bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevention of hyperglycemia-induced myocardial apoptosis by gene silencing of Toll-like receptor-4
Authors: Zhang Yuwei , Peng Tianqing , Zhu Huaqing , Zheng Xiufen , Zhang Xusheng , Jiang Nan , Cheng Xiaoshu , Lai Xiaoyan , Shunnar Aminah , Singh Manpreet , Riordan Neil , Bogin Vladimir , Tong Nanwei , Min Wei-Ping 
Published: December 2019

Abstract

Background
Apoptosis is an early event involved in cardiomyopathy associated with diabetes mellitus. Toll-like receptor (TLR) signaling triggers cell apoptosis through multiple mechanisms. Up-regulation of TLR4 expression has been shown in diabetic mice. This study aimed to delineate the role of TLR4 in myocardial apoptosis, and to block this process through gene silencing of TLR4 in the myocardia of diabetic mice.

Methods
Diabetes was induced in C57/BL6 mice by the injection of streptozotocin. Diabetic mice were treated with 50 μg of TLR4 siRNA or scrambled siRNA as control. Myocardial apoptosis was determined by TUNEL assay.

Results
After 7 days of hyperglycemia, the level of TLR4 mRNA in myocardial tissue was significantly elevated. Treatment of TLR4 siRNA knocked down gene expression as well as diminished its elevation in diabetic mice. Apoptosis was evident in cardiac tissues of diabetic mice as detected by a TUNEL assay. In contrast, treatment with TLR4 siRNA minimized apoptosis in myocardial tissues. Mechanistically, caspase-3 activation was significantly inhibited in mice that were treated with TLR4 siRNA, but not in mice treated with control siRNA. Additionally, gene silencing of TLR4 resulted in suppression of apoptotic cascades, such as Fas and caspase-3 gene expression. TLR4 deficiency resulted in inhibition of reactive oxygen species (ROS) production and NADPH oxidase activity, suggesting suppression of hyperglycemia-induced apoptosis by TLR4 is associated with attenuation of oxidative stress to the cardiomyocytes.

Conclusions
In summary, we present novel evidence that TLR4 plays a critical role in cardiac apoptosis. This is the first demonstration of the prevention of cardiac apoptosis in diabetic mice through silencing of the TLR4 gene.
A general strategy for synthesis of metal oxide nanoparticles attached on carbon nanomaterials
Authors: Zhao Yi , Li Jiaxin , Wu Chuxin , Guan Lunhui 
Published: December 2019

AbstractWe report a general strategy for synthesis of a large variety of metal oxide nanoparticles on different carbon nanomaterials (CNMs), including single-walled carbon nanotubes, multi-walled carbon nanotubes, and a few-layer graphene. The approach was based on the π-π interaction between CNMs and modified aromatic organic ligands, which acted as bridges connecting metal ions and CNMs. Our methods can be applicable for a large variety of metal ions, thus offering a great potential application.
Cytosolic phospholipase A2alpha amplifies early cyclooxygenase-2 expression, oxidative stress and MAP kinase phosphorylation after cerebral ischemia in mice
Authors: Kishimoto Koji , Li Rung-Chi , Zhang Jian , Klaus Judith A , Kibler Kathleen K , Doré Sylvain , Koehler Raymond C , Sapirstein Adam 
Published: December 2019

Abstract

Background
The enzyme cytosolic phospholipase A2 alpha (cPLA2α) has been implicated in the progression of cerebral injury following ischemia and reperfusion. Previous studies in rodents suggest that cPLA2α enhances delayed injury extension and disruption of the blood brain barrier many hours after reperfusion. In this study we investigated the role of cPLA2α in early ischemic cerebral injury.

Methods
Middle cerebral artery occlusion (MCAO) was performed on cPLA2α+/+ and cPLA2α-/- mice for 2 hours followed by 0, 2, or 6 hours of reperfusion. The levels of cPLA2α, cyclooxygenase-2, neuronal morphology and reactive oxygen species in the ischemic and contralateral hemispheres were evaluated by light and fluorescent microscopy. PGE2 content was compared between genotypes and hemispheres after MCAO and MCAO and 6 hours reperfusion. Regional cerebral blood flow was measured during MCAO and phosphorylation of relevant MAPKs in brain protein homogenates was measured by Western analysis after 6 hours of reperfusion.

