tbuckley/cabot-search huggingface dataset:
Tetrahedral framework nucleic acids promote the biological functions and related mechanism of synovium-derived mesenchymal stem cells and show improved articular cartilage regeneration activity in situ
Authors: Liwei Fu, Pinxue Li, Junyao Zhu, Zhiyao Liao, Cangjian Gao, Hao Li, Zhen Yang, Tianyuan Zhao, Wei Chen, Yu Peng, Fuyang Cao, Chao Ning, Xiang Sui, Quanyi Guo, Yunfeng Lin, Shuyun Liu
Journal: Bioactive Materials (2021)

Many recent studies have shown that joint-resident mesenchymal stem cells (MSCs) play a vital role in articular cartilage (AC) in situ regeneration. Specifically, synovium-derived MSCs (SMSCs), which have strong chondrogenic differentiation potential, may be the main driver of cartilage repair. However, both the insufficient number of MSCs and the lack of an ideal regenerative microenvironment in the defect area will seriously affect the regeneration of AC. Tetrahedral framework nucleic acids (tFNAs), notable novel nanomaterials, are considered prospective biological regulators in biomedical engineering. Here, we aimed to explore whether tFNAs have positive effects on AC in situ regeneration and to investigate the related mechanism. The results of in vitro experiments showed that the proliferation and migration of SMSCs were significantly enhanced by tFNAs. In addition, tFNAs, which were added to chondrogenic induction medium, were shown to promote the chondrogenic capacity of SMSCs by increasing the phosphorylation of Smad2/3. In animal models, the injection of tFNAs improved the therapeutic outcome of cartilage defects compared with that of the control treatments without tFNAs. In conclusion, this is the first report to demonstrate that tFNAs can promote the chondrogenic differentiation of SMSCs in vitro and enhance AC regeneration in vivo, indicating that tFNAs may become a promising therapeutic for AC regeneration.
Abstract 14947: Diagnostic Value of Exercise-Induced Post-Ischemic Left Ventricular Delayed Relaxation or Diastolic Stunning in Patients With Intermediate Coronary Lesions: Comparison With Myocardial Fractional Flow Reserve
Authors: Katsuhisa Ishii, Kazuaki Kataoka, Atsuko Furukawa, Takahiro Nagai, Yutaka Seino, Tamaki Suyama, Motoyoshi Maenaka
Journal: Circulation (2011)

Background: Quantitative analysis of prolonged regional left ventricular (LV) diastolic dysfunction or diastolic stunning has provided a more sensitive estimation of the myocardial ischemia. The ai...
GCH1 induces immunosuppression through metabolic reprogramming and IDO1 upregulation in triple-negative breast cancer
Authors: Jin-Li Wei, Si-Yu Wu, Yun-Song Yang, Yi Xiao, Xi Jin, Xiao-En Xu, Xin Hu, Da-Qiang Li, Yi-Zhou Jiang, Zhi-Ming Shao
Journal: Journal for ImmunoTherapy of Cancer (2021)

