Publications by authors named "Ping Kong"

50 Publications

Practice in Information Technology Support for Fangcang Shelter Hospital during COVID-19 Epidemic in Wuhan, China.

J Med Syst 2021 Feb 19;45(4):42. Epub 2021 Feb 19.

Information Center, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.

In confronting the sudden epidemic of COVID-19, China and other countries have been under great deal of pressure to block virus transmission and reduce death cases. Fangcang shelter hospital, which is converted from large-scale public venue, is proposed and proven to be an effective way for administering medical care and social isolation. This paper presents the practice in information technology support for a Fangcang shelter hospital in Wuhan, China. The experiences include the deployment strategy of IT infrastructure, the redesign of function modules in the hospital information system (HIS), equipment maintenance and medical staff training. The deployment strategy and HIS modules have ensured smoothness and efficiency of clinical work. The team established a quick response mechanism and adhered to the principle of nosocomial infection control. Deployment of network and modification of HIS was finished in the 48 hours before patient admittance. A repair hotline and remote support for equipment and software were available whenever medical workers met with any questions. No engineer ever entered the contaminated areas and no one was infected by the coronavirus during the hospital operation. Up to now, Fangcang shelter hospital is adopted by many regions around the world facing the collapse of their medical systems. This valuable experience in informatization construction and service in Wuhan may help participators involving in Fangcang shelter hospital get better information technology support, and find more practical interventions to fight the epidemic.
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http://dx.doi.org/10.1007/s10916-021-01721-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894969PMC
February 2021

Gut microbiome-related effects of berberine and probiotics on type 2 diabetes (the PREMOTE study).

Nat Commun 2020 10 6;11(1):5015. Epub 2020 Oct 6.

National Clinical Research Centre for Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

Human gut microbiome is a promising target for managing type 2 diabetes (T2D). Measures altering gut microbiota like oral intake of probiotics or berberine (BBR), a bacteriostatic agent, merit metabolic homoeostasis. We hence conducted a randomized, double-blind, placebo-controlled trial with newly diagnosed T2D patients from 20 centres in China. Four-hundred-nine eligible participants were enroled, randomly assigned (1:1:1:1) and completed a 12-week treatment of either BBR-alone, probiotics+BBR, probiotics-alone, or placebo, after a one-week run-in of gentamycin pretreatment. The changes in glycated haemoglobin, as the primary outcome, in the probiotics+BBR (least-squares mean [95% CI], -1.04[-1.19, -0.89]%) and BBR-alone group (-0.99[-1.16, -0.83]%) were significantly greater than that in the placebo and probiotics-alone groups (-0.59[-0.75, -0.44]%, -0.53[-0.68, -0.37]%, P < 0.001). BBR treatment induced more gastrointestinal side effects. Further metagenomics and metabolomic studies found that the hypoglycaemic effect of BBR is mediated by the inhibition of DCA biotransformation by Ruminococcus bromii. Therefore, our study reports a human microbial related mechanism underlying the antidiabetic effect of BBR on T2D. (Clinicaltrial.gov Identifier: NCT02861261).
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http://dx.doi.org/10.1038/s41467-020-18414-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538905PMC
October 2020

Pulmonary nodule detection on chest radiographs using balanced convolutional neural network and classic candidate detection.

Artif Intell Med 2020 07 22;107:101881. Epub 2020 May 22.

Shanghai University of Medicine and Health Sciences, Shanghai, China.

Computer-aided detection (CADe) systems play a crucial role in pulmonary nodule detection via chest radiographs (CXRs). A two-stage CADe scheme usually includes nodule candidate detection and false positive reduction. A pure deep learning model, such as faster region convolutional neural network (faster R-CNN), has been successfully applied for nodule candidate detection via computed tomography (CT). The model is yet to achieve a satisfactory performance in CXR, because the size of the CXR is relatively large and the nodule in CXR has been obscured by structures such as ribs. In contrast, the CNN has proved effective for false positive reduction compared to the shallow method. In this paper, we developed a CADe scheme using the balanced CNN with classic candidate detection. First, the scheme applied a multi-segment active shape model to accurately segment pulmonary parenchyma. The grayscale morphological enhancement technique was then used to improve the conspicuity of the nodule structure. Based on the nodule enhancement image, 200 nodule candidates were selected and a region of interest (ROI) was cropped for each. Nodules in CXR exhibit a large variation in density, and rib crossing and vessel tissue usually present similar features to the nodule. Compared to the original ROI image, the nodule enhancement ROI image has potential discriminative features from false positive reduction. In this study, the nodule enhancement ROI image, corresponding segmentation result, and original ROI image were encoded into a red-green-blue (RGB) color image instead of the duplicated original ROI image as input of the CNN (GoogLeNet) for false positive reduction. With the Japanese Society of Radiological Technology database, the CADe scheme achieved high performance of the published literatures (a sensitivity of 91.4 % and 97.1 %, with 2.0 false positives per image (FPs/image) and 5.0 FPs/image, respectively) for nodule cases.
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http://dx.doi.org/10.1016/j.artmed.2020.101881DOI Listing
July 2020

Identification of protein complexes and functional modules in E. coli PPI networks.

BMC Microbiol 2020 08 6;20(1):243. Epub 2020 Aug 6.

Research Center for Intelligence Information Technology, Nantong University, Nantong, 226019, Jiangsu, China.

Background: Escherichia coli always plays an important role in microbial research, and it has been a benchmark model for the study of molecular mechanisms of microorganisms. Molecular complexes, operons, and functional modules are valuable molecular functional domains of E. coli. The identification of protein complexes and functional modules of E. coli is essential to reveal the principles of cell organization, process, and function. At present, many studies focus on the detection of E. coli protein complexes based on experimental methods. However, based on the large-scale proteomics data set of E. coli, the simultaneous prediction of protein complexes and functional modules, especially the comparative analysis of them is relatively less.

Results: In this study, the Edge Label Propagate Algorithm (ELPA) of the complex biological network was used to predict the protein complexes and functional modules of two high-quality PPI networks of E. coli, respectively. According to the gold standard protein complexes and function annotations provided by EcoCyc dataset, most protein modules predicted in the two datasets matched highly with real protein complexes, cellular processes, and biological functions. Some novel and significant protein complexes and functional modules were revealed based on ELPA. Moreover, through a comparative analysis of predicted complexes with corresponding functional modules, we found the protein complexes were significantly overlapped with corresponding functional modules, and almost all predicted protein complexes were completely covered by one or more functional modules. Finally, on the same PPI network of E. coli, ELPA was compared with a well-known protein module detection method (MCL) and we found that the performance of ELPA and MCL is comparable in predicting protein complexes.

