Inflammation-mediated Diseases Research Articles

POLYMERIC NANOPARTICLES BASED TOPICAL DELIVERY SYSTEMS IN PSORIASIS

Psoriasis is a common inflammatory skin disease with an incompletely understood etiology. The disease is characterized by red, scaly and well-demarcated skin lesions. It is an immune – mediated chronic inflammatory skin disease affecting approximately 2-3% of worldwide population. Psoriasis has a negative impact on the patient’s health and quality of life and affects the quality of family members. Skin and joints affecting around 0.5-1% of children and 2-3% of adults. It can occur at any age, although the majority of cases develop before the age of 40 year and it is common in Children. Psoriasis is a chronic inflammatory disease, predominantly affecting the skin included in the group of immune mediated inflammatory disease and several systemic condition like metabolic syndrome, cardiovascular disease, diabetes, Arthritis, obesity, hypertension, Cancer are prevalent in psoriasis patients. This review offers inside into management of psoriasis and pharmaceutical approach for treatment for this disease. The review deals in details about topical drug delivery, phototherapy and biological against psoriasis. Review provides a detailed summary of the pathophysiology, epidemiology, of psoriasis. This review also summarizes different technology of nanotechnology methods of preparations.[26] Keywords: Psoriasis, skin disorder, inflammation, therapies for disease, Nanotechnology therapies.

Characteristics of our hypoxemic COVID-19 pneumonia patients receiving corticosteroids and mortality-associated factors

ABSTRACT Background COVID-19 is a disease associated with diffuse lung injury that has no proven effective treatment yet. It is thought that glucocorticoids may reduce inflammation-mediated lung injury, disease progression, and mortality. We aimed to evaluate our patient’s characteristics and treatment outcomes who received corticosteroids for COVID-19 pneumonia. Methods We conducted a multicenter retrospective study and reviewed 517 patients admitted due to COVID-19 pneumonia who were hypoxemic and administered steroids regarding demographic, laboratory, and radiological characteristics, treatment response, and mortality-associated factors. Results Of our 517 patients with COVID-19 pneumonia who were hypoxemic and received corticosteroids, the mortality rate was 24.4% (n = 126). The evaluation of mortality-associated factors revealed that age, comorbidities, a CURB-65 score of ≥ 2, higher SOFA scores, presence of MAS, high doses of steroids, type of steroids, COVID-19 treatment, stay in the intensive care unit, high levels of d-dimer, CRP, ferritin, and troponin, and renal dysfunction were associated with mortality. Conclusion Due to high starting and average steroid doses are more associated with mortality, high-dose steroid administration should be avoided. We believe that knowing the factors associated with mortality in these cases is essential for close follow-up. The use of CURB-65 and SOFA scores can predict prognosis in COVID-19 pneumonia.

Gasdermins: New Therapeutic Targets in Host Defense, Inflammatory Diseases, and Cancer.

Gasdermins (GSDMs) are a class of pore-forming proteins related to pyroptosis, a programmed cell death pathway that is induced by a range of inflammatory stimuli. Small-scale GSDM activation and pore formation allow the passive release of cytokines, such as IL-1β and IL-18, and alarmins, but, whenever numerous GSDM pores are assembled, osmotic lysis and cell death occur. Such GSDM-mediated pyroptosis promotes pathogen clearance and can help restore homeostasis, but recent studies have revealed that dysregulated pyroptosis is at the root of many inflammation-mediated disease conditions. Moreover, new homeostatic functions for gasdermins are beginning to be revealed. Here, we review the newly discovered mechanisms of GSDM activation and their prominent roles in host defense and human diseases associated with chronic inflammation. We also highlight the potential of targeting GSDMs as a new therapeutic approach to combat chronic inflammatory diseases and cancer and how we might overcome the current obstacles to realize this potential.

