Miracle-dz/UniFAR-FTUs huggingface dataset:
Human salivary cystatin SA exhibits antimicrobial effect against Aggregatibacter actinomycetemcomitans.

BACKGROUND AND OBJECTIVE Healthy subjects who do not have Aggregatibacter actinomycetemcomitans in their oral cavity may possess factors in saliva that might demonstrate antibacterial activity against the bacterium. The aim of this study was to identify and purify proteins from saliva of healthy subjects that might demonstrate antibacterial activity against A. actinomycetemcomitans and test the same against the bacteria. MATERIAL AND METHODS Saliva from 10 healthy volunteers was tested individually for its anti-A. actinomycetemcomitans activity. Among the 10 subjects, eight demonstrated anti-A. actinomycetemcomitans activity. Saliva was collected from one healthy volunteer who demonstrated the highest antimicrobial activity against A. actinomycetemcomitans. After clarifying the saliva, it was subjected to an affinity chromatography column with A. actinomycetemcomitans. The proteins bound to A. actinomycetemcomitans were eluted from the column and identified using mass spectrometry (MALDI-TOF/TOF MS). Among other proteins that bound to A. actinomycetemcomitans, which included lactoferrin, immunoglobulin A and kallikrein, cystatin SA was observed in significantly higher concentrations, and this was purified from the eluate. The purified cystatin SA was tested at different concentrations for its ability to kill A. actinomycetemcomitans in a 2 h cell killing assay. The bacteria were also treated with a proteinase inhibitor, leupeptin, to clarify whether the antimicrobial effect of cystatin SA was related to its protease inhibitory function. Cystatin SA was also tested for its ability to prevent binding of A. actinomycetemcomitans to buccal epithelial cells (BECs) in an A. actinomycetemcomitans-BEC binding assay. RESULTS Cystatin SA (0.1 mg/mL) demonstrated a statistically significant antimicrobial activity against A. actinomycetemcomitans. The effect of cystatin SA decreased with lower concentrations, with 0.01 mg/mL showing no effect. The addition of monoclonal cystatin SA antibodies to the purified sample completely negated the antimicrobial effect. Treatment of A. actinomycetemcomitans with leupeptin resulted in no antimicrobial effect, suggesting that the antimicrobial activity of cystatin SA is independent of its protease inhibitory function. A. actinomycetemcomitans pretreated with cystatin SA showed reduced binding to BECs, suggesting a potential role for cystatin SA in decreasing the colonization of A. actinomycetemcomitans. CONCLUSION The present study shows that cystatin SA demonstrates antimicrobial activity against the periodontopathogen A. actinomycetemcomitans, and future studies determining the mechanism of action are necessary. The study also shows the ability of cystatin SA to reduce significantly the binding of A. actinomycetemcomitans to BECs.
Dorsally‐derived oligodendrocytes in the spinal cord contribute to axonal myelination during development and remyelination following focal demyelination

In the developing spinal cord, the majority of oligodendrocytes are derived from the ventral ventricular zone. Several recent studies suggested that a small number of oligodendrocyte precursor cells (OPCs) can also be generated in the dorsal spinal cord. However, it is not clear whether these dorsal oligodendrocyte precursor cells participate in myelination and remyelination. To investigate the fate and potential function of these dorsally‐derived oligodendrocytes (dOLs) in the adult spinal cord, Cre‐lox genetic fate mapping in transgenic mice was employed. We used the Pax3Cre knock‐in mouse to drive Cre expression in the entire dorsal epithelium and the Rosa26‐lacZ or Z/EG reporter line to trace their spatial distribution and population dynamics in the spinal cord. The dorsal OPCs generated from the Pax3‐expressing domains migrate into all regions of spinal cord and subsequently undergo terminal differentiation and axonal myelination. In response to a focal demyelination injury, a large number of newly differentiated oligodendrocytes originated from dOLs, suggesting that dOLs may provide an important source of OPCs for axonal remyelination in multiple sclerosis or spinal cord injury. © 2011 Wiley‐Liss, Inc.
Transferring ARMin to the Clinics and Industry