Conclusions: In this paper, a link clustering method was used to predict protein complexes and functional modules in PPI networks of E. coli, and the correlation between them was compared, which could help us to understand the molecular functional units of E. coli better.
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http://dx.doi.org/10.1186/s12866-020-01904-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409450PMC
August 2020

Endophytic sp. SSG as a potential biofertilizer promoting boxwood growth.

PeerJ 2020 16;8:e9547. Epub 2020 Jul 16.

Hampton Roads Agricultural Research and Extension Center, Virginia Polytechnic Institute and State University (Virginia Tech), Virginia Beach, VA, United States of America.

Background: sp. SSG is a bacterial endophyte isolated from boxwood leaves showing a resistant response to infection by the boxwood blight pathogen . SSG acted as a protective and curative biocontrol agent for boxwood blight and as a bio-sanitizer of disease inoculum in the field. Many gene clusters involved in antibiotic production and plant growth promotion (PGP) were found in the genome, giving this endophyte great application potential as a treatment for plant protection. However, the PGP features have not been documented. This study investigated the plant growth promotion activity of SSG in boxwood.

Methods: To determine whether SSG is a plant growth promoting bacterium, four PGP traits, auxin and siderophore production, nitrogen fixation and phosphate solubilization, were examined in the laboratory with colorimetric or agar plate assays. The plant growth promoting activity of SSG was tested on three boxwood varieties characterized by slow, intermediate and fast growth rates, namely Justin Brouwers, Buddy and Winter Gem, respectively. These plants were drenched with an SSG cell suspension or water and washed plant weight was compared before and after treatment to determine growth changes after 10 months.

Results: The SSG culture was sustainable on nitrogen free media, suggesting that SSG may fix atmospheric nitrogen. It was also a strong phosphate solubilizer and a potent siderophore and indole-3-acetic acid (IAA) producer. Significant growth promotion was observed on boxwood cultivars Justin Brouwers, Buddy and Winter Gem 10 months after plant roots were drenched with SSG cells. The growth rate of treated plants was 76.1, 58.3, and 37.3% higher than that of the control, respectively. The degree of growth promotion was significantly different among plant varieties, notably more pronounced with the slow and intermediate growers. This study demonstrates that the SSG bacterium has multiple PGP traits and is a prospective plant biofertilizer.
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http://dx.doi.org/10.7717/peerj.9547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369026PMC
July 2020

Family Dinner and the Happiness of Chinese Adolescents: Identifying Mediators and Moderators.

J Youth Adolesc 2020 Aug 23;49(8):1674-1686. Epub 2020 Jun 23.

Faculty of Education, Shandong Normal University, No. 88 East Wenhua Road, Jinan, 250014, Shandong Province, China.

With China's fast-growing economy, family dinners are often overlooked. However, family dinner, as an important routine family activity, provides an opportunity for interaction between adolescents and their parents, which promotes adolescents' happiness. Guided by the positive youth development perspective, the character strength theory of happiness and the family investment model, the current study simultaneously investigated the mediating role of adolescents' internal assets and the moderating role of parental educational level in the influence of family dinner on adolescents' happiness in Chinese families. A three-wave longitudinal study spanning approximately three years was conducted among 817 Chinese seventh graders (52.4% male; M = 12.62 years). The frequency of family dinner at the first year was significantly positively correlated with adolescents' happiness in the first and third years. The cross-sectional and longitudinal results showed that adolescents' internal assets mediated the relationship between family dinner frequency and happiness. Specifically, family dinner with higher-educated parents was a stronger predictor of internal assets than family dinner with lower-educated parents after one year. These findings from the Chinese cultural context complement the research in this field and inform practical endeavors to promote adolescents' happiness worldwide based on the strengths of different cultures.
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http://dx.doi.org/10.1007/s10964-020-01275-1DOI Listing
August 2020

Complete genome sequence of a boxwood endophyte sp. SSG with broad biotechnological application potential.

Biotechnol Rep (Amst) 2020 Jun 14;26:e00455. Epub 2020 Apr 14.

Hampton Roads Agricultural Research and Extension Center, Virginia Tech, Virginia Beach, VA 23455, USA.

sp. strain SSG is a boxwood endophyte with potent antagonistic activities against a variety of plant pathogens. Here we present its complete genome sequence that is 8.6 Mb long with a GC content of 66.9%, 10,209 predicted protein-coding sequences, and 866 secondary metabolism gene clusters. Many of these genes and clusters involve antibiosis and other antagonistic activities against plant pathogens and insect pests as well as plant growth promoting traits but none for the epidemic strain marker. This genome sequence supports SSG as a potent biocontrol agent and source of other biotechnological applications.
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http://dx.doi.org/10.1016/j.btre.2020.e00455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184123PMC
June 2020

A Potent Burkholderia Endophyte against Boxwood Blight Caused by .

Microorganisms 2020 Feb 24;8(2). Epub 2020 Feb 24.

Virginia Tech, Hampton Roads Agricultural Research and Extension Center, 1444 Diamond Springs Road, Virginia Beach, VA 23455, USA.

() poses an increasing threat to boxwood, a major nursery crop and iconic landscape plant worldwide. Here, we report on a potent biocontrol agent that produces small sage green (SSG) colonies on potato dextrose agar. SSG is a bacterial strain recovered from Justin Brouwers boxwood leaves with unusual response to inoculation. Water-soaked symptoms developed on leaves 2 days after inoculation then disappeared a few days later. This endophyte affected several major steps of the boxwood blight disease cycle. SSG at 10 cfu/mL lysed all conidia in mixed broth culture. SSG at 10 cfu/mL reduced blight incidence by >98% when applied one day before or 3 h after boxwood were inoculated with . Its control efficacy decreased with decreasing bacterial concentration to 10 cfu/mL and increasing lead time up to 20 days. When applied on diseased leaf litter under boxwood plants, SSG reduced sporulation and consequently mitigated blight incidence by 90%. SSG was identified as a new member of the complex with distinct characters from known clinical strains. With these protective, curative, and sanitizing properties, this Burkholderia endophyte offers great promise for sustainable blight management at production and in the landscape.
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http://dx.doi.org/10.3390/microorganisms8020310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7074863PMC
February 2020

[A review of deep learning methods for the detection and classification of pulmonary nodules].

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 2019 Dec;36(6):1060-1068

Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine & Health Sciences, Shanghai 201318, P.R.China.

