Cannabinoids in the Pathophysiology of Skin Inflammation

Cannabinoids are increasingly-used substances in the treatment of chronic pain, some neuropsychiatric disorders and more recently, skin disorders with an inflammatory component. However, various studies cite conflicting results concerning the cellular mechanisms involved, while others suggest that cannabinoids may even exert pro-inflammatory behaviors. This paper aims to detail and clarify the complex workings of cannabinoids in the molecular setting of the main dermatological inflammatory diseases, and their interactions with other substances with emerging applications in the treatment of these conditions. Also, the potential role of cannabinoids as antitumoral drugs is explored in relation to the inflammatory component of skin cancer. In vivo and in vitro studies that employed either phyto-, endo-, or synthetic cannabinoids were considered in this paper. Cannabinoids are regarded with growing interest as eligible drugs in the treatment of skin inflammatory conditions, with potential anticancer effects, and the readiness in monitoring of effects and the facility of topical application may contribute to the growing support of the use of these substances. Despite the promising early results, further controlled human studies are required to establish the definitive role of these products in the pathophysiology of skin inflammation and their usefulness in the clinical setting.

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Therapeutic Role of miR-30a in Lipoteichoic Acid-Induced Endometritis via Targeting the MyD88/Nox2/ROS Signaling

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/5042048 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Kangfeng Jiang ◽

Weiqi Ye ◽

Qian Bai ◽

Jinyin Cai ◽

Haichong Wu ◽

...

Keyword(s):

Inflammatory Responses ◽

Inflammatory Diseases ◽

Lipoteichoic Acid ◽

In Vivo Studies ◽

Economic Losses ◽

Inflammatory Conditions ◽

Wide Range

Staphylococcus aureus (S. aureus), a notorious pathogenic bacterium prevalent in the environment, causes a wide range of inflammatory diseases such as endometritis. Endometritis is an inflammatory disease in humans and mammals, which prolongs uterine involution and causes great economic losses. MiR-30a plays an importan trole in the process of inflammation; however, the regulatory role of miR-30a in endometritis is still unknown. Here, we first noticed that there was an increased level of miR-30a in uterine samples of cows with endometritis. And then, bovine endometrial epithelial (BEND) cells stimulated with the virulence factor lipoteichoic acid (LTA) from S. aureus were used as an in vitro endometritis model to explore the potential role of miR-30a in the pathogenesis of endometritis. Our data showed that the induction of the miR-30a expression is dependent on NF-κB activation, and its overexpression significantly decreased the levels of IL-1β and IL-6. Furthermore, we observed that the overexpression of miR-30a inhibited its translation by binding to 3 ′ − UTR of MyD88 mRNA, thus preventing the activation of Nox2 and NF-κB and ROS accumulation. Meanwhile, in vivo studies further revealed that upregulation of miR-30a using chemically synthesized agomirs alleviates the inflammatory conditions in an experimental mouse model of endometritis, as indicated by inhibition of ROS and NF-κB. Taken together, these findings highlight that miR-30a can attenuate LTA-elicited oxidative stress and inflammatory responses through the MyD88/Nox2/ROS/NF-κB pathway and may aid the future development of novel therapies for inflammatory diseases caused by S. aureus, including endometritis.

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Cellular adaptations in fat tissue of exercise-trained miniature swine: role of excess energy intake

Journal of Applied Physiology ◽

10.1152/jappl.2000.88.3.881 ◽

2000 ◽

Vol 88 (3) ◽

pp. 881-887 ◽

Cited By ~ 5

Author(s):

Gale B. Carey

Keyword(s):

Adipose Tissue ◽

Energy Intake ◽

Excess Energy ◽

Fat Tissue ◽

Cellular Mechanisms ◽

Miniature Swine ◽

Extracellular Adenosine

This study examined the influence of energy expenditure and energy intake on cellular mechanisms regulating adipose tissue metabolism. 1 Twenty-four swine were assigned to restricted-fed sedentary, restricted-fed exercise-trained, full-fed sedentary, or full-fed exercise-trained groups. After 3 mo of treatment, adipocytes were isolated and adipocyte size, adenosine A1 receptor characteristics, and lipolytic sensitivity were measured. Swine were infused with epinephrine during which adipose tissue extracellular adenosine, plasma fatty acids, and plasma glycerol were measured. Results revealed that adipocytes isolated from restricted-fed exercised swine had a smaller diameter, a lower number of A1 receptors, and a greater sensitivity to lipolytic stimulation, compared with adipocytes from full-fed exercised swine. Extracellular adenosine levels were transiently increased on infusion of epinephrine in adipose tissue of restricted-fed exercised but not full-fed exercised swine. These results suggest a role for adenosine in explaining the discrepancy between in vitro and in vivo lipolysis findings and underscore the notion that excess energy intake dampens the lipolytic sensitivity of adipocytes to β-agonists and adenosine, even if accompanied by exercise training.

