scholarly journals Effective suppression of pro-inflammatory molecules by DHCA via IKK-NF-κB pathway,in vitroandin vivo

2015 ◽  
Vol 172 (13) ◽  
pp. 3353-3369 ◽  
Author(s):  
Junghun Lee ◽  
Jinyong Choi ◽  
Sunyoung Kim
Keyword(s):  
Effective Suppression ◽  
Inflammatory Molecules

Factorial Modeling for Effective Suppression of Directional Noise

2017 ◽  
Author(s):  
Osamu Ichikawa ◽  
Takashi Fukuda ◽  
Gakuto Kurata ◽  
Steven J. Rennie
Keyword(s):  
Effective Suppression

scholarly journals Radiofrequency Irradiation Modulates TRPV1-Related Burning Sensation in Rosacea

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1424
Author(s):  
Seyeon Oh ◽  
Myeongjoo Son ◽  
Joonhong Park ◽  
Donghwan Kang ◽  
Kyunghee Byun
Keyword(s):  
Burning Sensation ◽  
In Vivo Model ◽  
Molecular Evidence ◽  
Exposed Skin ◽  
Heat Treated ◽  
Vitro Model ◽  
Effective Use ◽  
Inflammatory Molecules

Rosacea is a skin inflammatory condition that is accompanied by not only redness and flushing but also unseen symptoms, such as burning, stinging, and itching. TRPV1 expression in UVB-exposed skin can lead to a painful burning sensation. Upregulated TRPV1 expression helps release neuropeptides, including calcitonin gene-related peptide, pituitary adenylate cyclase-activating polypeptide, and vasoactive intestinal peptide, which can activate macrophage and inflammatory molecules. In this study, we found that radiofrequency (RF) irradiation reduced TRPV1 activation and neuropeptide expression in a UVB-exposed in vivo model and UVB- or heat-treated in an in vitro model. RF irradiation attenuated neuropeptide-induced macrophage activation and inflammatory molecule expression. Interestingly, the burning sensation in the skin of UVB-exposed mice and patients with rosacea was significantly decreased by RF irradiation. These results can provide experimental and molecular evidence on the effective use of RF irradiation for the burning sensation in patients with rosacea.

scholarly journals Mesenchymal Stem Cell Derived Extracellular Vesicles for Repairing the Neurovascular Unit after Ischemic Stroke

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 767
Author(s):  
Courtney Davis ◽  
Sean I. Savitz ◽  
Nikunj Satani
Keyword(s):  
Ischemic Stroke ◽  
Extracellular Vesicles ◽  
Neurovascular Unit ◽  
Culture Conditions ◽  
Therapeutic Effects ◽  
Stroke Treatment ◽  
Inflammatory Molecules ◽  
The Brain

Ischemic stroke is a debilitating disease and one of the leading causes of long-term disability. During the early phase after ischemic stroke, the blood-brain barrier (BBB) exhibits increased permeability and disruption, leading to an influx of immune cells and inflammatory molecules that exacerbate the damage to the brain tissue. Mesenchymal stem cells have been investigated as a promising therapy to improve the recovery after ischemic stroke. The therapeutic effects imparted by MSCs are mostly paracrine. Recently, the role of extracellular vesicles released by these MSCs have been studied as possible carriers of information to the brain. This review focuses on the potential of MSC derived EVs to repair the components of the neurovascular unit (NVU) controlling the BBB, in order to promote overall recovery from stroke. Here, we review the techniques for increasing the effectiveness of MSC-based therapeutics, such as improved homing capabilities, bioengineering protein expression, modified culture conditions, and customizing the contents of EVs. Combining multiple techniques targeting NVU repair may provide the basis for improved future stroke treatment paradigms.

scholarly journals The Role of Circulating Biomarkers in Peripheral Arterial Disease

2021 ◽  
Vol 22 (7) ◽  
pp. 3601
Author(s):  
Goren Saenz-Pipaon ◽  
Esther Martinez-Aguilar ◽  
Josune Orbe ◽  
Arantxa González Miqueo ◽  
Leopoldo Fernandez-Alonso ◽  
...  
Keyword(s):  
Peripheral Arterial Disease ◽  
Lower Limb ◽  
Prediction Models ◽  
Arterial Disease ◽  
Cardiac Damage ◽  
Thrombotic Occlusion ◽  
Medical Treatments ◽  
Peripheral Arterial ◽  
Inflammatory Molecules

