scholarly journals Stress enhances hippocampal neuronal synchrony and prolongs sharp-wave ripples

2020 ◽  
Author(s):  
Anupratap Tomar ◽  
Denis Polygalov ◽  
Sumantra Chattarji ◽  
Thomas McHugh
Keyword(s):  
Chronic Stress ◽  
Cell Activity ◽  
Fixed Time ◽  
Behavioral Changes ◽  
Neuronal Synchrony ◽  
Sharp Wave ◽  
Neural Organization ◽  
Intact Brain ◽  
Stressful Experience

AbstractChronic stress affects hippocampal function at multiple levels of neural organization. However, much of this understanding is derived from postmortem analyses of molecular, morphological, physiological and behavioral changes at fixed time points. Neural signatures of an ongoing stressful experience in the intact brain of awake animals and their links to later hippocampal dysfunction remain poorly understood. Here we used in vivo tetrode recordings to analyze the dynamic impact of 10 days of immobilization stress on neuronal activity in area CA1 of mice. Unexpectedly, there was a net decrease in pyramidal cell activity in stressed animals. Although these results suggest a lack of stress-induced hyperexcitability, more detailed analysis revealed that a greater fraction of spikes occurred specifically during sharp-wave ripples, resulting in an increase in neuronal synchrony. After repeated stress some of these alterations were visible during rest even in the absence of stress. These findings offer new insights into stress-induced alterations in ripple-spike interactions and mechanisms through which chronic stress may interfere with subsequent information processing.

scholarly journals Osseointegrating and phase-oriented micro-arc-oxidized titanium dioxide bone implants

2021 ◽  
Vol 19 ◽  
pp. 228080002110068
Author(s):  
Hsien-Te Chen ◽  
Hsin-I Lin ◽  
Chi-Jen Chung ◽  
Chih-Hsin Tang ◽  
Ju-Liang He
Keyword(s):  
Titanium Dioxide ◽  
High Surface ◽  
Cell Activity ◽  
Active Surface ◽  
Rutile Phase ◽  
Hydroxyl Groups ◽  
Bone Implant ◽  
Implant System

Here, we present a bone implant system of phase-oriented titanium dioxide (TiO2) fabricated by the micro-arc oxidation method (MAO) on β-Ti to facilitate improved osseointegration. This (101) rutile-phase-dominant MAO TiO2 (R-TiO2) is biocompatible due to its high surface roughness, bone-mimetic structure, and preferential crystalline orientation. Furthermore, (101) R-TiO2 possesses active and abundant hydroxyl groups that play a significant role in enhancing hydroxyapatite formation and cell adhesion and promote cell activity leading to osseointegration. The implants had been elicited their favorable cellular behavior in vitro in the previous publications; in addition, they exhibit excellent shear strength and promote bone–implant contact, osteogenesis, and tissue formation in vivo. Hence, it can be concluded that this MAO R-TiO2 bone implant system provides a favorable active surface for efficient osseointegration and is suitable for clinical applications.

scholarly journals Nature Exposure and Its Effects on Immune System Functioning: A Systematic Review

2021 ◽  
Vol 18 (4) ◽  
pp. 1416
Author(s):  
Liisa Andersen ◽  
Sus Sola Corazon ◽  
Ulrika Karlsson Stigsdotter
Keyword(s):  
Systematic Review ◽  
Natural Killer Cell Activity ◽  
Public Health Practice ◽  
Killer Cell ◽  
Cell Activity ◽  
Natural Environments ◽  
Comprehensive Overview ◽  
Potential Health ◽  
Positive Effects

Given the drastic changes in our lifestyles and ecosystems worldwide, the potential health effects of natural environments have grown into a highly pervasive topic. Recent scientific findings suggest beneficial effects from nature exposure on human immune responses. This review aims at providing a comprehensive overview of literature published on immunomodulatory effects of nature exposure by inhalation of natural substances. A systematic database search was performed in SCOPUS and PubMed. The quality and potential bias of included studies (n = 33) were assessed by applying the EPHPP (Effective Public Health Practice Project) tool for human studies and the ARRIVE (Animal Research: Reporting of In Vivo Experiments) and SYRCLE (Systematic Review Centre for Laboratory Animal Experimentation) tools for animal studies. The synthesis of reviewed studies points to positive effects of nature exposure on immunological health parameters; such as anti-inflammatory, anti-allergic, anti-asthmatic effects or increased NK (natural killer) cell activity. Decreased expression of pro-inflammatory molecules, infiltration of leukocytes and release of cytotoxic mediators are outcomes that may serve as a baseline for further studies. However, partially weak study designs evoked uncertainties about outcome reproducibility and key questions remain open concerning effect sizes, duration of exposure and contributions of specific vegetation or ecosystem types.

scholarly journals Synthesis and Characterization of Exopolysaccharide Encapsulated PCL/Gelatin Skin Substitute for Full-Thickness Wound Regeneration

