Publications by authors named "Biao Xu"

463 Publications

Ultrasmall Fe(III)-Tannic Acid Nanoparticles To Prevent Progression of Atherosclerotic Plaques.

ACS Appl Mater Interfaces 2021 Jul 19. Epub 2021 Jul 19.

Department of Radiology, Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China.

Macrophage accumulation is central to the pathogenesis of atherosclerotic plaques. Reducing macrophages in plaques is an appealing approach to attenuate the development of atherosclerosis. Chemodynamic therapy, specifically inhibiting hydrogen peroxide (HO)-rich cells in slightly acidic microenvironment, has emerged as a new method in tumor treatment. Herein, we manufactured ultrasmall dopamine-modified hyaluronic acid (HD)-stabilized Fe(III)-tannic acid nanoparticles (HFTNPs). HFTNPs can specifically accumulate in inflammatory macrophages in atherosclerotic plaques, provide brighter magnetic resonance images, promote reactive oxygen species (ROS) generation, and induce the death of inflammatory macrophages without damaging normal cells and tissues. In conclusion, HFTNPs have a tremendous potential as safe and effective diagnostic and therapeutic reagents for atherosclerosis.
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http://dx.doi.org/10.1021/acsami.1c09480DOI Listing
July 2021

Utilization of preconception care and its impacts on health behavior changes among expectant couples in Shanghai, China.

BMC Pregnancy Childbirth 2021 Jul 7;21(1):491. Epub 2021 Jul 7.

School of Public Health, China Studies Centre, University of Sydney, Room 313, Edward Ford Building, Sydney, 2006, Australia.

Background: Preconception care is an opportunity for detecting potential health risks in future parents and providing health behavior education to reduce morbidity and mortality for women and their offspring. Preconception care has been established in maternal and child health hospitals in Shanghai, China, which consists of health checkups, health education and counseling. This study investigated factors associated with the utilization of preconception care, and the role of preconception care on health behavior changes before conception among pregnant women and their partners.

Methods: A cross-sectional study was conducted among pregnant women at three maternal and child health hospitals in Shanghai. The participants were invited to complete a self-administered questionnaire on the utilization of preconception care and health behavioral changes before conception.

Results: Of the 948 recruited pregnant women, less than half (42.2%) reported that they had utilized preconception care before the current pregnancy. Unplanned pregnancy, unawareness of preconception care and already having a general physical examination were the main reasons for not attending preconception care. The two main sources of information about preconception care were local community workers and health professionals. Younger women and the multipara were less likely to utilize preconception care. Women who utilized preconception care were more likely to take folic acid supplements before conception [Adjusted Odds Ration (aOR) 3.27, 95% Confidence Interval (CI) 2.45-4.36, P < 0.0001]. The partners of pregnant women who had attended preconception care services were more likely to stop smoking [aOR 2.76, 95%CI 1.48-5.17, P = 0.002] and to stop drinking [aOR 2.13, 95%CI 1.03-4.39, P = 0.041] before conception.

Conclusions: Utilization of preconception care was demonstrated to be positively associated with preconception health behavior changes such as women taking folic acid supplements before pregnancy, their male partner stopping smoking and drinking before conception. Future studies are needed to explore barriers to utilizing preconception care services and understand the quality of the services. Strategies of promoting preconception care to expectant couples, especially to young and multipara women, should be developed to further improve the utilization of the services at the community level.
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http://dx.doi.org/10.1186/s12884-021-03940-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262048PMC
July 2021

Coronary Plaque Characterization From Optical Coherence Tomography Imaging With a Two-Pathway Cascade Convolutional Neural Network Architecture.

Front Cardiovasc Med 2021 16;8:670502. Epub 2021 Jun 16.

School of Biological Science and Medical Engineering, Southeast University, Nanjing, China.

The morphological structure and tissue composition of a coronary atherosclerotic plaque determine its stability, which can be assessed by intravascular optical coherence tomography (OCT) imaging. However, plaque characterization relies on the interpretation of large datasets by well-trained observers. This study aims to develop a convolutional neural network (CNN) method to automatically extract tissue features from OCT images to characterize the main components of a coronary atherosclerotic plaque (fibrous, lipid, and calcification). The method is based on a novel CNN architecture called TwopathCNN, which is utilized in a cascaded structure. According to the evaluation, this proposed method is effective and robust in the characterization of coronary plaque composition from OCT imaging. On average, the method achieves 0.86 in F1-score and 0.88 in accuracy. The TwopathCNN architecture and cascaded structure show significant improvement in performance ( < 0.05). CNN with cascaded structure can greatly improve the performance of characterization compared to the conventional CNN methods and machine learning methods. This method has a higher efficiency, which may be proven to be a promising diagnostic tool in the detection of coronary plaques.
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http://dx.doi.org/10.3389/fcvm.2021.670502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241907PMC
June 2021

Mononuclear phagocyte system blockade using extracellular vesicles modified with CD47 on membrane surface for myocardial infarction reperfusion injury treatment.

Biomaterials 2021 Jun 28;275:121000. Epub 2021 Jun 28.

Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China; Institute of Biomedical Science, Fudan University, Shanghai, China. Electronic address:

Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) with anti-apoptotic and anti-inflammatory properties have been intensively studied. However, rapid clearance by the mononuclear phagocyte system remains a huge barrier for the delivery of extracellular vesicle contents into target organs and restricts its wider application, particularly in the heart. CD47 is a transmembrane protein that enables cancer cells to evade clearance by macrophages through CD47 signal regulatory proteinα binding, which initiates a "don't eat me" signal. This study aimed to explore the biodistribution and delivery efficiency of EVs carrying the membrane protein CD47 and specific anti-apoptotic miRNAs. EVs were isolated from MSCs overexpressing CD47 (CD47-EVs) and identified. Fluorescence-labeled EVs were injected through the tail vein and tracked using fluorescence imaging. In silico analysis was performed to determine miRNA profiles in MSCs and in a heart-derived H9c2 cardiomyoblast cell line under hypoxia vs. normoxia conditions. Electro CD47-EV was constructed by encapsulating purified CD47-EV with miR-21a via electroporation. The effect of miR21-EVs on the pro-apoptotic gene encoding phosphatase and tensin homolog (PTEN) was evaluated by dual-luciferase assay, qPCR, and western blotting. Exogenous miR21 distribution, PTEN protein level, blood vessel density, anti-apoptotic effect by TdT-mediated dUTP nick-end labeling staining, and macrophage and leukocyte infiltration in the myocardium were assessed by immunofluorescence staining. Cardiac functional recovery during the early stage and recovery period was evaluated using echocardiography. The results showed that CD47-EVs were still detectable in the plasma 120 min after the tail vein injection, compared to the detection time of less than 30 min observed with the unmodified EVs. More strikingly, CD47-EVs preferentially accumulated in the heart in the ischemia-reperfusion (I/R) + CD47-EV group [heart total fluorescence radiance ( × 10 Photons/sec/cm/sr) 51.62 ± 11.30 v.s. 10.08 ± 3.15 in the I/R + unmodified EVs group] 8 h post-injection. Exogenous miR-21 is efficiently internalized into cardiomyocytes, inhibits apoptosis, alleviates inflammation, and improves cardiac function. In conclusion, electro CD47-EVs efficiently improve biodistribution in the heart, shedding new light on the application of a two-step EV delivery method (CD47 genetic modification followed by therapeutic content electrotransfection) as a potential therapeutic tool for myocardial I/R injury that may benefit patients in the future.
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http://dx.doi.org/10.1016/j.biomaterials.2021.121000DOI Listing
June 2021

PM2.5 induces endothelial dysfunction via activating NLRP3 inflammasome.

