Development of an Inactivated Vaccine Candidate, BBIBP-CorV, with Potent Protection against SARS-CoV-2.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) threatens global public health. The development of a vaccine is urgently needed for the prevention and control of COVID-19. Here, we report the pilot-scale production of an inactivated SARS-CoV-2 vaccine candidate (BBIBP-CorV) that induces high levels of neutralizing antibodies titers in mice, rats, guinea pigs, rabbits, and nonhuman primates (cynomolgus monkeys and rhesus macaques) to provide protection against SARS-CoV-2. Two-dose immunizations using 2 µg/dose of BBIBP-CorV provided highly efficient protection against SARS-CoV-2 intratracheal challenge in rhesus macaques, without detectable antibody-dependent enhancement of infection. In addition, BBIBP-CorV exhibits efficient productivity and good genetic stability for vaccine manufacture. These results support the further evaluation of BBIBP-CorV in a clinical trial.

Potent Neutralizing Antibodies against SARS-CoV-2 Identified by High-Throughput Single-Cell Sequencing of Convalescent Patients' B Cells.

The COVID-19 pandemic urgently needs therapeutic and prophylactic interventions. Here, we report the rapid identification of SARS-CoV-2-neutralizing antibodies by high-throughput single-cell RNA and VDJ sequencing of antigen-enriched B cells from 60 convalescent patients. From 8,558 antigen-binding IgG1+ clonotypes, 14 potent neutralizing antibodies were identified, with the most potent one, BD-368-2, exhibiting an IC50 of 1.2 and 15 ng/mL against pseudotyped and authentic SARS-CoV-2, respectively. BD-368-2 also displayed strong therapeutic and prophylactic efficacy in SARS-CoV-2-infected hACE2-transgenic mice. Additionally, the 3.8 Å cryo-EM structure of a neutralizing antibody in complex with the spike-ectodomain trimer revealed the antibody's epitope overlaps with the ACE2 binding site. Moreover, we demonstrated that SARS-CoV-2-neutralizing antibodies could be directly selected based on similarities of their predicted CDR3H structures to those of SARS-CoV-neutralizing antibodies. Altogether, we showed that human neutralizing antibodies could be efficiently discovered by high-throughput single B cell sequencing in response to pandemic infectious diseases.

A vaccine targeting the RBD of the S protein of SARS-CoV-2 induces protective immunity.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a respiratory disease called coronavirus disease 2019 (COVID-19), the spread of which has led to a pandemic. An effective preventive vaccine against this virus is urgently needed. As an essential step during infection, SARS-CoV-2 uses the receptor-binding domain (RBD) of the spike protein to engage with the receptor angiotensin-converting enzyme 2 (ACE2) on host cells1,2. Here we show that a recombinant vaccine that comprises residues 319-545 of the RBD of the spike protein induces a potent functional antibody response in immunized mice, rabbits and non-human primates (Macaca mulatta) as early as 7 or 14 days after the injection of a single vaccine dose. The sera from the immunized animals blocked the binding of the RBD to ACE2, which is expressed on the cell surface, and neutralized infection with a SARS-CoV-2 pseudovirus and live SARS-CoV-2 in vitro. Notably, vaccination also provided protection in non-human primates to an in vivo challenge with SARS-CoV-2. We found increased levels of RBD-specific antibodies in the sera of patients with COVID-19. We show that several immune pathways and CD4 T lymphocytes are involved in the induction of the vaccine antibody response. Our findings highlight the importance of the RBD domain in the design of SARS-CoV-2 vaccines and provide a rationale for the development of a protective vaccine through the induction of antibodies against the RBD domain.

