bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microglial proliferation and monocyte infiltration contribute to microgliosis following status epilepticus
Authors: Feng Lijie , Murugan Madhuvika , Bosco Dale B. , Liu Yong , Peng Jiyun , Worrell Gregory A. , Wang Hai‐Long , Ta Lauren E. , Richardson Jason R. , Shen Yuxian , Wu Long‐Jun 
Published: April 2019

AbstractMicroglial activation has been recognized as a major contributor to inflammation of the epileptic brain. Seizures are commonly accompanied by remarkable microgliosis and loss of neurons. In this study, we utilize the CX3CR1GFP/+ CCR2RFP/+ genetic mouse model, in which CX3CR1+ resident microglia and CCR2+ monocytes are labeled with GFP and RFP, respectively. Using a combination of time‐lapse two‐photon imaging and whole‐cell patch clamp recording, we determined the distinct morphological, dynamic, and electrophysiological characteristics of infiltrated monocytes and resident microglia, and the evolution of their behavior at different time points following kainic acid‐induced seizures. Seizure activated microglia presented enlarged somas with less ramified processes, whereas, infiltrated monocytes were smaller, highly motile cells that lacked processes. Moreover, resident microglia, but not infiltrated monocytes, proliferate locally in the hippocampus after seizure. Microglial proliferation was dependent on the colony‐stimulating factor 1 receptor (CSF‐1R) pathway. Pharmacological inhibition of CSF‐1R reduced seizure‐induced microglial proliferation, which correlated with attenuation of neuronal death without altering acute seizure behaviors. Taken together, we demonstrated that proliferation of activated resident microglia contributes to neuronal death in the hippocampus via CSF‐1R after status epilepticus, providing potential therapeutic targets for neuroprotection in epilepsy.
Altered static and dynamic functional network connectivity in Alzheimer's disease and subcortical ischemic vascular disease: shared and specific brain connectivity abnormalities
Authors: Fu Zening , Caprihan Arvind , Chen Jiayu , Du Yuhui , Adair John C. , Sui Jing , Rosenberg Gary A. , Calhoun Vince D. 
Published: April 2019

AbstractSubcortical ischemic vascular disease (SIVD) is a major subtype of vascular dementia with features that overlap clinically with Alzheimer's disease (AD), confounding diagnosis. Neuroimaging is a more specific and biologically based approach for detecting brain changes and thus may help to distinguish these diseases. There is still a lack of knowledge regarding the shared and specific functional brain abnormalities, especially functional connectivity changes in relation to AD and SIVD. In this study, we investigated both static functional network connectivity (sFNC) and dynamic FNC (dFNC) between 54 intrinsic connectivity networks in 19 AD patients, 19 SIVD patients, and 38 age‐matched healthy controls. The results show that both patient groups have increased sFNC between the visual and cerebellar (CB) domains but decreased sFNC between the cognitive‐control and CB domains. SIVD has specifically decreased sFNC within the sensorimotor domain while AD has specifically altered sFNC between the default‐mode and CB domains. In addition, SIVD has more occurrences and a longer dwell time in the weakly connected dFNC states, but with fewer occurrences and a shorter dwell time in the strongly connected dFNC states. AD has both similar and opposite changes in certain dynamic features. More importantly, the dynamic features are found to be associated with cognitive performance. Our findings highlight similar and distinct functional connectivity alterations in AD and SIVD from both static and dynamic perspectives and indicate dFNC to be a more important biomarker for dementia since its progressively altered patterns can better track cognitive impairment in AD and SIVD.
Dynamic stream network intermittence explains emergent dissolved organic carbon chemostasis in headwaters
Authors: Hale Rebecca L. , Godsey Sarah E. 
Published: April 2019

