bluuebunny/crossref_metadata_2025 huggingface dataset:
SiO2 nanosphere coated tough catheter with superhydrophobic surface for improving the antibacteria and hemocompatibility
Authors: Zhang Weixing , Du Juan , Zhu Tonghe , Wang Ruilan
Published: January 2023

Catheter infection is the most common complication after vascular catheter placement, which seriously threatens the survival of critically ill patients. Although catheters with antibacterial drug coatings have been used, catheter infections have not been effectively resolved. In this research, a SiO2 nanosphere-coated PTFE catheter (PTFE-SiO2) with enhanced antibacterial and excellent mechanical properties was prepared via dopamine as a graft bridge. The microscopic morphology results show that the nanospheres are uniformly dispersed on the surface of the catheter. The physicochemical characterization confirmed that PTFE-SiO2 had reliable bending resistance properties, superhydrophobicity, and cytocompatibility and could inhibit thrombosis. Antibacterial results revealed that PTFE-SiO2 could hinder the reproduction of E. coli and S. aureus. This research demonstrates the hydroxyl-rich materials obtained by hydroboration oxidation have the advantages of better dispersion of functional coatings, indicating their potential for helpful modification of catheters.
Rapid detection of SARS-CoV-2: The gradual boom of lateral flow immunoassay
Authors: He Jing , Zhu Shuying , Zhou Jiawei , Jiang Wenjie , Yin Liliang , Su Lan , Zhang Xinling , Chen Qi , Li Xiaoping
Published: January 2023

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is still in an epidemic situation, which poses a serious threat to the safety of people and property. Rapid diagnosis and isolation of infected individuals are one of the important methods to control virus transmission. Existing lateral flow immunoassay techniques have the advantages of rapid, sensitive, and easy operation, and some new options have emerged with the continuous development of nanotechnology. Such as lateral flow immunoassay test strips based on colorimetric-fluorescent dual-mode and gold nanoparticles, Surface Enhanced Raman Scattering, etc., these technologies have played an important role in the rapid diagnosis of COVID-19. In this paper, we summarize the current research progress of lateral flow immunoassay in the field of Severe Acute Respiratory Syndrome Coronavirus 2 infection diagnosis, analyze the performance of Severe Acute Respiratory Syndrome Coronavirus 2 lateral flow immunoassay products, review the advantages and limitations of different detection methods and markers, and then explore the competitive CRISPR-based nucleic acid chromatography detection method. This method combines the advantages of gene editing and lateral flow immunoassay and can achieve rapid and highly sensitive lateral flow immunoassay detection of target nucleic acids, which is expected to be the most representative method for community and clinical point-of-care testing. We hope that researchers will be inspired by this review and strive to solve the problems in the design of highly sensitive targets, the selection of detection methods, and the enhancement of CRISPR technology, to truly achieve rapid, sensitive, convenient, and specific detection of novel coronaviruses, thus promoting the development of novel coronavirus diagnosis and contributing our modest contribution to the world’s fight against epidemics.
Apoptosis inhibition restrains primary malignant traits in different Drosophila cancer models
Authors: Sollazzo Manuela , Paglia Simona , Di Giacomo Simone , Grifoni Daniela
Published: January 2023

Tumor cells exploit multiple mechanisms to evade apoptosis, hence the strategies aimed at reactivating cell death in cancer. However, recent studies are revealing that dying cells play remarkable pro-oncogenic roles. Among the mechanisms promoting cell death, cell competition, elicited by disparities in MYC activity in confronting cells, plays the primary role of assuring tissue robustness during development from Drosophila to mammals: cells with high MYC levels (winners) overproliferate while killing suboptimal neighbors (losers), whose death is essential to process completion. This mechanism is coopted by tumor cells in cancer initiation, where host cells succumb to high-MYC-expressing precancerous neighbors. Also in this case, inhibition of cell death restrains aberrant cell competition and rescues tissue structure. Inhibition of apoptosis may thus emerge as a good strategy to counteract cancer progression in competitive contexts; of note, we recently found a positive correlation between cell death amount at the tumor/stroma interface and MYC levels in human cancers. Here we used Drosophila to investigate the functional role of competition-dependent apoptosis in advanced cancers, observing dramatic changes in mass dimensions and composition following a boost in cell competition, rescued by apoptosis inhibition. This suggests the role of competition-dependent apoptosis be not confined to the early stages of tumorigenesis. We also show that apoptosis inhibition, beside restricting cancer mass, is sufficient to rescue tissue architecture and counteract cell migration in various cancer contexts, suggesting that a strong activation of the apoptotic pathways intensifies cancer burden by affecting distinct phenotypic traits at different stages of the disease.
Functionally active TRPA1 ion channel is downregulated in peptidergic neurons of the Edinger-Westphal nucleus upon acute alcohol exposure
Authors: Al-Omari Ammar , Kecskés Miklós , Gaszner Balázs , Biró-Sütő Tünde , Fazekas Balázs , Berta Gergely , Kuzma Mónika , Pintér Erika , Kormos Viktória
Published: January 2023

Introduction:The centrally projecting Edinger-Westphal nucleus (EWcp) contributes to the control of alcohol consumption by its urocortin 1 (UCN1) and cocaine- and amphetamine-regulated transcript (CART) co-expressing peptidergic neurons. Our group recently showed that the urocortinergic centrally projecting EWcp is the primary seat of central nervous system transient receptor potential ankyrin 1 (TRPA1) cation channel mRNA expression. Here, we hypothesized that alcohol and its metabolites, that pass through the blood-brain barrier, may influence the function of urocortinergic cells in centrally projecting EWcp by activating TRPA1 ion channels. We aimed to examine the functional activity of TRPA1 in centrally projecting EWcp and its possible role in a mouse model of acute alcohol exposure.