The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19), which has become a public health emergency of international concern1. Angiotensin-converting enzyme 2 (ACE2) is the cell-entry receptor for severe acute respiratory syndrome coronavirus (SARS-CoV)2. Here we infected transgenic mice that express human ACE2 (hereafter, hACE2 mice) with SARS-CoV-2 and studied the pathogenicity of the virus. We observed weight loss as well as virus replication in the lungs of hACE2 mice infected with SARS-CoV-2. The typical histopathology was interstitial pneumonia with infiltration of considerable numbers of macrophages and lymphocytes into the alveolar interstitium, and the accumulation of macrophages in alveolar cavities. We observed viral antigens in bronchial epithelial cells, macrophages and alveolar epithelia. These phenomena were not found in wild-type mice infected with SARS-CoV-2. Notably, we have confirmed the pathogenicity of SARS-CoV-2 in hACE2 mice. This mouse model of SARS-CoV-2 infection will be valuable for evaluating antiviral therapeutic agents and vaccines, as well as understanding the pathogenesis of COVID-19.

BATF promotes tumor progression and association with FDG PET-derived parameters in colorectal cancer.

PURPOSE: The purpose of the study was to evaluate the expression and function of basic leucine zipper ATF-like transcription factor (BATF) in colorectal cancer (CRC), and its correlation with 2-deoxy-2[18F]fluoro-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) parameters. METHODS: The TIMER database, GEPIA database, TCGA, and GEO database were used to analyze the expression profile of BATF in human cancers. The reverse transcription­quantitative PCR and western blot analyses were used to evaluate the mRNA level and protein expression in different CRC cell lines. The expression of BATF in SW620 and HCT116 cells was silenced and cell counting kit-8 assays and clonogenic assay were utilized to evaluate the role of BATF in CRC proliferation. The expression of tumor BATF and glucose transporter 1 (GLUT-1) were examined using immunohistochemical tools in 37 CRC patients undergoing preoperative 18F-FDG PET/CT imaging. The correlation between the PET/CT parameters and immunohistochemical result was evaluated. RESULTS: In database, BATF was highly expressed in pan-cancer analyses, including CRC, and was associated with poor prognosis in CRC. In vitro, the results showed that knocking down of BATF expression could inhibit the proliferation of SW620 and HCT116 cells. In CRC patients, BATF expression was upregulated in tumor tissues compared with matched para-tumoral tissues, and was related with gender and Ki-67 levels. BATF expression was positively related to GLUT-1 expression and PET/CT parameters, including tumor size, maximum standard uptake value, metabolic tumor volume, and total lesion glycolysis. The multiple logistic analyses showed that SUVmax was an independent predictor of BATF expression. With 15.96 g/cm3 as the cutoff, sensitivity was 85.71%, specificity 82.61%, and area-under-the-curve 0.854. CONCLUSION: BATF may be an oncogene associated with 18F-FDG PET/CT parameters in CRC. SUVmax may be an independent predictor of BATF expression.

Identification of six genes associated with COVID-19-related circadian rhythm dysfunction by integrated bioinformatic analysis.

Patients with coronavirus disease 2019 (COVID-19) might cause long-term burden of insomnia, while the common pathogenic mechanisms are not elucidated. The gene expression profiles of COVID-19 patients and healthy controls were retrieved from the GEO database, while gene set related with circadian rhythm was obtained from GeneCards database. Seventy-six shared genes were screened and mainly enriched in cell cycle, cell division, and cell proliferation, and 6 hub genes were found out including CCNA2, CCNB1, CDK1, CHEK1, MKI67, and TOP2A, with positive correlation to plasma cells. In the TF-gene regulatory network, NFYA, NFIC, MEF2A, and FOXC1 showed high connectivity with hub genes. This study identified six hub genes and might provide new insights into pathogenic mechanisms and novel clinical management strategies.

Study on the correlation between false-positive filling defect in LAA CT and LAA structure in patients with atrial fibrillation based on TEE.