Peripheral arterial disease (PAD) of the lower extremities is a chronic illness predominantly of atherosclerotic aetiology, associated to traditional cardiovascular (CV) risk factors. It is one of the most prevalent CV conditions worldwide in subjects >65 years, estimated to increase greatly with the aging of the population, becoming a severe socioeconomic problem in the future. The narrowing and thrombotic occlusion of the lower limb arteries impairs the walking function as the disease progresses, increasing the risk of CV events (myocardial infarction and stroke), amputation and death. Despite its poor prognosis, PAD patients are scarcely identified until the disease is advanced, highlighting the need for reliable biomarkers for PAD patient stratification, that might also contribute to define more personalized medical treatments. In this review, we will discuss the usefulness of inflammatory molecules, matrix metalloproteinases (MMPs), and cardiac damage markers, as well as novel components of the liquid biopsy, extracellular vesicles (EVs), and non-coding RNAs for lower limb PAD identification, stratification, and outcome assessment. We will also explore the potential of machine learning methods to build prediction models to refine PAD assessment. In this line, the usefulness of multimarker approaches to evaluate this complex multifactorial disease will be also discussed.

scholarly journals Proteolysis-targeting chimera against BCL-XL destroys tumor-infiltrating regulatory T cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ryan Kolb ◽  
Umasankar De ◽  
Sajid Khan ◽  
Yuewan Luo ◽  
Myung-Chul Kim ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Molecular Target ◽  
Therapeutic Strategies ◽  
Normal Tissues ◽  
Effective Suppression ◽  
Immunosuppressive Microenvironment ◽  
Cancer Immunotherapies

AbstractRegulatory T cells (Tregs) play an important role in maintaining immune homeostasis and, within tumors, their upregulation is common and promotes an immunosuppressive microenvironment. Therapeutic strategies that can eliminate Tregs in the tumor (i.e., therapies that do not run the risk of affecting normal tissues), are urgently needed for the development of cancer immunotherapies. Here we report our discovery of B-cell lymphoma extra-large (BCL-XL) as a potential molecular target of tumor-infiltrating (TI) Tregs. We show that pharmacological degradation of BCL-XL using a newly developed platelet-sparing BCL-XL Proteolysis-targeting chimera (PROTAC) induces the apoptosis of TI-Tregs and the activation of TI-CD8+ T cells. Moreover, these activities result in an effective suppression of syngeneic tumor growth in immunocompetent, but not in immunodeficient or CD8+ T cell-depleted mice. Notably, treatment with BCL-XL PROTAC does not cause detectable damage within several normal tissues or thrombocytopenia. These findings identify BCL-XL as a target in the elimination of TI-Tregs as a component of cancer immunotherapies, and that the BCL-XL-specific PROTAC has the potential to be developed as a therapeutic for cancer immunotherapy.

scholarly journals Lactobacillus acidophilus LA5 improves saturated fat-induced obesity mouse model through the enhanced intestinal Akkermansia muciniphila

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Thunnicha Ondee ◽  
Krit Pongpirul ◽  
Peerapat Visitchanakun ◽  
Wilasinee Saisorn ◽  
Suthicha Kanacharoen ◽  
...  
Keyword(s):  
Liver Injury ◽  
Lactobacillus Acidophilus ◽  
Hepg2 Cells ◽  
Saturated Fat ◽  
Liver Weight ◽  
Gram Negative ◽  
Fecal Microbiome ◽  
Akkermansia Muciniphila ◽  
Anti Inflammatory ◽  
Inflammatory Molecules

AbstractObesity, a major healthcare problem worldwide, induces metabolic endotoxemia through the gut translocation of lipopolysaccharides (LPS), a major cell wall component of Gram-negative bacteria, causing a chronic inflammatory state. A combination of several probiotics including Lactobacillus acidophilus 5 (LA5), a potent lactic acid-producing bacterium, has previously been shown to attenuate obesity. However, data on the correlation between a single administration of LA5 versus microbiota alteration might be helpful for the probiotic adjustment. LA5 was administered daily together with a high-fat diet (HFD) for 8 weeks in mice. Furthermore, the condition media of LA5 was also tested in a hepatocyte cell-line (HepG2 cells). Accordingly, LA5 attenuated obesity in mice as demonstrated by weight reduction, regional fat accumulation, lipidemia, liver injury (liver weight, lipid compositions, and liver enzyme), gut permeability defect, endotoxemia, and serum cytokines. Unsurprisingly, LA5 improved these parameters and acidified fecal pH leads to the attenuation of fecal dysbiosis. The fecal microbiome analysis in obese mice with or without LA5 indicated; (i) decreased Bacteroidetes (Gram-negative anaerobes that predominate in non-healthy conditions), (ii) reduced total fecal Gram-negative bacterial burdens (the sources of gut LPS), (iii) enhanced Firmicutes (Gram-positive bacteria with potential benefits) and (iv) increased Verrucomycobia, especially Akkermansia muciniphila, a bacterium with the anti-obesity property. With LA5 administration, A. muciniphila in the colon were more than 2,000 folds higher than the regular diet mice as determined by 16S rRNA. Besides, LA5 produced anti-inflammatory molecules with a similar molecular weight to LPS that reduced cytokine production in LPS-activated HepG2 cells. In conclusion, LA5 attenuated obesity through (i) gut dysbiosis attenuation, partly through the promotion of A. muciniphila (probiotics with the difficulty in preparation processes), (ii) reduced endotoxemia, and (iii) possibly decreased liver injury by producing the anti-inflammatory molecules.