Inhibitory Effects of Myrrha Water Extract on Atopic Dermatitis Related Chemokines in HaCaT Cells

Due to high therapeutic potentials of natural products, the use of medicinal plants is highlighted to treat the various inflammationmediated diseases. Myrrha have been used as a traditional remedy to treat infectious and inflammatory diseases. But, its effects and mechanisms of anti atopic dermatitis (AD) have not been elucidated. The aim of this study is to evaluate anti-allergic and antiinflammatory effects of the water extract of Myrrha, in cell models and also to suggest a putative mechanism of AD actions of Myrrha. HaCaT cells were pre-treated with Myrrha for 1 h and stimulated with tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN- γ) (10 ng/mL each). After 24 h, cells were harvested To evaluate the expression of Th2 chemokines, such as C-C motif chemokine ligand 5 (CCL5, also known as RANTES), C-C chemokine ligand 17 (CCL17, also known as TARC) and C-C chemokine ligand 22 (CCL22, also known as MDC). To investigate the regulatory mechanisms of Myrrha, we also assessed the phosphorylation of signal transducer and activator of transcription 1 (STAT1) signaling pathways in HaCaT cells. Treatment of Myrrha decreased the mRNA levels of RANTES, TARC and MDC with a concentration dependent manner. In addition, Myrrha significantly reduced TNF-α and IFN-γ induced phosphorylation of STAT1. This could indicate that the Myrrha shows anti AD activity mainly through STAT1. Thus, we propose that Myrrha may be a promising anti AD skin protector, which could suggest the clinical basis for cosmetics development.

EE294 Burden of Behavioral Health Conditions Among Individuals with Vitiligo in an Insured US Population

Vitiligo is an inflammation-mediated chronic autoimmune disease characterized by the destruction of melanocytes, resulting in pale or white patches of skin. Individuals with vitiligo often experience substantial psychosocial burden. Here we describe behavioral health burden in individuals with vitiligo in the United States.

Bioscreening and pre-clinical evaluation of the impact of bioactive molecules from Ptychotis verticillata on the multilineage potential of mesenchymal stromal cells towards immune- and inflammation-mediated diseases.

Mesenchymal stromal cells (MSCs) are currently used in cell reparative medicine due to their trophic and ant-inflammatory properties. The modulation of stem cell properties by phytochemicals has been suggested as a tool to empower their tissue repair capacity. In vitro, MSCs are characterized by their tri-lineage potential that holds great interest for tissue regeneration. Ptychotis Verticillata (PV), an aromatic and medicinal plant, may be thus used to modulate the in vitro multilineage potential of MSCs. We screened the impact of PV-derived essential oil and their bioactive molecules (thymol and carvacrol) on the in vitro multilineage potential of MSCs. Different concentrations and incubation times of these compounds were assessed during the osteogenesis and adipogenesis of MSCs. The analysis of 75 conditions indicates that these compounds are biologically active by promoting two major differentiation lineages from MSCs. In a time- and dose-dependent manner, thymol and carvacrol increased the osteogenesis and adipogenesis. According to these preliminary observations, the addition of PV extract may stimulate the tissue regenerative and repair functions of MSCs. Further optimization of compound extraction and characterization from PV as well as cell treatment conditions should increase their therapeutic value in combination with MSCs.

Vitamin D: A Potential Mitigation Tool for the Endemic Stage of the COVID-19 Pandemic?

The impact of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and associated development of clinical symptoms of COVID-19 have presented an enormous global impact on our health care systems, public health and economy. To date several observational epidemiological studies consistently found that vitamin D deficiency, measured as low levels of circulating 25-hydroxyvitamin D, is associated with cardiovascular diseases, diabetes, certain cancers, autoimmune diseases and many infectious diseases, including acute respiratory infections. Since vitamin D is not merely immunosuppressive but also acts as an immunomodulator in tolerance and homeostasis, many experts have considered a role of vitamin D in the prevalence and severity of immune mediated inflammatory diseases, such as SARS-CoV-2, adding to the evidence of the importance of vitamin D in the immune response against viral respiratory infections and reinforcing the need for targeted vitamin D supplementation, with a focus on high-risk populations and a high-dose supplementation treatment for COVID-19 hospitalized patients. The expected transition to endemicity of SARS-CoV-2 even further corroborates as a potential of vitamin D as an potential mitigation tool for the prevention of COVID-19. The aim of this paper is to analyse the current evidence regarding vitamin D and present a hypothesis of its potential role in the current COVID-19 pandemic and in the future as a potential preventive measurement in public health.