OBJECTIVE: This study aims to explore the actual meaning of "false positive filling defect" in left atrial appendage (LAA) computed tomography (CT) in patients with atrial fibrillation (AF), with transesophageal echocardiography (TEE) as the gold standard. METHODS: Patients with AF undergoing cardiac CT angiography and TEE examinations for proposed radiofrequency catheter ablation between October 2020 and October 2021 were selected as the study subjects. Transesophageal echocardiography was taken as the "gold standard," and spontaneous echocardiographic contrast (SEC) and thrombus events were defined as positive events. The CT manifestations were classified into three groups (true positive, false positive, and true negative) to evaluate the differences in left atrium (LA) anterior-posterior diameter (LAAP), LA anterior wall thickness, and LAA orifice long diameter and short diameter, area, and depth between the three groups. RESULTS: (1) There was no statistical difference in LA anterior wall thickness between the three groups (p > .05); there was a statistical difference in LAAP (only) between the true-positive group and the true-negative group (p < .05). (2) There was a statistical difference in LAA orifice long diameter, short diameter, and area between the true-positive group and the true-negative group as well as between the false-positive group and the true-negative group (p < .05). (3) There was a statistical difference in LAA depth between the true-positive group and the false-positive group as well as between the true-positive group and the true-negative group (p < .05). (4) The area under the receiver operator characteristic curve (AUC) of LAA depth affecting the LAA thrombus and SEC was 0.863 (confidence interval = 0.718-1.000), the sensitivity was 77.8%, and the specificity was 90.6% for predicting the occurrence of LAA thrombus and SEC in patients with nonvalvular AF (NVAF) and an LAA depth of ≥50.84 mm. CONCLUSIONS: There was a difference in LAA diameter between the TEE-based CT false-positive group and the other groups. A "CT false positive" is an objectively existing state, and CT might be able to identify the LAA hemodynamic disorder earlier than TEE. Furthermore, a CT + TEE combined application could more accurately evaluate LAA hemodynamics in patients with AF.

Coronary computed tomography angiography study on the relationship between the Ramus Intermedius and Atherosclerosis in the bifurcation of the left main coronary artery.

OBJECTIVE: This study aimed to explore the relationship between the ramus intermedius (RI) and atherosclerosis in the bifurcation of the left coronary artery (LCA). METHODS: Screening patients who underwent CCTA from January to September 2021, 100 patients with RI (RI group) and 100 patients without RI (no-RI group) were randomly enrolled, Evaluation of RI distribution characteristics and left main coronary artery(LM),Left anterior descending branch(LAD),left circumflex branch(LCX) proximal segment plaque distribution, measurement of LAD-LCX bifurcation angle(∠LAD-LCX),Comparison of the three distribution characteristics with the incidence of plaques in the left main trunk bifurcation area (LM, LAD, LCX) between groups and within the RI group. RESULTS: The difference in the incidence of plaques in the proximal LCX and the LM between the RI group and the no-RI group were not statistically significant (P > 0.05). The incidence of plaques in the proximal LAD in the RI group was significantly higher than that in the non-RI group (77% versus 53%, P < 0.05). However, there was no statistically significant difference between the two groups after PSM. A univariate logistic regression analysis revealed that an RI was a risk factor for plaque formation in the proximal LAD (P < 0.001), and a multivariate logistic regression analysis revealed that an RI was not an independent risk factor for plaque formation in the proximal LAD (P > 0.05). When compared within the RI group, the difference in the incidence of plaques in the proximal segment of LAD, the proximal segment of LCX, and the LM among the different distribution groups of RI was not statistically significant, respectively (P > 0.05). CONCLUSION: RI is not an independent risk factor for atherosclerosis in the left coronary artery bifurcation zone, but it may indirectly increase the risk of atherosclerosis in the proximal segment of the LAD.

Prognostic value of 18F-FDG PET/CT in malignant pleural mesothelioma: a meta-analysis.