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Re-appraising the potential of naringin for natural, novel orthopedic biotherapies

Therapeutic Advances in Musculoskeletal Disease ◽

10.1177/1759720x20966135 ◽

2020 ◽

Vol 12 ◽

pp. 1759720X2096613

Author(s):

Kristin E. Yu ◽

Kareme D. Alder ◽

Montana T. Morris ◽

Alana M. Munger ◽

Inkyu Lee ◽

...

Keyword(s):

Bone Morphogenetic Proteins ◽

Degenerative Joint Disease ◽

Joint Disease ◽

Cellular Mechanisms ◽

Native Bone ◽

Inflammatory Conditions ◽

Osteolytic Bone Disease ◽

Cost Efficient

Naringin is a naturally occurring flavonoid found in plants of the Citrus genus that has historically been used in traditional Chinese medical regimens for the treatment of osteoporosis. Naringin modulates signaling through numerous molecular pathways critical to musculoskeletal development, cellular differentiation, and inflammation. Administration of naringin increases in vitro expression of bone morphogenetic proteins (BMPs) and activation of the Wnt/β-catenin and extracellular signal-related kinase (Erk) pathways, thereby promoting osteoblastic proliferation and differentiation from stem cell precursors for bone formation. Naringin also inhibits osteoclastogenesis by both modifying RANK/RANKL interactions and inducing apoptosis in osteoclasts in vitro. In addition, naringin acts on the estrogen receptor in bone to mimic the native bone-preserving effects of estrogen, with few systemic side effects on other estrogen-sensitive tissues. The efficacy of naringin therapy in reducing the osteolysis characteristic of common musculoskeletal pathologies such as osteoporosis, degenerative joint disease, and osteomyelitis, as well as inflammatory conditions affecting bone such as diabetes mellitus, has been extensively demonstrated in vitro and in animal models. Naringin thus represents a naturally abundant, cost-efficient agent whose potential for use in novel musculoskeletal biotherapies warrants re-visiting and further exploration through human studies. Here, we review the cellular mechanisms of action that have been elucidated regarding the action of naringin on bone resident cells and the bone microenvironment, in vivo evidence of naringin’s osteostimulative and chondroprotective properties in the setting of osteolytic bone disease, and current limitations in the development of naringin-containing translational therapies for common musculoskeletal conditions.

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Role of macrophage CD44 in the disposal of inflammatory cell corpses*

Clinical Science ◽

10.1042/cs1030441 ◽

2002 ◽

Vol 103 (5) ◽

pp. 441-449 ◽

Cited By ~ 1

Author(s):

Sharon VIVERS ◽

Ian DRANSFIELD ◽

Simon P. HART

Keyword(s):

Molecular Mechanisms ◽

Inflammatory Diseases ◽

Surrounding Tissue ◽

Human Macrophage ◽

Neutrophil Granulocytes ◽

Apoptotic Cells ◽

Tissue Destruction

Understanding the cellular and molecular mechanisms that determine whether inflammation resolves or progresses to scarring and tissue destruction should lead to the development of effective therapeutic strategies for inflammatory diseases. Apoptosis of neutrophil granulocytes is an important determinant of the resolution of inflammation, providing a mechanism for down-regulation of function and triggering clearance by macrophages without inducing a pro-inflammatory response. However, if the rate of cell death by apoptosis is such that the macrophage clearance capacity is exceeded, apoptotic cells may progress to secondary necrosis, resulting in the release of harmful cellular contents and in damage to the surrounding tissue. There are many possible ways in which the rate and capacity of the macrophage-mediated clearance of apoptotic cells may be enhanced or suppressed. Ligation of human macrophage surface CD44 by bivalent monoclonal antibodies rapidly and profoundly augments the capacity of macrophages to phagocytose apoptotic neutrophils in vitro. The molecular mechanism behind this effect and its potential significance in vivo is a current focus of research.

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The Role of IL-1βin the Bone Loss during Rheumatic Diseases

Mediators of Inflammation ◽

10.1155/2015/782382 ◽

2015 ◽

Vol 2015 ◽

pp. 1-10 ◽

Cited By ~ 63

Author(s):

Piero Ruscitti ◽

Paola Cipriani ◽

Francesco Carubbi ◽

Vasiliki Liakouli ◽

Francesca Zazzeroni ◽

...