scholarly journals Stem Cell-Derived Exosomes in Autism Spectrum Disorder

2020 ◽  
Vol 17 (3) ◽  
pp. 944 ◽  
Author(s):  
Nicola Alessio ◽  
Anna Lisa Brigida ◽  
Gianfranco Peluso ◽  
Nicola Antonucci ◽  
Umberto Galderisi ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Stem Cells ◽  
Stem Cell ◽  
Cell Communication ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Molecular Action ◽  
Definition Of ◽  
Inflammatory Molecules ◽  
Therapeutic Activities

Neurodevelopmental lifelong pathologies defined by problems with social interaction, communication capacity and presence of repetitive/stereotyped clusters of behavior and interests are grouped under the definition of autism spectrum disorder (ASD). ASD prevalence is still increasing, indicating the need to identify specific biomarkers and novel pharmacotherapies. Neuroinflammation and neuro-immune cross-talk dysregulation are specific hallmarks of ASD, offering the possibility of treating these disorders by stem cell therapy. Indeed, cellular strategies have been postulated, proposed and applied to ASD. However, less is known about the molecular action mechanisms of stem cells. As a possibility, the positive and restorative effects mediated by stem cells could be due to their paracrine activity, by which stem cells produce and release several ameliorative and anti-inflammatory molecules. Among the secreted complex tools, exosomes are sub-organelles, enriched by RNA and proteins, that provide cell-to-cell communication. Exosomes could be the mediators of many stem cell-associated therapeutic activities. This review article describes the potential role of exosomes in alleviating ASD symptoms.

scholarly journals The Implications of Pruritogens in the Pathogenesis of Atopic Dermatitis

2021 ◽  
Vol 22 (13) ◽  
pp. 7227
Author(s):  
Lai-San Wong ◽  
Yu-Ta Yen ◽  
Chih-Hung Lee
Keyword(s):  
Atopic Dermatitis ◽  
Environmental Factors ◽  
Immune Responses ◽  
Immune Cells ◽  
Inflammatory Disease ◽  
Targeted Therapies ◽  
Skin Barrier ◽  
Skin Barrier Function ◽  
Inflammatory Molecules

Atopic dermatitis (AD) is a prototypic inflammatory disease that presents with intense itching. The pathophysiology of AD is multifactorial, involving environmental factors, genetic susceptibility, skin barrier function, and immune responses. A recent understanding of pruritus transmission provides more information about the role of pruritogens in the pathogenesis of AD. There is evidence that pruritogens are not only responsible for eliciting pruritus, but also interact with immune cells and act as inflammatory mediators, which exacerbate the severity of AD. In this review, we discuss the interaction between pruritogens and inflammatory molecules and summarize the targeted therapies for AD.

scholarly journals Sesquiterpene Lactones: Promising Natural Compounds to Fight Inflammation

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 991
Author(s):  
Melanie S. Matos ◽  
José D. Anastácio ◽  
Cláudia Nunes dos Santos
Keyword(s):  
Biological Activities ◽  
Sesquiterpene Lactones ◽  
Physiological State ◽  
Plant Secondary Metabolites ◽  
Inflammatory Pathways ◽  
Inflammatory State ◽  
Anti Inflammatory ◽  
Inflammatory Molecules

Inflammation is a crucial and complex process that reestablishes the physiological state after a noxious stimulus. In pathological conditions the inflammatory state may persist, leading to chronic inflammation and causing tissue damage. Sesquiterpene lactones (SLs) are composed of a large and diverse group of highly bioactive plant secondary metabolites, characterized by a 15-carbon backbone structure. In recent years, the interest in SLs has risen due to their vast array of biological activities beneficial for human health. The anti-inflammatory potential of these compounds results from their ability to target and inhibit various key pro-inflammatory molecules enrolled in diverse inflammatory pathways, and prevent or reduce the inflammatory damage on tissues. Research on the anti-inflammatory mechanisms of SLs has thrived over the last years, and numerous compounds from diverse plants have been studied, using in silico, in vitro, and in vivo assays. Besides their anti-inflammatory potential, their cytotoxicity, structure–activity relationships, and pharmacokinetics have been investigated. This review aims to gather the most relevant results and insights concerning the anti-inflammatory potential of SL-rich extracts and pure SLs, focusing on their effects in different inflammatory pathways and on different molecular players.

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