric Food Chem ; 68(44): 12259-12270, 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33084337

RESUMO

In this study, a bioactive peptide YGPSSYGYG (YG-9) with immunomodulatory activity was isolated and identified from Pseudostellaria heterophylla protein hydrolysate. The highest proliferation index of mouse spleen lymphocytes reached 1.19 in the presence of 50 µg/mL YG-9. YG-9 could activate RAW264.7 cells by promoting the secretions of NO, the pinocytosis activity, and the productions of ROS and TNF-α. Moreover, YG-9 enhanced the expressions of TLR2 and TLR4 in RAW264.7 cells. TNF-α secretions induced by YG-9 were reduced in TLR2 and TLR4 siRNAs knockdown cells, and this suggested that macrophage activation of YG-9 was through TLR2 and TLR4. Furthermore, YG-9 promoted the translocation of NF-κB through the acceleration of IκB-α phosphorylation and degradation. Also, TNF-α secretions promoted by YG-9 were inhibited by NF-κB-specific inhibitors pyrrolidine dithiocarbamate and BAY11-7082. Altogether, these results suggested YG-9 activated RAW264.7 cells via the TLRs/NF-κB/TNF-α signaling pathway.

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