Regulatory T cells (Tregs) heavily infiltrate triple-negative breast cancer (TNBC), and their accumulation is affected by the metabolic reprogramming in cancer cells. In the present study, we sought to identify cancer cell-intrinsic metabolic modulators correlating with Tregs infiltration in TNBC.Using the RNA-sequencing data from our institute (n=360) and the Molecular Taxonomy of Breast Cancer International Consortium TNBC cohort (n=320), we calculated the abundance of Tregs in each sample and evaluated the correlation between gene expression levels and Tregs infiltration. Then, in vivo and in vitro experiments were performed to verify the correlation and explore the underlying mechanism.We revealed that GTP cyclohydrolase 1 (GCH1) expression was positively correlated with Tregs infiltration and high GCH1 expression was associated with reduced overall survival in TNBC. In vivo and in vitro experiments showed that GCH1 increased Tregs infiltration, decreased apoptosis, and elevated the programmed cell death-1 (PD-1)-positive fraction. Metabolomics analysis indicated that GCH1 overexpression reprogrammed tryptophan metabolism, resulting in L-5-hydroxytryptophan (5-HTP) accumulation in the cytoplasm accompanied by kynurenine accumulation and tryptophan reduction in the supernatant. Subsequently, aryl hydrocarbon receptor, activated by 5-HTP, bound to the promoter of indoleamine 2,3-dioxygenase 1 (IDO1) and thus enhanced the transcription of IDO1. Furthermore, the inhibition of GCH1 by 2,4-diamino-6-hydroxypyrimidine (DAHP) decreased IDO1 expression, attenuated tumor growth, and enhanced the tumor response to PD-1 blockade immunotherapy.Tumor-cell-intrinsic GCH1 induced immunosuppression through metabolic reprogramming and IDO1 upregulation in TNBC. Inhibition of GCH1 by DAHP serves as a potential immunometabolic strategy in TNBC.
Dolutegravir or Darunavir in Combination with Zidovudine or Tenofovir to Treat HIV
Authors: Nicholas I. Paton, Joseph Musaazi, Cissy Kityo, Stephen Walimbwa, Anne Hoppe, Apolo Balyegisawa, Arvind Kaimal, Grace Mirembe, Phionah Tukamushabe, Gilbert Ategeka, James Hakim, Henry Mugerwa, Abraham Siika, Jesca Asienzo, Barbara Castelnuovo, Agnes Kiragga, Andrew Kambugu
Journal: New England Journal of Medicine (2021)

The World Health Organization recommends dolutegravir with two nucleoside reverse-transcriptase inhibitors (NRTIs) for second-line treatment of human immunodeficiency virus type 1 (HIV-1) infection. Evidence is limited for the efficacy of this regimen when NRTIs are predicted to lack activity because of drug resistance, as well as for the recommended switch of an NRTI from tenofovir to zidovudine.
Cerebral Autosomal‐Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy Syndrome, a CentralNervous System Vasculitis Mimic
Authors: Mithu Maheswaranathan, Anne F. Buckley, Andrew B. Cutler, Lisa Criscione‐Schreiber, Ankoor Shah
Journal: Arthritis & Rheumatology (2021)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Abstract 17320: Signaling Mechanisms Involved In Beta3-adrenergic Receptor Regulation of Nnos in Isolated Cardiomyocytes
Authors: Vabren L Watts, Xiaolin Niu, Karen L Miller, Lili A Barouch
Journal: Circulation (2011)

Beta3 -adrenergic (beta3-AR) receptors play a pivotal role in modulating cardiac function, though their precise role in the heart remains controversial. We have recently demonstrated that beta3-mediated cardiac protection via negative inotropy is lost in nNOS-/- animals under pressure overload as compared with WT. However, the exact manner in which beta3-AR activation regulates nNOS signaling to stimulate NOS activity at the cardiomyocyte level is unknown. In this study we used a specific beta3-AR agonist, BRL37344 (BRL), to assess the role of beta3-AR in nNOS regulation in hypertrophied isolated neonatal rat ventricular cardiomyocytes (NRVM). To induce hypertrophy we pretreated cells with norepinephrine for 72 hours, which resulted in a 70% increase in cell size and a 25% increase in beta3-AR mRNA expression as compared with non-hypertrophied cells, analyzed by immunocytochemistry and real-time PCR. In hypertrophied cardiomyocytes, BRL administration lead to a time-dependent 5-fold increase in NOS activity, which was significantly suppressed by nNOS specific inhibitor LVNIO. NOS activity was measured by the arginine-to-citrulline conversion assay. BRL also cause a time-dependent 1.5-fold increase in nNOS phosphorylation at positive regulatory site Ser1416, dephosphorylation of negative regulatory site Ser847, and decreased superoxide generation as compared with unstimulated control. In addition BRL induced phosphorylation eNOS-Ser114, which indicates eNOS deactivation. Pretreatment with pertussis toxin (PTX) suppressed BRL-induced nNOS-Ser1416 phosphorylation, nNOS-Ser847 dephosphorylation, and NOS activity, and unaltered superoxide generation, suggesting Gi/o dependency. Taken together, our data suggest that BRL regulates NOS signaling in ventricular cardiomyocytes via phosphorylation regulation of nNOS. To our knowledge this is first study to demonstrate a role for nNOS phosphorylation as a key factor in beta3-AR signaling. These results contribute significantly to our understanding the negative inotropic properties of myocardial beta3-AR at cellular levels during cardiac sympathetic overstimulation, and will ultimately aid in drug discoveries that target the molecular mechanisms associated heart failure.
Cardiac natriuretic peptide deficiency sensitizes the heart to stress-induced ventricular arrhythmias via impaired CREB signalling
Authors: Eric J Hall, Soumojit Pal, Michael S Glennon, Puneeth Shridhar, Sidney L Satterfield, Beth Weber, Qinkun Zhang, Guy Salama, Hind Lal, Jason R Becker
Journal: Cardiovascular Research (2021)