Lung cancer has the highest mortality rate among all malignant tumors. The key to reducing lung cancer mortality is the accurate diagnosis of pulmonary nodules in early-stage lung cancer. Computer-aided diagnostic techniques are considered to have potential beyond human experts for accurate diagnosis of early pulmonary nodules. The detection and classification of pulmonary nodules based on deep learning technology can continuously improve the accuracy of diagnosis through self-learning, and is an important means to achieve computer-aided diagnosis. First, we systematically introduced the application of two dimension convolutional neural network (2D-CNN), three dimension convolutional neural network (3D-CNN) and faster regions convolutional neural network (Faster R-CNN) techniques in the detection of pulmonary nodules. Then we introduced the application of 2D-CNN, 3D-CNN, multi-stream multi-scale convolutional neural network (MMCNN), deep convolutional generative adversarial networks (DCGAN) and transfer learning technology in classification of pulmonary nodules. Finally, we conducted a comprehensive comparative analysis of different deep learning methods in the detection and classification of pulmonary nodules.
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http://dx.doi.org/10.7507/1001-5515.201903027DOI Listing
December 2019

Host responses and impact on the boxwood blight pathogen, Calonectria pseudonaviculata.

Planta 2019 Mar 13;249(3):831-838. Epub 2018 Nov 13.

Hampton Roads Agricultural Research and Extension Centre, Virginia Tech, Virginia Beach, VA, 23455, USA.

Main Conclusion: Boxwood leaves are more susceptible to Calonectria pseudonaviculata (Cps) and better suited for Cps reproduction than those of pachysandra and sweet box. Passages through a non-boxwood host may alter Cps ability to sporulate. Calonectria pseudonaviculata (Cps) infects boxwood and its two common companion plants-pachysandra and sweet box. This study investigated how boxwood, pachysandra, and sweet box respond to Cps isolates of different host origin. Detached leaves were inoculated with nine isolates, three from each host, and evaluated for colonization, infection rate, lesion size, and production of conidia and microsclerotia. Cps colonized boxwood leaf tissue within 12 h of inoculation, and 60 h ahead of pachysandra and sweet box. Cps also produced significantly larger lesions and more conidia on boxwood than on pachysandra and sweet box. Isolates originating from different host plants did not differ in all the components evaluated except for conidia production. Isolates from boxwood and sweet box produced significantly more conidia than those from pachysandra. Overall, boxwood leaves are more susceptible to the disease and are better suited for Cps reproduction than those of pachysandra and sweet box. Passages through a non-boxwood host may alter Cps ability to sporulate. These results advance the understanding of Cps biology and affirm the importance of taking pachysandra and sweet box into consideration in disease management planning.
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http://dx.doi.org/10.1007/s00425-018-3041-4DOI Listing
March 2019

Opposing Actions of Fibroblast and Cardiomyocyte Smad3 Signaling in the Infarcted Myocardium.

Circulation 2018 02 11;137(7):707-724. Epub 2017 Dec 11.

Department of Medicine (Cardiology), Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, NY (P.K., A.V.S., Y.S., I.R., B.C., A.S., N.G.F.)

Background: Transforming growth factor-βs regulate a wide range of cellular responses by activating Smad-dependent and Smad-independent cascades. In the infarcted heart, Smad3 signaling is activated in both cardiomyocytes and interstitial cells. We hypothesized that cell-specific actions of Smad3 regulate repair and remodeling in the infarcted myocardium.

Methods: To dissect cell-specific Smad3 actions in myocardial infarction, we generated mice with Smad3 loss in activated fibroblasts or cardiomyocytes. Cardiac function was assessed after reperfused or nonreperfused infarction using echocardiography. The effects of cell-specific Smad3 loss on the infarcted heart were studied using histological studies, assessment of protein, and gene expression levels. In vitro, we studied Smad-dependent and Smad-independent actions in isolated cardiac fibroblasts.

Results: Mice with fibroblast-specific Smad3 loss had accentuated adverse remodeling after reperfused infarction and exhibited an increased incidence of late rupture after nonreperfused infarction. The consequences of fibroblast-specific Smad3 loss were not a result of effects on acute infarct size but were associated with unrestrained fibroblast proliferation, impaired scar remodeling, reduced fibroblast-derived collagen synthesis, and perturbed alignment of myofibroblast arrays in the infarct. Polarized light microscopy in Sirius red-stained sections demonstrated that the changes in fibroblast morphology were associated with perturbed organization of the collagenous matrix in the infarcted area. In contrast, α-smooth muscle actin expression by infarct myofibroblasts was not affected by Smad3 loss. Smad3 critically regulated fibroblast function, activating integrin-mediated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-2 (NOX-2) expression. Smad3 loss in cardiomyocytes attenuated remodeling and dysfunction after infarction. Cardiomyocyte-specific Smad3 loss did not affect acute infarct size but was associated with attenuated cardiomyocyte apoptosis in the remodeling myocardium, accompanied by decreased myocardial NOX-2 levels, reduced nitrosative stress, and lower matrix metalloproteinase-2 expression.

Conclusions: In healing myocardial infarction, myofibroblast- and cardiomyocyte-specific activation of Smad3 has contrasting functional outcomes that may involve activation of an integrin/reactive oxygen axis.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.117.029622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5812838PMC
February 2018

Polyphenol- and Caffeine-Rich Postfermented Pu-erh Tea Improves Diet-Induced Metabolic Syndrome by Remodeling Intestinal Homeostasis in Mice.

Infect Immun 2018 01 19;86(1). Epub 2017 Dec 19.

School of Life Sciences, Jilin University, Changchun Jilin, People's Republic of China

Postfermented Pu-erh tea (PE) protects against metabolic syndrome (MS), but little is known regarding its underlying mechanisms. Animal experiments were performed to determine whether the gut microbiota mediated the improvement in diet-induced MS by PE and its main active components (PEAC). We confirmed that PE altered the body composition and energy efficiency, attenuated metabolic endotoxemia and systemic and multiple-tissue inflammation, and improved the glucose and lipid metabolism disorder in high-fat diet (HFD)-fed mice via multiple pathways. Notably, PE promoted the lipid oxidation and browning of white adipose tissue (WAT) in HFD-fed mice. Polyphenols and caffeine (CAF) played critical roles in improving these parameters. Meanwhile, PE remodeled the disrupted intestinal homeostasis that was induced by the HFD. Many metabolic changes observed in the mice were significantly correlated with alterations in specific gut bacteria. and were speculated to be the key gut bacterial links between the PEAC treatment and MS at the genus and species levels. Interestingly, administration altered body composition and energy efficiency, promoted the browning of WAT, and improved the lipid and glucose metabolism disorder in the HFD-fed mice, whereas administration reduced the HFD-induced liver and intestinal inflammatory responses. In summary, polyphenol- and CAF-rich PE improved diet-induced MS, and this effect was associated with a remodeling of the gut microbiota.
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http://dx.doi.org/10.1128/IAI.00601-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5736808PMC
January 2018

Integrated microarray analysis provided a new insight of the pathogenesis of Parkinson's disease.