AbstractDissolved organic carbon (DOC) concentrations vary among headwaters, with variation typically decreasing with watershed area. We hypothesized that streamflow intermittence could be an important source of variation in DOC concentrations across a small watershed, through (a) temporal legacies of drying on organic matter accumulation and biotic communities and (b) spatial patterns of connectivity with DOC sources. To test these hypotheses, we conducted three synoptic water chemistry sampling campaigns across a 25.5‐km2 watershed in south‐eastern Idaho during early spring, late summer, and late fall. Using changepoint analysis, we found that DOC variability collapsed at a consistent location (watershed areas ~1.3 to ~1.8 km2) across seasons, which coincided with the watershed area where variability in streamflow intermittence collapsed (~1.5 km2). To test hypothesized mechanisms through which intermittence may affect DOC, we developed temporal, spatial, and spatio‐temporal metrics of streamflow intermittence and related these to DOC concentrations. Streamflow intermittence was a strong predictor of DOC across seasons, but different metrics predicted DOC depending on season. Seasonal changes in the effects of intermittence on DOC reflected seasonal changes from instream to flowpath controls. A metric that captured spatial connectivity to sources significantly predicted DOC during high flows, when DOC is typically controlled by transport. In contrast, a reach‐scale temporal metric of intermittence predicted DOC during the late growing season, when DOC is typically controlled by instream processes and when legacy effects of drying (e.g., diminished biological communities) would likely affect DOC. The effects of intermittence on DOC extend beyond temporal legacies at a point. Our results suggest that legacy effects of intermittence do not propagate downstream in this system. Instead, snapshots of spatial patterns of intermittence upstream of a reach are critical for understanding spatial patterns of DOC through connectivity to DOC sources, and these processes drive patterns of DOC even in perennial reaches.
Dissipative Self‐Assembly of Peptides
Authors: Tena‐Solsona Marta , Boekhoven Job 
Published: April 2019

AbstractIn molecular self‐assembly, molecules interact with each other by non‐covalent interactions to form larger structures. The process occurs in‐equilibrium, which means that molecules can leave the assembly and reassemble elsewhere, but that occurs on average with equal rates. For self‐assembly, peptides have proven to be a particularly useful building block, in part because of their versatility. Biology also uses self‐assembly to create functional materials. For example, components of the cytoskeleton, like actin filament and microtubules, are self‐assembled proteins. In other words, biology uses the same building blocks and design rules as supramolecular chemists to create functional structures. However, biological assemblies are vastly more complex than their synthetic counterparts. The discrepancy is in part because proteins are more complex than the peptides we use as building blocks. Another contributing factor to the difference in complexity is that most assemblies in living systems exist out of equilibrium. To use peptides for complex functions as biology does, we should understand and be able to create peptide assemblies out of equilibrium. In this work, we review recent advances towards the creation of peptide assemblies that exist out of equilibrium driven by an external energy source.
Strontium enhances BMP‐2 mediated bone regeneration in a femoral murine bone defect model
Authors: Quade Mandy , Vater Corina , Schlootz Saskia , Bolte Julia , Langanke Robert , Bretschneider Henriette , Gelinsky Michael , Goodman Stuart B. , Zwingenberger Stefan 
Published: April 2019

AbstractThe application of strontium is one option for the clinical treatment of osteoporosis—a disease characterized by reduced bone density and quality—in order to reduce the risk of vertebral and nonvertebral fractures. Unlike other drugs used in osteoporosis therapy, strontium shows a dual effect on bone metabolism by attenuating cellular resorption and simultaneously enhancing new bone tissue formation. Current concerns regarding the systemic application of highly dosed strontium ranelate led to the development of strontium‐modified scaffolds based on mineralized collagen (MCM) capable to release biologically active Sr2+ ions directly at the fracture site. In this study, we investigated the regenerative potential of these scaffolds. For in vitro investigations, human mesenchymal stromal cells were cultivated on the scaffolds for 21 days (w/ and w/o osteogenic supplements). Biochemical analysis revealed a significant promoting effect on proliferation rate and osteogenic differentiation on strontium‐modified scaffolds. In vivo, scaffolds were implanted in a murine segmental bone defect model—partly additionally functionalized with the osteogenic growth factor bone morphogenetic protein 2 (BMP‐2). After 6 weeks, bridging calluses were obtained in BMP‐2 functionalized scaffolds; the quality of the newly formed bone tissue by means of morphological scores was clearly enhanced in strontium‐modified scaffolds. Histological analysis revealed increased numbers of osteoblasts and blood vessels, decreased numbers of osteoclasts, and significantly enhanced mechanical properties. These results indicate that the combined release of Sr2+ ions and BMP‐2 from the biomimetic scaffolds is a promising strategy to enhance bone regeneration, especially in patients suffering from osteoporosis. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 108B:174–182, 2020.
Adverse events during apheresis: A 10‐year experience at a tertiary academic medical center
Authors: Kundrapu Sirisha , Datla Sireesha , Griffin Vanessa , Maitta Robert W. 
Published: April 2019