BACKGROUND: Several FDG PET/CT parameters have been utilized to evaluate the prognosis in malignant pleural mesothelioma (MPM). However, there are still controversial results due to the low incidence of MPM. PURPOSE: To assess the prognostic value of 18F-FDG PET/CT in MPM. MATERIAL AND METHODS: A systematic literature search was performed in PubMed, Embase, Medline, and The Cochrane Library to identify eligible studies from inception to 12 February 2020. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) of several variables, such as maximum standardized uptake value (SUVmax), the reduction of SUVmax after treatment (ΔSUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and the reduction of TLG after treatment (ΔTLG), were calculated. Meta-regression with subsequent subgroup analyses were conducted to determine the heterogeneity of cutoff values, treatment regimen, study design, uptake time, and scanners across various studies. RESULTS: In total, 19 eligible studies including 1819 patients were enrolled in the meta-analysis. The univariate analysis showed that the pooled HRs (95% CI) of SUVmax, ΔSUVmax, MTV, TLG, and ΔTLG were 1.29 (1.16-1.42), 1.12 (1.05-1.19), 1.15 (1.00-1.33), 1.47 (1.23-1.76), and 1.27 (1.12-1.45), respectively. The multivariate analysis showed that the pooled HRs (95% CI) of SUVmax, ΔSUVmax, MTV, and TLG for overall survival (OS) were 1.20 (1.08-1.33), 1.10 (1.02-1.19), 0.95 (0.81-1.11), and 1.13 (1.08-1.18), respectively. CONCLUSION: SUVmax, ΔSUVmax, TLG, and ΔTLG are significant prognostic indicators for OS, while more clinical studies are needed to confirm the prognostic value of MTV in MPM.

PM2.5 exposure promotes asthma in aged Brown-Norway rats: Implication of multiomics analysis.

Children are disproportionately represented among those who suffer asthma, which is a kind of chronic airway inflammation. Asthma symptoms might worsen when exposed to the air pollutant particulate matter 2.5 (PM2.5). However, it is becoming more prevalent among older adults, with more asthma-related deaths occurring in this pollution than in any other age group, and symptoms caused by asthma can reduce the quality of life of the elderly, whose asthma is underdiagnosed due to physiological factors. Therefore, in an effort to discover a therapy for older asthma during exposure to air pollution, we sought to ascertain the effects of pre-exposure (PA) and persistent exposure (PAP) to PM2.5 in aged asthma rats. In this study, we exposed aged rats to PM2.5 at different times (PA and PAP) and established an ovalbumin-mediated allergic asthma model. The basic process of elderly asthma caused by PM2.5 exposure was investigated by lung function detection, enzyme-linked immunosorbent assay (ELISA), histopathology, cytology, cytokine microarray, untargeted metabolomics, and gut microbiota analysis. Our findings demonstrated that in the PA and PAP groups, exposure to PM2.5 reduced lung function and exacerbated lung tissue damage, with varying degrees of effect on immunoglobulin levels, the findings of a cytological analysis, cytokines, and chemokines. The PA and PAP rats had higher amounts of polycyclic aromatic hydrocarbons (PAHs), such as naphthalene, 2-methylNaphthalene, 1-methylNaphthalene and flourene. Moreover, exposure to PM2.5 at different times showed different effects on plasma metabolism and gut microbiota. Bioinformatics analysis showed a strong correlation between PAHs, cytokines, and gut microbiota, and PAHs may cause metabolic disorders through the gut microbiota. These findings point to a possible mechanism for the development of asthma in older people exposure to PM2.5 that may be related to past interactions between PAHs, cytokines, gut microbiota, and plasma metabolites.

The temporal characteristics of the disruption of gut microbiota, serum metabolome, and cytokines by silica exposure in wistar rats.