Neurosci Lett 2018 Jan 28;662:51-58. Epub 2017 Sep 28.

Department of Neurology, Tianjin Medical University General Hospital, China. Electronic address:

Background: Parkinson's disease (PD) is the second most common neurodegenerative disease and the exact pathogenic mechanism remains mostly elusive. Our study aims to identify the key differentially expressed genes (DEGs) and up regulators in PD.

Methods: An integrated analysis of microarray studies of PD was performed to identify the DEGs in PD compared to normal control (NC). Based on these DEGs, we performed the functional annotation and transcriptional regulatory network constructions. Q-RT-PCR was performed to verify the expression of DEGs.

Results: Seven datasets were obtained from GEO. A total of 276 DEGs (262 up-regulated and 14 down-regulated DEGs) in PD compared to normal control were identified with selecting criteria of p-value<0.05. GO terms of respiratory electron transport chain, protein binding and cytoplasm were significantly enriched in PD. Pathways of oxidative phosphorylation, Parkinson's disease, Alzheimer's disease and Huntington's disease were significantly enriched in PD. SNCA was the hub protein in PD according to the protein-protein interaction (PPI) network. The top 3 transcription factor (TFs) covering the most downstream DEGs were Oct-1, Pax-4 and Evi-1. A total of 19 DEGs were firstly identified in our integrated analysis, not from the other individual datasets enrolled in this study.

Conclusions: Several DEGs including SNCA, COX17, COX4I1, COX7B, COX6A1 and ATP5J targeted by Pax-4, Oct-1 and Evi-1 may involve in the neurodegeneration and pathogenesis of PD by regulating oxidative phosphorylation, ATP production and oxidative stress, which was benefit for uncovering the mechanism of PD and developing new diagnostic and therapeutic strategies.
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http://dx.doi.org/10.1016/j.neulet.2017.09.051DOI Listing
January 2018

Zoospore exudates from Phytophthora nicotianae affect immune responses in Arabidopsis.

PLoS One 2017 29;12(6):e0180523. Epub 2017 Jun 29.

Hampton Roads Agricultural Research and Extension Center, Virginia Tech, Virginia Beach, Virginia, United States of America.

Zoospore exudates play important roles in promoting zoospore communication, homing and germination during plant infection by Phytophthora. However, it is not clear whether exudates affect plant immunity. Zoospore-free fluid (ZFF) and zoospores of P. nicotianae were investigated comparatively for effects on resistance of Arabidopsis thaliana Col-0 and mutants that affect signaling mediated by salicylic acid (SA) and jasmonic acid (JA): eds16 (enhanced disease susceptibility16), pad4 (phytoalexin deficient4), and npr1 (nonexpressor of pathogenesis-related genes1). Col-0 attracted more zoospores and had severe tissue damage when flooded with a zoospore suspension in ZFF. Mutants treated with ZFF alone developed disease symptoms similar to those inoculated with zoospores and requirements of EDS16 and PAD4 for plant responses to zoospores and the exudates was apparent. Zoospore and ZFFs also induced expression of the PR1 and PDF1.2 marker genes for defense regulated by SA and JA, respectively. However, ZFF affected more JA defense signaling, down regulating PR1 when SA signaling or synthesis is deficient, which may be responsible for Arabidopsis mutant plants more susceptible to infection by high concentration of P. nicotianae zoospores. These results suggest that zoospore exudates can function as virulence factors and inducers of plant immune responses during plant infection by Phytophthora.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0180523PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5491255PMC
October 2017

Metabolic adaptation to the aqueous leaf extract of Moringa oleifera Lam.-supplemented diet is related to the modulation of gut microbiota in mice.

Appl Microbiol Biotechnol 2017 Jun 5;101(12):5115-5130. Epub 2017 Apr 5.

School of Life Sciences, Jilin University, Changchun, Jilin, 130012, People's Republic of China.

The aqueous leaf extract of Moringa oleifera Lam. (LM-A) is reported to have many health beneficial bioactivities and no obvious toxicity, but have mild adverse effects. Little is known about the mechanism of these reported adverse effects. Notably, there has been no report about the influence of LM-A on intestinal microecology. In this study, animal experiments were performed to explore the relationships between metabolic adaptation to an LM-A-supplemented diet and gut microbiota changes. After 8-week feeding with normal chow diet, the body weight of mice entered a stable period, and one of the group received daily doses of 750-mg/kg body weight LM-A by gavage for 4 weeks (assigned as LM); the other group received the vehicle (assigned as NCD). The liver weight to body weight ratio was enhanced, and the ceca were enlarged in the LM group compared with the NCD group. LM-A-supplemented-diet mice elicited a uniform metabolic adaptation, including slightly influenced fasting glucose and blood lipid profiles, significantly reduced liver triglycerides content, enhanced serum lipopolysaccharide level, activated inflammatory responses in the intestine and liver, compromised gut barrier function, and broken intestinal homeostasis. Many metabolic changes in mice were significantly correlated with altered specific gut bacteria. Changes in Firmicutes, Eubacterium rectale/Clostridium coccoides group, Faecalibacterium prausnitzii, Akkermansia muciniphila, segmented filamentous bacteria, Enterococcus spp., and Sutterella spp. may play an important role in the process of host metabolic adaptation to LM-A administration. Our research provides an explanation of the adverse effects of LM-A administration on normal adult individuals in the perspective of microecology.
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http://dx.doi.org/10.1007/s00253-017-8233-5DOI Listing
June 2017

Diversity and community structure of cyanobacteria and other microbes in recycling irrigation reservoirs.

PLoS One 2017 16;12(3):e0173903. Epub 2017 Mar 16.

Hampton Roads Agricultural Research and Extension Center, Virginia Tech, Virginia Beach, Virginia, United States of America.