Keyword(s):

Bone Resorption ◽

Bone Loss ◽

Rheumatic Diseases ◽

Nuclear Factor Kappa B ◽

Inflammatory Diseases ◽

Receptor Activator ◽

Main Factor

Several inflammatory diseases have been associated with increased bone resorption and fracture rates and different studies supported the relation between inflammatory cytokines and osteoclast activity. The main factor required for osteoclast activation is the stimulation by receptor activator of nuclear factor kappa-B ligand (RANKL) expressed on osteoblasts. In this context, interleukin- (IL-) 1β, one of the most powerful proinflammatory cytokines, is a strong stimulator of in vitro and in vivo bone resorption via upregulation of RANKL that stimulates the osteoclastogenesis. The resulting effects lead to an imbalance in bone metabolism favouring bone resorption and osteoporosis. In this paper, we review the available literature on the role of IL-1βin the pathogenesis of bone loss. Furthermore, we analysed the role of IL-1βin bone resorption during rheumatic diseases and, when available, we reported the efficacy of anti-IL-1βtherapy in this field.

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Inhibitory Role of Berberine, an Isoquinoline Alkaloid, on NLRP3 Inflammasome Activation for the Treatment of Inflammatory Diseases

Molecules ◽

10.3390/molecules26206238 ◽

2021 ◽

Vol 26 (20) ◽

pp. 6238

Author(s):

Paromita Sarbadhikary ◽

Blassan P. George ◽

Heidi Abrahamse

Keyword(s):

Nlrp3 Inflammasome ◽

Inflammatory Diseases ◽

In Vivo Studies ◽

Inflammasome Activation ◽

Inflammatory Disorders ◽

Nlrp3 Inflammasome Activation ◽

Anti Inflammatory

The pyrin domain-containing multiprotein complex NLRP3 inflammasome, consisting of the NLRP3 protein, ASC adaptor, and procaspase-1, plays a vital role in the pathophysiology of several inflammatory disorders, including neurological and metabolic disorders, chronic inflammatory diseases, and cancer. Several phytochemicals act as promising anti-inflammatory agents and are usually regarded to have potential applications as complementary or alternative therapeutic agents against chronic inflammatory disorders. Various in vitro and in vivo studies have reported the anti-inflammatory role of berberine (BRB), an organic heteropentacyclic phytochemical and natural isoquinoline, in inhibiting NLRP3 inflammasome-dependent inflammation against many disorders. This review summarizes the mechanism and regulation of NLRP3 inflammasome activation and its involvement in inflammatory diseases, and discusses the current scientific evidence on the repressive role of BRB on NLRP3 inflammasome pathways along with the possible mechanism(s) and their potential in counteracting various inflammatory diseases.

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The therapeutic use of the zonulin inhibitor AT-1001 (Larazotide) for a variety of acute and chronic inflammatory diseases

Current Medicinal Chemistry ◽

10.2174/0929867328666210104110053 ◽

2021 ◽

Vol 28 ◽

Author(s):

Jacopo Troisi ◽

Giorgia Venutolo ◽

Concetta Terracciano ◽

Matteo Delli Carri ◽

Simone Di Micco ◽

...

Keyword(s):

Therapeutic Strategy ◽

Inflammatory Diseases ◽

Endothelial Permeability ◽

Careful Examination ◽

Subsequent Increase ◽

Inflammatory Bowel

Background: The involvement of intercellular tight junctions and, in particular, the modulation of their competency by the zonulin pathway with a subsequent increase in epithelial and endothelial permeability, has been described in several chronic and acute inflammatory diseases. In this scenario, Larazotide, a zonulin antagonist, could be employed as a viable therapeutic strategy. Objective: The present review aims to describe recent research and current observations about zonulin involvement in several diseases and the use of its inhibitor Larazotide for their treatment. Methods: A systematic search was conducted on PubMed and Google Scholar, resulting in 209 publications obtained with the following search query: “Larazotide,” “Larazotide acetate,” “AT-1001,” “FZI/0” and “INN-202.” After careful examination, some publications were removed from consideration because they were either not in English or were not directly related to Larazotide. Results: The obtained publications were subdivided according to Larazotide’s mechanism of action and different diseases: celiac disease, type 1 diabetes, other autoimmune diseases, inflammatory bowel disease, Kawasaki disease, respiratory (infective and/or non-infective) diseases, and other. Conclusions: A substantial role of zonulin in many chronic and acute inflammatory diseases has been demonstrated in both in vivo and in vitro, indicating the possible efficacy of a Larazotide treatment. Moreover, new possible molecular targets for this molecule have also been demonstrated.