Environ Toxicol 2021 Jun 26. Epub 2021 Jun 26.

Department of Cardiology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China.

PM2.5 (particulate matter <2.5 μm in diameter) is proven to contribute to the development of atherosclerosis. Endothelial cell dysfunction is the initial step of atherosclerosis. The underlying mechanisms of endothelial cell damage exposed to PM2.5 are still obscure. In our study, PM2.5 was administrated to C57BL/6 male mice by intranasal instillation for 2 weeks. Human umbilical vein endothelial cells (HUVECs) were also treated with PM2.5 to evaluate the adverse effect in vitro. The immunohistochemical staining of aortas showed that the expressions of proinflammatory cytokines and endothelial adhesion markers were significantly increased in PM2.5-exposed mice than that in saline-exposed mice. In vitro, PM2.5 could inhibit HUVECs viability and impair cell migration in a concentration-dependent manner. Besides, PM2.5 exposure downregulated eNOS expression while upregulated reactive oxygen species (ROS) levels. Mechanistically, PM2.5 activated the NLRP3 inflammasome in HUVECs while knockdown of NLRP3 could effectively reverse the downregulation of eNOS expression and production of ROS after PM2.5 exposure. In summary, our data showed that PM2.5 could cause endothelial dysfunction, and probably via NLRP3 inflammasome activation.
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http://dx.doi.org/10.1002/tox.23309DOI Listing
June 2021

Factors associated with microvascular occlusion in patients with ST elevation myocardial infarction after primary percutaneous coronary intervention.

J Int Med Res 2021 Jun;49(6):3000605211024490

Department of Cardiology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China.

Objective: This study aimed to determine predictors of microvascular occlusion (MVO) in patients with ST elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (pPCI).

Methods: This retrospective, observational study consecutively included 113 patients with STEMI undergoing pPCI. Cardiac magnetic resonance imaging was used to determine the presence of MVO in these patients. Biomarkers in serum were routinely tested 1 day after pPCI. Multivariable logistic regression analysis was used to evaluate significant predictors of occurrence of MVO.

Results: There were 62 patients in the MVO group and 51 patients in the non-MVO group. C-reactive protein (CRP), thrombomodulin, lymphatic vessel endothelial hyaluronan receptor-1, syndecan-1, and troponin T (TnT) levels after the procedure were significantly higher in the MVO group than in the non-MVO group. CRP (hazard ratio [HR]=1.036), TnT (HR=1.316), and syndecan-1 (HR=1.986) levels were independently associated with MVO in patients with acute myocardial infarction after pPCI.

Conclusions: Levels of CRP, TnT, and syndecan-1 can be used as serum biomarkers for MVO in patients with STEMI receiving pPCI.
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http://dx.doi.org/10.1177/03000605211024490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236804PMC
June 2021

Clinical characteristics and predictive factors of erythema nodosum in granulomatous lobular mastitis.

Australas J Dermatol 2021 Jun 9. Epub 2021 Jun 9.

Department of Mammary Disease, The Second affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.

Background/objectives: In recent years, there is a growing incidence of granulomatous lobular mastitis (GLM), but studies about the coexistence of erythema nodosum (EN) and GLM are rare. In this study, we assess the clinical characteristics and predictive factors of EN in GLM.

Methods: A total of 303 patients diagnosed with GLM were enrolled from January 2012 to October 2018 at the second affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, including 78 patients with EN. Follow-up data included: lesion site, lesion size, therapy approaches, course of GLM, course of EN, the recurrence of disease, possible causes. All patients had pathologic confirmation of GLM based on core needle biopsy (CNB) or surgical excision.

Result: Fever in the EN group was significantly more common compared to the non-EN group (44.87% vs 12.89%, P < 0.001). The proportion of lesion range >2 quadrants in the EN group was significantly higher than that in the non-EN group (42.31% vs 16.00%, P < 0.001). The course of the disease was longer in the EN group compared to the non-EN group (10.32 moths vs 8.74 moths, P < 0.001). Patients with EN had a trend towards a higher risk of recurrence (5.13% vs 1.33%, P = 0.055).

Conclusion: EN is more likely to be found in GLM patients with breast lesion range >2 quadrants. The presence of EN in GLM indicates that the condition becomes more severe and the course of GLM also becomes longer.
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http://dx.doi.org/10.1111/ajd.13640DOI Listing
June 2021

Empagliflozin Alleviates Atherosclerosis Progression by Inhibiting Inflammation and Sympathetic Activity in a Normoglycemic Mouse Model.

J Inflamm Res 2021 31;14:2277-2287. Epub 2021 May 31.

Department of Cardiology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, 210008, Jiangsu, People's Republic of China.

Background: Recent clinical studies have revealed that sodium glucose co-transporter 2 inhibitors (SGLT2i) reduced cardiovascular events in type 2 diabetes. Here, we investigated whether empagliflozin, as a kind of SGLT2i, could alleviate atherosclerosis progression in non-diabetic mice.

Methods: -/- mice were fed on a western diet for 12 weeks to induce atherosclerosis. The treatment group of mice was treated with drinking water containing empagliflozin (10mg/kg/day). On the 12th week, the whole aortas of each group were harvested. HE and Movat staining were performed for atherosclerotic lesion area and size. CD 68 and MCP-1 immunohistochemistry were used to evaluate inflammatory cell infiltration. Mouse serum lipid profiles (total cholesterol, triglyceride, low-density lipoprotein-C, and high-density lipoprotein-C), systemic inflammation level (IL-1β, IL-6 and IL-10), renin-angiotensin-aldosterone system (RAAS) and sympathetic activity (norepinephrine and neuropeptide Y) were measured by ELISA.

Results: Empagliflozin could reduce the atherosclerotic lesion areas. Specifically, empagliflozin could significantly decreased inflammatory levels, RAAS and sympathetic activity in vivo. In vitro studies also showed that empagliflozin could inhibit IL-1β expression in oxLDL-treated macrophages by regulating NF-κB signaling.

Conclusion: Empagliflozin could prevent atherosclerosis by repressing inflammation and sympathetic activity.
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http://dx.doi.org/10.2147/JIR.S309427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180283PMC
May 2021

Oral Health Status of 12-Year-Old Hani Children in the Yunnan Province of China: A Cross-Sectional Study.

