scholarly journals Osteoblasts-derived Exosomes as Novel Communicators in Particle Induced Periprosthetic Osteolysis

2021 ◽  
Author(s):  
Wanderson de Souza ◽  
Sara G. Piperni ◽  
Carolina F. Ruivo ◽  
Nuno Bastos ◽  
Patrícia Cardoso ◽  
...  
Keyword(s):  
Wear Debris ◽  
Bone Cells ◽  
The Body ◽  
Mass Spectrometry Analysis ◽  
Functional Tests ◽  
Periprosthetic Osteolysis ◽  
Human Macrophages ◽  
Joint Replacement Surgery ◽  
Anti Inflammatory ◽  
External Stimuli

Abstract BackgroundThe inflammatory response to titanium implant-derived wear particles is considered as the hallmark of periprosthetic osteolysis, an event that cause pain, reduce patient motility, ultimately leading to the need of a revision surgery. Although macrophages are major cell players, other cell types such as bone cells can indirectly contribute to periprosthetic osteolysis, however the mechanisms are not fully understood. Exosomes (Exos) has been related with several bone pathologies, with growing body of literature recognizing them as actively shuttle molecules through the body, with their cargo being completely dependent of external stimuli (e.g. chemicals and metals ions and particles). Till the moment, the role of wear debris on osteoblasts exosomes biogenesis is absent and the possible contribution of Exos to osteoimmune communication and periprosthetic osteolysis is still in its infancy. Taking that in consideration, in this work we investigate the effect of wear debris on Exo biogenesis, where two bone cell models were exposed to titanium dioxide nanoparticles (TiO2 NPs) similar in size and composition to wear debris associated with prosthetic implants. The contribution of Exos to periprosthetic osteolysis was evaluated performing functional tests stimulating primary human macrophages with bone-derived Exos.ResultsFor the first time, we report that TiO2 NPs enter in multivesicular bodies, the nascent of Exos and altered osteoblasts derived exosomes secretion and cargo. No significant differences were observed in Exos morphology and size, however mass spectrometry analysis identified urokinase-type plasminogen activator (uPA), specifically enriched in Exos derived from bone cells pre-incubated with TiO2 NPs. Functional tests confirmed the activation of human macrophages towards a mixed phenotype with consequent secretion of pro and anti-inflammatory cytokines. ConclusionsThe external stimuli of osteoblasts to TiO2 NPs induced a dose dependent secretion of Exos, suggesting alterations in their biogenesis as well as in their cargo. Functional tests reveal that enriched uPA exosomal cargo is stimulating macrophages towards a mixed M1 and M2 phenotype inducing the release of pro-and anti-inflammatory signals that are characteristic of periprosthetic osteolysis. Interestingly, uPA may be proposed, in the future, as a possible candidate biomarker to early diagnose particle induced periprosthetic osteolysis, since uPA was also detected in the pseudocapsular interface around implants of patients with loosening of total hip prosthesis and joint replacement surgery, suggesting their active role in disease progression.

scholarly journals The drug likeness analysis of anti-inflammatory clerodane diterpenoids

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Zheling Feng ◽  
Jun Cao ◽  
Qingwen Zhang ◽  
Ligen Lin
Keyword(s):  
Marine Sponges ◽  
The Body ◽  
Low Grade ◽  
Active Defense ◽  
Inflammatory Drugs ◽  
Clerodane Diterpenoids ◽  
Anti Inflammatory ◽  
External Stimuli

AbstractInflammation is an active defense response of the body against external stimuli. Long term low-grade inflammation has been considered as a deteriorated factor for aging, cancer, neurodegeneration and metabolic disorders. The clinically used glucocorticoids and non-steroidal anti-inflammatory drugs are not suitable for chronic inflammation. Therefore, it’s urgent to discover and develop new effective and safe drugs to attenuate inflammation. Clerodane diterpenoids, a class of bicyclic diterpenoids, are widely distributed in plants of the Labiatae, Euphorbiaceae and Verbenaceae families, as well as fungi, bacteria, and marine sponges. Dozens of anti-inflammatory clerodane diterpenoids have been identified on different assays, both in vitro and in vivo. In the current review, the up-to-date research progresses of anti-inflammatory clerodane diterpenoids were summarized, and their druglikeness was analyzed, which provided the possibility for further development of anti-inflammatory drugs.