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Host-Microbe Interactions in Airway Disease: toward Disease Mechanisms and Novel Therapeutic Strategies

mSystems ◽

10.1128/msystems.00158-17 ◽

2018 ◽

Vol 3 (2) ◽

Cited By ~ 2

Author(s):

Emily K. Cope

Keyword(s):

Inflammatory Diseases ◽

Airway Disease ◽

Microbiota Composition ◽

Disease Mechanisms ◽

Airway Microbiome ◽

Host Microbe Interactions ◽

Novel Therapeutic Strategies

ABSTRACT Despite growing efforts to understand the role of the microbiota in airway disease, mechanisms that link microbial community dysbiosis to chronic inflammation remain elusive. Our laboratory is interested in how altered microbiota composition or function influences airway inflammatory diseases, including chronic rhinosinusitis, asthma, and cystic fibrosis. Given the tight interplay between host-associated microbes and host immunity, the potential for translational microbiome research to guide clinical decisions and novel therapeutics is becoming better appreciated. We hope to advance our understanding of the ecology of airway disease through integrating multiple omics assays and in vitro and in vivo experimental validation. An increased understanding of the role of the microbiota in chronic airway inflammation will ultimately lead to the rational development of therapeutics aimed at manipulation of microbiota composition or activity to treat these important and costly diseases. In this perspective, I discuss our current research investigating the microbiology and ecology of the airway microbiome.

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Gle1 Regulates RNA Binding of the DEAD-Box Helicase Ded1 in Its Complex Role in Translation Initiation

Molecular and Cellular Biology ◽

10.1128/mcb.00139-17 ◽

2017 ◽

Vol 37 (21) ◽

Cited By ~ 8

Author(s):

Peyman P. Aryanpur ◽

Chelsea A. Regan ◽

John M. Collins ◽

Telsa M. Mittelmeier ◽

David M. Renner ◽

...

Keyword(s):

Gene Expression ◽

Rna Binding ◽

Mrna Export ◽

Binding Assays ◽

Cellular Mechanisms ◽

Ribonucleoprotein Complexes ◽

Dead Box

ABSTRACT DEAD-box proteins (DBPs) are required in gene expression to facilitate changes to ribonucleoprotein complexes, but the cellular mechanisms and regulation of DBPs are not fully defined. Gle1 is a multifunctional regulator of DBPs with roles in mRNA export and translation. In translation, Gle1 modulates Ded1, a DBP required for initiation. However, DED1 overexpression causes defects, suggesting that Ded1 can promote or repress translation in different contexts. Here we show that GLE1 expression suppresses the repressive effects of DED1 in vivo and Gle1 counteracts Ded1 in translation assays in vitro. Furthermore, both Ded1 and Gle1 affect the assembly of preinitiation complexes. Through mutation analysis and binding assays, we show that Gle1 inhibits Ded1 by reducing its affinity for RNA. Our results are consistent with a model wherein active Ded1 promotes translation but inactive or excess Ded1 leads to translation repression. Gle1 can inhibit either role of Ded1, positioning it as a gatekeeper to optimize Ded1 activity to the appropriate level for translation. This study suggests a paradigm for finely controlling the activity of DEAD-box proteins to optimize their function in RNA-based processes. It also positions the versatile regulator Gle1 as a potential node for the coordination of different steps of gene expression.

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Functional Role of AKNA: A Scoping Review

Biomolecules ◽

10.3390/biom11111709 ◽

2021 ◽

Vol 11 (11) ◽

pp. 1709

Author(s):

Abrahán Ramírez-González ◽

Joaquín Manzo-Merino ◽

Carla Olbia Contreras-Ochoa ◽

Margarita Bahena-Román ◽

José Manasés Aguilar-Villaseñor ◽

...

Keyword(s):

Immune System ◽

Scoping Review ◽

Functional Role ◽

Inflammatory Diseases ◽

Data Extraction ◽

Negative Regulator ◽

Cellular Processes

Human akna encodes an AT-hook transcription factor whose expression participates in various cellular processes. We conducted a scoping review on the literature regarding the functional role of AKNA according to the evidence found in human and in vivo and in vitro models, stringently following the “PRISMA-ScR” statement recommendations. Methods: We undertook an independent PubMed literature search using the following search terms, AKNA OR AKNA ADJ gene OR AKNA protein, human OR AKNA ADJ functions. Observational and experimental articles were considered. The selected studies were categorized using a pre-determined data extraction form. A narrative summary of the evidence was produced. Results: AKNA modulates the expression of CD40 and CD40L genes in immune system cells. It is a negative regulator of inflammatory processes as evidenced by knockout mouse models and observational studies for several autoimmune and inflammatory diseases. Furthermore, AKNA contributes to the de-regulation of the immune system in cancer, and it has been proposed as a susceptibility genetic factor and biomarker in CC, GC, and HNSCC. Finally, AKNA regulates neurogenesis by destabilizing the microtubules dynamics. Conclusion: Our results provide evidence for the role of AKNA in various cellular processes, including immune response, inflammation, development, cancer, autoimmunity, and neurogenesis.

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