Results
Neuronal cPLA2α protein increased by 2-fold immediately after MCAO and returned to pre-MCAO levels after 2 hours reperfusion. Neuronal cyclooxygenase-2 induction and PGE2 concentration were greater in cPLA2α+/+ compared to cPLA2α-/- ischemic cortex. Neuronal swelling in ischemic regions was significantly greater in the cPLA2α+/+ than in cPLA2α-/- brains (+/+: 2.2 ± 0.3 fold vs. -/-: 1.7 ± 0.4 fold increase; P < 0.01). The increase in reactive oxygen species following 2 hours of ischemia was also significantly greater in the cPLA2α+/+ ischemic core than in cPLA2α-/- (+/+: 7.12 ± 1.2 fold vs. -/-: 3.1 ± 1.4 fold; P < 0.01). After 6 hours of reperfusion ischemic cortex of cPLA2α+/+, but not cPLA2α-/-, had disruption of neuron morphology and decreased PGE2 content. Phosphorylation of the MAPKs-p38, ERK 1/2, and MEK 1/2-was significantly greater in cPLA2a+/+ than in cPLA2α-/- ischemic cortex 6 hours after reperfusion.

Conclusions
These results indicate that cPLA2α modulates the earliest molecular and injury responses after cerebral ischemia and have implications for the potential clinical use of cPLA2α inhibitors.
Integrative analysis of large scale expression profiles reveals core transcriptional response and coordination between multiple cellular processes in a cyanobacterium
Authors: Singh Abhay K , Elvitigala Thanura , Cameron Jeffrey C , Ghosh Bijoy K , Bhattacharyya-Pakrasi Maitrayee , Pakrasi Himadri B 
Published: December 2019

Abstract

Background
Cyanobacteria are the only known prokaryotes capable of oxygenic photosynthesis. They play significant roles in global biogeochemical cycles and carbon sequestration, and have recently been recognized as potential vehicles for production of renewable biofuels. Synechocystis sp. PCC 6803 has been extensively used as a model organism for cyanobacterial studies. DNA microarray studies in Synechocystis have shown varying degrees of transcriptome reprogramming under altered environmental conditions. However, it is not clear from published work how transcriptome reprogramming affects pre-existing networks of fine-tuned cellular processes.

Results
We have integrated 163 transcriptome data sets generated in response to numerous environmental and genetic perturbations in Synechocystis. Our analyses show that a large number of genes, defined as the core transcriptional response (CTR), are commonly regulated under most perturbations. The CTR contains nearly 12% of Synechocystis genes found on its chromosome. The majority of genes in the CTR are involved in photosynthesis, translation, energy metabolism and stress protection. Our results indicate that a large number of differentially regulated genes identified in most reported studies in Synechocystis under different perturbations are associated with the general stress response. We also find that a majority of genes in the CTR are coregulated with 25 regulatory genes. Some of these regulatory genes have been implicated in cellular responses to oxidative stress, suggesting that reactive oxygen species are involved in the regulation of the CTR. A Bayesian network, based on the regulation of various KEGG pathways determined from the expression patterns of their associated genes, has revealed new insights into the coordination between different cellular processes.

Conclusion
We provide here the first integrative analysis of transcriptome data sets generated in a cyanobacterium. This compilation of data sets is a valuable resource to researchers for all cyanobacterial gene expression related queries. Importantly, our analysis provides a global description of transcriptional reprogramming under different perturbations and a basic framework to understand the strategies of cellular adaptations in Synechocystis.
Therapeutic management of intestinal fibrosis induced by radiation therapy: from molecular profiling to new intervention strategies et vice et versa
Authors: Hamama Saad , Delanian Sylvie , Monceau Virginie , Vozenin Marie-Catherine 
Published: December 2019