Invivo Activity of Polyherbal Gels Prepared Using Carbopol

2020 ◽  
Vol 10 (3) ◽  
pp. 63-66
Author(s):  
Parasakthi N ◽  
Deepika R ◽  
Sivanathan C ◽  
Abubackkar Sithiq PD ◽  
Venkateshan N
Keyword(s):  
Physiological Stress ◽  
Defense Responses ◽  
The Body ◽  
Peptic Ulcers ◽  
Onset Of Action ◽  
Standard Drug ◽  
Root Extracts ◽  
Carbopol 940 ◽  
Anti Inflammatory ◽  
Rich Countries

Pain and inflammation are the basic defense responses of the body that the result of the injury and any other damage to the body. During the years the concerns were raised towards the inflammation that is caused to the oxidative damage that is resulted in the physiological stress due to oxidation. There are a lot of drugs that are used to treat the condition effectively and the typical examples are NSAID’s and SAID’s which have a noted mechanism to show the anti-inflammatory activity. They have serious problems with the side effects like Gastrointestinal irritation, Gastric pain, Gastric perforations and peptic ulcers. Herbs have been used as better alternatives that are used to treat diseases. The significance of the medicinal plants had been emphasized significantly in tradition rich countries like India and all over the world. The research proof of those herbs for their activities and their traditional claims were proven. Poly Herbal Gels were prepared using the root extracts of the plant Corchorus olitorius. The gels were prepared using the Carbopol 940 and the prepared gels were investigated for their anti-inflammatory property and the gels showed a significantly better activity compared to the plant extract and the standard drug too. The addition of other drugs in to the gels added and advantage to the increase in the activity and faster onset of action as the gel was applied directly in the place of the inflammation.

ANALGESIC AND ANTI-INFLAMMATORY EFFECTS OF ACETYLSALICYLIC ACID: PHYSIOLOGICAL MECHANISMS

2020 ◽  
Vol 6(72) (1) ◽  
pp. 197-219
Author(s):  
I. V. Cheretaev ◽  
D. R. Khusainov ◽  
E. N. Chuyan ◽  
M. Yu. Ravaeva ◽  
A. N. Gusev ◽  
...  
Keyword(s):  
Acetylsalicylic Acid ◽  
Physiological Mechanism ◽  
The Body ◽  
Physiological Mechanisms ◽  
Scientific Publications ◽  
Thermal Pain ◽  
Order Of Magnitude ◽  
Anti Inflammatory ◽  
Number Of Publications ◽  
Electrical Stimuli

The purpose of the review is to summarize current literature data and the results of our own research on the analgesic and anti-inflammatory effects of acetylsalicylic acid, as well as the physiological mechanisms underlying them. This acid is the most studied reference representative of salicylates, which is convenient to consider the physiological effects characteristic in general for this group of chemical and medicinal products. Acetylsalicylic acid has analgesic properties against thermal pain and pain caused by electrical stimuli, as well as a pronounced anti-inflammatory effect. The realization of these properties depends on the peculiarities of aspirin metabolism in the body, ion and synaptic mechanisms for controlling the functional state of the cell, neurotransmitter systems of the сentral nervous system, and mechanisms of peripheral and сentral analgesia. Analgesic properties of acetylsalicylic acid founded not only in normal, but also in ultra-small doses. Various physical and especially chemical factors significantly change their effects. This increases the interest in studying the analgesic activity of salicylates and their physiological mechanisms, since such studies can serve as a basis for creating new non-steroidal anti-inflammatory drugs with low toxicity and high safety for patients, and improve the strategy of their practical use. Currently, the most detailed study of the physiological mechanism of analgesic and anti-inflammatory action of aspirin and its main metabolite – salicylic acid. However, it should be note that despite the abundance of existing data obtained in scientific studies of the effects of aspirin and its practical use, there are a number of unexplained aspects of the action of this drug, the mechanism of which has not yet been deciphered. The continuing interest in the effects and mechanisms of action of this drug and in connection with the expansion of its use evidenced by a consistently high number of scientific publications on aspirin in the most famous foreign and domestic publications. At the same time, the number of publications about aspirin is an order of magnitude higher than about any other drug known to humanity.

scholarly journals Empagliflozin Improves Metabolic and Hepatic Outcomes in a Non-Diabetic Obese Biopsy-Proven Mouse Model of Advanced NASH