Investigating the NLRP3 inflammasome and its regulator miR-223-3p in multiple sclerosis and experimental demyelination.

Innate immune signaling pathways are essential mediators of inflammation and repair following myelin injury. Inflammasome activation has recently been implicated as a driver of myelin injury in multiple sclerosis (MS) and its animal models, although the regulation and contributions of inflammasome activation in the demyelinated central nervous system (CNS) are not completely understood. Herein, we investigated the NLRP3 (NBD-, LRR- and pyrin domain-containing protein 3) inflammasome and its endogenous regulator microRNA-223-3p within the demyelinated CNS in both MS and an animal model of focal demyelination. We observed that NLRP3 inflammasome components and microRNA-223-3p were upregulated at sites of myelin injury within activated macrophages and microglia. Both microRNA-223-3p and a small-molecule NLRP3 inhibitor, MCC950, suppressed inflammasome activation in macrophages and microglia in vitro; compared with microglia, macrophages were more prone to inflammasome activation in vitro. Finally, systemic delivery of MCC950 to mice following lysolecithin-induced demyelination resulted in a significant reduction in axonal injury within demyelinated lesions. In conclusion, we demonstrate that NLRP3 inflammasome activity by macrophages and microglia is a critical component of the inflammatory microenvironment following demyelination and represents a potential therapeutic target for inflammatory-mediated demyelinating diseases, including MS. Cover Image for this issue: https://doi.org/10.1111/jnc.15422.

The mitochondrial associated endoplasmic reticulum membranes: A platform for the pathogenesis of inflammation-mediated metabolic diseases.

Mitochondria‐associated endoplasmic reticulum membranes (MAM) are specialized subcellular compartments that are shaped by endoplasmic reticulum (ER) subdomains placed side by side to the outer membrane of mitochondria (OMM) being connected by tethering proteins in mammalian cells. Studies showed that MAM has multiple physiological functions. These include regulation of lipid synthesis and transport, Ca2+ transport and signaling, mitochondrial dynamics, apoptosis, autophagy, and formation and activation of an inflammasome. However, alterations of MAM integrity lead to deleterious effects due to an increased generation of mitochondrial reactive oxygen species (ROS) via increased Ca2+ transfer from the ER to mitochondria. This, in turn, causes mitochondrial damage and release of mitochondrial components into the cytosol as damage‐associated molecular patterns which rapidly activate MAM‐resident Nod‐like receptor protein‐3 (NLRP3) inflammasome components. This complex induces the release of pro‐inflammatory cytokines that initiate low‐grade chronic inflammation that subsequently causes the development of metabolic diseases. But, the mechanisms of how MAM is involved in the pathogenesis of these diseases are not exhaustively reviewed. Therefore, this review was aimed to highlight the contribution of MAM to a variety of cellular functions and consider its significance pertaining to the pathogenesis of inflammation‐mediated metabolic diseases.

Diode laser – A cure for obstinate oral lichen planus: A case series and review of the literature

Oral lichen planus (OLP) is a chronic T-cell mediated inflammatory disease of unknown etiology. Hence, no gold standard treatment modalities are available. Due to therapeutic challenges offered by conventional therapy, there is a need for effective alternate treatment with minimal side effects. The development of lasers has brought light to the treatment of obstinate OLP. Three cases of male patients in the age group 30–40 years complaining of a burning sensation in the mouth have been mentioned. Clinical and histopathological investigations showed typical findings of OLP. The treatment was started with conventional therapy of corticosteroids. The symptoms were assessed on the visual analog scale (VAS) and showed marked reduction but without complete alleviation. Hence, ablation of the lesion using a 980 nm soft-tissue diode laser was planned. The outcome of the treatment was successful, VAS 0, and no recurrence occurred in 11 months follow-up. The results of a 980 nm diode laser for the treatment of OLP are satisfactory and should be considered as a treatment alternative to conventional remedies.