Polymers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 854
Author(s):  
Ahmad Hivechi ◽  
Peiman Brouki Milan ◽  
Khashayar Modabberi ◽  
Moein Amoupour ◽  
Kaveh Ebrahimzadeh ◽  
...  
Keyword(s):  
Cell Activity ◽  
Average Diameter ◽  
Skin Substitute ◽  
Full Thickness ◽  
Skin Integrity ◽  
Hematoxylin And Eosin ◽  
First Time ◽  
Full Thickness Wound

Loss of skin integrity can lead to serious problems and even death. In this study, for the first time, the effect of exopolysaccharide (EPS) produced by cold-adapted yeast R. mucilaginosa sp. GUMS16 on a full-thickness wound in rats was evaluated. The GUMS16 strain’s EPS was precipitated by adding cold ethanol and then lyophilized. Afterward, the EPS with polycaprolactone (PCL) and gelatin was fabricated into nanofibers with two single-needle and double-needle procedures. The rats’ full-thickness wounds were treated with nanofibers and Hematoxylin and eosin (H&E) and Masson’s Trichrome staining was done for studying the wound healing in rats. Obtained results from SEM, DLS, FTIR, and TGA showed that EPS has a carbohydrate chemical structure with an average diameter of 40 nm. Cell viability assessments showed that the 2% EPS loaded sample exhibits the highest cell activity. Moreover, in vivo implantation of nanofiber webs on the full-thickness wound on rat models displayed a faster healing rate when EPS was loaded into a nanofiber. These results suggest that the produced EPS can be used for skin tissue engineering applications.

scholarly journals Anti-tumor effects of RTX-240: an engineered red blood cell expressing 4-1BB ligand and interleukin-15

2021 ◽  
Author(s):  
Shannon L. McArdel ◽  
Anne-Sophie Dugast ◽  
Maegan E. Hoover ◽  
Arjun Bollampalli ◽  
Enping Hong ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Blood Cell ◽  
Nk Cells ◽  
Red Blood Cell ◽  
Safety Profile ◽  
Nk Cell ◽  
Cell Activity ◽  
In Vivo Studies

AbstractRecombinant agonists that activate co-stimulatory and cytokine receptors have shown limited clinical anticancer utility, potentially due to narrow therapeutic windows, the need for coordinated activation of co-stimulatory and cytokine pathways and the failure of agonistic antibodies to recapitulate signaling by endogenous ligands. RTX-240 is a genetically engineered red blood cell expressing 4-1BBL and IL-15/IL-15Rα fusion (IL-15TP). RTX-240 is designed to potently and simultaneously stimulate the 4-1BB and IL-15 pathways, thereby activating and expanding T cells and NK cells, while potentially offering an improved safety profile through restricted biodistribution. We assessed the ability of RTX-240 to expand and activate T cells and NK cells and evaluated the in vivo efficacy, pharmacodynamics and tolerability using murine models. Treatment of PBMCs with RTX-240 induced T cell and NK cell activation and proliferation. In vivo studies using mRBC-240, a mouse surrogate for RTX-240, revealed biodistribution predominantly to the red pulp of the spleen, leading to CD8 + T cell and NK cell expansion. mRBC-240 was efficacious in a B16-F10 melanoma model and led to increased NK cell infiltration into the lungs. mRBC-240 significantly inhibited CT26 tumor growth, in association with an increase in tumor-infiltrating proliferating and cytotoxic CD8 + T cells. mRBC-240 was tolerated and showed no evidence of hepatic injury at the highest feasible dose, compared with a 4-1BB agonistic antibody. RTX-240 promotes T cell and NK cell activity in preclinical models and shows efficacy and an improved safety profile. Based on these data, RTX-240 is now being evaluated in a clinical trial.

scholarly journals Cellular sources of TSPO expression in healthy and diseased brain

2021 ◽  
Author(s):  
Erik Nutma ◽  
Kelly Ceyzériat ◽  
Sandra Amor ◽  
Stergios Tsartsalis ◽  
Philippe Millet ◽  
...  
Keyword(s):  
Cell Activity ◽  
Brain Regions ◽  
Cellular Level ◽  
Translocator Protein ◽  
Disease Stage ◽  
Animal Models Of Disease ◽  
Positron Emission ◽  
Neuropsychiatric Diseases ◽  
Tspo Expression

AbstractThe 18 kDa translocator protein (TSPO) is a highly conserved protein located in the outer mitochondrial membrane. TSPO binding, as measured with positron emission tomography (PET), is considered an in vivo marker of neuroinflammation. Indeed, TSPO expression is altered in neurodegenerative, neuroinflammatory, and neuropsychiatric diseases. In PET studies, the TSPO signal is often viewed as a marker of microglial cell activity. However, there is little evidence in support of a microglia-specific TSPO expression. This review describes the cellular sources and functions of TSPO in animal models of disease and human studies, in health, and in central nervous system diseases. A discussion of methods of analysis and of quantification of TSPO is also presented. Overall, it appears that the alterations of TSPO binding, their cellular underpinnings, and the functional significance of such alterations depend on many factors, notably the pathology or the animal model under study, the disease stage, and the involved brain regions. Thus, further studies are needed to fully determine how changes in TSPO binding occur at the cellular level with the ultimate goal of revealing potential therapeutic pathways.