Abstract Aims The cardiac natriuretic peptides [atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP)] are important regulators of cardiovascular physiology, with reduced natriuretic peptide (NP) activity linked to multiple human cardiovascular diseases. We hypothesized that deficiency of either ANP or BNP would lead to similar changes in left ventricular structure and function given their shared receptor affinities. Methods and results We directly compared murine models deficient of ANP or BNP in the same genetic backgrounds (C57BL6/J) and environments. We evaluated control, ANP-deficient (Nppa−/−) or BNP-deficient (Nppb−/−) mice under unstressed conditions and multiple forms of pathological myocardial stress. Survival, myocardial structure, function and electrophysiology, tissue histology, and biochemical analyses were evaluated in the groups. In vitro validation of our findings was performed using human-derived induced pluripotent stem cell cardiomyocytes (iPS-CMs). In the unstressed state, both ANP- and BNP-deficient mice displayed mild ventricular hypertrophy which did not increase up to 1 year of life. NP-deficient mice exposed to acute myocardial stress secondary to thoracic aortic constriction (TAC) had similar pathological myocardial remodelling but a significant increase in sudden death. We discovered that the NP-deficient mice are more susceptible to stress-induced ventricular arrhythmias using both in vivo and ex vivo models. Mechanistically, deficiency of either ANP or BNP led to reduced myocardial cGMP levels and reduced phosphorylation of the cAMP response element-binding protein (CREBS133) transcriptional regulator. Selective CREB inhibition sensitized wild-type hearts to stress-induced ventricular arrhythmias. ANP and BNP regulate cardiomyocyte CREBS133 phosphorylation through a cGMP-dependent protein kinase 1 (PKG1) and p38 mitogen-activated protein kinase (p38 MAPK) signalling cascade. Conclusions Our data show that ANP and BNP act in a non-redundant fashion to maintain myocardial cGMP levels to regulate cardiomyocyte p38 MAPK and CREB activity. Cardiac natriuretic peptide deficiency leads to a reduction in CREB signalling which sensitizes the heart to stress-induced ventricular arrhythmias.
Probiotics Stimulate Bone Formation in Obese Mice via Histone Methylations
Authors: Jyotirmaya Behera, Jessica Ison, Michael J. Voor, Neetu Tyagi
Journal: Theranostics (2021)

Rationale: Manipulation of the gut microbiome can prevent pathologic bone loss.However, the effects of probiotics on mitochondrial epigenetic remodeling and skeletal homeostasis in the high-fat diet (HFD)-linked obesity remains to be explored.Here, we examined the impact of probiotics supplementation on mitochondrial biogenesis and bone homeostasis through the histone methylation mechanism in HFD fed obese mice.Methods: 16S rRNA gene sequencing was performed to study the microbiota composition in the gut and microbial dysbiosis in obese mouse model.High resolution (microPET/CT) imaging was performed to demonstrate the obese associated colonic inflammation.Obese-associated upregulation of target miRNA in osteoblast was investigated using a microRNA qPCR array.Osteoblastic mitochondrial mass was evaluated using confocal imaging.Overexpression of mitochondrial transcription factor (Tfam) was used to investigate the glycolysis and mitochondrial bioenergetic metabolism using Tfam-transgenic (Tg) mice fed on HFD.The bone formation and mechanical strength was evaluated by microCT analysis and three-point bending analysis.Results: High-resolution imaging (µ-CT) and mechanical testing revealed that probiotics induced a significant increase of trabecular bone volume and bone mechanical strength respectively in obese mice.Probiotics or Indole-3-propionic acid (IPA) treatment directly to obese mice, prevents gut inflammation, and improved osteoblast mineralization.Mechanistically, probiotics treatment increases mitochondrial transcription factor A (Tfam) expression in osteoblasts by promoting Kdm6b/Jmjd3 histone demethylase, which inhibits H3K27me3 epigenetic methylation at the Tfam promoter.Furthermore, Tfam-transgenic (Tg) mice, fed with HFD, did not experience obesity-linked reduction of glucose uptake, mitochondrial biogenesis and mineralization in osteoblasts.Conclusions: These results suggest that the probiotics mediated changes in the gut microbiome and its derived metabolite, IPA are potentially be a novel agent for regulating bone anabolism via the gut-bone axis.
Abstract 8817: Niacin Promotes Macrophage Reverse Cholesterol Transport in Hypercholesterolemic Mice In a CETP-Dependent Manner
Authors: Kazuhiro Nakaya, Yohei Komaru, Junichiro Tohyama, John S Millar, Jeffrey T Billheimer, Daniel J Rader
Journal: Circulation (2011)