Int J Environ Res Public Health 2021 05 16;18(10). Epub 2021 May 16.

Faculty of Dentistry, The University of Hong Kong, Hong Kong, China.

Background: The aim of this cross-sectional study was to investigate the oral health status of Hani 12-year-old children in Yunnan, a province in Southwest China.

Method: This study employed a multistage sampling method to recruit children from local primary schools. Two calibrated dentists examined the status of dental caries, gingival bleeding and dental fluorosis by adopting the diagnosis criteria recommended by the World Health Organization. A self-administrated questionnaire was distributed. The chi-square test and multivariate logistic regression were conducted.

Results: This study invited 480 Hani children, and recruited 413 children (52% boys) (response rate: 86%). The dental caries prevalence was 52%, and the caries experience associated with the mean (standard deviation) decayed, missing and filled teeth (DMFT) score was 1.10 (1.46). Gingival bleeding was diagnosed in 252 children (61%), and dental fluorosis was found in two children (0.5%). The results of the regression model indicated the prevalence of dental caries were associated with sugary snacking habits ( = 0.002). The prevalence of gingival bleeding was related to the mother's education level as well as the child's monthly pocket money ( < 0.05).

Conclusion: Dental caries and gingival bleeding were prevalent among 12-year-old Hani children in the Yunnan province in China. Dental fluorosis was uncommon.
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http://dx.doi.org/10.3390/ijerph18105294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156634PMC
May 2021

Osteoporosis was associated with severe abdominal aortic calcification based on a cross-sectional study.

Arch Osteoporos 2021 05 19;16(1):79. Epub 2021 May 19.

Department of Cardiology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China.

Abdominal aortic calcification and osteoporosis are age-related diseases. Based on a nationally representative US population, we concluded that osteoporosis may be independently associated with severe abdominal aortic calcification, which could improve our insights into the prevention and management of vascular disease.

Introduction: Abdominal aortic calcification (AAC) and osteoporosis are age-related diseases and share similar pathological mechanisms. However, the association between osteoporosis and AAC is uncertain.

Methods: A total of 3134 participants with complete record of AAC score calculated from dual-energy X-ray absorptiometry (DXA) were enrolled from the National Health and Nutrition Examination Survey (NHANES) 2013-2014. The diagnosis of osteoporosis was obtained from self-reported interview. The baseline covariates were compared between participants with and without osteoporosis. Multivariable logistic regression was performed to examine the association between abdominal aortic calcification and osteoporosis.

Results: Compared with those without osteoporosis, participants with osteoporosis had higher AAC scores. Osteoporosis was positively associated with higher odds of severe AAC (OR = 2.65; 95%CI, 1.89-3.71; P < 0.001), and the association was not altered (OR = 2.17; 95%CI, 1.23-3.83; P = 0.008) after adjusting for numerous covariates.

Conclusions: Our findings suggest that osteoporosis may be independently associated with severe abdominal aortic calcification.
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http://dx.doi.org/10.1007/s11657-021-00927-4DOI Listing
May 2021

Predictive Value of Blood Ammonia in the Prognosis of Acute Liver Failure Evaluated by Receiver Operating Characteristic Curves.

Turk J Gastroenterol 2021 02;32(2):164-168

Critical Care Center, Fifth Medical Center of Chinese PLA Hospital, Beijing, China.

Background: To investigate the predictive value of blood ammonia (BLA) quantification in the prognosis of acute liver failure (ALF).

Methods: Seventy-one patients with ALF were enrolled and BLA concentration was measured in all patients. After following up for 28 days, patients were divided into two groups: the surviving group (n = 21) and the deceased group (n = 50). An independent-samples t-test was used to compare BLA concentrations between the two groups, and receiver operating characteristic curves were used to ¬evaluate the predictive value of BLA in the prognosis of ALF. A fourfold table analysis was performed with the determined BLA cutoff value.

Results: The average concentration of BLA in the deceased group was significantly higher compared with the surviving group (144.50 µmol/L vs. 106 µmol/L, respectively; P = .035). The cutoff BLA concentration for a good ALF prognosis was 122.5 µmol/L. The area under the curve was 0.659. Both the sensitivity and specificity were >0.6. The 95% CIs for sensitivity and specificity were 0.452-0.733 and 0.477-0.878, respectively. The fourfold table analysis revealed a positive predictive value of 83.3%, a negative predictive value of 42.9%, a misdiagnosis rate of 28.6%, and an accuracy of 63.4%.

Conclusion: With a cutoff BLA concentration of 122.5 µmol/L, the prognosis of ALF could be predicted with high sensitivity and specificity, a positive predictive value, a low misdiagnosis rate, and good accuracy.
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http://dx.doi.org/10.5152/tjg.2021.19663DOI Listing
February 2021

Cardioprotective Roles of β-Hydroxybutyrate Against Doxorubicin Induced Cardiotoxicity.

Front Pharmacol 2020 15;11:603596. Epub 2021 Apr 15.

Department of Cardiology, Nanjing Drum Tower Hospital as Affiliated Drum Tower Hospital, Nanjing, China.

β-Hydroxybutyrate (BHB) is produced by fatty acid oxidation in the liver under the fasting state and confirmed to play a cardioprotective role in ischemia and hypertensive settings. Doxorubicin (DOX) is an effective chemotherapeutic drug, but limited by serious irreversible cardiotoxicity. However, whether BHB can protect from DOX-induced cardiotoxicity remains unknown. C57BL/6 mice were intraperitoneally injected with DOX to induce cardiac toxicity and intragastrically administered into BHB for treatment. They were randomly divided into three groups, namely a sham group (Sham), a doxorubicin group (DOX), and a doxorubicin+β-Hydroxybutyrate group (DOX + BHB). Echocardiography and pathological staining were performed to evaluate cardiac function and fibrosis. H9c2 cardiomyocyte was treated with DOX or BHB for experiments. Cell apoptosis and ROS were determined by flow cytometry. BHB significantly restored DOX-induced cardiac function decline and partially prevented cardiac reverse remodeling, characterized by increased cell size and decreased fibrosis. , BHB treatment decreased cellular injury and apoptosis. Also, BHB alleviated oxidative stress level and increased mitochondrial membrane potential. Our results suggested that BHB could protected from DOX-induced cardiotoxicity by inhibiting cell apoptosis and oxidative stress and maintaining mitochondrial membrane integrity.
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http://dx.doi.org/10.3389/fphar.2020.603596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082360PMC
April 2021

Spinal endomorphins attenuate burn-injury pain in male mice by inhibiting p38 MAPK signaling pathway through the mu-opioid receptor.

Eur J Pharmacol 2021 Jul 30;903:174139. Epub 2021 Apr 30.