Recycling irrigation reservoirs (RIRs) are emerging aquatic environments of global significance to crop production, water conservation and environmental sustainability. This study characterized the diversity and population structure of cyanobacteria and other detected microbes in water samples from eight RIRs and one adjacent runoff-free stream at three ornamental crop nurseries in eastern (VA1 and VA3) and central (VA2) Virginia after cloning and sequencing the 16S rRNA gene targeting cyanobacteria and chloroplast of eukaryotic phytoplankton. VA1 and VA2 utilize a multi-reservoir recycling irrigation system with runoff channeled to a sedimentation reservoir which then overflows into transition and retention reservoirs where water was pumped for irrigation. VA3 has a single sedimentation reservoir which was also used for irrigation. A total of 208 operational taxonomic units (OTU) were identified from clone libraries of the water samples. Among them, 53 OTUs (358 clones) were cyanobacteria comprising at least 12 genera dominated by Synechococcus species; 59 OTUs (387 clones) were eukaryotic phytoplankton including green algae and diatoms; and 96 were other bacteria (111 clones). Overall, cyanobacteria were dominant in sedimentation reservoirs, while eukaryotic phytoplankton and other bacteria were dominant in transition/retention reservoirs and the stream, respectively. These results are direct evidence demonstrating the negative impact of nutrient-rich horticultural runoff, if not contained, on natural water resources. They also help in understanding the dynamics of water quality in RIRs and have practical implications. Although both single- and multi-reservoir recycling irrigation systems reduce the environmental footprint of horticultural production, the former is expected to have more cyanobacterial blooming, and consequently water quality issues, than the latter. Thus, a multi-reservoir recycling irrigation system should be preferred where feasible.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0173903PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5354426PMC
September 2017

Expression and Characterization of a Single-Chain Variable Fragment against Human LOX-1 in and .

J Microbiol Biotechnol 2017 May;27(5):965-974

School of Life Science, Jilin University, Changchun, Jilin 130012, P.R. China.

The single-chain variable fragment (scFv) against lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a promising molecule for its potential use in the diagnosis and immunotherapy of atherosclerosis. Producing this scFv in several milligram amounts could be the starting point for further engineering and application of the scFv. In this study, the abundant expression of the anti-LOX-1 scFv was attempted using () and . The scFv had limited soluble yield in , but it was efficiently secreted by . The optimized fermentation was determined using the Plackett-Burman screening design and response surface methodology, under which the yield reached up to 1.5 g/l in a 5-L fermentor. Moreover, the properties of the scFvs obtained from the two expression systems were different. The antigen affinity, transition temperature, and particle diameter size were 1.01E-07 M, 55.2 ± 0.3°C, and 9.388 nm for the scFv expressed by , and 4.53E-07 M, 52.5 ± 0.3°C, and 13.54 nm for the scFv expressed by . This study established an efficient scale-up production methodology for the anti-LOX-1 scFv, which will boost its use in LOX-1-based therapy.
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http://dx.doi.org/10.4014/jmb.1702.02007DOI Listing
May 2017

Soil bacteria as sources of virulence signal providers promoting plant infection by Phytophthora pathogens.

Sci Rep 2016 09 12;6:33239. Epub 2016 Sep 12.

Hampton Roads Agricultural Research and Extension Center, Virginia Tech, 1444 Diamond Springs Road, Virginia Beach, VA 23455, USA.

Phytophthora species are known as "plant destroyers" capable of initiating single zoospore infection in the presence of a quorum of chemical signals from the same or closely related species of oomycetes. Since the natural oomycete population is too low to reach a quorum necessary to initiate a disease epidemic, creation of the quorum is reliant on alternate sources. Here, we show that a soil bacterial isolate, Bacillus megaterium Sb5, promotes plant infection by Phytophthora species. In the presence of Sb5 exudates, colonization of rhododendron leaf discs by 12 Phytophthora species/isolates was significantly enhanced, single zoospores of P. nicotianae infected annual vinca and P. sojae race 25 successfully attacked a non-host plant, Nicotiana benthamiana as well as resistant soybean cultivars with RPS1a or RPS3a. Sb5 exudates, most notably the fractions larger than 3 kDa, promoted plant infection by improving zoospore swimming, germination and plant attachment. Sb5 exudates also stimulated infection hypha growth and upregulated effector gene expression. These results suggest that environmental bacteria are important sources of virulence signal providers that promote plant infection by Phytophthora species, advancing our understanding of biotic factors in the environmental component of the Phytophthora disease triangle and of communal infection of plant pathogens.
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http://dx.doi.org/10.1038/srep33239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5018965PMC
September 2016

P2X7 as a new target for chrysophanol to treat lipopolysaccharide-induced depression in mice.

Neurosci Lett 2016 Feb 24;613:60-5. Epub 2015 Dec 24.

Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 210009, China. Electronic address:

P2X7 receptor is a ligand gated ion channel found peripheral macrophages and microglia in the nervous system. The current study investigated the relationship between the activated P2X7 and depression for the first time. Chrysophanol (Chr) was examined for its protective effects against depression targeting P2X7. Chr (20mg/kg, 40mg/kg) and fluoxetine (20mg/kg) were intragastrically treated once daily for 7 consecutive days. Lipopolysaccharide (LPS, 0.5mg/kg) was intraperitoneally injected to develop depression model 30min after drug administration on day 7. Behavioral tests were measured 24h after LPS injection. Interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)-α levels in serum and hippocampus were measured by enzyme-linked immunosorbent assay (ELISA). The expressions of P2X7/NF-κB pathway-related proteins were assessed by western blot. The findings showed that Chr remarkably reduced the elevations of IL-6, IL-1β and TNF-α caused by LPS stimulation. The expressions of P2X7, p-IKKα, p-IKKβ, p-IκBα and p-NF-κBp65 were significantly decreased by Chr pretreatment. In addition, immobility time in tail suspension test (TST) and forced swimming test (FST) were reduced by Chr without affecting spontaneous locomotor activity in open filed test (OFT) and the preference for sucrose was also recovered in sucrose preference test (SPT) with Chr preconditioning. Thus, it is reasonable to speculate that Chr might exert antidepressant effect through inhibiting P2X7/NF-κB signaling pathway.
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http://dx.doi.org/10.1016/j.neulet.2015.12.043DOI Listing
February 2016

Smad3 Signaling Promotes Fibrosis While Preserving Cardiac and Aortic Geometry in Obese Diabetic Mice.

Circ Heart Fail 2015 Jul 18;8(4):788-98. Epub 2015 May 18.

From the Department of Medicine (Cardiology), Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, NY (A.B., M.C., J.W., I.R., A.S., P.K., C.G.-Q., V.R., M.D., D.-W.L., N.G.F.); Department of Medicine, Baylor College of Medicine, Houston, TX (C.G.-Q., M.D., N.G.F.); and Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC (X.-F.W.).

Background: Heart failure in diabetics is associated with cardiac hypertrophy, fibrosis and diastolic dysfunction. Activation of transforming growth factor-β/Smad3 signaling in the diabetic myocardium may mediate fibrosis and diastolic heart failure, while preserving matrix homeostasis. We hypothesized that Smad3 may play a key role in the pathogenesis of cardiovascular remodeling associated with diabetes mellitus and obesity.