In vivo enhancement of natural killer cell activity through tea fortified with Ayurvedic herbs

2009 ◽  
Vol 24 (1) ◽  
pp. 129-135 ◽  
Author(s):  
Jyoti Bhat ◽  
Aparna Damle ◽  
Pankaj P Vaishnav ◽  
Ruud Albers ◽  
Manoj Joshi ◽  
...  
Keyword(s):  
Natural Killer Cell ◽  
Natural Killer ◽  
Natural Killer Cell Activity ◽  
Killer Cell ◽  
Cell Activity ◽  
Killer Cell Activity

scholarly journals A Critical Role for Fas Ligand in the Active Suppression of Systemic Immune Responses by Ultraviolet Radiation

1999 ◽  
Vol 189 (8) ◽  
pp. 1285-1294 ◽  
Author(s):  
Laurie L. Hill ◽  
Vijay K. Shreedhar ◽  
Margaret L. Kripke ◽  
Laurie B. Owen-Schaub
Keyword(s):  
Dna Damage ◽  
Immune Responses ◽  
Immune Suppression ◽  
Fas Ligand ◽  
Critical Role ◽  
Cell Activity ◽  
Contact Hypersensitivity ◽  
Delayed Type Hypersensitivity ◽  
Intact Cells

Induction of antigen-specific suppression elicited by environmental insults, such as ultraviolet (UV)-B radiation in sunlight, can inhibit an effective immune response in vivo and may contribute to the outgrowth of UV-induced skin cancer. Although UV-induced DNA damage is known to be an initiating event in the immune suppression of most antigen responses, the underlying mechanism(s) of such suppression remain undefined. In this report, we document that Fas ligand (FasL) is critical for UV-induced systemic immune suppression. Normal mice acutely exposed to UV exhibit a profound suppression of both contact hypersensitivity and delayed type hypersensitivity (DTH) reactions and the development of transferable antigen-specific suppressor cells. FasL-deficient mice exposed to UV lack both transferable suppressor cell activity and primary suppression to all antigens tested, with the exception of the DTH response to allogeneic spleen cells. Interestingly, suppression of this response is also known to occur independently of UV-induced DNA damage. Delivery of alloantigen as protein, rather than intact cells, restored the requirement for FasL in UV-induced immune suppression of this response. These results substantiate that FasL/Fas interactions are essential for systemic UV-induced suppression of immune responses that involve host antigen presentation and suggest an interrelationship between UV-induced DNA damage and FasL in this phenomenon. Collectively, our results suggest a model whereby UV-induced DNA damage disarms the immune system in a manner similar to that observed in immunologically privileged sites.

scholarly journals In VitroandIn VivoCharacterization of the Novel Oxabicyclooctane-Linked Bacterial Topoisomerase Inhibitor AM-8722, a Selective, Potent Inhibitor of Bacterial DNA Gyrase

2016 ◽  
Vol 60 (8) ◽  
pp. 4830-4839 ◽  
Author(s):  
Christopher M. Tan ◽  
Charles J. Gill ◽  
Jin Wu ◽  
Nathalie Toussaint ◽  
Jingjun Yin ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Antibacterial Agents ◽  
Cell Activity ◽  
Dna Gyrase ◽  
Topoisomerase Iv ◽  
Bacterial Dna ◽  
Whole Cell ◽  
Content Type

ABSTRACTOxabicyclooctane-linked novel bacterial topoisomerase inhibitors (NBTIs) represent a new class of recently described antibacterial agents with broad-spectrum activity. NBTIs dually inhibit the clinically validated bacterial targets DNA gyrase and topoisomerase IV and have been shown to bind distinctly from known classes of antibacterial agents directed against these targets. Herein we report the molecular, cellular, andin vivocharacterization of AM-8722 as a representative N-alkylated-1,5-naphthyridone left-hand-side-substituted NBTI. Consistent with its mode of action, macromolecular labeling studies revealed a specific effect of AM-8722 to dose dependently inhibit bacterial DNA synthesis. AM-8722 displayed greater intrinsic enzymatic potency than levofloxacin versus both DNA gyrase and topoisomerase IV fromStaphylococcus aureusandEscherichia coliand displayed selectivity against human topoisomerase II. AM-8722 was rapidly bactericidal and exhibited whole-cell activity versus a range of Gram-negative and Gram-positive organisms, with no whole-cell potency shift due to the presence of DNA or human serum. Frequency-of-resistance studies demonstrated an acceptable rate of resistance emergencein vitroat concentrations 16- to 32-fold the MIC. AM-8722 displayed acceptable pharmacokinetic properties and was shown to be efficacious in mouse models of bacterial septicemia. Overall, AM-8722 is a selective and potent NBTI that displays broad-spectrum antimicrobial activityin vitroandin vivo.

Sign in / Sign up

Export Citation Format

Share Document