Silicosis is one of the most frequent, rapidly developing, and lethal types of pneumoconiosis. However, our understanding of the underlying mechanisms of its pathogenesis and progress remains unclear. We investigated the fundamental processes of silicosis incidence and progression using a combination of lung function testing, histopathology, 16 S rRNA, untargeted metabolomics, and cytokine chips at different exposure times (4 or 8 weeks). The results show that silica exposure damages lung tissue reduces lung function, and increases with time. Cytokines with time-specific properties were found in lung lavage fluid: IFN-γ (4 weeks; P＜0.05), TNF-α, M-CSF, GM-CSF (8 weeks; P＜0.01). In addition, silica exposure for different periods interferes to varying degrees with the metabolism of lipids. The composition of the intestinal microbiota changed with increasing exposure time and there were time-specific: Allobaculum, Turicibacter、Jeotgalicoccu、Coprococcus 1 (4 weeks; P＜0.05), Ruminococcaceae NK4A214 group、Ruminiclostridium 5 (8 weeks; P＜0.05). We found strong associations between cytokines, gut microbiota changes, and metabolic disturbances at different exposure times. These results suggest that time-specific changes in crosstalk among cytokines, the gut microbiota, and metabolites may be a potential mechanism for silica-induced lung injury.

Excitation mechanism and application of continuous-order mode for one-dimensional thickness vibration.

The main method to expand the operating bandwidth of the transducer is by exciting multi-order vibration modes, which develop from the earliest excitation of odd-order modes to the excitation of multi-order continuous modes. However, no detailed theoretical characterization of the excitation mechanism and electroacoustic properties of continuous-order modes has been given. In this paper, the excitation mechanism of continuous-order modes for one-dimensional thickness vibration is studied in detail. From the perspective of analytical characterization, the mathematical and physical conditions of mode excitation are analyzed and extended to continuous-order modes. Partial 1-3 piezocomposite consists of two parts; one part is complete lead zirconate-titanate and the other part is 1-3 composite, which is helpful for exciting continuous-order modes. Based on the excitation mechanism of continuous-order modes, a design method of broadband transducer used of partial 1-3 piezocomposite is proposed, and large bandwidth and good pulse response are obtained. The excitation mechanism of continuous-order modes proposed in this paper provides an idea for the theoretical analysis and design of multi-resonant broadband transducers.

Comparative pathology of the nasal epithelium in K18-hACE2 Tg mice, hACE2 Tg mice, and hamsters infected with SARS-CoV-2.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes severe viral pneumonia and is associated with a high fatality rate. A substantial proportion of patients infected by SARS-CoV-2 suffer from mild hyposmia to complete loss of olfactory function, resulting in anosmia. However, the pathogenesis of the olfactory dysfunction and comparative pathology of upper respiratory infections with SARS-CoV-2 are unknown. We describe the histopathological, immunohistochemical, and in situ hybridization findings from rodent models of SARS-CoV-2 infection. The main histopathological findings in the olfactory epithelia of K8-hACE2 Tg mice, hACE2 Tg mice, and hamsters were varying degrees of inflammatory lesions, including disordered arrangement, necrosis, exfoliation, and macrophage infiltration of the olfactory epithelia, and inflammatory exudation. On the basis of these observations, the nasal epithelia of these rodent models appeared to develop moderate, mild, and severe rhinitis, respectively. Correspondingly, SARS-CoV-2 viral RNA and antigen were mainly identified in the olfactory epithelia and lamina propria. Moreover, viral RNA was abundant in the cerebrum of K18-hACE2 Tg mice, including the olfactory bulb. The K8-hACE2 Tg mouse, hACE2 Tg mouse, and hamster models could be used to investigate the pathology of SARS-CoV-2 infection in the upper respiratory tract and central nervous system. These models could help to provide a better understanding of the pathogenic process of this virus and to develop effective medications and prophylactic treatments.

Impact of relative dose intensity of R-CCOP regimen in elderly patients with diffuse large B-cell lymphoma in China.