AbstractBackgroundApheresis can be associated with adverse events (AEs). Available studies published on apheresis‐associated AEs lack uniformity of data. Unfortunately, there is no common database in the United States (US) to report apheresis‐associated AEs. We evaluated our institutional incidence of apheresis‐associated AEs and compared it with published literature.Study design and methodsWe conducted a 10‐year retrospective study of apheresis procedures and associated AEs at our facility, a tertiary academic medical center, from 2007 to 2016. Concurrently, a literature search was conducted on AEs associated with apheresis procedures. Twenty‐eight studies including data from US and other countries' facilities were analyzed.ResultsThe overall AE incidence was 6.9% (396/5684 procedures). Frequency of AEs associated with therapeutic plasma exchange (TPE) was higher (8.5%, P < .0001) compared to other apheresis procedures. Significant correlation between number of TPE and AEs (Spearman rho [rs] = 0.7, P = .002) was encountered. Furthermore, there was a significant decrease over time of moderate and severe AEs (rs = −0.64, P = .04 and rs = −0.83, P = .003 respectively). Comparison of our institutional AEs (6.9%) to data from other countries (9.8%) and US (22.6%) indicated a significant difference (P < .0001).ConclusionOverall our incidence of AEs was significantly lower than current published literature. Incidence of AEs published in other countries is significantly lower than US rates. Differences in incidence of AEs emphasize need for uniform reporting and stratification of AEs and development of a common database to report AEs. Therefore, we propose a grading rationale in order to standardize reporting of AEs.
Tao‐Hong‐Si‐Wu decoction reduces ischemia reperfusion rat myoblast cells calcium overloading and inflammation through the Wnt/IP3R/CAMKII pathway
Authors: Fuping Zhu , Wuping Li , Linhua Wang , Chengxi Pan , Fuqiang Zhou , Yi Zhang , Aijun Wang 
Published: April 2019

AbstractLimb ischemia reperfusion (LIRI) injury is associated with serious local and systemic effects. Reperfusion may augment tissue injury in excess of that produced by ischemia alone. Calcium overloading and inflammation are considered to be two of the pathological mechanisms of limb ischemia/reperfusion (I/R) injury. Tao‐Hong‐Si‐Wu decoction (THSWD) is a traditional Chinese herbal medicine with a powerful anti‐inflammatory properties. We studied the probable restorative effect of THSWD on limb I/R‐induced calcium overloading and inflammation in myoblast obtained from gastrocnemius muscle tissues of Sprague‐Dawley rats (Frizzled Z5,a wnt5a blocker; KN‐93, a calmodulin‐dependent protein kinase II (CamkII) blocker; XeC, a IP3R blocker as positive controls). The simulated ischemia and reperfusion(I/R) solutions were used to imitate LIRI environment. The results showed that after I/R treatment, the secretion of proinflammatory factors (TNF‐α and IL‐1β) and Wnt5a/Ca2+ signal molecules (wnt5a, camkII, and IP3R) upregulated significantly, the Ca2+ concentration enhanced too in myoblast cells. THSWD pretreatment decreased the secretion of TNF‐α and IL‐1β, Ca2+ concentration; and abated the Wnt5a/Ca2+ signal molecules of wnt5a, camkII and IP3R expression activated by I/R injury; but could not abated the Wnt11 and protein kinase C (PKC) expression significantly, the results was similar with Frizzled Z5 treatment cells. Our research illustrated that THSWD may have a mitigating effect on LIRI targeting Wnt/IP3R/CAMKII but not Wnt/IP3R/PKC signaling pathway for the first time. This study may encourage the use of THSWD in the critical clinical settings with LIRI.
Proteasome‐associated cysteine deubiquitinases are molecular targets of environmental optical brightener compounds
Authors: Castro Isel , Ekinci Elmira , Huang Xuemei , Cheaito Hassan Ali , Ahn Young‐Hoon , Olivero‐Verbel Jesus , Dou Q. Ping 
Published: April 2019