Abstract
Chronic toxicities of locoregional and systemic oncological treatments commonly develop in long-term cancer survivors. Amongst these toxicities, post-radiotherapeutic complications alter patient's quality of life. Reduction of exposure of normal tissues can be achieved by optimization of radiotherapy. Furthermore, understanding of the fibrogenic mechanisms has provided targets to prevent, mitigate, and reverse late radiation-induced damages. This mini-review shows how (i) global molecular studies using gene profiling can provide tools to develop new intervention strategies and (ii) how successful clinical trials, conducted in particular with combined pentoxifylline-vitamin E, can take benefice of biological and molecular evidences to improve our understanding of fibrogenic mechanisms, enhance the robustness of proposed treatments, and lead ultimately to better treatments for patient's benefice.
The myofibroblast, multiple origins for major roles in normal and pathological tissue repair
Authors: Micallef Ludovic , Vedrenne Nicolas , Billet Fabrice , Coulomb Bernard , Darby Ian A , Desmoulière Alexis 
Published: December 2019

Abstract
Myofibroblasts differentiate, invade and repair injured tissues by secreting and organizing the extracellular matrix and by developing contractile forces. When tissues are damaged, tissue homeostasis must be re-established, and repair mechanisms have to rapidly provide harmonious mechanical tissue organization, a process essentially supported by (myo)fibroblasts. Under physiological conditions, the secretory and contractile activities of myofibroblasts are terminated when the repair is complete (scar formation) but the functionality of the tissue is only rarely perfectly restored. At the end of the normal repair process, myofibroblasts disappear by apoptosis but in pathological situations, myofibroblasts likely remain leading to excessive scarring. Myofibroblasts originate from different precursor cells, the major contribution being from local recruitment of connective tissue fibroblasts. However, local mesenchymal stem cells, bone marrow-derived mesenchymal stem cells and cells derived from an epithelial-mesenchymal transition process, may represent alternative sources of myofibroblasts when local fibroblasts are not able to satisfy the requirement for these cells during repair. These diverse cell types probably contribute to the appearance of myofibroblast subpopulations which show specific biological properties and which are important to understand in order to develop new therapeutic strategies for treatment of fibrotic and scarring diseases.
Nigrostriatal neuronal death following chronic dichlorvos exposure: crosstalk between mitochondrial impairments, α synuclein aggregation, oxidative damage and behavioral changes
Authors: BK Binukumar , Bal Amanjit , Kandimalla Ramesh JL , Gill Kiran Dip 
Published: December 2019

Abstract

Background
In recent years, several lines of evidence have shown an increase in Parkinson's disease prevalence in rural environments where pesticides are heavily used. Although, the underlying mechanism for neuronal degeneration in sporadic PD remains unknown, mitochondrial dysfunction, oxidative stress and proteasomal dysfunction are proposed as contributing factors. In this study rats were chronically and continuously exposed to the pesticide, dichlorvos to identify the molecular mechanism of nigrostaital neuronal degeneration.

Result
Chronic dichlorvos exposure (2.50 mg/kg b.wt.s.c/daily for 12 weeks) caused nigrostriatal dopaminergic degeneration. The degenerative changes were accompanied by a loss of 60-80% of the nigral dopamine neurons and 60-70% reduction in striatal dopamine and tyrosine hydroxylase levels. Dichlorvos exposed animals also showed α -synuclein and ubiquitin positive inclusions along with swollen, dystrophic neurites and mitochondrial abnormalities like decreased complex I&IV activities, increased mitochondrial size, axonal degeneration and presence of electron dense perinuclear cytoplasmic inclusions in the substantia nigra of rats. These animals also showed evidence of oxidative stress, including increased mitochondrial ROS levels, decreased MnSOD activity and increased lipid peroxidation. Measurable impairments in neurobehavioral indices were also observed. Notable exacerbations in motor impairments, open field and catalepsy were also evident in dichlorvos exposed animals.

Conclusion
All these findings taken together indicate that chronic dichlorvos exposure may cause nigrostaital neurodegenaration and significant behavioral impairments.
Gradient estimation in dendritic reinforcement learning
Authors: Schiess Mathieu , Urbanczik Robert , Senn Walter 
Published: December 2019