BACKGROUND: The actual relative dose intensity (RDI) of the attenuated R-CCOP regimen (rituximab, cytoxan, pegylated liposomal doxorubicin [PLD], vincristine, and prednisone) has not been fully investigated in Chinese geriatric patients with diffuse large B-cell lymphoma (DLBCL). In particular, the optimum dose for PLD remains unclear. METHODS: We retrospectively collected clinical data from patients with untreated DLBCL aged 65-80 years subsequently treated with the R-CCOP. The restricted cubic spline model (RCS) was used to test the non-linear relationship between the predictors and outcomes. RESULTS: Eighty-four patients were enrolled, with a median age of 73.5 years. More than half of the patients (54.8%) received at least 6 cycles. The median dose per cycle of cytoxan and PLD were 605.5 and 19.9 mg/m2. The 5-year progression-free survival (PFS), overall survival rate, and disease-specific survival rates were 38.7%, 44.8%, and 57.2%, respectively. The RDI of PLD (PLD-RDI, <70% vs ≥ 70%) was only significant in the univariate analysis (P = 0.002) but not in the multivariate analysis. The RCS model showed a decreasing trend of hazards with an increasing PLD dose per cycle after adjustment. No significant difference was observed between the low- and high-risk groups with PLD-RDI ≥ 70% (P = 0.548). However, patients in the high-risk group had unfavorable PFS with PLD-RDI < 70% (P = 0.006). CONCLUSION: The optimal dose of PLD for elderly patients with DLBCL in China remains to be determined. Evaluating the tolerance and identifying risk categories are critical for clinical decision-making in this population.

Diacylglycerol Acyltransferase 3(DGAT3) Is Responsible for the Biosynthesis of Unsaturated Fatty Acids in Vegetative Organs of Paeonia rockii.

'Diacylglycerol acyltransferase (DGAT)' acts as a key rate-limiting enzyme that catalyzes the final step of the de novo biosynthesis of triacylglycerol (TAG). The study was to characterize the function of the DGAT3 gene in Paeonia rockii, which is known for its accumulation of high levels of unsaturated fatty acids (UFAs). We identified a DGAT3 gene which encodes a soluble protein that is located within the chloroplasts of P. rockii. Functional complementarity experiments in yeast demonstrated that PrDGAT3 restored TAG synthesis. Linoleic acid (LA, C18:2) and α-linolenic acid (ALA, C18:3) are essential unsaturated fatty acids that cannot be synthesized by the human body. Through the yeast lipotoxicity test, we found that the yeast cell density was largely increased by adding exogenous LA and, especially, ALA to the yeast medium. Further ectopic transient overexpression in Nicotiana benthamiana leaf tissue and stable overexpression in Arabidopsis thaliana indicated that PrDGAT3 significantly enhanced the accumulation of the TAG and UFAs. In contrast, we observed a significant decrease in the total fatty acid content and in several major fatty acids in PrDGAT3-silenced tree peony leaves. Overall, PrDGAT3 is important in catalyzing TAG synthesis, with a substrate preference for UFAs, especially LA and ALA. These results suggest that PrDGAT3 may have practical applications in improving plant lipid nutrition and increasing oil production in plants.

Risk and protective factors associated with grandparent kinship caregivers' psychological distress in COVID-19: Kinship license status as a moderator.

COVID-19 and its related policy measures have increased the psychological distress of individuals, including grandparent kinship caregivers. Guided by the Resilience Model of Family Stress, Adjustment, and Adaptation, this study examines relationships between material hardship, parenting stress, social support, resilience and psychological distress of grandparent kinship caregivers during the COVID-19 pandemic, as well as the moderating role of kinship license status on these relationships. Kinship care licensing is a prerequisite to receiving financial assistance and other supporting services from the government. We administered a cross-sectional survey of grandparent kinship caregivers (N = 362) in the United States. Logistic regression results indicated that material hardship was associated with higher odds of experiencing psychological distress, whereas resilience and social support were associated with lower odds. Kinship license status moderated the relationships of social support and resilience with psychological distress. Results suggest that additional emergency funds and more tailored financial services should be provided to meet material needs, and interventions with a focus on resilience and social support are particularly needed. The moderating effects of license status indicate that some interventions should be specifically implemented among licensed kinship caregivers, whereas parallel services should be provided to kinship caregivers regardless of their license status.