AbstractThe levels of organic pollutants, such as optical brightener (OB) compounds, in the global environment have been increasing in recent years. The toxicological effects and signal transduction systems associated with OB toxicity have not been thoroughly studied. The ubiquitin‐proteasome system (UPS) plays a crucial role in regulating multiple essential cellular processes, and proteasome‐associated cysteine deubiquitinases (DUBs), ubiquitin C‐terminal hydrolase L5 (UCHL5) and USP14, are two major regulators for (de)ubiquitination and stability of many important target proteins. Therefore, potential inhibition of UCHL5 and USP14 activities by some environmental chemicals might cause in vivo toxicity. In the current study we hypothesize that electrophilic OB compounds, such as 4,4′‐diamino‐2,2′‐stilbenedisulfonic acid(DAST), fluorescent brightener 28 (FB‐28) and FB‐71, can interact with the catalytic triads (CYS, HIS, and ASP) of UCHL5 and USP14 and inhibit their enzymatic activities, leading to cell growth suppression. This hypothesis is supported by our findings presented in this study. Results from in silico computational docking and ubiquitin vinyl sulfone assay confirmed the UCHL5/USP14‐inhibitory activities of these OB compounds that have potencies in an order of: FB‐71 > FB‐28 > DAST. Furthermore, inhibition of these two proteasomal DUBs by OBs resulted in cell growth inhibition and apoptosis induction in two human breast cancer cell models. In addition, we found that OB‐mediated DUB inhibition triggers a feedback reaction in which expression of UCHL5 and USP14 proteins is increased to compromise the suppressed activities. Our study suggests that these commonly used OB compounds may target and inhibit proteasomal cysteine DUBs, which should contribute to their toxicological effects in vivo.
INHBA gene silencing inhibits gastric cancer cell migration and invasion by impeding activation of the TGF‐β signaling pathway
Authors: Chen Zong‐Lin , Qin Lu , Peng Xu‐Bin , Hu Yu , Liu Bo 
Published: April 2019

AbstractGastric cancer (GC) is the fourth largest cancer in the world, with a 5‐year survival rate of <30%. Thus, this study intends to investigate the effects of inhibin βA (INHBA) gene silencing on the migration and invasion of GC cells via the transforming growth factor‐β (TGF‐β) signaling pathway. Initially, this study determined the expression of INHBA and the TGF‐β signaling pathway‐related genes in GC tissues. After that, to assess the effect of INHBA silencing on GC progression, GC cells were transfected with short hairpin RNAs that targeted INHBA in order to detect the expression of INHBA and the TGF‐β signaling pathway‐related genes, as well as cell migration, invasion, and proliferation abilities. Finally, a tumor xenograft model in nude mice was constructed to verify the effect that the silencing of INHBA had on tumor growth. Highly expressed INHBA and activated TGF‐β signaling pathways were observed in GC tissues. In response to shINHBA‐1 and shINHBA‐2, the TGF‐β signaling pathway was inhibited in GC cells, whereas the GC cell migration, invasion, proliferation, and tumor growth were significantly dampened. On the basis of the observations and findings of this study, INHBA gene silencing inhibited the progression of GC by inactivating the TGF‐β signaling pathway, which provides a potential target in the treatment of GC.
C1q/TNF‐related protein‐9 promotes macrophage polarization and improves cardiac dysfunction after myocardial infarction
Authors: Liu Mingxin , Yin Lin , Li Wei , Hu Juan , Wang Huibo , Ye Bingjie , Tang Yanhong , Huang Congxin 
Published: April 2019

AbstractThe timely regulation of inflammatory M1 macrophage polarization toward regenerative M2 macrophages suggests the possibility of immunotherapy after myocardial infarction (MI). C1q/TNF‐related protein‐9 (CTRP9) has anti‐inflammatory effects and can ameliorate heart function in mice after long‐term myocardial infarction. The role of CTRP9 in macrophage polarization remains completely unclear. This study determined whether CTRP9 can preserve post‐MI early cardiac function through the regulation of macrophage polarization. In the present study, an adenovirus‐delivered CTRP9 supplement promoted macrophage polarization at Day 3 post MI and improved cardiac function at Day 7 post MI. Pretreatment with gCTRP9 promoted the M1 to M2 polarization transition and attenuated inflammation after lipopolysaccharide + interferon‐γ stimulation; the effects were partly abrogated by the adenosine monophosphate kinase (AMPK) inhibitor compound C and were obviously reinforced by pyrrolidine dithiocarbamate, a nuclear factor‐κB (NF‐κB) inhibitor. Meanwhile, CTPR9 markedly reduced the expression of toll‐like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and NF‐κB p65 phosphorylation by promoting AMPK phosphorylation in vivo and in vitro. Moreover, the competitive binding of gCTRP9 and LPS to the myeloid differentiation protein 2 (MD2)/TLR4 complex was associated with direct binding to MD2, thereby inhibiting the downstream signaling molecule MyD88. Taken together, we demonstrated that CTRP9 improved post‐MI early cardiac function, at least in part, by modulating M1/M2 macrophage polarization, largely via the TLR4/MD2/MyD88 and AMPK‐NF‐κB pathways.
FGF23 regulates atrial fibrosis in atrial fibrillation by mediating the STAT3 and SMAD3 pathways
Authors: Dong Quanbin , Li Shaochuan , Wang Weixue , Han Lu , Xia Zirong , Wu Yanqing , Tang Yanhua , Li Juxiang , Cheng Xiaoshu 
Published: April 2019