Key Laboratory of Preclinical Study for New Drugs of Gansu Province, And Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou, Gansu, 730000, China. Electronic address:

Burn injury is one of the main causes of mortality worldwide and frequently associated with severe and long-lasting pain that compromises the quality of patient life. Several studies have shown that the mu-opioid system plays an important role in burn pain relief. In this study, we investigated the spinal antinociception induced by the endogenous mu-opioid receptor (MOR) agonists endomorphins and explored their mechanisms of actions in burn injury-induced pain model. Our results showed that intrathecal injection of endomorphin-1 and -2 dose-dependently attenuated mechanical allodynia and thermal hyperalgesia via the mu-opioid receptor in mice on day 3 after burn injury, which was consistent with the data obtained from the mu-opioid receptor knockout mice. Western blot showed that the phosphorylation levels of extracellular signal-regulated kinase1/2 (ERK1/2) and p38 mitogen-activated protein kinase (p38 MAPK) in ipsilateral spinal cord tissues were significantly up-regulated after burn injury. Intrathecal injection of endomorphins selectively inhibited the activation of p38 MAPK on day 3 after burn injury via the mu-opioid receptor. Further studies found that repeated application of the specific p38 MAPK inhibitor SB203580 dose-dependently inhibited burn-injury pain, as well as the activation of spinal p38 MAPK. Taken together, our present study demonstrates that intrathecal injection of endomorphins attenuates burn-injury pain in male mice by affecting the spinal activation of p38 MAPK via the mu-opioid receptor.
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http://dx.doi.org/10.1016/j.ejphar.2021.174139DOI Listing
July 2021

Danon disease: a case report and literature review.

Diagn Pathol 2021 May 1;16(1):39. Epub 2021 May 1.

Department of Cardiology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210008, P.R. China.

Background: Danon disease (DD) is a rare x-linked dominant multisystemic disorder with a clinical triad of severe cardiomyopathy, skeletal myopathy, and mental retardation. It is caused by a defect in the lysosomal-associated membrane protein-2 (LAMP2) gene, which leads to the formation of autophagic vacuoles containing glycogen granule deposits in skeletal and cardiac muscle fibers. So far, more than 50 different mutations in LAMP2 have been identified.

Case Presentation: Here, we report an 18-year-old male patient who was hospitalized for heart failure. Biopsy of the left lateral femoral muscle revealed scattered autophagic vacuoles in the muscle fibers with increased glycogen. Next generation sequencing (NGS) was used to detect gene mutations of the proband sample and a novel frameshift mutation (c.1052delG) has been identified in exon 8 of LAMP2, which leads to truncation of the protein.

Conclusion: We found a novel frameshift mutation, a hemizygous mutation (c.1052delG) in exon 8 of LAMP2, identified as presenting the hypertrophic cardiomyopathy (HCM) phenotype. Genetic analysis is the gold standard for the diagnosis of DD and is essential to determine appropriate treatment strategies and to confirm the genetic risk of family members.
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http://dx.doi.org/10.1186/s13000-021-01100-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088694PMC
May 2021

The effects of tocotrienols intake on obesity, blood pressure, inflammation, liver and glucose biomarkers: a meta-analysis of randomized controlled trials.

Crit Rev Food Sci Nutr 2021 Apr 28:1-14. Epub 2021 Apr 28.

School of Basic Medical Sciences, Mudanjiang Medical University, Mudanjiang, China.

The objective of this study is to accomplish a systematic review and meta-analysis of all randomized controlled trials that dissected the influence of tocotrienol supplementation on various anthropometric and cardiometabolic indices in all individuals, irrespective of health condition. This research was carried out in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement guidelines. 17 eligible articles were included in the final quantitative analysis. Current study revealed that tocotrienol consumption was not associated with CRP, WC, MDA, BMI, IL-6, HbA1C, ALT, AST, creatinine TNF-α, FPG, BW, DBP, and SBP. We did observe an overall increase in BW (SMD: 0.063 kg, 95% CI: -0.200, 0.327,  = 0.637) and DBP (SMD: 0.249 mmHg, 95% CI: 0.053, 0.446,  = 0.013). In addition, a significant reduction in SBP was observed (SMD: -0.616 mmHg, 95% CI: -1.123, -0.110,  = 0.017). In summary, our meta-analysis revealed that tocotrienol consumption was associated with increase in BW and DBP and decrease in SBP. Significant associations were not observed for other outcomes.
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http://dx.doi.org/10.1080/10408398.2021.1911926DOI Listing
April 2021

Emergence of additional drug resistance during treatment of multidrug-resistant tuberculosis in China: a prospective cohort study.

Clin Microbiol Infect 2021 Apr 23. Epub 2021 Apr 23.

Department of Epidemiology, School of Public Health and Key Laboratory of Public Health Safety, Fudan University, Shanghai, China. Electronic address:

Objectives: Little is known about how additional second-line drug resistance emerges during multidrug-resistant tuberculosis (MDR-TB) treatment. The present study aimed to investigate the influence of microevolution, exogenous reinfection and mixed infection on second-line drug resistance during the recommended 2-year MDR-TB treatment.

Methods: Individuals with MDR-TB were enrolled between 2013 and 2016 in a multicentre prospective observational cohort study and were followed up for 2 years until treatment completion. Whole-genome sequencing (WGS) was applied for serial Mycobacterium tuberculosis isolates from study participants throughout the treatment, to study the role of microevolution, exogenous reinfection and mixed infection in the development of second-line drug resistance.

Results: Of the 286 enrolled patients with MDR-TB, 63 (22.0%) M. tuberculosis isolates developed additional drug resistance during the MDR-TB treatment, including 5 that fulfilled the criteria of extensively drug-resistant TB. By comparing WGS data of serial isolates retrieved from the patients throughout treatment, 41 (65.1%) of the cases of additional second-line drug resistance were the result of exogenous reinfection, 18 (28.6%) were caused by acquired drug resistance, i.e. microevolution, while the remaining 4 (6.3%) were caused by mixed infections with drug-resistant and drug-susceptible strains. In multivariate analysis, previous TB treatment (adjusted hazard ratio (aHR) 2.51, 95% CI 1.51-4.18), extensive disease on chest X-ray (aHR 3.39, 95% CI 2.03-5.66) and type 2 diabetes mellitus (aHR 4.00, 95% CI 2.22-7.21) were independent risk factors associated with the development of additional second-line drug resistance.

Conclusions: A large proportion of additional second-line drug resistance emerging during MDR-TB treatment was attributed to exogenous reinfection, indicating the urgency of infection control in health facilities as well as the need for repeated drug susceptibility testing throughout MDR-TB treatment.
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http://dx.doi.org/10.1016/j.cmi.2021.04.001DOI Listing
April 2021

[Genetic analysis of three patients with Kleefstra syndrome].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021 Apr;38(4):347-350

Xianning Central Hospital (the First Affiliated Hospital of Hubei University of Science and Technology), Xianning, Hubei 437100, China.