Methods:Electrophysiological measurements were performed on acute brain slices of C57BL/6J male mice containing the centrally projecting EWcp to prove the functional activity of TRPA1 using a selective, potent, covalent agonist JT010. Male TRPA1 knockout (KO) and wildtype (WT) mice were compared with each other in the morphological studies upon acute alcohol treatment. In both genotypes, half of the animals was treated intraperitoneally with 1 g/kg 6% ethanol vs. physiological saline-injected controls. Transcardial perfusion was performed 2 h after the treatment. In the centrally projecting EWcp area, FOS immunohistochemistry was performed to assess neuronal activation. TRPA1, CART, and urocortin 1 mRNA expression as well as urocortin 1 and CART peptide content was semi-quantified by RNAscopein situhybridization combined with immunofluorescence.

Results:JT010 activated TRPA1 channels of the urocortinergic cells in acute brain slices. Alcohol treatment resulted in a significant FOS activation in both genotypes. Alcohol decreased theTrpa1mRNA expression in WT mice. The assessment of urocortin 1 peptide immunoreactivity revealed lower basal urocortin 1 in KO mice compared to WTs. The urocortin 1 peptide content was affected genotype-dependently by alcohol: the peptide content decreased in WTs while it increased in KO mice. Alcohol exposure influenced neither CART and urocortin 1 mRNA expression nor the centrally projecting EWcp/CART peptide content.

Conclusion:We proved the presence of functional TRPA1 receptors on urocortin 1 neurons of the centrally projecting EWcp. DecreasedTrpa1mRNA expression upon acute alcohol treatment, associated with reduced neuronal urocortin 1 peptide content suggesting that this cation channel may contribute to the regulation of the urocortin 1 release.
Hypoxia-sensitive miRNA regulation via CRISPR/dCas9 loaded in hybrid exosomes: A novel strategy to improve embryo implantation and prevent placental insufficiency during pregnancy
Authors: Yaghoobi Alireza , Nazerian Yasaman , Meymand Arman Zeinaddini , Ansari Ali , Nazerian Amirhossein , Niknejad Hassan
Published: January 2023

Assisted reproductive techniques as a new regenerative medicine approach have significantly contributed to solving infertility problems that affect approximately 15% of couples worldwide. However, the success rate of an in vitro fertilization (IVF) cycle remains only about 20%–30%, and 75% of these losses are due to implantation failure (the crucial rate-limiting step of gestation). Implantation failure and abnormal placenta formation are mainly caused by defective adhesion, invasion, and angiogenesis. Placental insufficiency endangers both the mother’s and the fetus’s health. Therefore, we suggested a novel treatment strategy to improve endometrial receptivity and implantation success rate. In this strategy, regulating mir-30d expression as an upstream transcriptomic modifier of the embryo implantation results in modified expression of the involved genes in embryonic adhesion, invasion, and angiogenesis and consequently impedes implantation failure. For this purpose, “scaffold/matrix attachment regions (S/MARs)” are employed as non-viral episomal vectors, transfecting into trophoblasts by exosome-liposome hybrid carriers. These vectors comprise CRISPR/dCas9 with a guide RNA to exclusively induce miR-30d gene expression in hypoxic stress conditions. In order to avoid concerns about the fetus’s genetic manipulation, our vector would be transfected specifically into the trophoblast layer of the blastocyst via binding to trophoblast Erb-B4 receptors without entering the inner cell mass. Additionally, S/MAR episomal vectors do not integrate with the original cell DNA. As an on/off regulatory switch, a hypoxia-sensitive promoter (HRE) is localized upstream of dCas9. The miR-30d expression increases before and during the implantation and placental insufficiency conditions and is extinguished after hypoxia elimination. This hypothesis emphasizes that improving the adhesion, invasion, and angiogenesis in the uterine microenvironment during pregnancy will result in increased implantation success and reduced placental insufficiency, as a new insight in translational medicine.
The tendon interfascicular basement membrane provides a vascular niche for CD146+ cell subpopulations
Authors: Marr Neil , Zamboulis Danae E. , Werling Dirk , Felder Alessandro A. , Dudhia Jayesh , Pitsillides Andrew A. , Thorpe Chavaunne T.
Published: January 2023

Introduction: The interfascicular matrix (IFM; also known as the endotenon) is critical to the mechanical adaptations and response to load in energy-storing tendons, such as the human Achilles and equine superficial digital flexor tendon (SDFT). We hypothesized that the IFM is a tendon progenitor cell niche housing an exclusive cell subpopulation.

Methods: Immunolabelling of equine superficial digital flexor tendon was used to identify the interfascicular matrix niche, localising expression patterns of CD31 (endothelial cells), Desmin (smooth muscle cells and pericytes), CD146 (interfascicular matrix cells) and LAMA4 (interfascicular matrix basement membrane marker). Magnetic-activated cell sorting was employed to isolate and compare in vitro properties of CD146+ and CD146− subpopulations.

Results: Labelling for CD146 using standard histological and 3D imaging of large intact 3D segments revealed an exclusive interfascicular cell subpopulation that resides in proximity to a basal lamina which forms extensive, interconnected vascular networks. Isolated CD146+ cells exhibited limited mineralisation (osteogenesis) and lipid production (adipogenesis).