In the last few years, novel robotic technology has been developed that has the potential to improve upper extremity function after spinal cord injury (SCI), stroke, and other neurological diseases. Three generations of the arm therapy robot ARMin were developed and clinically evaluated on many patients. Key focus was on the training of functional tasks incorporating activities of daily living (ADL) with large range of motion of the entire arm in order to enhance transfer to daily life and improve quality of life. Encouraged by the promising results in first single-case studies performed with ARMin I and ARMin II, an optimized ARMin III was developed and duplicated and is currently being used within a 4-center randomized clinical trial. A fourth generation of ARMin is currently under development that will have further functional benefits with respect to patient-cooperative control and therapy assessment. Intellectual property has been identified for technology transfer and commercial exploitation. The con.
Bridging the gap for lipid lowering therapy: plaque regression, coronary computed tomographic angiography, and imaging-guided personalized medicine

ABSTRACT Introduction: Lipid-lowering therapy effectively decreases cardiovascular risk on a population level, but it remains difficult to identify an individual patient’s personal risk reduction while following guideline directed medical therapy, leading to overtreatment in some patients and cardiovascular events in others. Recent improvements in cardiac CT technology provide the ability to directly assess an individual’s atherosclerotic disease burden, which has the potential to personalize risk assessment for lipid-lowering therapy. Areas covered: We review the current unmet need in identifying patients at elevated residual risk despite guideline directed medical therapy, the evidence behind plaque regression as a potential marker of therapeutic response, and highlight state-of-the-art advances in coronary computed tomographic angiography (CCTA) for measurement of quantitative and qualitative changes in coronary atherosclerosis over time. Literature search was performed using PubMed and Google Scholar for literature relevant to statin therapy and residual risk, coronary plaque regression measurement, and CCTA assessment of quantitative and qualitative change in coronary atherosclerosis. Expert commentary: We discuss the potential ability of CCTA to guide lipid-lowering therapy as a bridge between population and personalized medicine in the future, as well as the potential barriers to its use.
Who Administers Wraparound?

The wraparound care management process has been cited as a promising means for making evidence-based treatments relevant and accessible to youth with mental health needs and their families. However, there has been little research on the background and training of providers who participate on wraparound teams. In the current study, the authors examined the prevalence of wraparound implementation nationally in systems of care and the background,training,organizational supports, and perceptions of evidence-based treatments (EBTs) for professionals who implement wraparound. Results suggest that wraparound implementation is common across communities and that wraparound providers are different from other professionals.They are,for example,less likely to have an advanced degree, more likely to have received their training from agency inservices, less likely to receive manuals with their training, and more likely to report fully implementing treatment protocols.Wraparound providers are also more likely to report that their agency or organization mandated implementation of EBTs. Results provide several implications for wraparound model specification, development of quality assurance supports, and a need for higher education to better orient trainees to models and philosophies such as wraparound.
Personalizing antiplatelet prescribing using genetics for patients undergoing percutaneous coronary intervention

ABSTRACT Introduction. Clopidogrel is commonly prescribed with aspirin to reduce the risk for adverse cardiovascular events after percutaneous coronary intervention (PCI). However, there is significant inter-patient variability in clopidogrel response. The CYP2C19 enzyme is involved in the biotransformation of clopidogrel to its pharmacologically active form, and variation in the CYP2C19 gene contributes to clopidogrel response variability. Areas covered. This article describes the impact of CYP2C19 genotype on clopidogrel pharmacokinetics, pharmacodynamics, and effectiveness. Examples of clinical implementation of CYP2C19 genotype-guided antiplatelet therapy for patients undergoing PCI are also described as are emerging outcomes data with this treatment approach. Expert commentary. A large clinical trial evaluating outcomes with CYP2C19 genotype-guided antiplatelet therapy after PCI is on-going. In the meantime, data from pragmatic and observational studies and smaller trials support improved outcomes with genotyping after PCI and use of alternative antiplatelet therapy in patients with a CYP2C19 genotype associated with reduced clopidogrel effectiveness.
Individualizing dual antiplatelet therapy duration after percutaneous coronary intervention: from randomized control trials to personalized medicine