Objective: To analyze the clinical and genetic features of three patient diagnosed with Kleefstra syndrome.

Methods: Whole exome sequencing (WES) was carried out for the probands and their parents. Suspected variants were validated by Sanger sequencing. Copy number variations (CNV) were detected by CNV-seq and validated by real-time PCR.

Results: Proband 1 was found to carry a de novo heterogeneous variant (c.823+1G>T) of the EHMT1 gene, which may affect its expression. Based on the guidelines of the American College of Medical Genetics and Genomics, the variant was predicted to be pathogenic (PVS1+PS2+PM2). Proband 2 was found to carry a de novo missense variant c.439C>G (p.L147V) of the EHMT1 gene, which was predicted to be likely pathogenic (PS2+PM1+PM2+PP3). Proband 3 was found to carry a heterozygous 520 kb deletion at 9q34.3 by CNV-seq. The deletion has encompassed the whole of the EHMT1 gene. Real-time PCR has detected no CNV of this region in her parents.

Conclusion: Variants of the EHMT1 gene probably underlay the disease in these patients. Genetic testing has provided a basis for their clinical diagnosis.
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http://dx.doi.org/10.3760/cma.j.cn511374-20200814-00602DOI Listing
April 2021

High-mobility group box-1 promotes vascular calcification in diabetic mice via endoplasmic reticulum stress.

J Cell Mol Med 2021 Apr 16;25(8):3724-3734. Epub 2021 Mar 16.

Department of Cardiology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China.

Several studies reported the role of endoplasmic reticulum stress (ERS) in vascular calcification. High-mobility group box-1 (HMGB-1) plays a substantial role in diabetes and its complications. However, relatively little information is available regarding the association between HMGB-1 and calcification, and the underlying mechanism has still remained elusive. Therefore, in the present study, we attempted to indicate whether HMGB-1 could promote vascular calcification via ERS in diabetes. After induction of diabetes by Streptozotocin (STZ), mice were treated with glycyrrhizin (Gly) or 4-phenylbutyrate (4-PBA). Mineral deposition was confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and calcium assay. In cell experiments, calcification of vascular smooth muscle cells (VSMCs) was performed with Alizarin Red staining, alkaline phosphatase (ALP) activity and RT-PCR. Expression and location of HMGB-1 in aortic tissue were detected by Western blotting, immunocytochemistry (ICC) and immunohistochemistry (IHC). Diabetic mice demonstrated increased HMGB-1 expression, ERS and vascular calcification. However, inhibition of HMGB-1 with Gly or inhibition of ERS with 4-PBA ameliorated the enhanced vascular calcification and ERS in diabetic mice. In vitro experiments unveiled that inhibition of HMGB-1 attenuated advanced glycation end products (AGEs)-induced ERS in VSMCs. In addition, AGEs promoted translocation and secretion of HMGB-1 in VSMCs, which was reversed by 4-PBA. Moreover, VSMCs exhibited increased mineralization and osteogenic gene expressions in response to HMGB-1 and AGEs. However, inhibition of ERS with 4-PBA partially, although noticeably, attenuated VSMC calcification induced by HMGB-1. Thus, diabetes induced translocation and secretion of HMGB-1 via ERS, which resulted in calcification in diabetic mice and in AGEs-treated VSMCs.
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http://dx.doi.org/10.1111/jcmm.16075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051722PMC
April 2021

Empagliflozin prevents from early cardiac injury post myocardial infarction in non-diabetic mice.

Eur J Pharm Sci 2021 Jun 6;161:105788. Epub 2021 Mar 6.

Department of Cardiology, Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, 210008, Jiangsu, China. Electronic address:

Objectives: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been confirmed to reduce the rate of rehospitalization for heart failure and cardiovascular death in diabetic patients. The aim of our study was to investigate the cardioprotective role of SGLT2 inhibitors in early myocardial infarction (MI) of non-diabetic mice.

Methods: C57BL/6 mice underwent left artery coronary artery descending (LAD) ligation to induce MI. Following the surgery, animals were randomized to receive saline or empagliflozin. Empagliflozin (EMPA) was administrated at 10 mg/kg per day by oral gavage for 2 weeks. Echocardiography, histological staining and qualitative RT-PCR were performed to assess the cardiac remodeling post MI. In vitro experiments were performed to evaluate the effect of empagliflozin on apoptosis, oxidative stress and mitochondrial membrane potential of cardiomyocyte subjected to hypoxic treatment.

Results: Compared with MI group, the empagliflozin treatment group showed improved cardiac function, reduced infarct size and interstitial fibrosis. Empagliflozin also inhibited cardiomyocyte apoptosis by alleviating oxidative stress and restoring mitochondrial membrane potential. Immunoblotting analysis revealed activated AMP-activated protein kinase (AMPK) signaling may mediated the cardioprotective role of empagliflozin.

Conclusions: In summary, empagliflozin could inhibit cardiomyocyte apoptosis and improve cardiac remodeling early MI, which provided insights into the benefic effect of empagliflozin on MI patients without diabetes.
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http://dx.doi.org/10.1016/j.ejps.2021.105788DOI Listing
June 2021

Economic Burden of Myocardial Infarction Combined With Dyslipidemia.

Front Public Health 2021 19;9:648172. Epub 2021 Feb 19.

Department of Health Economics, China Pharmaceutical University, Nanjing, China.

Dyslipidemia is a common comorbidity and an important risk factor for myocardial infarction (MI). This study aimed to examine the economic burden of MI combined with dyslipidemia in China. Patients who were hospitalized due to MI combined with dyslipidemia in 2016 were enrolled. Costs were measured based on electronic medical records and questionnaires. The annual costs were analyzed by conducting descriptive statistics, univariable, and multivariable analyses. Data of 900 patients were analyzed, and 144 patients were dead during the follow-up. The majority of patients were aged 51-70 years ( = 563, 62.55%) and males ( = 706, 78.44%). For all-cause costs, the median annual direct medical costs, direct non-medical costs, indirect costs, and total costs were RMB 13,168 (5,212-29,369), RMB 600 (0-1,750), RMB 676 (0-1,787), RMB 15,361 (6,440-33,943), respectively; while for cardiovascular-related costs, the corresponding costs were RMB 12,233 (3,795-23,746), RMB 515 (0-1,680), RMB 587 (0-1,655), and RMB 14,223 (4,914-28,975), respectively. Lifestyle and complications significantly affected both all-cause costs and cardiovascular-related costs. Increasing attention should be paid to encourage healthy lifestyle, and evidence-based medicine should focus on optimal precautions and treatments for complications, to reduce the economic burden among MI patients with a comorbid dyslipidemia.
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http://dx.doi.org/10.3389/fpubh.2021.648172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933193PMC
May 2021

Prognostic relevance and clinical features of papillary muscle infarction with mitral regurgitation in patients with ST segment elevation myocardial infarction.

J Thorac Dis 2021 Jan;13(1):334-342

Department of Cardiology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China.