Discussion: This study demonstrates that the interfascicular matrix is a unique tendon cell niche, containing a vascular-rich network of basement membrane, CD31+ endothelial cells, Desmin+ mural cells, and CD146+ cell populations that are likely essential to tendon structure and/or function. Contrary to our hypothesis, interfascicular CD146+ subpopulations did not exhibit stem cell-like phenotypes. Instead, our results indicate CD146 as a pan-vascular marker within the tendon interfascicular matrix. Together with previous work demonstrating that endogenous tendon CD146+ cells migrate to sites of injury, our data suggest that their mobilisation to promote intrinsic repair involves changes in their relationships with local interfascicular matrix vascular and basement membrane constituents.
Macrophage elastase derived from adventitial macrophages modulates aortic remodeling
Authors: Chen Yajie , Yang Xiawen , Kitajima Shuji , Quan Longquan , Wang Yao , Zhu Maobi , Liu Enqi , Lai Liangxue , Yan Haizhao , Fan Jianglin
Published: January 2023

Abdominal aortic aneurysm (AAA) is pathologically characterized by intimal atherosclerosis, disruption and attenuation of the elastic media, and adventitial inflammatory infiltrates. Although all these pathological events are possibly involved in the pathogenesis of AAA, the functional roles contributed by adventitial inflammatory macrophages have not been fully documented. Recent studies have revealed that increased expression of matrix metalloproteinase-12 (MMP-12) derived from macrophages may be particularly important in the pathogenesis of both atherosclerosis and AAA. In the current study, we developed a carrageenan-induced abdominal aortic adventitial inflammatory model in hypercholesterolemic rabbits and evaluated the effect of adventitial macrophage accumulation on the aortic remodeling with special reference to the influence of increased expression of MMP-12. To accomplish this, we compared the carrageenan-induced aortic lesions of transgenic (Tg) rabbits that expressed high levels of MMP-12 in the macrophage lineage to those of non-Tg rabbits. We found that the aortic medial and adventitial lesions of Tg rabbits were greater in degree than those of non-Tg rabbits, with the increased infiltration of macrophages and prominent destruction of elastic lamellae accompanied by the frequent appearance of dilated lesions, while the intimal lesions were slightly increased. Enhanced aortic lesions in Tg rabbits were focally associated with increased dilation of the aortic lumens. RT-PCR and Western blotting revealed high levels of MMP-12 in the lesions of Tg rabbits that were accompanied by elevated levels of MMP-2 and -3, which was caused by increased number of macrophages. Our results suggest that adventitial inflammation constitutes a major stimulus to aortic remodeling and increased expression of MMP-12 secreted from adventitial macrophages plays an important role in the pathogenesis of vascular diseases such as AAA.
An update on the biological characteristics and functions of tuft cells in the gut
Authors: Du Yixuan , Gao Han , He Chengwei , Xin Shuzi , Wang Boya , Zhang Sitian , Gong Fengrong , Yu Xinyi , Pan Luming , Sun Fanglin , Wang Wen , Xu Jingdong
Published: January 2023

The intestine is a powerful digestive system and one of the most sophisticated immunological organs. Evidence shows that tuft cells (TCs), a kind of epithelial cell with distinct morphological characteristics, play a significant role in various physiological processes. TCs can be broadly categorized into different subtypes depending on different molecular criteria. In this review, we discuss its biological properties and role in maintaining homeostasis in the gastrointestinal tract. We also emphasize its relevance to the immune system and highlight its powerful influence on intestinal diseases, including inflammations and tumors. In addition, we provide fresh insights into future clinical diagnostic and therapeutic strategies related to TCs.
A novel class of C14-sulfonate-tetrandrine derivatives as potential chemotherapeutic agents for hepatocellular carcinoma
Authors: Jiang Taibai , Xie Guangtong , Zeng Zhirui , Lan Junjie , Liu Hanfei , Li Jinyu , Ren Hai , Chen Tengxiang , Pan Weidong
Published: January 2023

Hepatocellular carcinoma (HCC), the most common malignancy of the liver, exhibits high recurrence and metastasis. Structural modifications of natural products are crucial resources of antitumor drugs. This study aimed to synthesize C-14 derivatives of tetrandrine and evaluate their effects on HCC. Forty C-14 sulfonate tetrandrine derivatives were synthesized and their in vitro antiproliferative was evaluated against four hepatoma (HepG-2, SMMC-7721, QGY-7701, and SK-Hep-1) cell lines. For all tested cells, most of the modified compounds were more active than the lead compound, tetrandrine. In particular, 14-O-(5-chlorothiophene-2-sulfonyl)-tetrandrine (33) exhibited the strongest antiproliferative effect, with half-maximal inhibitory concentration values of 1.65, 2.89, 1.77, and 2.41 μM for the four hepatoma cell lines, respectively. Moreover, 33 was found to induce apoptosis via a mitochondria-mediated intrinsic pathway via flow cytometry and western blotting analysis. In addition, colony formation, wound healing, and transwell assays demonstrated that 33 significantly inhibited HepG-2 and SMMC-7721 cell proliferation, migration, and invasion, indicating that it might potentially be a candidate for an anti-HCC therapy in the future.
Gαq modulates the energy metabolism of osteoclasts
Authors: Chakraborty Sushmita , Handrick Bianca , Yu Dayoung , Bode Konrad A. , Hafner Anna , Schenz Judith , Schaack Dominik , Uhle Florian , Tachibana Taro , Kamitani Shigeki , Vogl Thomas , Kubatzky Katharina F.
Published: January 2023

Introduction

The bacterial protein toxinPasteurella multocidatoxin (PMT) mediates RANKL-independent osteoclast differentiation. Although these osteoclasts are smaller, their resorptive activity is high which helps in efficient destruction of nasal turbinate bones of pigs.