Hostility in medication-resistant major depression and comorbid generalized anxiety disorder is related to increased hippocampal-amygdala 5-HT2A receptor density.

Major depressive disorder (MDD) and generalized anxiety disorder (GAD) are severe and difficult-to-treat psychiatric illnesses with high rates of comorbidity. Although both disorders are treated with serotonergic based psychotropic agents, little is known on the influence of the serotonergic neurotransmitter system on the occurrence of comorbid GAD when clinically depressed. To investigate this poorly understood clinical question, we examined the involvement of frontolimbic post-synaptic 5-HT2A receptors in 20 medication-resistant depressed (MRD) patients with half of them diagnosed with comorbid GAD with 123I-5-I-R91150 SPECT. To explore whether 5-HT2A receptor-binding indices (BI) associated with comorbid GAD could be related to distinct psychopathological symptoms, all were assessed with the symptom Checklist-90-Revised (SCL-90-R). MRD patients with comorbid GAD displayed significantly higher 5-HT2A receptor BI in the hippocampal-amygdala complex, compared to MRD patients without GAD. Correlation analyses revealed that the 5-HT2A receptor BI in these areas were significantly related to the SCL-90-R subscale hostility (HOS), especially for those MRD patients with comorbid GAD. Comorbid MRD-GAD may be characterized with increased hippocampal-amygdala 5-HT2A receptor BI which could represent enhanced levels in hostility in such kinds of patients. Adapted psychotherapeutic interventions may be warranted.

Ganoderma lucidum triterpenoids and polysaccharides attenuate atherosclerotic plaque in high-fat diet rabbits.

BACKGROUND AND AIMS: Atherosclerosis is characterized by lipid deposition, oxidative stress, and inflammation in the arterial intima. Ganoderma lucidum triterpenoids (GLTs) and polysaccharides (GLPs) are traditional Chinese medicines with potential cardiovascular benefits. We aimed to comprehensively evaluate the effect of GLTs and GLPs on atherosclerosis and the associated underlying mechanisms in vivo and in vitro. METHODS AND RESULTS: Japanese big-ear white rabbits were randomly divided into three groups of blank, model, and treatment, and the treatment group was fed with GLSO and GLSP (0.3 g/kg body-weight/day) for 4 months. Serum levels of triglyceride (TG), total (TC), and low density lipoprotein cholesterol (LDL-C) in GL treatment group were significantly lower than those in the model group. The area of aortic plaques was significantly reduced in the treatment group. Further, GL administration in oxidized low-density lipoprotein (ox-LDL) stimulated human umbilical vein endothelial cells (HUVECs) reduced the generation of reactive oxygen species (ROS) and malondialdehyde (MDA) by inhibiting the upregulation of the nuclear transcription factor (NF)-κB p65 and the relative receptor LOX-1. In THP-1 cells treated with phorbol myristate acetate, GL inhibited the inflammatory polarization of macrophages (as evidenced by reduced TNF-α levels) via regulation of Notch1 and DLL4 pathways. Ox-LDL-stimulated THP-1 cells treated with GL showed an increase in the apoptosis of foam cells. CONCLUSIONS: GLTs and GLPs attenuated the progression of atherosclerosis by alleviating endothelial dysfunction and inflammatory polarization of macrophages, thus promoting apoptosis of foam cells.

Correction: Yang et al. Chebulagic Acid, a Hydrolyzable Tannin, Exhibited Antiviral Activity in Vitro and in Vivo against Human Enterovirus 71. Int. J. Mol. Sci. 2013, 14, 9618.

The authors wish to make the following corrections to this paper [...].