Abstract
We study synaptic plasticity in a complex neuronal cell model where NMDA-spikes can arise in certain dendritic zones. In the context of reinforcement learning, two kinds of plasticity rules are derived, zone reinforcement (ZR) and cell reinforcement (CR), which both optimize the expected reward by stochastic gradient ascent. For ZR, the synaptic plasticity response to the external reward signal is modulated exclusively by quantities which are local to the NMDA-spike initiation zone in which the synapse is situated. CR, in addition, uses nonlocal feedback from the soma of the cell, provided by mechanisms such as the backpropagating action potential. Simulation results show that, compared to ZR, the use of nonlocal feedback in CR can drastically enhance learning performance. We suggest that the availability of nonlocal feedback for learning is a key advantage of complex neurons over networks of simple point neurons, which have previously been found to be largely equivalent with regard to computational capability.
The relationship between hand osteoarthritis and serum leptin concentration in participants of the Third National Health and Nutrition Examination Survey
Authors: Massengale Mei , Reichmann William M , Losina Elena , Solomon Daniel H , Katz Jeffrey N 
Published: December 2019

Abstract

Introduction

Leptin has been suspected to contribute to the development of osteoarthritis (OA). However, this hypothesis has not been tested in large-scale hand OA cohorts. Our study aimed to determine whether there is a cross-sectional relationship between serum leptin levels and hand OA in a population-based sample of US adults.

Method

We used the Third National Health and Nutrition Examination Survey (NHANES III), a national cross-sectional population-based survey, to study the relationship between hand OA and serum leptin concentration. We applied previously established classification criteria for hand OA. Patients with rheumatoid arthritis were excluded. Potential confounders included sex, body mass index, the presence of polyarticular OA, diabetes, and total cholesterol. We estimated unadjusted mean leptin concentration by hand OA status and by all confounders. We further developed a linear regression model to assess mean leptin levels, adjusted for appropriate confounders.

Results

Of 2,477 subjects in the NHANES III sample that had a hand examination and did not have rheumatoid arthritis, 1,056 (42.6%) had a leptin measurement and were included in the analysis. Subjects with and without leptin measurement had similar demographic characteristics. We did not find any significant differences in mean serum leptin levels in subjects with symptomatic hand OA (7.38 ng/ml in males (95% confidence interval (CI) = 5.31, 9.46) and 21.55 ng/ml in females (95% CI = 17.08, 26.02)), asymptomatic hand OA (6.69 ng/ml in males (95% CI = 5.19, 8.18) and 17.09 ng/ml in females (95% CI = 15.00, 19.18)), and no hand OA (8.22 ng/ml in males (95% CI = 7.47, 8.97) and 20.77 ng/ml in females (95% CI = 18.01, 23.53)) in the unadjusted analysis. In a multivariable linear regression model that included variables of hand OA status, age, race/ethnicity, and obesity status, we found no statistically significant association between serum leptin and hand OA status.

Conclusions

In this cross-sectional study of a large representative US cohort, we did not find any evidence to support the hypothesis that serum leptin is associated with hand OA.
A few of our favorite unconfirmed ideas
Authors: Marini John J , Gattinoni Luciano , Ince Can , Kozek-Langenecker Sibylle , Mehta Ravindra L , Pichard Claude , Westphal Martin , Wischmeyer Paul , Vincent Jean-Louis 
Published: December 2019

AbstractMedical practice is rooted in our dependence on the best available evidence from incremental scientific experimentation and rigorous clinical trials. Progress toward determining the true worth of ongoing practice or suggested innovations can be glacially slow when we insist on following the stepwise scientific pathway, and a prevailing but imperfect paradigm often proves difficult to challenge. Yet most experienced clinicians and clinical scientists harbor strong thoughts about how care could or should be improved, even if the existing evidence base is thin or lacking. One of our Future of Critical Care Medicine conference sessions encouraged sharing of novel ideas, each presented with what the speaker considers a defensible rationale. Our intent was to stimulate insightful thinking and free interchange, and perhaps to point in new directions toward lines of innovative theory and improved care of the critically ill. In what follows, a brief background outlines the rationale for each novel and deliberately provocative unconfirmed idea endorsed by the presenter.
Intravenous fluids: should we go with the flow?
Authors: Kozek-Langenecker Sibylle A 
Published: December 2019