2021 ◽  
Vol 22 (12) ◽  
pp. 6332
Author(s):  
Nikolaos Perakakis ◽  
Pavlina Chrysafi ◽  
Michael Feigh ◽  
Sanne Skovgard Veidal ◽  
Christos S. Mantzoros
Keyword(s):  
Mouse Model ◽  
Cell Activation ◽  
Stellate Cell ◽  
Liver Steatosis ◽  
Tolerance Test ◽  
The Body ◽  
Oral Glucose ◽  
Alcoholic Fatty Liver ◽  
Metabolic Outcomes ◽  
Anti Inflammatory

Empagliflozin, an established treatment for type 2 diabetes (T2DM), has shown beneficial effects on liver steatosis and fibrosis in animals and in humans with T2DM, non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH). However, little is known about the effects of empagliflozin on liver function in advanced NASH with liver fibrosis and without diabetes. This study aimed to assess the effects of empagliflozin on hepatic and metabolic outcomes in a diet-induced obese (DIO) and insulin-resistant but non-diabetic biopsy-confirmed mouse model of advanced NASH. Male C57BL/6JRj mice with a biopsy-confirmed steatosis and fibrosis on AMLN diet (high fat, fructose and cholesterol) for 36-weeks were randomized to receive for 12 weeks: (a) Empagliflozin (10 mg/kg/d p.o.), or (b) vehicle. Metabolic outcomes, liver pathology, markers of Kupffer and stellate cell activation and lipidomics were assessed at the treatment completion. Empagliflozin did not affect the body weight, body composition or insulin sensitivity (assessed by intraperitoneal insulin tolerance test), but significantly improved glucose homeostasis as assessed by oral glucose tolerance test in DIO-NASH mice. Empagliflozin improved modestly the NAFLD activity score compared with the vehicle, mainly by improving inflammation and without affecting steatosis, the fibrosis stage and markers of Kupffer and stellate cell activation. Empagliflozin reduced the hepatic concentrations of pro-inflammatory lactosylceramides and increased the concentrations of anti-inflammatory polyunsaturated triglycerides. Empagliflozin exerts beneficial metabolic and hepatic (mainly anti-inflammatory) effects in non-diabetic DIO-NASH mice and thus may be effective against NASH even in non-diabetic conditions.

scholarly journals Strategies for the Development of pH-Responsive Synthetic Polypeptides and Polymer-Peptide Hybrids: Recent Advancements

Polymers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 624
Author(s):  
Cintya Dharmayanti ◽  
Todd A. Gillam ◽  
Manuela Klingler-Hoffmann ◽  
Hugo Albrecht ◽  
Anton Blencowe
Keyword(s):  
Functional Groups ◽  
Hybrid Materials ◽  
Tumour Microenvironment ◽  
The Body ◽  
Supramolecular Interactions ◽  
Biological Interactions ◽  
Ph Responsive ◽  
Form Complex ◽  
Synthetic Polypeptides ◽  
External Stimuli

Synthetic polypeptides and polymer-peptide hybrid materials have been successfully implemented in an array of biomedical applications owing to their biocompatibility, biodegradability and ability to mimic natural proteins. In addition, these materials have the capacity to form complex supramolecular structures, facilitate specific biological interactions, and incorporate a diverse selection of functional groups that can be used as the basis for further synthetic modification. Like conventional synthetic polymers, polypeptide-based materials can be designed to respond to external stimuli (e.g., light and temperature) or changes in the environmental conditions (e.g., redox reactions and pH). In particular, pH-responsive polypeptide-based systems represent an interesting avenue for the preparation of novel drug delivery systems that can exploit physiological or pathological pH variations within the body, such as those that arise in the extracellular tumour microenvironment, intracellularly within endosomes/lysosomes, or during tissue inflammation. Here, we review the significant progress made in advancing pH-responsive polypeptides and polymer-peptide hybrid materials during the last five years, with a particular emphasis on the manipulation of ionisable functional groups, pH-labile linkages, pH-sensitive changes to secondary structure, and supramolecular interactions.

scholarly journals Could Lipoxins Represent a New Standard in Ischemic Stroke Treatment?