Methods

The proteome of bone marrow-derived macrophages differentiated into osteoclasts with either RANKL or PMT was analysed. The results were verified by characterizing the metabolic activity using Seahorse analysis, a protein translation assay, immunoblots, real-time PCR as well as flow cytometry-based monitoring of mitochondrial activity and ROS production. A Gαq overexpression system using ER-Hoxb8 cells was used to identify Gαq-mediated metabolic effects on osteoclast differentiation and function.

Results

PMT induces the upregulation of metabolic pathways, which included strong glycolytic activity, increased expression of GLUT1 and upregulation of the mTOR pathway. As OxPhos components were expressed more efficiently, cells also displayed increased mitochondrial respiration. The heterotrimeric G protein Gαq plays a central role in this hypermetabolic cell activation as it triggers mitochondrial relocalisation of pSerSTAT3 and an increase in OPA1 expression. This seems to be caused by a direct interaction between STAT3 and OPA1 resulting in enhanced mitochondrial respiration. Overexpression of Gαq mimicked the hypermetabolic phenotype observed for PMT-induced osteoclasts and resulted in higher glycolytic and mitochondrial activity as well as increased bone resorptive activity. In addition, rheumatoid arthritis (RA) patients showed an increase inGNAQexpression, especially in the synovial fluid.

Discussion

Our study suggests that Gαq plays a key role in PMT-induced osteoclastogenesis. Enhanced expression ofGNAQat the site of inflammation in RA patients indicates its pathophysiological relevance in the context of inflammatory bone disorders.
In vitro leishmanicidal effect of Yangambin and Epi-yangambin lignans isolated from Ocotea fasciculata (Nees) Mez
Authors: Rebouças-Silva Jéssica , Santos Gabriel Farias , Filho José Maria Barbosa , Berretta Andresa A. , Marquele-Oliveira Franciane , Borges Valéria M.
Published: January 2023

Introduction

Yangambin and epi-yangambin are the main lignans found in Louro-de-Cheiro [Ocotea fasciculata (Nees) Mez], a tree native to the Atlantic forests of northeastern Brazil whose leaves and bark are widely used in folk medicine. The present study investigated the leishmanicidal and immunomodulatory effects of both lignans in in vitro models of infection by Leishmania amazonensis or Leishmania braziliensis, both etiological agents of Cutaneous Leishmaniasis in Brazil.

Methods

Bone marrow-derived mouse macrophages were infected with L. amazonensis or L. braziliensis and then treated for 48 h at varying concentrations of yangambin or epi-yangambin.

Results

Yangambin and epi-yangambin were found to reduce the intracellular viability of either Leishmania species in a concentration-dependent manner, with respective IC50 values of: 43.9 ± 5 and 22.6 ± 4.9 µM for L. amazonensis, compared to IC50 values of 76 ± 17 and 74.4 ± 9.8 µM for L. braziliensis. In this context, epi-yangambin proved more selective and effective against in vitro infection by L. amazonensis. However, both lignans were found to distinctly modulate the production of inflammatory mediators and other cytokines by macrophages infected by either of the Leishmania species evaluated. While yangambin increased the production of IL-10 by L. braziliensis-infected macrophages, both compounds were observed to lower the production of NO, PGE2, IL-6 and TNF-α in both Leishmania species.

Discussion

The present results serve to encourage the development of novel studies aimed at screening natural bioactive compounds with the hope of discovering new therapeutic options for the treatment of Cutaneous Leishmaniasis.
Targeting bacterial pathogenesis by inhibiting virulence-associated Type III and Type IV secretion systems
Authors: Blasey Nadja , Rehrmann Daria , Riebisch Anna Katharina , Mühlen Sabrina
Published: January 2023

Infections caused by Gram-negative pathogens pose a major health burden. Both respiratory and gastrointestinal infections are commonly associated with these pathogens. With the increase in antimicrobial resistance (AMR) over the last decades, bacterial infections may soon become the threat they have been before the discovery of antibiotics. Many Gram-negative pathogens encode virulence-associated Type III and Type IV secretion systems, which they use to inject bacterial effector proteins across bacterial and host cell membranes into the host cell cytosol, where they subvert host cell functions in favor of bacterial replication and survival. These secretion systems are essential for the pathogens to cause disease, and secretion system mutants are commonly avirulent in infection models. Hence, these structures present attractive targets for anti-virulence therapies. Here, we review previously and recently identified inhibitors of virulence-associated bacterial secretions systems and discuss their potential as therapeutics.
The evolution of Aotearoa New Zealand's policy discourses on Pacific climate mobilities from 2006–2021
Authors: Dyer Cathrine , Neef Andreas
Published: January 2023

In 2006 New Zealand government officials found themselves facing a barrage of enquiries arising from an erroneous claim contained in Al Gore's Academy Award-winning climate change documentary An Inconvenient Truth. The documentary suggested that the government of Aotearoa had agreed to take “all climate refugees” from Tuvalu, an archipelago of nine atolls and coral-reef islands in the South Pacific, as part of a planned response to climate change. At the time, New Zealand did not have any plan, or indeed any intention to create a plan, for addressing climate-induced displacement. The ensuing 15 years saw Aotearoa's official response evolve from one of “correcting misperceptions about New Zealand's position on climate-induced migration” to an adaptive development approach focused on Pacific-led solutions. This paper traces the evolution of that approach through a series of official reviews, focusing on the discursive frames and narratives that were employed by officials and government representatives. The current New Zealand government has expressed a desire to play a role in the development of world-leading approaches to climate-induced mobilities within the region, whilst it also seeks to avoid establishing overly broad policy precedents on climate migration that could apply beyond the Pacific. The paper discusses some of the avenues being explored by government departments, in particular the potential for existing temporary migrant programs to be developed into schemes that actively support an adaptive development framework in response to climate-related mobilities. We consider the range of possible solutions that could be contained within such a response, the opportunities for mutually beneficial approaches and the challenges that they would pose to long-accepted norms and processes embedded in the country's current immigration programs.
The association between denture use and cardiovascular diseases. The United States National Health and Nutrition Examination Survey 2009–2018
Authors: Liang Xiaopeng , Chou Oscar Hou In , Cheung Bernard M. Y.
Published: January 2023