Background- Niacin is the most effective drug currently available to increase HDL-cholesterol. The aim of the present study was to examine the effect of niacin on macrophage reverse cholesterol transport (RCT), a primary atheroprotective property of HDL, and to determine the mechanisms by which this occurs. Methods and Results- Niacin increased HDL-cholesterol in homozygous LDL receptor-deficient ( Ldlr -/- ) mice expressing human cholesterol ester transfer protein (CETP) ( Ldlr -/- . CETP ), but not in the mice without CETP. Niacin promoted macrophage RCT in the mice in a CETP-dependent manner. Treatment of Ldlr -/- . CETP mice with niacin decreased plasma CETP activity ex vivo , without the alteration of hepatic CETP expression or plasma CETP mass. Niacin also promoted macrophage RCT by reducing CETP activity even in the setting of partial lack of LDL receptor with CETP expression ( Ldlr +/- . CETP mice). Ldlr -/- . CETP mice and Ldlr +/- . CETP mice with niacin had the enhanced plasma capacity to promote macrophage cholesterol efflux. Moreover, niacin attenuated the transfer of cholesteryl esters from HDL to VLDL/LDL fractions in vivo , consistent with its inhibitory effect on CETP activity. Kinetic studies showed that niacin increased fecal excretion of HDL-derived cholesteryl esters in Ldlr -/- . CETP , but not in Ldlr -/- mice. Conclusions- Our observations demonstrate that niacin promotes macrophage RCT in vivo by decreasing plasma CETP activity in the setting of both complete and partial lack of LDL receptor. Niacin-mediated reduction in CETP activity leads to the enhanced direct pathway of RCT from HDL fractions into feces with the promotion of plasma efflux capacity from macrophages in the mice.
Abstract 9935: Characteristics and Relative Improvements in Clinical Cardio Metabolic Profiles Among Adults With and Without Type 2 Diabetes Participating in a Cardiac Rehabilitation Program
Authors: Deepika Laddu, Cemal Ozemek, Trina Hauer, Codie R Rouleau, Tavis Campbell, Stephen Wilton, Sandeep Aggarwal, Leslie Austford, Ross Arena
Journal: Circulation (2019)

Introduction: Type 2 diabetes (T2DM) and cardiometabolic comorbidities manifesting as the metabolic syndrome (MetS) are highly prevalent in coronary heart disease (CHD) patients attending cardiac r...
The Cancer Therapy-Related Clonal Hematopoiesis Driver Gene <i>Ppm1d</i> Promotes Inflammation and Non-Ischemic Heart Failure in Mice
Authors: Yoshimitsu Yura, Emiri Miura-Yura, Yasufumi Katanasaka, Kyung-Duk Min, Nicholas Chavkin, Ariel H. Polizio, Hayato Ogawa, Keita Horitani, Heather Doviak, Megan A. Evans, Miho Sano, Ying Wang, Katharina Boroviak, George Philippos, Ana Filipa Domingues, George Vassiliou, Soichi Sano, Kenneth Walsh
Journal: Circulation Research (2021)