Comorbidity in Adult Psoriasis: Considerations for the Clinician.

Psoriasis is associated with several comorbidities ranging from cardiovascular comorbidity and mental disorders to other immune mediated inflammatory diseases. However, most of these co-morbidities are often overlooked or diagnosed late. Furthermore, evidence suggests that comorbidities are undertreated. Here, we provide an overview of comorbidities in psoriasis and present a simple rundown of considerations of relevance to the clinician. We hope that this review may raise clinicians’ awareness of comorbidities in psoriasis and provide simple guidance regarding screening tools and treatment decisions in psoriasis with comorbidities.

LncRNA-Dependent Mechanisms of Transforming Growth Factor-β: From Tissue Fibrosis to Cancer Progression.

Transforming growth factor-β (TGF-β) is a crucial pathogenic mediator of inflammatory diseases. In tissue fibrosis, TGF-β regulates the pathogenic activity of infiltrated immunocytes and promotes extracellular matrix production via de novo myofibroblast generation and kidney cell activation. In cancer, TGF-β promotes cancer invasion and metastasis by enhancing the stemness and epithelial mesenchymal transition of cancer cells. However, TGF-β is highly pleiotropic in both tissue fibrosis and cancers, and thus, direct targeting of TGF-β may also block its protective anti-inflammatory and tumor-suppressive effects, resulting in undesirable outcomes. Increasing evidence suggests the involvement of long non-coding RNAs (lncRNAs) in TGF-β-driven tissue fibrosis and cancer progression with a high cell-type and disease specificity, serving as an ideal target for therapeutic development. In this review, the mechanism and translational potential of TGF-β-associated lncRNAs in tissue fibrosis and cancer will be discussed.

Recommendations of diagnosis and treatment of relapsing polychondritis in China

Relapsing polychondritis is an immune mediated systemic inflammatory disease, involving the cartilaginous and proteoglycan rich structures. The characteristic manifestations were inflammation and deformity of ear and nasal cartilage. Here, Chinese Rheumatology Association summarized manifestations, diagnosis and disease activity index evaluation of relapsing polychondritis, standardized treatment regimens, to improve disease prognosis.

Chitosan-Coated Solid Lipid Nano-Encapsulation Improves the Therapeutic Antiairway Inflammation Effect of Berberine against COPD in Cigarette Smoke-Exposed Rats.

Berberine (Ber) is an isoquinoline alkaloid that has shown therapeutic potential in mice with chronic obstructive pulmonary disease (COPD). However, the therapeutic efficiency of Ber is restricted by its low aqueous solubility and bioavailability. Chitosan and solid lipid nanoparticles (SLNs) have demonstrated great abilities as delivery systems in enhancing the bioavailability of therapeutic compounds. The present study aimed to get together the biological features of SLNs with the advantages of chitosan to formulate an efficient nano-carrier platform for the oral delivery of Ber and evaluate the therapeutic effect of the prepared Ber-encapsulated nanoparticles on airway inflammation in cigarette smoke (CS)-induced COPD rats. The Ber-encapsulated SLE-chitosan formulation was manufactured using a modified solvent-injection method followed by a homogenization process. Physicochemical properties, encapsulation efficiency, in vitro stability and Ber release, and pharmacokinetics of the manufactured formulation were evaluated. The COPD rat model was developed by exposing animals to CS. To study the therapeutic efficiency of Ber-encapsulated SLE-chitosan nanoparticles and pure berberine, the histopathological changes of the lung tissues, levels of inflammatory cells and cytokines, and activities of myeloperoxidase (MPO) and superoxide dismutase (SOD) enzymes were evaluated in bronchoalveolar lavage fluid (BALF). Ber-encapsulated SLE-chitosan showed the particle size in nano-range with high stability and controlled slow-release profile in vitro in simulated gastric (pH 1.5) and intestinal (pH 6.8) fluids. Administration of Ber-loaded SLE-chitosan nanoparticles could significantly ameliorate inflammation scores in lung tissues and reduce levels of inflammatory cells (neutrophils and macrophages) and inflammatory cytokines (IL-1β, Il-6, Il-17, and TNFα) in BALF when compared with the pure Ber. SLE-chitosan-based nanoparticles can strongly improve the therapeutic anti-inflammatory impact of Ber against CS-induced airway inflammation in COPD rats, suggesting the promising application of Ber-encapsulated SLN-chitosan nanoparticles for treating COPD and other inflammation-mediated diseases.