Introduction

Poor dental health is associated with cardiovascular diseases (CVD). However, the relationship between CVD and denture use is currently unknown. This study aimed to investigate whether denture use is associated with CVD among American adults.

Methods

10,246 non-pregnant subjects aged 30–59 years from five cycles (2009–2018) of the United States National Health and Nutrition Examination Survey (NHANES) were included in this study. Participants who were observed by a dental examiner wearing denture/partial denture/plates were defined as denture users. CVD was defined as self-reported coronary heart disease, myocardial infarction, angina pectoris, stroke, and congestive heart failure. The association between denture use and CVD was analyzed using logistic regression with adjustment for potential cofounders.

Results

4.4% (95% CI, 3.9–5.0) participants had CVD, and 3.5% (95% CI, 2.8–4.5) participants were denture users. Denture use was associated with CVD [OR = 4.26, 95% CI (2.90–6.28), P < 0.01], which remained significant [adjusted OR = 1.82, 95% CI (1.15–2.88), P < 0.01] after adjustments for sociodemographic characteristics, smoking, alcohol use, drug addiction, body mass index (BMI), and abnormal medical conditions including gum problem, hypertension, diabetes, and hyperlipidemia. Women with dentures had significantly higher odds of CVD [adjusted OR = 2.13, 95% CI (1.10–4.11), P = 0.025].

Conclusion

In this nationally representative survey, denture use was associated with CVD. Denture use may be an unconventional risk factor for assessing CVD risks, especially in women. Future studies are required to investigate whether CVD and denture use is causally related.
Amiodarone vs. metoprolol succinate in HFrEF complicated with persistent atrial fibrillation with rapid ventricular response: A prospective observational study
Authors: Liu Yongrong , Hong Yali
Published: January 2023

Background

β-blockers have been recommended for patients with heart failure (HF) and atrial fibrillation (AF), but studies have shown that β-blockers do not reduce all-cause mortality or cardiovascular mortality in patients with HF and AF.

Objective

To investigate the difference in efficacy between oral amiodarone and metoprolol succinate for patients with HF with reduced ejection fraction (HFrEF) and persistent atrial fibrillation (pAF) with rapid ventricular response (RVR).

Methods

Patients with HFrEF complicated with pAF with RVR treated in the People's Hospital of Chongqing Hechuan between March 2018 and March 2019 were enrolled in this prospective observational study. The primary outcomes were cardiovascular mortality and the first hospitalization for HF rate. The secondary outcomes were type B pro-brain natriuretic peptide (NT-proBNP) before/after treatment, left ventricular ejection fraction (LVEF) before/after treatment, average heart rate (AhR), and the rate of sinus rhythm after 1 year of follow-up.

Results

A total of 242 patients with HFrEF complicated with pAF with RVR were enrolled and divided into amiodarone + perindopril + spironolactone+ routine drug (amiodarone group, n = 121) and metoprolol succinate + perindopril + spironolactone +routine drug (metoprolol succinate group, n = 121) according to their treatment strategy. Cardiovascular mortality (4.9 vs. 12.4%, HR: 2.500, 95%CI: 1.002–6.237, P = 0.040) and first hospitalization for HF (52.9 vs. 67.8%, HR: 1.281, 95%CI: 1.033–1.589, P = 0.024) were significantly lower in the amiodarone group than in the metoprolol group. The mean ventricular rate in the amiodarone group was significantly lower than in the metoprolol group (64.5 ± 3.2 vs. 72.4 ± 4.2, P < 0.001). After 1 year of follow-up, the sinus rhythm rate was significantly higher in the amiodarone group than in the metoprolol group (38.8 vs. 7.4%, HR: 0.191, 95%CI: 0.098–0.374, P < 0.001). The difference in proBNP (3,914.88 vs. 2,558.07, P < 0.001) and LVEF (−6.89 vs. −0.98, P < 0.001) before and after treatment was significantly higher in the amiodarone group than in the metoprolol group.

Conclusion

In conclusion, in this prospective observational study, the amiodarone group had lower risk of cardiovascular death and the first hospitalization for HF than metoprolol in HFrEF and persistent atrial fibrillation (pAF) with RVR. The mechanism may be related to improved cardiac function, rhythm control and ventricular rate control.

Registration number

ChiCTR2200057816; Registered 7 March 2022–Retrospectively registered: http://www.medresman.org.cn/pub/cn/proj/projectshshow.aspx?proj=4222.
Secondary prevention of antithrombotic therapy in patients with stable cardiovascular disease at high ischemic risk: A network meta-analysis of randomized controlled trials
Authors: Zhu Houyong , Xu Xiaoqun , Wang Hanxin , Chen Qilan , Fang Xiaojiang , Zheng Jianwu , Gao Beibei , Tong Guoxin , Zhou Liang , Chen Tielong , Huang Jinyu
Published: January 2023

Aims

Antithrombotic secondary prevention in stable cardiovascular disease (SCVD) patients at high ischemic risk remains unclear. We compared the efficacy and safety of aspirin monotherapy, clopidogrel monotherapy, ticagrelor monotherapy, rivaroxaban monotherapy, clopidogrel plus aspirin, ticagrelor plus aspirin, and rivaroxaban plus aspirin in the high-risk ischemic cohorts.