2021 ◽  
Vol 22 (8) ◽  
pp. 4207
Author(s):  
Nikola Tułowiecka ◽  
Dariusz Kotlęga ◽  
Andrzej Bohatyrewicz ◽  
Małgorzata Szczuko
Keyword(s):  
Ischemic Stroke ◽  
Cardiovascular Diseases ◽  
Blood Brain Barrier ◽  
Inflammatory Cytokines ◽  
The Body ◽  
Brain Barrier ◽  
Lipoxin A4 ◽  
Stroke Treatment ◽  
Blood Brain ◽  
Anti Inflammatory

Introduction: Cardiovascular diseases including stroke are one of the most common causes of death. Their main cause is atherosclerosis and chronic inflammation in the body. An ischemic stroke may occur as a result of the rupture of unstable atherosclerotic plaque. Cardiovascular diseases are associated with uncontrolled inflammation. The inflammatory reaction produces chemical mediators that stimulate the resolution of inflammation. One of these mediators is lipoxins—pro-resolving mediators that are derived from the omega-6 fatty acid family, promoting inflammation relief and supporting tissue regeneration. Aim: The aim of the study was to review the available literature on the therapeutic potential of lipoxins in the context of ischemic stroke. Material and Methods: Articles published up to 31 January 2021 were included in the review. The literature was searched on the basis of PubMed and Embase in terms of the entries: ‘stroke and lipoxin’ and ‘stroke and atherosclerosis’, resulting in over 110 articles in total. Studies that were not in full-text English, letters to the editor, and conference abstracts were excluded. Results: In animal studies, the injection/administration of lipoxin A4 improved the integrity of the blood–brain barrier (BBB), decreased the volume of damage caused by ischemic stroke, and decreased brain edema. In addition, lipoxin A4 inhibited the infiltration of neutrophils and the production of cytokines and pro-inflammatory chemokines, such as interleukin (Il-1β, Il-6, Il-8) and tumor necrosis factor-α (TNF-α). The beneficial effects were also observed after introducing the administration of lipoxin A4 analog—BML-111. BML-111 significantly reduces the size of a stroke and protects the cerebral cortex, possibly by reducing the permeability of the blood–brain barrier. Moreover, more potent than lipoxin A4, it has an anti-inflammatory effect by inhibiting the production of pro-inflammatory cytokines and increasing the amount of anti-inflammatory cytokines. Conclusions: Lipoxins and their analogues may find application in reducing damage caused by stroke and improving the prognosis of patients after ischemic stroke.

scholarly journals Anti-Inflammatory and Anticancer Properties of Bioactive Compounds from Sesamum indicum L.—A Review

Molecules ◽  
2019 ◽  
Vol 24 (24) ◽  
pp. 4426 ◽  
Author(s):  
Ming-Shun Wu ◽  
Levent Bless B. Aquino ◽  
Marjette Ylreb U. Barbaza ◽  
Chieh-Lun Hsieh ◽  
Kathlia A. De Castro-Cruz ◽  
...  
Keyword(s):  
Chronic Diseases ◽  
Inflammatory Diseases ◽  
Antioxidant Properties ◽  
Sesamum Indicum ◽  
The Body ◽  
Anticancer Activities ◽  
Anticancer Properties ◽  
Pharmacological Significance ◽  
Anti Inflammatory ◽  
Natural Medicines

The use of foodstuff as natural medicines has already been established through studies demonstrating the pharmacological activities that they exhibit. Knowing the nutritional and pharmacological significance of foods enables the understanding of their role against several diseases. Among the foods that can potentially be considered as medicine, is sesame or Sesamum indicum L., which is part of the Pedaliaceae family and is composed of its lignans such as sesamin, sesamol, sesaminol and sesamolin. Its lignans have been widely studied and are known to possess antiaging, anticancer, antidiabetes, anti-inflammatory and antioxidant properties. Modern chronic diseases, which can transform into clinical diseases, are potential targets of these lignans. The prime example of chronic diseases is rheumatic inflammatory diseases, which affect the support structures and the organs of the body and can also develop into malignancies. In line with this, studies emphasizing the anti-inflammatory and anticancer activities of sesame have been discussed in this review.

scholarly journals Anti-Inflammatory Properties of Diet: Role in Healthy Aging

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 922
Author(s):  
Kristine Stromsnes ◽  
Angela G. Correas ◽  
Jenny Lehmann ◽  
Juan Gambini ◽  
Gloria Olaso-Gonzalez
Keyword(s):  
Cardiovascular Disease ◽  
Autoimmune Disease ◽  
Neurological Disease ◽  
Healthy Aging ◽  
Dietary Guidelines ◽  
The Body ◽  
Inflammatory Activity ◽  
Allergic Reactions ◽  
Inflammatory Processes ◽  
Anti Inflammatory