AbstractSensitive monitoring should be used when prescribing intravenous fluids for volume resuscitation. The extent and duration of tissue hypoperfusion determine the severity of cellular damage, which should be kept to a minimum with timely volume substitution. Optimizing the filling status to normovolaemia may boost the resuscitation success. Macrocirculatory pressure values are not sensitive in this indication. While the Surviving Sepsis Campaign guidelines focus on these conventional pressure parameters, the guidelines from the European Society of Anaesthesiology (ESA) on perioperative bleeding management recommend individualized care by monitoring the actual volume status and correcting hypovolaemia promptly if present. The motto is: 'give what is missing'. The credo of the ESA guidelines is to use management algorithms with predefined intervention triggers. Stop signals should help in avoiding hyper-resuscitation. The high-quality evidence-based S3 guidelines on volume therapy in adults have recently been prepared by 14 German scientific societies. Statements include, for example, repeated clinical inspection including turgor of the skin and mucosa. Adjunctive laboratory parameters such as central venous oxygen saturation, lactate, base excess and haematocrit should be considered. The S3 guidelines propose the use of flow-based and/or dynamic preload parameters for guiding volume therapy. Fluid challenges and/or the leg-raising test (autotransfusion) should be performed. The statement from the Co-ordination group for Mutual Recognition and Decentralized Procedures--Human informs healthcare professionals to consider applying individualized medicine and using sensitive monitoring to assess hypovolaemia. The authorities encourage a personalized goal-directed volume resuscitation technique.
Paradigm shifts in critical care medicine: the progress we have made
Authors: Vincent Jean-Louis , Creteur Jacques 
Published: December 2019

AbstractThere have really been no single, major, advances in critical care medicine since the specialty came into existence. There has, however, been a gradual, continuous improvement in the process of care over the years, which has resulted in improved patient outcomes. Here, we will highlight just a few of the paradigm shifts we have seen in processes of critical care, including the move from small, closed units to larger, more open ICUs; from a paternal "dictatorship" to more "democratic" team-work; from intermittent to continuous, invasive to less-invasive monitoring; from "more" interventions to "less" thus reducing iatrogenicity; from consideration of critical illness as a single event to realization that it is just one part of a trajectory; and from "four walls" to "no walls" as we take intensive care outside the physical ICU. These and other paradigm shifts have resulted in improvements in the whole approach to patient management, leading to more holistic, humane care for patients and their families. As critical care medicine continues to develop, further paradigm shifts in processes of care are inevitable and must be embraced if we are to continue to provide the best possible care for all critically ill patients.
The race against the "septic shark"
Authors: Westphal Martin , Kampmeier Tim 
Published: December 2019

AbstractGreat white sharks are responsible for about 10 cases of death annually worldwide, as compared with millions of deaths caused by sepsis. However, the basic principles of avoiding shark attacks and fighting sepsis seem to be similar: avoidance, attention, and speed, if necessary. The present review discusses the current status of the systemic inflammatory response syndrome (SIRS) criteria, which are actually content for discussion because of their low specificity. Current data suggest that one in eight patients with severe sepsis does not fulfill the SIRS criteria and is consequently missed, and therefore the calls for new definitions of sepsis are getting louder. Furthermore, the need for early treatment of sepsis and fast admission to an intensive care unit (ICU) with experienced stuff is reviewed as well as the early and appropriate initiation of therapy, namely antibiotic and volume therapy. A key feature is the analysis of the studies from the so-called "Sepsis Trilogy" (ProCESS, ARISE, and ProMiSe studies), with a focus on the status of early goal-directed therapy (EGDT). The authors of the "Sepsis Trilogy" concluded that there is no benefit regarding survival in septic patients by using EGDT as compared with standard therapy. However, the low mortality of the control groups within the "Sepsis Trilogy" studies as compared with the Rivers et al. study from 2001 leads to the conclusion that there has been an improvement in the therapy of septic patients, most probably due to the early initiation of therapy as a kind of "standard" in sepsis therapy. Finally, the phenomenon of a "large trial disease" is discussed, exemplary in a trial which investigated the maintenance of the "right" mean arterial pressure in sepsis patients. Even if the result of a large randomized trial might be that there is no difference between two study groups, the real exercise is to identify the patient collectives who might benefit or experience harm due to an intervention. In summary, as compared with swimming in dangerous waters, high attention is needed in handling septic patients. Once an attack has occurred, speed is of utmost importance (i.e., initiation of therapy and admission to the ICU) because it appears logical that time is critical in septic patients This may have resulted in the implementation of early (goal-directed) treatment as a "standard" in the treatment of sepsis with significant improvement in survival.