Methods and results

Eleven randomized controlled trials were included (n = 111737). The primary outcomes were major cardiovascular and cerebrovascular events (MACEs) and major bleeding. A random effects model was used for frequentist network meta-analysis. Odds ratio (OR) and 95% credible intervals (CI) were reported as a summary statistic. Compared with aspirin monotherapy, rivaroxaban plus aspirin [OR 0.79 (95% CI, 0.69, 0.89)], ticagrelor plus aspirin [0.88 (0.80, 0.98)], clopidogrel plus aspirin [0.56 (0.41, 0.77)] were associated with a reduced risk of MACEs, but rivaroxaban monotherapy [0.92 (0.79, 1.07)], ticagrelor monotherapy [0.68 (0.45, 1.05)], and clopidogrel monotherapy [0.67 (0.43, 1.05)] showed no statistically significant difference. However, rivaroxaban monotherapy and all dual antithrombotic strategies increased the risk of major bleeding to varying degrees, with ticagrelor plus aspirin associated with the highest risk of major bleeding. The net clinical benefit favored clopidogrel or ticagrelor monotherapy, which have a mild anti-ischemic effect without an increase in bleeding risk.

Conclusion

The present network meta-analysis suggests that clopidogrel or ticagrelor monotherapy may be recommended first in this cohort of SCVD at high ischemic risk. But clopidogrel plus aspirin or rivaroxaban plus aspirin can still be considered for use in patients with recurrent MACEs.
Association between sedentary time and plasma leptin levels in middle-aged and older adult population in Taiwan: A community-based, cross-sectional study
Authors: Shih Yu-Lin , Shih Yun-Hsiang , Huang Tzu-Cheng , Shih Chin-Chuan , Chen Jau-Yuan
Published: January 2023

Background

Association of sedentary behavior and plasma leptin levels is a popular topic in recent research. Aged populations often suffer from cardiometabolic diseases, and leptin is considered a novel marker for many cardiometabolic diseases. To further explore this topic, our research investigates the relationship between sedentary time and serum leptin levels in middle-aged and older populations.

Methods

A total of 396 middle-aged and older adult Taiwanese participants were included in this study. We recorded their self-reported sitting time as sedentary time. Participants were categorized into low leptin, medium leptin group, and high leptin groups according to the tertile of serum leptin level in the study. We also analyzed the anthropometric and cardiometabolic parameters between the three groups. Spearman's correlation coefficient was used to analyze the correlation between leptin level, sedentary time, and other cardiometabolic risk factors. The relationsip between leptin and sedentary time was also shown in a scatter plot. Multivariate linear regression was performed to determine the association between serum leptin levels and sedentary time after adjusting for age, sex, alcohol consumption, smoking, triglycerides, body mass index (BMI), fasting plasma glucose, systolic blood pressure, uric acid, creatinine, and alanine transaminase (ALT).

Results

In our study, data from a total of 396 participants were analyzed. The average age of participants was 64.75 (±8.75) years, and ~41.4% were male. A longer period of sedentary time was observed in the high leptin group. A positive correlation was found between serum leptin level and sedentary time in Spearman's correlation, in all BMI groups. Serum leptin levels were positively associated with sedentary time (B = 0.603, p = 0.016) in the multivariate linear regression after adjusting for age, sex, alcohol consumption, smoking, triglycerides, BMI, fasting plasma glucose, systolic blood pressure, uric acid, creatinine, and ALT.

Conclusion

Prolonged sedentary time can be an independent risk factor for high serum leptin levels, and high leptin levels can be a novel marker in future healthcare to screen the individual with prolonged sedentary time. Furthermore, based on our study, future research can further explore the relationship between leptin levels and health promotion, especially decreasing sedentary time in the middle-aged and elder population, which is vulnerable to cardiometabolic diseases.
Predicting the survival benefit of cardiac resynchronization therapy with defibrillator function for non-ischemic heart failure—Role of the Goldenberg risk score
Authors: Merkel Eperke D. , Schwertner Walter R. , Behon Anett , Kuthi Luca , Veres Boglárka , Osztheimer István , Papp Roland , Molnár Levente , Zima Endre , Gellér László , Kosztin Annamária , Merkely Béla
Published: January 2023

Aims

Primary prevention of sudden cardiac death (SCD) in non-ischemic heart failure (HF) patients remains a topic of debate at cardiac resynchronization therapy (CRT) implantation requiring individual risk assessment. Using the Goldenberg SCD risk score, we aimed to predict, which non-ischemic HF patients will benefit from the addition of an implantable cardioverter defibrillator (ICD) to CRT at long-term.

Methods

Between 2000 and 2018 non-ischemic HF patients undergoing CRT implantation were collected into our retrospective registry. The Goldenberg risk score (GRS) was calculated by the presence of atrial fibrillation, New York Heat Association (NYHA) class > 2, age > 70 years, blood urea nitrogen > 26 mg/dl and QRS > 120 ms. The primary endpoint was all-cause mortality, heart transplantation or left ventricular assist device implantation.