ABSTRACT Introduction: Improved stent technologies have lead to reduced minimum durations of dual antiplatelet therapy (DAPT) to prevent stent thrombosis. However, the anti-ischemic benefits seen in extended DAPT in both stent and non-stent related lesions have called into question the optimum duration of DAPT after stent placement. Areas covered: We review the evidence for varying durations of DAPT after drug eluting stent placement including for patients on oral anticoagulation; decision tools available for clinicians to optimize patient selection for extended therapy and insight into application of these risk assessment tools in clinical practice. Expert commentary: The use of risk assessment tools in optimizing DAPT duration after stent placement provides an opportunity for improved outcomes by means of a personalized approach to care while allowing clinicians to engage with patients in shared-decision making.
Systematic analysis of tobacco treatment interventions implemented in worksite settings

Abstract Introduction: Smoking remains the leading cause of preventable death in the United States. The purpose of this investigation was to systematically analyze smoking cessation interventions conducted in worksite settings. Methods: Three researchers conducted a search of CINAHL, MEDLINE, ERIC and Psychology and Behavioral Sciences Collection databases, independently. Eligibility of articles was evaluated by the following criteria: (1) primary research; (2) tobacco/smoking treatment interventions; (3) implemented in worksite settings; (4) conducted in the United States and abroad; (5) used a quantitative design; (6) published between March 2009 and January 2013 (based on articles published after a similar review). Results: A total of 12 articles satisfied the inclusion criteria. Nine programs reported a positive effect on tobacco/smoking treatment. Seven of the interventions were theory-based, with six of these applying the transtheoretical stages of change model. Four of the programs included pharmacotherapy and six incorporated incentives. Conclusions: Worksite smoking treatment intervention design can be improved by incorporation of more robust designs with extended follow-up measures, explicit operationalization of theoretical frameworks, inclusion of ecological theory-based frameworks and integration of fidelity process evaluation. Pharmacotherapy in conjunction with behavior modification appears efficacious; however, the ability of financial incentives to motivate behavior change is still unconfirmed.
Bioactive 3D cell culture system minimizes cellular stress and maintains the in vivo‐like morphological complexity of astroglial cells

We tested the hypothesis that astrocytes grown in a suitable three‐dimensional (3D) cell culture system exhibit morphological and biochemical features of in vivo astrocytes that are otherwise lost upon transfer from the in vivo to a two‐dimensional (2D) culture environment. First, we report development of a novel bioactively coated nanofiber‐based 3D culture system (Bioactive3D) that supports cultures of primary mouse astrocytes. Second, we show that Bioactive3D culture system maintains the in vivo‐like morphological complexity of cultured cells, allows movement of astrocyte filopodia in a way that resembles the in vivo situation, and also minimizes the cellular stress, an inherent feature of standard 2D cell culture systems. Third, we demonstrate that the expression of gap junctions is reduced in astrocytes cultured in a 3D system that supports well‐organized cell–cell communication, in contrast to the enforced planar tiling of cells in a standard 2D system. Finally, we show that astrocytes cultured in the Bioactive3D system do not show the undesired baseline activation but are fully responsive to activation‐inducing stimuli. Thus, astrocytes cultured in the Bioactive3D appear to more closely resemble astrocytes in vivo and represent a superior in vitro system for assessing (patho)physiological and pharmacological responses of these cells and potentially also in co‐cultures of astrocytes and other cell types. © 2013 Wiley Periodicals, Inc.
Micropropagation and production of Camptothecin from in vitro plants of Ophiorrhiza rugosa var. decumbens