Methods And Results: We generated leptin-resistant db/db Smad3 null mice and db/db Smad3+/- animals. Smad3 haploinsufficiency did not affect metabolic function in db/db mice, but protected from myocardial diastolic dysfunction, while causing left ventricular chamber dilation. Improved cardiac compliance and chamber dilation in db/db Smad3+/- animals were associated with decreased cardiomyocyte hypertrophy, reduced collagen deposition, and accentuated matrix metalloproteinase activity. Attenuation of hypertrophy and fibrosis in db/db Smad3+/- hearts was associated with reduced myocardial oxidative and nitrosative stress. db/db Smad3 null mice had reduced weight gain and decreased adiposity associated with attenuated insulin resistance, but also exhibited high early mortality, in part, because of spontaneous rupture of the ascending aorta. Ultrasound studies showed that both lean and obese Smad3 null animals had significant aortic dilation. Aortic dilation in db/db Smad3 null mice occurred despite reduced hypertension and was associated with perturbed matrix balance in the vascular wall.

Conclusions: Smad3 mediates diabetic cardiac hypertrophy, fibrosis, and diastolic dysfunction, while preserving normal cardiac geometry and maintaining the integrity of the vascular wall.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.114.001963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4512850PMC
July 2015

Neurotoxicity of cerebro-spinal fluid from patients with Parkinson's disease on mesencephalic primary cultures as an in vitro model of dopaminergic neurons.

Mol Med Rep 2015 Aug 31;12(2):2217-24. Epub 2015 Mar 31.

Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin 300192, P.R. China.

Parkinson's disease is a degenerative disorder of the central nervous system. In spite of extensive research, neither the cause nor the mechanisms have been firmly established thus far. One assumption is that certain toxic substances may exist in the cerebro-spinal fluid (CSF) of Parkinson's disease patients. To confirm the neurotoxicity of CSF and study the potential correlation between neurotoxicity and the severity of Parkinson's disease, CSF was added to cultured cells. By observation of cell morphology, changes in the levels of lactate dehydrogenase, the ratio of tyrosine hydroxylase-positive cells, and the expression of tyrosine hydroxylase mRNA and protein, the differences between the two groups were shown. The created in vitro model of dopaminergic neurons using primary culture of mouse embryonic mesencephalic tissue is suitable for the study of neurotoxicity. The observations of the present study indicated that CSF from Parkinson's disease patients contains factors that can cause specific injury to cultured dopaminergic neurons. However, no obvious correlation was found between the neurotoxicity of CSF and the severity of Parkinson's disease.
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http://dx.doi.org/10.3892/mmr.2015.3575DOI Listing
August 2015

Neuroprotection of MAO-B inhibitor and dopamine agonist in Parkinson disease.

Int J Clin Exp Med 2015 15;8(1):431-9. Epub 2015 Jan 15.

Department of Geriatrics, Tianjin Medical University General Hospital Tianjin, China.

Parkinson disease is characterized by the death of dopaminergic neurons in the substantia nigra pars compacta. We explored the neuroprotective effect of Selegiline and Piribedil, the Monoamine Oxidase Type B (MAO-B) and dopamine agonist to Parkinson disease (PD). After embryonic Wistar rat were induced by cerebrospinal fluid (CSF) from PD patients, Selegiline and Piribedil were administered to Wistar rat. Immunohistochemical staining, RT-PCR and western blot were adopted to analyze the changes of morphology, lactate dehydrogenase activity, tyrosine hydroxylase positive neurons rate, and tyrosine hydroxylase (TH) expression in Wistar rat. The two drugs do not affect the normal growth of dopamine neurons. Selegiline and Piribedil both decreased the injury caused by CSF of PD patients in Wistar rat. We observed decreased lactate dehydrogenase (LDH) activity, increased TH (+)/total cells ratio and increased the TH expression in treated Wistar rat with dose-dependent effects. The morphological changes of cells are consistent with above observation. Selegiline and Piribedil have neuroprotective effects to induced PD Wistar rat with dose-dependent effect. Selegiline demonstrated stronger neuroprotective effect than Piribedil, and the two drugs have potential treatment effect in clinical for PD patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358469PMC
March 2015

Rumen Degradability and Post-ruminal Digestion of Dry Matter, Nitrogen and Amino Acids of Three Protein Supplements.

Asian-Australas J Anim Sci 2015 Apr;28(4):485-93

This study evaluated the in situ ruminal degradability, and subsequent small intestinal digestibility (SID) of dry matter, crude protein (CP), and amino acids (AA) of cottonseed meal (CSM), sunflower seed meal (SFSM) and distillers dried grains with solubles (DDGS) by using the modified three-step in vitro procedure. The ruminal degradability and subsequent SID of AA in rumen-undegradable protein (RUP-AA) varied among three protein supplements. The result show that the effective degradability of DM for SFSM, CSM, and DDGS was 60.8%, 56.4%, and 41.0% and their ruminal fermentable organic matter was 60.0%, 55.9%, and 39.9%, respectively. The ruminal degradable protein (RDP) content in CP for SFSM, CSM, and DDGS was 68.3%, 39.0%, and 32.9%, respectively, at the ruminal solid passage rate of 1.84%/h. The SFSM is a good source of RDP for rumen micro-organisms; however, the SID of RUP of SFSM was lower. The DDGS and CSM are good sources of RUP for lambs to digest in the small intestine to complement ruminal microbial AA of growing lambs. Individual RUP-AA from each protein source was selectively removed by the rumen micro-organisms, especially for Trp, Arg, His, and Lys (p<0.01). The SID of individual RUP-AA was different within specific RUP origin (p<0.01). Limiting amino acid was Leu for RUP of CSM and Lys for both RUP of SFSM and DDGS, respectively. Therefore, different protein supplements with specific limitations should be selected and combined carefully in growing lambs ration to optimize AA balance.
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http://dx.doi.org/10.5713/ajas.14.0572DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4341097PMC
April 2015

Oxygen stress reduces zoospore survival of Phytophthora species in a simulated aquatic system.

BMC Microbiol 2014 May 13;14:124. Epub 2014 May 13.

Virginia Tech, Hampton Roads Agricultural Research and Extension Center, Virginia Beach, VA 23455, USA.

Background: The genus Phytophthora includes a group of agriculturally important pathogens and they are commonly regarded as water molds. They produce motile zoospores that can move via water currents and on their own locomotion in aquatic environments. However, zoosporic response to dissolved oxygen, an important water quality parameter, is not known. Like other water quality parameters, dissolved oxygen concentration in irrigation reservoirs fluctuates dramatically over time. The aim of this study was to determine whether and how zoospore survival may be affected by elevated and low concentrations of dissolved oxygen in water to better understand the aquatic biology of these pathogens in irrigation reservoirs.