Results

From 667 patients, 347 (52%) underwent cardiac resynchronization therapy-pacemaker (CRT-P), 320 (48%) cardiac resynchronization therapy-defibrillator (CRT-D) implantations. During the median follow up time of 4.3 years, 306 (46%) patients reached the primary endpoint (CRT-D 37% vs. CRT-P 63%; p < 0.001). CRT-D patients were younger (64 vs. 69 years; p < 0.001), infrequently females (26 vs. 39%; p < 0.001), and had a lower ejection fraction (27 vs. 29%; p < 0.01) compared to CRT-P patients. After GRS calculation, patients were dichotomized by low (< 3) and high (≥ 3) scores. CRT-D patients with low GRS showed a mortality benefit compared to CRT-P (HR 0.68; 95% CI 0.48–0.96; p = 0.03), high-risk patients did not (HR 0.84; 95% CI 0.62–1.13; p = 0.26).

Conclusion

In our non-ischemic cohort, patients with low GRS showed a clear long-term mortality benefit by adding ICD to CRT, however, in high-risk patients no further benefit could be observed.
Endovascular treatment for acute M2 occlusion stroke within 6 hours-a retrospective real-world evidence
Authors: Xu Yi , Fu Wang , Wang Yongpeng , Bi Qianqian , Wang Qiwei , Yang Lu , Zhang Quanbin , Wang Feng
Published: January 2023

Background

We compared the efficacy and safety of endovascular therapy (EVT), intravenous (IV) thrombolysis and conservative treatment in M2 segment occlusion stroke based on a real-world database.

Methods

We retrospectively analyzed the database of admitted patients with M2 segment occlusion between January 2018 and December 2020. The patients who were eligible for reperfusion treatment were assigned to EVT, IV thrombolysis or conservative treatment according to the exact management proceeding. The primary outcome was a score of 0 and 1 on the modified Rankin scale (mRS) at 90 days. The odds ratio (OR) for the primary outcome was adjusted for age, baseline National Institute of Health Stroke Scale score, and door-to-treatment time. The secondary outcomes were based on a mRS score from 0 to 2 at 90 days and the safety outcomes including symptomatic intracranial hemorrhage, and all-cause mortality. The data were analyzed by the logistical regression model, including baseline adjustments.

Results

A total of 109 patients were included. Among them, 42 (38.5%) patients received EVT, 45 (42.5%) received IV thrombolysis and 22 (20.8%) received conservative treatment. The primary outcome based on a mRS score of 0 and 1, occurred in 66.7% of patients in the EVT group and 40% in the IV thrombolysis group (adjusted OR, 1.79; 95% confidence interval [CI], 1.19-2.68; P = 0.01). Symptomatic intracranial hemorrhage occurred in 1 patient (2.3%) in the EVT group and in 2 patients (4.4%) in the IV thrombolysis group (adjusted OR = 0.71, 95% CI: 0.13-4.07).

Conclusion

EVT showed better functional outcomes than IV thrombolysis and conservative treatment in moderate to severe acute stoke patients with M2 occlusion. There was no significant difference in the three groups concerning the incidence of symptomatic intracranial hemorrhage.
Prognostic value of interleukin-34 and interleukin-38 in patients with newly diagnosed atrial fibrillation
Authors: Ma Jiaxue , Wu Na , Yuan Zhiquan , Chen Yanxiu , Li Chengying , Xie Weijia , Zhang Zhihui , Li Yafei , Zhong Li
Published: January 2023

Background

Interleukin (IL)-34 and IL-38 are associated with cardiovascular disease (CVD). However, their involvement in atrial fibrillation (AF) and AF-associated adverse events remains uncertain. Therefore, we aimed to investigate their association with various AF prognostic factors in a cohort study and assessed their predictive value for the prognosis of patients with AF.

Methods

Patients with new-onset non-valvular AF were consecutively enrolled between 2013 and 2015 at the Department of Cardiovascular Medicine of the Southwest Hospital of the Army Medical University (Third Military Medical University) in Chongqing, China. The endpoints included stroke and all-cause mortality. The baseline levels of plasma IL-34, IL-38, NT-proBNP, high-sensitivity cardiac troponin T (hs-cTnT), and GDF-15 were measured and their correlation with AF-related adverse events were analyzed in a Cox proportional-hazards regression model. The C-statistic, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to evaluate the performance of the AF prognostic models. Decision curve analysis (DCA) was used to evaluate the clinical net benefit of the original and modified models.

Results

A total of 299 patients with new-onset AF were enrolled. During the median follow-up time of 28 (IQR: 27, 29) months, the higher levels of IL-34 were associated with a lower risk of stroke, and the higher levels of IL-38 were associated with an increased risk of all-cause death (all adjusted P < 0.05). In addition, elevated hs-cTnT and NT-proBNP concentrations were associated with a higher risk of stroke and all-cause mortality (all adjusted P < 0.05). Furthermore, the CHA2DS2-VASc score combined with IL-38 and NT-proBNP significantly improved the C-statistic, IDI, and NRI (all P < 0.01). There was no statistically significant difference (all P > 0.05) in the discrimination power between the preference models and the ABC (age, biomarkers, and clinical history) score for the two prognostic outcomes.

Conclusion

Our results suggested that IL-34 and IL-38 were independently associated with stroke and all-cause mortality in patients with AF. Moreover, adding IL-38 and NT-proBNP to the CHA2DS2-VASc score significantly improved its predictive ability of AF-related all-cause death. Finally, the preference model performed equally well as the ABC score in predicting AF prognosis.
Determining the prevalence of childhood hypertension and its concomitant metabolic abnormalities using data mining methods in the Northeastern region of Hungary
Authors: Kovács Beáta , Németh Ákos , Daróczy Bálint , Karányi Zsolt , Maroda László , Diószegi Ágnes , Nádró Bíborka , Szabó Tamás , Harangi Mariann , Páll Dénes
Published: January 2023

Objective

Identifying hypertension in children and providing treatment for it have a marked impact on the patients’ long-term cardiovascular outcomes. The global prevalence of childhood hypertension is increasing, yet its investigation has been rather sporadic in Eastern Europe. Therefore, our goal was to determine the prevalence of childhood hypertension and its concomitant metabolic abnormalities using data mining methods.