Background: Papillary muscle infarction (PapMI) combined with mitral regurgitation (MR) is a severe complication of ST-segment elevation myocardial infarction (STEMI). The features detected by cardiac magnetic resonance (CMR) imaging in PapMI have not been characterized. The aim of the present study was to assess the incidence, determinants, and the prognostic significance of PapMI with MR at 1-year follow-up in a study of patients with STEMI after primary percutaneous coronary intervention (pPCI).

Methods: We enrolled 209 patients with STEMI reperfused by pPCI (<12 hours after symptom onset) at 2 centers. CMR and echocardiography were performed within 1 week after infarction using a standardized protocol. According to the results of CMR and echocardiography, patients were divided into PapMI with MR, PapMI (PapMI without MR), and non-PapMI groups. The primary clinical endpoint of the study was the occurrence of major adverse cardiovascular events (MACE).

Results: PapMI with MR was found in 27 patients (13%). The existence of PapMI with MR was associated with age (P<0.001), impaired left ventricular ejection fraction (LVEF) (P=0.005), higher SYNTAX score (P=0.002), concentration of troponin I (P<0.001), longer time to reperfusion (P<0.001), more diabetics (P<0.001), and microvascular occlusion (MVO) (P<0.001). Binary logistic regression with stepwise backward selection analysis showed that advanced age, MVO, and impaired LVEF were independent risk factors for PapMI with MR. Patients in the PapMI with MR group had significantly more MACE compared with the PapMI and non-PapMI groups [PapMI with MR, 23 (85.2%) PapMI, 21 (55.3%) non-PapMI, 29 (20.1%)] at 1-year follow-up (P<0.001). However, there were no pronounced differences in mortality rates among the 3 groups (P=0.071).

Conclusions: The presence of PapMI with MR in patients with STEMI is associated with advanced age, MVO, and impaired LVEF, which can increase the rates of MACE.
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http://dx.doi.org/10.21037/jtd-20-3476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867801PMC
January 2021

Synthesis, biological evaluation and structure-activity relationship of novel dichloroacetophenones targeting pyruvate dehydrogenase kinases with potent anticancer activity.

Eur J Med Chem 2021 Mar 28;214:113225. Epub 2021 Jan 28.

School of Pharmaceutical Sciences, Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Chongqing University, Chongqing, 401331, PR China. Electronic address:

Pyruvate dehydrogenase kinases (PDKs) are promising therapeutic targets that have received increasing attentions in cancer metabolism. In this paper, we report the synthesis and biological evaluation of a series of novel dichloroacetophenones as potent PDKs inhibitors. Structure-activity relationship analysis enabled us to identify a potent compound 6u, which inhibited PDKs with an EC value of 0.09 μM, and reduced various cancer cells proliferation with IC values ranging from 1.1 to 3.8 μM, while show weak effect against non-cancerous L02 cell (IC > 10 μM). In the A375 xenograft model, 6u displayed an obvious antitumor activity at a dose of 5 mg/kg, but with no negative effect to the mice weight. Molecular docking suggested that 6u formed direct hydrogen bond interactions with Ser75 and Gln61 in PDK1, and meanwhile the aniline skeleton in 6u was sandwiched by the conserved hydrophobic residues Phe78 and Phe65, which contribute to the biochemical activity improvement. Moreover, 6u induced A375 cell apoptosis and cell arrest in G1 phase, and inhibited cancer cell migration. In addition, 6u altered glucose metabolic pathway in A375 cell by decreasing lactate formation and increasing ROS production and OCR consumption, which could serve as a potential modulator to reprogram the glycolysis pathway in cancer cell.
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http://dx.doi.org/10.1016/j.ejmech.2021.113225DOI Listing
March 2021

Negative correlation between bone mineral density and subclinical fractures in patients with human immunodeficiency virus.

J Int Med Res 2021 Feb;49(2):300060520980639

Department of Orthopedics, Beijing Ditan Hospital, Capital Medical University, Beijing, China.

Background: Although low bone mineral density (BMD) is associated with an increased risk of fracture, few studies have assessed fracture rates in patients with human immunodeficiency virus (HIV).

Methods: The occurrence of subclinical fractures in patients with HIV was assessed. Pearson's chi-square test was used to analyze the relationship between subclinical fractures and related factors.

Results: Fifty patients with HIV were included, among whom 11 were diagnosed with subclinical fractures. These 11 patients had a mean body mass index of 24.127 ± 3.482 kg/m, smoked a mean of 142.091 ± 3.482 cigarettes/month, drank a mean of 61.545 ± 13.026 mL/day of alcohol, had a mean CD4 T cell count of 247.727 ± 181.679 cells/mm, had a mean duration of acquired immunodeficiency syndrome (AIDS) of 4.27 ± 0.786 years, and had a mean BMD of the third lumbar spine of 0.810 ± 0.063 g/cm. The AIDS duration and BMD of the third lumbar spine were significantly associated with subclinical fractures. The BMD of the third lumbar spine was negatively correlated with subclinical fractures.

Conclusion: A significant negative correlation was found between the BMD of the third lumbar spine and subclinical fractures.
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http://dx.doi.org/10.1177/0300060520980639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871090PMC
February 2021

Ripple mapping-guided atrial tachycardia ablation following open-heart surgery.

Heart Vessels 2021 Jul 29;36(7):1016-1026. Epub 2021 Jan 29.

Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, No. 321, Zhongshan Road, Nanjing, 210008, China.

Ripple mapping can make the visualization of activation conduction on a 3-dimensional voltage map and is useful tool for scar-related organized atrial tachycardia (AT). This study sought to assess the efficacy of ripple mapping for interpreting reentrant circuits and critical isthmus in postoperative ATs. 34 consecutive patients with a history of mitral valve surgery (mean age, 54.5 ± 12.4 years) underwent high density (HD) RM during ATs with CARTO3v4 CONFIDENSE system. The voltage activation threshold was determined by RM over a bipolar voltage map. The identification of underlying mechanisms and ablation setting was based on RM without reviewing activation mapping. A total of 41 ATs (35 spontaneous, 6 induced) were characterized. 39 reentry circuits were successfully mapped (cycle length, 256 ± 43 ms). Of the 41 ATs, 28 were confirmed by ripple mapping alone (68%), and 12 (29%) by ripple mapping and entrainment mapping. Of 12 ATs in the left atrium, 9 (75%) needed entrainment to confirm, compared with 5 (17.8%) in the right atrium. Primary endpoint after initial ablation set was achieved in 32 of the 34 patients (94.1%). Freedom from atrial arrhythmias was 79.4% after the follow-up of 12 ± 5 months. Of the seven patients with recurrence, three underwent the repeated catheter ablation. Ripple mapping precisely delineated reentrant circuits in post-cardiac surgery AT resulting in a high success rate of ablation. Entrainment maneuvers remain useful for elucidation of complex AT circuits.
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http://dx.doi.org/10.1007/s00380-021-01772-8DOI Listing
July 2021

First Report of White Rust Disease Caused by Albugo koreana on Camelina sativa in China.