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Biomarker Discovery: Novel Insights into Red Blood Cell Metabolomics in Patients with Sickle Cell Disease at Risk for Early Mortality
Authors: Claudia R. Morris, Chunyu Ma, Shuzhao Li, Dean Jones, Lou Ann Brown, Roberto F. Machado, Gregory J. Kato, Yingze Zhang, Seyed Mehdi Nouraie, Mark T Gladwin
Journal: Blood (2017)
The circadian clock regulates rhythmic erythropoietin expression in the murine kidney
Authors: Lina K. Sciesielski, Matthias Felten, Laura Michalick, Karin M. Kirschner, Georgia Lattanzi, Charlotte L.J. Jacobi, Thomas Wallach, Veronika Lang, Dominic Landgraf, Achim Kramer, Christof Dame
Journal: Kidney International (2021)
Clinical Images: The appearance of scurvy on magnetic resonance imaging
Authors: Sami Giryes, Daniela Militianu, Yolanda Braun‐Moscovici
Journal: Arthritis & Rheumatology (2021)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Final Analysis of Day +100 Survival By Prior Hematopoietic Stem Cell Transplant Type from an Expanded Access Study of Defibrotide for Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome
Authors: Paul G Richardson, Angela R. Smith, Brandon Triplett, Nancy Kernan, Leslie Lehmann, Robert J. Ryan, Robin L. Hume, William Martin Tappe, Stephan A Grupp
Journal: Blood (2017)
Early-Life Adversity and Executive Functioning—Highlighting an Urgent Need for Identification, Prevention, and Intervention in Childhood
Authors: Beth S. Slomine, Nikeea Copeland-Linder
Journal: JAMA Pediatrics (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Are patients benefiting from participation in the German skin cancer screening programme? A large cohort study based on administrative data
Authors: T. Datzmann, O. Schoffer, F. Meier, A. Seidler, J. Schmitt
Journal: British Journal of Dermatology (2021)

The German programme for skin cancer screening was established in 2008 with the aim of reducing skin cancer mortality. However, the effectiveness and risk-benefit ratio of the programme remain unclear.To compare the mortality rates of patients with melanoma who participate in a screening programme to those who do not.A retrospective cohort study, based on pseudonymized health insurance data of 1 431 327 individuals from Saxony, Germany, was conducted for the period 2010-2016. Patients with prevalent and incident melanoma were defined based on diagnosis, medical procedures and prescriptions. Patients who underwent screening and had a first diagnosis of melanoma within 2 years of screening were assigned to the intervention group. Relative survival and Cox regression were used to assess potential differences in mortality.We identified 4552 individuals with prevalent and 2475 individuals with incident melanoma. The percentage of screening participants (n = 1801) who had locoregional (4·2% vs. 13·5%) and/or distant metastases (4·3% vs. 8·0%), or who were treated with systemic anticancer therapies (11·6% vs. 21·8%) was lower vs. nonparticipants (n = 674). Screening participants had significantly better survival rates. The unadjusted Cox model gave a hazard ratio (HR) of 0·37 [95% confidence interval (CI) 0·30-0·46]. After adjusting for named confounders, the effect remained (HR 0·62, 95% CI 0·48-0·80).Patients who participated in the screening programme had lower mortality than those who had not undergone screening. However, these findings may result from a healthy screen bias and/or overdiagnosis associated with screening, and not from the screening itself.
P-103 Associations between quality-of-life, symptom burden, and demographic characteristics in long-term esophageal and gastroesophageal junction cancer survivors
Authors: E. McGillivray, R. Jain, C. Ramamurthy, J. Sheng, E. Granina, D. Yu, X. Lu, A. Abbas, E. Dotan, J. Meyer, C. Fang, C. Denlinger
Journal: Annals of Oncology (2021)
MO37-3 Is bronchoscopic cytology pellets useful for oncomine comprehensive assay? – from the samples submitted to LC-SCRUM
Authors: Motoko Tachihara, Koichi Furukawa, Tatsunori Kiriu, Chihiro Mimura, Hiroki Satoh, Naoya Takara, Junya Yoshioka, Masako Yumura, Takehiro Otoshi, Yuichiro Yasuda, Naoko Katsurada, Masatsugu Yamamoto, Yoshihiro Nishimura
Journal: Annals of Oncology (2021)