Methods

We evaluated data from 3 to 18-year-old children who visited the University of Debrecen Clinical Center’s hospital throughout a 15-year study period (n = 92,198; boys/girls: 48/52%).

Results

We identified a total of 3,687 children with hypertension (2,107 boys and 1,580 girls), with a 4% calculated prevalence of hypertension in the whole study population and a higher prevalence in boys (4.7%) as compared to girls (3.2%). Among boys we found an increasing prevalence in consecutive age groups in the study population, but among girls the highest prevalences are identified in the 12-15-year age group. Markedly higher BMI values were found in hypertensive children as compared to non-hypertensives in all age groups. Moreover, significantly higher total cholesterol (4.27 ± 0.95 vs. 4.17 ± 0.88 mmol/L), LDL-C (2.62 ± 0.79 vs. 2.44 ± 0.74 mmol/L) and triglyceride (1.2 (0.85-1.69) vs. 0.94 (0.7-1.33) mmol/L), and lower HDL-C (1.2 ± 0.3 vs. 1.42 ± 0.39 mmol/L) levels were found in hypertensive children. Furthermore, significantly higher serum uric acid levels were found in children with hypertension (299.2 ± 86.1 vs. 259.9 ± 73.3 μmol/L), while glucose levels did not differ significantly.

Conclusion

Our data suggest that the calculated prevalence of childhood hypertension in our region is comparable to data from other European countries and is associated with early metabolic disturbances. Data mining is an effective method for identifying childhood hypertension and its metabolic consequences.
Association between a body shape index and abdominal aortic calcification in general population: A cross-sectional study
Authors: Li Wei , Wang Zhenwei , Li Min , Xie Jing , Gong Jing , Liu Naifeng
Published: January 2023

Background

The association between a body shape index (ABSI) and abdominal aortic calcification (AAC) is still unclear, so we tried to prove the association between ABSI and AAC in the general population in this cross-sectional study.

Materials and methods

After excluding participants with missing data on height, weight, waist circumference (WC), and AAC, we finally selected 3,140 participants aged 40–80 years from the 2013–2014 National Health and Nutrition Examination Survey. Using multivariate logistic regression and receiver operating characteristic (ROC) curves to test the association between ABSI and AAC.

Results

Participants (median age: 58.0 years; 48.3% men) were divided into two groups by the optimal cutoff point of ABSI: higher ABSI (> 0.84) and lower ABSI (≤ 0.84). Participants with higher ABSI showed significantly higher proportion of AAC than those with lower ABSI (39.8 vs. 23.7%, P < 0.001). Participants with higher ABSI had an increased risk of developing AAC in crude model (ABSI as a continuous variable: OR = 2.485, 95% CI: 2.099–2.942, P < 0.001; as a categorical variable: OR = 2.132, 95% CI: 1.826–2.489, P < 0.001), and ABSI was still independently associated with AAC in all adjusted models (all P < 0.05). Further subgroup analyses showed that higher ABSI was consistently associated with AAC in subgroups with sex (male or female), age (≤ 65 or > 65 years), smoking history (yes or no), hypertension (yes or no), diabetes (yes or no), sleep disorder (yes or no), body mass index (BMI) (< 23 or ≥ 23 kg/m2), systolic blood pressure (< 140 or ≥ 140 mmHg), diastolic blood pressure (< 90 or ≥ 90 mmHg), fasting plasma glucose (< 126 or ≥ 126 mg/dL), and low-density lipoprotein cholesterol (≤ 130 or > 130 mg/dL) (P for interaction > 0.05). While in other subgroups, the association was no longer synchronized. The ROC showed that the area under the curve of ABSI was significantly higher than height, weight, BMI, WC, and waist-to-height ratio (WHtR).

Conclusion

Higher ABSI was closely associated with higher risk of AAC, and discriminant ability of ABSI for AAC was significantly higher than height, weight, BMI, WC, and WHtR.
Approaches for the isolation and long-term expansion of pericytes from human and animal tissues
Authors: Alvino Valeria Vincenza , Mohammed Khaled Abdelsattar Kassem , Gu Yue , Madeddu Paolo
Published: January 2023

Pericytes surround capillaries in every organ of the human body. They are also present around the vasa vasorum, the small blood vessels that supply the walls of larger arteries and veins. The clinical interest in pericytes is rapidly growing, with the recognition of their crucial roles in controlling vascular function and possible therapeutic applications in regenerative medicine. Nonetheless, discrepancies in methods used to define, isolate, and expand pericytes are common and may affect reproducibility. Separating pure pericyte preparations from the continuum of perivascular mesenchymal cells is challenging. Moreover, variations in functional behavior and antigenic phenotype in response to environmental stimuli make it difficult to formulate an unequivocal definition of bona fide pericytes. Very few attempts were made to develop pericytes as a clinical-grade product. Therefore, this review is devoted to appraising current methodologies’ pros and cons and proposing standardization and harmonization improvements. We highlight the importance of developing upgraded protocols to create therapeutic pericyte products according to the regulatory guidelines for clinical manufacturing. Finally, we describe how integrating RNA-seq techniques with single-cell spatial analysis, and functional assays may help realize the full potential of pericytes in health, disease, and tissue repair.