Inflammation is a physiological process involved in the defenses of the body and the repair of tissues. It is acutely activated by infections, trauma, toxins, or allergic reactions. However, if it becomes chronic, inflammation can end up stimulating the development of diseases such as cardiovascular disease, autoimmune disease, neurological disease, or cancer. Additionally, during aging, inflammation becomes increasingly more chronic. Furthermore, we found that certain foods, such as saturated fats, have pro-inflammatory activity. Taking this into account, in this review we have discussed different diets with possible anti-inflammatory activity, the commonly ingested components of each diet and their active compounds. In addition, we have proposed some dietary guidelines, as well as a list of compounds present in foods with anti-inflammatory activity, outlining how to combine them to achieve optimal anti-inflammatory effects. Therefore, we can conclude that the compounds in our diet with anti-inflammatory activity could help alleviate the inflammatory processes derived from diseases and unhealthy diets, and thereby promote healthy aging.

An Overview of Novel Bioactive Compounds with Potent Anti-Inflammatory Activity via Dual COX-2 and 5-LOX Enzyme Inhibition

2021 ◽  
Vol 18 ◽  
Author(s):  
Roopal Mittal ◽  
Shailesh Sharma ◽  
Ajay Singh Kushwah
Keyword(s):  
Bioactive Compounds ◽  
Enzyme Inhibitors ◽  
World Health Organisation ◽  
The Body ◽  
Inflammatory Activity ◽  
World Health ◽  
Quality Data ◽  
The World ◽  
Cox 2 ◽  
Anti Inflammatory

Background: Inflammation is the earliest body defence mechanism in which the immune system recognises and counters the antigens and aids in healing the disease. The World Health Organisation suggests that inflammation is one of the greatest causes of death in the world. Inflammation could be acute or chronic due to the release of inflammatory mediators i.e. prostaglandins, leukotrienes due to mitogens, antigens or cytokines found in the body. Methods: Bibliographic database using pub med cites for peer-reviewed research articles with titles containing dual COX-2 and 5-LOX enzyme inhibitors, heterocyclic moieties, with AND Boolean operator's terms since last ten years of literature work. The quality papers containing the natural or synthetic lead compounds were extracted; the detailed study and conceptual framework attracted its attention. Results: Out of 127 research and review articles evaluated, 54 articles were cited to provide high quality data regarding pharmacoactive molecules having anti-inflammatory activity via dual COX-2/5-LOX inhibition. In addition, highlighting their in silico and experimental wet laboratory studies in increasing order over the past decade with the best illustration of dual enzyme inhibitory activity. Conclusion: This review gathered details of isolated bioactive compounds such as pyrazole, coumaperine, indoles, phenanthrene derivatives that have been significantly reported for anti-inflammatory activities.

scholarly journals Regular Practice of Moderate Physical Activity by Older Adults Ameliorates Their Anti-Inflammatory Status

Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1780 ◽  
Author(s):  
Miguel Ferrer ◽  
Xavier Capó ◽  
Miquel Martorell ◽  
Carla Busquets-Cortés ◽  
Cristina Bouzas ◽  
...  
Keyword(s):  
Physical Activity ◽  
Older Adults ◽  
Body Composition ◽  
Healthy Aging ◽  
The Body ◽  
Moderate Physical Activity ◽  
Metabolic Equivalents ◽  
Inflammatory Status ◽  
Anti Inflammatory ◽  
Regular Practice

A chronic inflammatory state is a major characteristic of the aging process, and physical activity is proposed as a key component for healthy aging. Our aim was to evaluate the body composition, hypertension, lipid profile, and inflammatory status of older adults, and these factors’ association with physical activity. A total of 116 elderly volunteers were categorized into terciles of quantitative metabolic equivalents of task (MET). Subjects in the first and third terciles were defined as sedentary and active subjects, respectively. Anthropometric and biochemical parameters, hemograms, and inflammatory markers were measured in plasma or peripheral mononuclear blood cells (PBMCs). The active groups exercised more than their sedentary counterparts. The practice of physical activity was accompanied by lower weight, fat mass, body mass index, and diastolic blood pressure when compared to a more sedentary life-style. Physical activity also lowered the haematocrit and total leukocyte, neutrophil, and lymphocyte counts. The practice of exercise induced a decrease in the IL-6 circulating levels and the TLR2 protein levels in PBMCs, while the expression of the anti-inflammatory IL-10 was activated in active subjects. The regular practice of physical activity exerts beneficial effects on body composition and the anti-inflammatory status of old people.

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