Results: Zoospores of P. megasperma, P. nicotianae, P. pini and P. tropicalis were assessed for survival in 10% Hoagland's solution at a range of dissolved concentrations from 0.9 to 20.1 mg L(-1) for up to seven exposure times from 0 to 72 h. Zoospore survival was measured by resultant colony counts per ml. Zoospores of these species survived the best in control Hoagland's solution at dissolved oxygen concentrations of 5.3 to 5.6 mg L(-1). Zoospore survival rates decreased with increasing and decreasing concentration of dissolved oxygen, depending upon Phytophthora species and exposure time. Overall, P. megasperma and P. pini are less sensitive than P. nicotianae and P. tropicalis to hyperoxia and hypoxia conditions.

Conclusion: Zoospores in the control solution declined over time and this natural decline process was enhanced under hyperoxia and hypoxia conditions. These findings suggest that dramatic fluctuations of dissolved oxygen in irrigation reservoirs contribute to the population decline of Phytophthora species along the water path in the same reservoirs. These findings advanced our understanding of the aquatic ecology of these pathogens in irrigation reservoirs. They also provided a basis for pathogen risk mitigation by prolonging the turnover time of runoff water in recycling irrigation systems via better system designs.
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http://dx.doi.org/10.1186/1471-2180-14-124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4028286PMC
May 2014

Tbx1 is required autonomously for cell survival and fate in the pharyngeal core mesoderm to form the muscles of mastication.

Hum Mol Genet 2014 Aug 4;23(16):4215-31. Epub 2014 Apr 4.

Department of Genetics, Albert Einstein College of Medicine, 1301 Morris Park Avenue, Bronx, NY 10461, USA,

Velo-cardio-facial/DiGeorge syndrome, also known as 22q11.2 deletion syndrome, is a congenital anomaly disorder characterized by craniofacial anomalies including velo-pharyngeal insufficiency, facial muscle hypotonia and feeding difficulties, in part due to hypoplasia of the branchiomeric muscles. Inactivation of both alleles of mouse Tbx1, encoding a T-box transcription factor, deleted on chromosome 22q11.2, results in reduction or loss of branchiomeric muscles. To identify downstream pathways, we performed gene profiling of microdissected pharyngeal arch one (PA1) from Tbx1(+/+) and Tbx1(-/-) embryos at stages E9.5 (somites 20-25) and E10.5 (somites 30-35). Basic helix-loop-helix (bHLH) transcription factors were reduced, while secondary heart field genes were increased in expression early and were replaced by an increase in expression of cellular stress response genes later, suggesting a change in gene expression patterns or cell populations. Lineage tracing studies using Mesp1(Cre) and T-Cre drivers showed that core mesoderm cells within PA1 were present at E9.5 but were greatly reduced by E10.5 in Tbx1(-/-) embryos. Using Tbx1(Cre) knock-in mice, we found that cells are lost due to apoptosis, consistent with increase in expression of cellular stress response genes at E10.5. To determine whether Tbx1 is required autonomously in the core mesoderm, we used Mesp1(Cre) and T-Cre mesodermal drivers in combination with inactivate Tbx1 and found reduction or loss of branchiomeric muscles from PA1. These mechanistic studies inform us that Tbx1 is required upstream of key myogenic genes needed for core mesoderm cell survival and fate, between E9.5 and E10.5, resulting in formation of the branchiomeric muscles.
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http://dx.doi.org/10.1093/hmg/ddu140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4103673PMC
August 2014

The role of thrombospondin (TSP)-1 in obesity and diabetes.

Adipocyte 2014 Jan 5;3(1):81-4. Epub 2013 Nov 5.

The Wilf Family Cardiovascular Research Institute; Department of Medicine (Cardiology); Albert Einstein College of Medicine; Bronx, NY USA.

Matricellular proteins are extracellular macromolecules that do not serve a structural role, but when incorporated into the matrix, modulate cell:cell and cell:matrix interactions. The matricellular protein thrombospondin (TSP)-1, a potent angiostatic mediator and activator of transforming growth factor (TGF)-β, is upregulated in diabetes and obesity and may be involved in the pathogenesis of metabolic dysregulation and organ dysfunction. This manuscript discusses recently published observations on the role of TSP-1 in metabolic disease. In obesity models induced by a high-fat diet, adipose tissue TSP-1 upregulation induces inflammation and promotes weight gain and metabolic dysfunction. TSP-1 may have direct effects on adipocyte proliferation and fatty acid uptake. In diabetic subjects, TSP-1 upregulation in kidney, myocardium, and vascular tissue may promote dysfunction. In the myocardium, TSP-1 upregulation may transduce angiostatic signals inducing vascular rarefaction. Dissection of the functional domains involved in TSP-1 actions may lead to the development of peptide-based strategies for treatment of diabetes and its complications.
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http://dx.doi.org/10.4161/adip.26990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3917940PMC
January 2014

Thrombospondin-1 induction in the diabetic myocardium stabilizes the cardiac matrix in addition to promoting vascular rarefaction through angiopoietin-2 upregulation.

Circ Res 2013 Dec 30;113(12):1331-44. Epub 2013 Sep 30.

From the Department of Medicine (Cardiology), Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, NY (C.G.-Q., M.C., A.B., P.K., D.-W.L., A.S., O.F., M.D., A.S., N.G.F.); and Department of Medicine, Baylor College of Medicine, Houston, TX (C.G.-Q., A.B., M.D., N.G.F.).

Rationale: Diabetes mellitus is associated with cardiac fibrosis. Matricellular proteins are induced in fibrotic conditions and modulate fibrogenic and angiogenic responses by regulating growth factor signaling.

Objective: Our aim was to test the hypothesis that the prototypical matricellular protein thrombospondin (TSP)-1, a potent angiostatic molecule and crucial activator of transforming growth factor-β, may play a key role in remodeling of the diabetic heart.

Methods And Results: Obese diabetic db/db mice exhibited marked myocardial TSP-1 upregulation in the interstitial and perivascular space. To study the role of TSP-1 in remodeling of the diabetic heart, we generated and characterized db/db TSP-1(-/-) (dbTSP) mice. TSP-1 disruption did not significantly affect weight gain and metabolic function in db/db animals. When compared with db/db animals, dbTSP mice had increased left ventricular dilation associated with mild nonprogressive systolic dysfunction. Chamber dilation in dbTSP mice was associated with decreased myocardial collagen content and accentuated matrix metalloproteinase-2 and -9 activity. TSP-1 disruption did not affect inflammatory gene expression and activation of transforming growth factor-β/small mothers against decapendaplegic signaling in the db/db myocardium. In cardiac fibroblasts populating collagen pads, TSP-1 incorporation into the matrix did not activate transforming growth factor-β responses, but inhibited leptin-induced matrix metalloproteinase-2 activation. TSP-1 disruption abrogated age-associated capillary rarefaction in db/db mice, attenuating myocardial upregulation of angiopoietin-2, a mediator that induces vascular regression. In vitro, TSP-1 stimulation increased macrophage, but not endothelial cell, angiopoietin-2 synthesis.