Plant Dis 2021 Jan 26. Epub 2021 Jan 26.

Tarim University, 12483, College of Life Sciences, Aral, Xinjiang, China;

Camelina sativa, an herbaceous annual plant in the family Brassicaceae, is especially well known for its oilseed crop that produce camelina oil (Hovsepyan et al. 2008). In April 2016, white blister rust disease on C. sativa were observed in a cultivated farmland with an incidence of about 60% in Xinyuan County (43°33'39.17"N, 83°14'54.04"E), Xinjiang, China. Symptoms appeared as light-yellow chlorotic spots on the upper surface of the leaves and white blister on the corresponding lower surface. Blister sori were white, oval to ellipsoidal, scattered or coalesce, and 1.8 to 4 mm in diameter. Two representative voucher specimens were deposited in the Mycological Herbarium of Tarim University (HMUT 2527 and HMUT 2528), Aral, China. Sporangiophores hyaline, clavate or cylindrical, straight to slightly curved, (23.7 to) 27.9 to 37.9 (to 42.1) (av. 31) × (7.9 to) 9.6 to 13.7 (to 15.1) (av. 11.4) μm (n = 30), thick-walled on their lower parts, bearing sporangia in chains. Primary sporangia were globose to subglobose, wall equal thickness, and (9.5 to) 10.6 to 13.2 (to 14.3) (av. 11.9) μm in diameter (n = 50). Secondary sporangia were mostly subglobose to ovoid, with a subtruncated base, and (12.1 to) 13.2 to 16.9 (to 18) (av. 15.1) μm × (11 to) 12.1 to 15 (to 16.1) (av. 13.4) μm in size (n = 50). Oogonia were globose to subglobose, (39.7 to) 42.7 to 51.7 (to 54.1) (av. 48.3) μm in diameter (n = 30), irregular. Oospores were globose to subglobose, brown, (34.5 to) 37 to 42.7 (to 45.2) (av. 41.1) μm in diameter (n = 30), 3 to 5 μm wall in thickness, with single warts, 1.5 to 4 × 2 to 3.5 μm (n = 30). The morphological characteristics of specimens were consistent with those of Albugo koreana (Choi et al. 2007). To confirm the identification, genomic DNA were extracted directly from sori on diseased leaves from isolates HMUT 2527 and HMUT 2528, respectively. The internal transcribed spacer (ITS) rDNA and cytochrome oxidase II (cox2) mtDNA were amplified with primers DC6/LR-0 described by Choi et al. (2006) and cox2-F/cox2-R described by Hudspeth et al. (2000), respectively. A BLASTn search revealed that the ITS rDNA sequences (GenBank accession Nos. MW135444 and MW135445) were 99% (838/844 nucleotides)identical to that of A. koreana from Capsella bursa-pastoris (AY929829), and the cox2 sequences (GenBank accession Nos. MW147150 and MW147151) were 100% (567/567 nucleotides) identical to that of A. koreana from C. bursa-pastoris (AY927048). Based on the concatenated ITS and cox2 sequences, Maximum Likelihood and Bayesian analysis showed that pathogen from C. sativa with the reference isolate of A. koreana (ex C. bursa-pastoris) with high bootstrap support values and maximum posterior probability (100 ML BS and 1.00 BPP, respectively). For pathogenicity, sporangia collected from the infected leaves were suspended in sterile water at 4°C for 2 hours to improve zoospore release, and the zoospore suspension obtained from sporangial suspension (1×105 sporangia/ml) was inoculated to the lower surface of six healthy potted plants. Three non-inoculated plants were served as controls. Each plant was kept in a separate plastic humid chamber in a greenhouse with 25°C and 80% humidity for 15 days. Typical symptoms of white rust pustules developed on the inoculated plants were identical to that observed on the originally infected leaves. Control plants remained symptomless.. Based on morphological characteristics, molecular data, as well as pathogenicity tests, the pathogen on C. sativa was identified as Albugo koreana. A. koreana aslo is reported only on C. bursa-pastoris in Korea (Choi et al. 2007; Farr and Rossman 2020). To our knowledge, this is the first record of white rust disease caused by A. koreana on C. sativa, and the species is new to China. This report represents a new host plant association and a new geographical expansion for this species, presenting a potential threat to camelina production in northwest China.
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http://dx.doi.org/10.1094/PDIS-11-20-2332-PDNDOI Listing
January 2021

Empagliflozin protects against atherosclerosis progression by modulating lipid profiles and sympathetic activity.

Lipids Health Dis 2021 Jan 12;20(1). Epub 2021 Jan 12.

Department of Cardiology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Jiangsu, 210008, Nanjing, China.

Background: Several large clinical trials have confirmed the cardioprotective role of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with type 2 diabetes. However, whether empagliflozin, as an SGLT2i, could alleviate atherosclerosis progression in non-diabetic states remain unknown.

Methods: ApoE-/- mice were fed a Western diet for 12 weeks to induce atherosclerosis. On the 7th week, a group of mice were treated with drinking water containing empagliflozin (10 mg/kg/day), while another group was given normal water. At the 12th week, the whole aortas of each group were harvested. Oil Red O, HE and Movat staining were performed for atherosclerotic lesion area and size. Mouse serum lipid profiles (total cholesterol [TC], triglyceride [TG], low-density lipoprotein-c [LDL], and high-density lipoprotein-c [HDL]), systemic inflammation levels (IL-1β, IL-6 and IL-10), renin-angiotensin-aldosterone system (RAAS) components and sympathetic activity (norepinephrine and neuropeptide Y) indicators were measured by ELISA.

Results: Empagliflozin reduced the atherosclerotic lesion burden (-8.6 %, P = 0.004) at aortic root in ApoE-/- mice. In addition, empagliflozin decreased body weight (-3.27 g, P = 0.002), lipid profiles (TC: [-15.3 mmol/L, P = 0.011]; TG: [-2.4 mmol/L, P < 0.001]; LDL: [-2.9 mmol/L, P = 0.010]), RAAS (renin [-9.3 ng/L, P = 0.047]; aldosterone [-16.7 ng/L, P < 0.001]) and sympathetic activity (norepinephrine [-8.9 ng/L, P = 0.019]; neuropeptide Y [-8.8 ng/L, P = 0.002]). However, the anti-inflammatory effect of empagliflozin was not significantly evident.

Conclusions: The early atherosclerotic lesion size was less visible in empagliflozin-treated mice. Empagliflozin could decrease lipid profiles and sympathetic activity in atherosclerosis.
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http://dx.doi.org/10.1186/s12944-021-01430-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802233PMC
January 2021

Oral health status of 12-year-old children in Lisu minority ethnic group in China: a cross-sectional study.

BMC Oral Health 2021 01 12;21(1):27. Epub 2021 Jan 12.