AbstractHigh fibroblast growth factor 23 (FGF23) concentrations are a strong predictor of atrial fibrillation (AF), but researchers have not clearly determined the mechanism by which FGF23 causes atrial fibrosis in patients with AF. This study aims to elucidate the mechanism by which FGF23 induces atrial fibrosis in patients with AF. Immunohistochemistry was used to study the expression of FGF23, FGFR4, and fibrotic factors in patients with a normal sinus rhythm (SR) and patients with AF. Cardiac fibroblasts (CFs) were cocultured with different concentrations of the recombinant FGF23 protein. Compared with the SR group, the levels of FGF23, FGFR4, α‐smooth muscle actin (α‐SMA), and collagen‐1 were significantly increased in the AF group. Exposure to high concentrations of the recombinant FGF23 protein increased the accumulation of reactive oxygen species (ROS) and activated α‐SMA, collagen‐1, signal transducer and activator of transcription 3 (STAT3) and SMAD3 signaling in cultured CFs. The levels of fibrotic proteins in CFs stimulated with high concentrations of the recombinant FGF23 protein were reversed by N‐acetylcysteine (NAC, a ROS inhibitor), ship information system 3 (a SMAD3 inhibitor), and Stattic (a STAT3 inhibitor). Furthermore, compared to untreated CFs, CFs treated with the recombinant FGF23 protein were characterized by an increased interaction between STAT3 and SMAD3. Based on these results, FGF23 induces atrial fibrosis in patients with AF by increasing ROS production and subsequently activating STAT3 and SMAD3 signaling.
Mesoglycan induces keratinocyte activation by triggering syndecan‐4 pathway and the formation of the annexin A1/S100A11 complex
Authors: Bizzarro Valentina , Belvedere Raffaella , Pessolano Emanuela , Parente Luca , Petrella Francesco , Perretti Mauro , Petrella Antonello 
Published: April 2019

AbstractWound healing is a dynamic process comprising multiple events, such as inflammation, re‐epithelialization, and tissue remodeling. Re‐epithelialization phase is characterized by the engagement of several cell populations, mainly of keratinocytes that sequentially go through cycles of migration, proliferation, and differentiation to restore skin functions. Troubles can arise during the re‐epithelialization phase of skin wound healing particularly in keratinocyte migration, resulting in chronic non‐healing lesions, which represent a serious clinical problem. Over the last decades, the efforts aimed to find new pharmacological approaches for wound care were made, yet almost all current therapeutic strategies used remain inadequate or even ineffective. As such, it is crucial to identify new drugs that can enable a proper regeneration of the epithelium in wounded skin. Here, we have investigated the effects of the fibrinolytic drug mesoglycan, a glycosaminoglycans mixture derived from porcine intestinal mucosa on HaCaT human keratinocytes that were used as in vitro experimental model of skin re‐epithelialization. We found that mesoglycan induces keratinocyte migration and early differentiation by triggering the syndecan‐4/PKCα pathway and that these effects were at least in part, because of the formation of the annexin A1/S100A11 complex. Our data suggest that mesoglycan may be useful as a new pro‐healing drug for skin wound care.
miR‐218‐5p regulates skin and hair follicle development through Wnt/β‐catenin signaling pathway by targeting SFRP2
Authors: Zhao Bohao , Chen Yang , Yang Naisu , Chen Qiuran , Bao Zhiyuan , Liu Ming , Hu Shuaishuai , Li Jiali , Wu Xinsheng 
Published: April 2019

AbstractThe hair follicle is a complex biological system involved in a dynamic process governed by gene regulation. MicroRNAs play a critical role in the regulation of gene expression. We demonstrated that the expression of miR‐218‐5p and SFRP2 showed the opposite relationship in catagen and telogen phases and that miR‐218‐5p promoted the growth of hair shafts. The luciferase reporter assays confirmed that SFRP2 is the direct target of miR‐218‐5p. The expression of miR‐218‐5p may decrease the expression of SFRP2, which activates the Wnt signaling pathway, including the regulation of downstream genes and β‐catenin/T‐cell‐specific factor transcriptional activity. Moreover, miR‐218‐5p enhanced apoptosis, but inhibition of miR‐218‐5p decreased apoptosis and inhibited RAB‐9 cell proliferation. In this study, we show that miR‐218‐5p positively regulates the Wnt signaling pathway by targeting SFRP2 and acts as a dynamic governor during skin and hair follicle development.