Conclusions: TSP-1 upregulation in the diabetic heart prevents chamber dilation by exerting matrix-preserving actions on cardiac fibroblasts and mediates capillary rarefaction through effects that may involve angiopoietin-2 upregulation.
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http://dx.doi.org/10.1161/CIRCRESAHA.113.302593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4408537PMC
December 2013

Lack of specificity of fibroblast-specific protein 1 in cardiac remodeling and fibrosis.

Am J Physiol Heart Circ Physiol 2013 Nov 30;305(9):H1363-72. Epub 2013 Aug 30.

Wilf Family Cardiovascular Research Institute, Department of Medicine (Cardiology Albert Einstein College of Medicine, Bronx, New York.

Understanding the role of fibroblasts in pathologic conditions is hampered by the absence of specific markers. Fibroblast-specific protein (FSP)1 has been suggested as a fibroblast-specific marker in normal and fibrotic tissues; FSP1 reporter mice and FSP1-Cre-driven gene deletion are considered reliable strategies to investigate fibroblast biology. Because fibroblasts are abundant in normal and injured mammalian hearts, we studied the identity of FSP1(+) cells in the infarcted and remodeling myocardium using mice with green fluorescent protein (GFP) expression driven by the FSP1 promoter. Neonatal and adult mouse hearts had low numbers of FSP1(+) cells. Myocardial infarction induced marked infiltration with FSP1-expressing cells that peaked after 72 h of reperfusion. Using flow cytometry, we identified 50% of FSP1(+) cells as hematopoietic cells; many endothelial cells were also FSP1(+). Increased infiltration with FSP1(+) cells was also noted in the pressure-overloaded myocardium. Although some FSP1(+) cells had fibroblast morphology, >30% were identified as hematopoietic cells, endothelial cells, or vascular smooth muscle cells. In contrast, periostin did not stain leukocytes or vascular cells but labeled spindle-shaped interstitial cells and, as a typical matricellular protein, was deposited in the matrix. CD11b(+) myeloid cells sorted from the infarcted heart had higher FSP1 expression than corresponding CD11b-negative cells, highlighting the predominant expression by hematopoietic cells. FSP1 is not a specific marker for fibroblasts in cardiac remodeling and fibrosis.
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http://dx.doi.org/10.1152/ajpheart.00395.2013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3840245PMC
November 2013

Thrombospondin-1 regulates adiposity and metabolic dysfunction in diet-induced obesity enhancing adipose inflammation and stimulating adipocyte proliferation.

Am J Physiol Endocrinol Metab 2013 Aug 11;305(3):E439-50. Epub 2013 Jun 11.

The Wilf Family Cardiovascular Research Institute, Department of Medicine Cardiology Albert Einstein College of Medicine, Bronx, New York, USA.

As a typical matricellular protein, thrombospondin (TSP)-1, binds to the structural matrix and regulates cellular behavior by modulating growth factor and cytokine signaling. Obesity and diabetes are associated with marked upregulation of TSP-1 in adipose tissue. We hypothesized that endogenous TSP-1 may play an important role in the pathogenesis of diet-induced obesity and metabolic dysfunction. Accordingly, we examined the effects of TSP-1 gene disruption on weight gain, adiposity, and adipose tissue inflammation in mice receiving a high-fat diet (HFD: 60% fat, 20% carbohydrate) or a high-carbohydrate low-fat diet (HCLFD: 10% fat, 70% carbohydrate). HFD mice had significantly higher TSP-1 expression in perigonadal adipose tissue; TSP-1 was predominantly localized in the adipose interstitium. TSP-1 loss attenuated weight gain and fat accumulation in HFD and HCLFD groups. Compared with corresponding wild-type animals, TSP-1-null mice had decreased insulin levels but exhibited elevated free fatty acid and triglyceride levels, suggesting impaired fatty acid uptake. TSP-1 loss did not affect adipocyte size and had no effect on adipose vascular density. However, TSP-1-null mice exhibited attenuated tumor necrosis factor-α mRNA expression and reduced macrophage infiltration, suggesting a role for TSP-1 in mediating obesity-associated inflammation. In vitro, TSP-1 enhanced proliferation of 3T3-L1 preadipocytes but did not modulate inflammatory cytokine and chemokine synthesis. In conclusion, TSP-1 upregulation contributes to weight gain, adipose growth, and the pathogenesis of metabolic dysfunction. The effects of TSP-1 may involve stimulation of adipocyte proliferation, activation of inflammatory signaling, and facilitated fatty acid uptake by adipocytes.
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http://dx.doi.org/10.1152/ajpendo.00006.2013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3742854PMC
August 2013

The pathogenesis of cardiac fibrosis.

Cell Mol Life Sci 2014 Feb 7;71(4):549-74. Epub 2013 May 7.

The Wilf Family Cardiovascular Research Institute, Department of Medicine (Cardiology), Albert Einstein College of Medicine, 1300 Morris Park Avenue Forchheimer G46B, Bronx, NY, 10461, USA.

Cardiac fibrosis is characterized by net accumulation of extracellular matrix proteins in the cardiac interstitium, and contributes to both systolic and diastolic dysfunction in many cardiac pathophysiologic conditions. This review discusses the cellular effectors and molecular pathways implicated in the pathogenesis of cardiac fibrosis. Although activated myofibroblasts are the main effector cells in the fibrotic heart, monocytes/macrophages, lymphocytes, mast cells, vascular cells and cardiomyocytes may also contribute to the fibrotic response by secreting key fibrogenic mediators. Inflammatory cytokines and chemokines, reactive oxygen species, mast cell-derived proteases, endothelin-1, the renin/angiotensin/aldosterone system, matricellular proteins, and growth factors (such as TGF-β and PDGF) are some of the best-studied mediators implicated in cardiac fibrosis. Both experimental and clinical evidence suggests that cardiac fibrotic alterations may be reversible. Understanding the mechanisms responsible for initiation, progression, and resolution of cardiac fibrosis is crucial to design anti-fibrotic treatment strategies for patients with heart disease.
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http://dx.doi.org/10.1007/s00018-013-1349-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3769482PMC
February 2014