Faculty of Dentistry, The University of Hong Kong, Pok Fu Lam, Hong Kong SAR, China.

Background: Lisu is an ethnic minority group and most of them are living in Yunnan, China. This study investigated the oral health status among 12-year-old Lisu children in Yunnan.

Method: This survey employed a multistage sampling method to recruit 12-year-old Lisu children. Two calibrated dentists performed the oral examinations in the primary schools. They examined dental caries, gingival bleeding and dental fluorosis using the diagnosis criteria recommended by the World Health Organization. A self-administrated questionnaire was distributed to the children to collect their sociodemographic background information and oral health-related behaviours. A chi-square test, the Mann-Whitney U test, zero-inflated negative binomial (ZINB) regression and multivariate logistic regression were used for statistical analysis.

Results: This survey invited 512 children, and 482 children (48% boys) participated in the study (response rate: 94%). Their caries prevalence was 35% and their caries experience in mean (SD) DMFT scores was 0.63 (0.10). The mean (SD) DT score was 0.60 (1.10), consisting 95% of the mean DMFT scores. No dental fluorosis was observed; whereas 426 children (88%) had gingival bleeding. Results of ZINB model indicated sex and sugary-snacking habits were related to the dental caries experience (p < 0.05). The gingival-bleeding prevalence was associated with the mother's education level, the child's monthly-pocket money and daily toothbrushing frequency (p < 0.05).

Conclusion: Dental caries and gingival bleeding were prevalent among 12-year-old Lisu children in the Yunnan province in China, and most of the decayed teeth were unrestored. Dental fluorosis was not observed in the children.
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http://dx.doi.org/10.1186/s12903-020-01358-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805177PMC
January 2021

Trinor- and tetranor-eremophilane sesquiterpenoids with anti-neuroinflammatory activity from cultures of the fungus Septoria rudbeckiae.

Phytochemistry 2021 Mar 6;183:112642. Epub 2021 Jan 6.

Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling, Shaanxi, 712100, People's Republic of China. Electronic address:

Fifteen eremophilane sesquiterpenoids, including nine undescribed congeners, septeremophilane A-H, and chaetopenoid G, together with four conjugated unsaturated polyketide fatty acids, including an undescribed derivative, were isolated from cultures of the fungus Septoria rudbeckiae, a plant pathogenic fungus isolated from the halophyte Karelinia caspia. Septeremophilane A represents an unprecedented tetranor-eremophilane sesquiterpenoid with an α,β-unsaturated δ-lactone unit bearing a hemiacetal group, while septeremophilane B-H possesses a trinor-eremophilane skeleton. Their structures and absolute configurations were established based on spectroscopic data (NMR and HRESIMS), quantum chemical calculations and electronic circular dichroism (ECD) experiments. All metabolites were tested for nitric oxide (NO) production inhibition in lipopolysaccharide (LPS)-activated BV-2 microglial cells, while dendryphiellin D, septeremophilane D, and septeremophilane E were found to display significant inhibition, with IC values of 11.9 ± 1.0, 8.5 ± 0.1, and 6.0 ± 0.2 μM, respectively.
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http://dx.doi.org/10.1016/j.phytochem.2020.112642DOI Listing
March 2021

Growth differentiation factor-15 is a biomarker for all-cause mortality but less evident for cardiovascular outcomes: A prospective study.

Am Heart J 2021 04 6;234:81-89. Epub 2021 Jan 6.

Department of Clinical Sciences, Malmö, Lund University, Malmö, Sweden. Electronic address:

Background: Previous studies have proposed growth differentiation factor-15 (GDF-15) as a predictor of adverse cardiovascular outcomes and mortality. The present study aimed to determine if such associations remain after accounting for death as a competing risk, and if GDF-15 provides superior prediction performance than other biomarkers.

Methods: Plasma GDF-15 levels and cardiovascular risk factors were measured in individuals without cardiovascular diseases (n = 4,143, aged 57.4 ± 5.96 years, 38.6 % men) from Malmö Diet and Cancer-Cardiovascular Cohort and were followed up for more than 20 years. Incidence of coronary events, ischemic stroke, cardiovascular mortality, and all-cause mortality was studied in relation to GDF-15 using Cox proportional hazards regression, with adjustment for potential confounders. Confounding from death as competing risk was carefully checked using the Fine and Gray subdistribution hazard model. Predictive capabilities were further evaluated using C-statistics, continuous net reclassification improvement, and integrated discrimination improvement.

Results: During follow-up, 424 coronary events, 327 ischemic stroke, 368 cardiovascular deaths, and 1,308 all-cause deaths occurred. After controlling for death from other causes as competing events, only all-cause mortality remained significantly related to GDF-15. The addition of GDF-15 significantly improved prediction for all-cause mortality in addition to the traditional risk factors, high-sensitive C-reactive protein and N-terminal prohormone of brain natriuretic peptide. Only N-terminal prohormone of brain natriuretic peptide improved prediction for CVD mortality.

Conclusions: GDF-15 is a robust biomarker for all-cause mortality but less reliable for coronary event, ischemic stroke or cardiovascular mortality. Competing risk from death is an important consideration when interpreting the results.
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http://dx.doi.org/10.1016/j.ahj.2020.12.020DOI Listing
April 2021

Trophoblast Stem-Cell-Derived Exosomes Improve Doxorubicin-Induced Dilated Cardiomyopathy by Modulating the let-7i/YAP Pathway.

Mol Ther Nucleic Acids 2020 Dec 15;22:948-956. Epub 2020 Oct 15.

Department of Cardiology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing 21008, P.R. China.

Trophoblast stem cells (TSCs) have been confirmed to play a cardioprotective role in heart failure. However, whether TSC-derived exosomes (TSC-exos) can protect against cardiac injury remains unclear. In the present study, TSC-exos were isolated from the supernatant of TSCs using the ultracentrifugation method and characterized by transmission electron microscopy and western blotting. Utilizing the public Gene Expression Omnibus (GEO) database, we found that let-7i and Yes-associated protein 1 (YAP) could participate in the development of heart failure. , AC16 cardiomyocytes subjected to doxorubicin (DOX) were treated with TSC-exos or let-7i mimic. Flow cytometry showed that TSC-exos and let-7i both decreased cardiomyocyte apoptosis. , mice that were intraperitoneally injected into DOX received either PBS, TSC-exos, or AAV9-let7i for let-7i overexpression. Mice receiving TSC-exos and AAV9-let7i showed improved cardiac function and decreased inflammatory responses, accompanied by downregulated YAP signaling. Mechanistically, TSC-exos could transfer let-7i to cardiomyocytes and silence the YAP signaling pathway. In conclusion, TSC-exos could alleviate DOX-induced cardiac injury via the let-7i/YAP pathway, which sheds new light on the application of TSC-exos as a potential therapeutic tool for heart failure.
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http://dx.doi.org/10.1016/j.omtn.2020.10.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680701PMC
December 2020