Camptothecin and its derivatives are used as anticancer alkaloids. At present, they are obtained by the extraction from the Chinese tree Camptotheca acuminata and the indigenous tree Nothapodytes foetida. Identification of alternate species of plants like Ophiorrhiza species and development of tissue culture methods may be a suitable alternative for large-scale micropropagation as well as for the production of camptothecin. Plantlets were successfully regenerated from shoot cultures of Ophiorrhiza rugosa initiated from axillary meristems on medium containing benzyladenine (BA) (4.0 mg L−1) + α-naphthalene acetic acid (NAA) (0.05 mg L−1). Rooting was initiated in half concentration of Murashige and Skoog's (MS) basal medium devoid of growth hormones. Tissue culture derived plants of O. rugosa were similar to the normal plants in their morphological characteristics and chemical constitution. Ten O. rugosa plants that were obtained through micropropagation showed when analysed a higher alkaloid content compared to the normal plant. Chemical analysis of the different organs of the tissue culture plant of O. rugosa established in soil indicated 0.002% dry weight of camptothecin in the roots, 0.011% dry weight in the stems, 0.090% dry weight in the leaves and 0.015% in the floral parts.
Anti-inflammatory and antioxidant activities and constituents of Platostoma africanum P. Beauv.

Hexane and dichloromethane extracts of Platostoma africanum P. Beauv. , a plant popularly employed in Nigeria in the treatment of rheumatic symptoms, were evaluated for anti-inflammatory and antioxidant activities. Acute inflammatory effects were studied in the egg-albumin-induced rat paw edema. Both extracts produced significant (p < 0.05) and dose-dependent inhibition of the egg-albumin-induced pedal edema with the 400 mg kg−1 dose being markedly better than piroxicam. The hexane and dichloromethane extracts also showed significant antioxidant activity with the dichloromethane extract exhibiting an IC50 comparable to that of BHT, a synthetic antioxidant. Phytochemical investigation of the extracts afforded eight acidic pentacyclic triterpenes, namely, ursolic acid, oleanolic acid, epimaslinic acid, maslinic acid, corosolic acid, hyptadienic, euscaphic acid and tomentic acid, and a mixture of β-sitosterol and stigmasterol. These constituents are reported for the first time in the genus.
Comparative study of the chemical composition and antioxidant activity of six essential oils and their components

The antioxidant activities and the determined major components of six popular and commercially available herb essential oils, including lavender (Lavendular angustifolia), peppermint (Mentha piperita), rosemary (Rosmarius officinalis), lemon (Citrus limon), grapefruit (Citrus paradise), and frankincense (Boswellia carteri), were compared. The essential oils were analysed by GC–MS and their antioxidant activities were determined by testing free radical-scavenging capacity and lipid peroxidation in the linoleic acid system. The major components of the essential oils of lavender, peppermint, rosemary, lemon, grapefruit, and frankincense were linalyl acetate (28.2%), menthol (33.4%), 1,8-cineole (46.1%), limonene (64.5 and 94.2%), and p-menth-2-en-ol (34.5%), respectively. The highest DPPH radical-scavenging activity was obtained by the lavender essential oil and limonene, with RC50 values of 2.1 ± 0.23% and 2.1 ± 0.04%, respectively. Radical-scavenging activity against the ABTS radical was highest in peppermint essential oil (1.6 ± 0.09). Lavender oil was most effective for inhibiting linoleic acid peroxidation after 10 days.
Ammonia‐induced senescence in cultured rat astrocytes and in human cerebral cortex in hepatic encephalopathy

Hepatic encephalopathy (HE) is a frequent complication of liver cirrhosis and is due to a low‐grade cerebral edema associated with oxidative/nitrosative stress. Recent reports suggest that cognitive impairment in cirrhotic patients may not resolve completely after an attack of manifest HE. As astrocyte dysfunction is central to the pathogenesis of HE and astrocytes are critically involved in synaptic plasticity, we tested for sustained impairment of astrocyte function by analyzing expression levels of senescence biomarkers in ammonia‐treated cultured rat astrocytes and in postmortem brain samples from cirrhotic patients with or without HE. NH4Cl time‐ and dose‐dependently inhibited proliferation of cultured astrocytes by up to 45% (5 mmol/L, 72 h) and strongly increased senescence‐associated β‐galactosidase activity. Inhibition of astrocyte proliferation by ammonia was mediated by a l‐methionine sulfoximine‐, oxidative stress‐, and p38MAPK‐dependent activation of p53 associated with enhanced transcription of cell cycle inhibitory genes GADD45α and p21. Mitochondria and the nucleus were identified as sources of oxygen radical formation after prolonged NH4Cl exposure. Concurrently, NH4Cl (5 mmol/L) treatment inhibited both epidermal growth factor‐ and brain‐derived neurotrophic factor (BDNF)‐induced proliferation as well as BDNF‐mediated astrocyte morphology changes through downregulation of the respective growth factor receptors epidermal growth factor receptor and truncated tyrosine receptor kinase B. Increased mRNA expression levels of senescence‐associated genes were also found in post mortem brain samples from patients with liver cirrhosis with HE, but not in those without HE. The data suggest that ammonia toxicity and HE are associated with premature astrocyte senescence, which may impair neurotransmission and contribute to persistence of cognitive disturbances after resolution of episodes of overt HE. GLIA 2015;63:37–50
Melatonin protects liver against ischemia and reperfusion injury through inhibition of toll‐like receptor signaling pathway

Abstract: This study investigated the immunomodulating effect of melatonin on toll‐like receptor (TLR)‐stimulated signal transduction. Rats were subjected to 60 min of ischemia followed by 1 or 5 hr of reperfusion. Melatonin (10 mg/kg) or the vehicle was administered intraperitoneally 15 min prior to ischemia and immediately before reperfusion. Melatonin treatment significantly reduced the level of serum alanine aminotransferase activity. Increased levels of TLR3 and TLR4 protein expression induced by ischemia/reperfusion (I/R) were attenuated by melatonin. Serum level of high‐mobility group box 1 (HMGB1), a potent alarmin of the TLR system, increased significantly in the I/R group, and melatonin inhibited this release. Melatonin suppressed the increase in myeloid differentiation factor 88 (MyD88) protein expression, extracellular signal‐regulated kinase (ERK) and c‐Jun N‐terminal kinase (JNK) phosphorylation and nuclear translocation of nuclear factor κB (NF‐κB) and phosphorylated c‐Jun, a component of activator protein 1. The increased level of toll‐receptor‐associated activator of interferon (TRIF) expression, phosphorylation of interferon (IFN) regulatory factor 3 (IRF3) and serum IFN‐β was attenuated by melatonin. Melatonin attenuated the levels of tumor necrosis factor alpha (TNF‐α), interleukin (IL)‐6 and inducible nitric oxide synthase (iNOS) protein and mRNA expression, while the level of heme oxygenase‐1 (HO‐1) was augmented. Our results suggest that melatonin ameliorates I/R‐induced liver damage by modulation of TLR‐mediated inflammatory responses.
GC-MS analysis of the leaf surface components of four Bulgarian grapevines grown under different conditions

Four grapevine seedlings were propagated and planted both in a greenhouse and in an experimental field. Surface components of their fresh leaves were easily obtained and analysed by gas chromatography-mass spectrometry. In total, 21 surface metabolites were identified. Unlike the greenhouse samples, the field ones possessed semiochemicals and compounds contributing to their survival under environmental stress. This study shows that the leaf surface of the grapevine possesses compounds indicating the conditions of breeding.
Slow degradation in phagocytic astrocytes can be enhanced by lysosomal acidification

Inefficient lysosomal degradation is central in the development of various brain disorders, but the underlying mechanisms and the involvement of different cell types remains elusive. We have previously shown that astrocytes effectively engulf dead cells, but then store, rather than degrade the ingested material. In the present study we identify reasons for the slow digestion and ways to accelerate degradation in primary astrocytes. Our results show that actin‐rings surround the phagosomes for long periods of time, which physically inhibit the phago‐lysosome fusion. Furthermore, astrocytes express high levels of Rab27a, a protein known to reduce the acidity of lysosomes by Nox2 recruitment, in order to preserve antigens for presentation. We found that Nox2 colocalizes with the ingested material, indicating that it may influence antigen processing also in astrocytes, as they express MHC class II. By inducing long‐time acidification of astrocytic lysosomes using acidic nanoparticles, we could increase the digestion of astrocyte‐ingested, dead cells. The degradation was, however, normalized over time, indicating that inhibitory pathways are up‐regulated in response to the enhanced acidification. GLIA 2015;63:1997–2009