Microarray analysis of autoantibodies can identify future Systemic Lupus Erythematosus patients

ObjectiveReliable early ascertainment in patients with SLE is important to prevent the accumulation of irreversible organ damage. Autoantibodies are often present in the serum of patients before the first symptoms arise, therefore they are of potential use as early diagnostic tools. MethodsWe used a custom-made antibody microarray containing 57 autoantigens to analyze serum samples of 1519 patients previously tested for anti-dsDNA and 361 samples of self-reported healthy blood bank donors (BBD). The 1519 patients included 483 patients with SLE, 346 patients with other immune mediated inflammatory diseases (IMID), 218 patient controls without relevant clinical symptoms (Non-IMID), and 472 patients that did not fit in any of the previous groups (Rest). The Non-IMID and BBD groups were used individually to create multivariable prediction models to distinguish samples of patients with SLE from these control groups. We subsequently used these models to predict the outcome for samples of patients who developed SLE while in follow-up (pre-SLE). ResultsOut of 1036 patients with no diagnosis of SLE at the moment of sample collection, 17 patients developed SLE while in follow-up (mean time to diagnosis 7.2 months). The best performing model (AUC 0.83) identified 9 out of 17 (53%) pre-SLE samples as SLE, with a specificity of 94%. ConclusionSerum samples of patients who will develop SLE in the future already show a shift of the autoantibody profile prior to diagnosis. In this study, we show that these autoantibody profiles can be used to identify these future SLE patients.

Progress in Assays of HMGB1 Levels in Human Plasma-The Potential Prognostic Value in COVID-19.

Extracellular HMGB1 protein is known to induce inflammatory responses leading to an inflammatory storm. The outbreak of the Severe Acute Respiratory Syndrome COVID-19 due to the SARS-CoV-2 virus has resulted in a huge health concern worldwide. Recent data revealed that plasma/serum HMGB1 levels of patients suffering from inflammation-mediated disorders—such as COVID-19, cancer, and autoimmune disorders—correlate positively with disease severity and vice versa. A late release of HMGB1 in sepsis suggests the existence of a wide therapeutic window for treating sepsis. Rapid and accurate methods for the detection of HMGB1 levels in plasma/serum are, therefore, of great importance for monitoring the occurrence, treatment success, and survival prediction of patients with inflammation-mediated diseases. In this review, we briefly explain the role of HMGB1 in the cell, and particularly the involvement of extracellular HMGB1 (released from the cells) in inflammation-mediated diseases, with an emphasis on COVID-19. The current assays to measure HMGB1 levels in human plasma—Western blotting, ELISA, EMSA, and a new approach based on electrochemical immunosensors, including some of our preliminary results—are presented and thoroughly discussed.

Adiponectin, May Be a Potential Protective Factor for Obesity-Related Osteoarthritis.

Osteoarthritis (OA) is the most common joint disease in elderly individuals and seriously affects quality of life. OA has often been thought to be caused by body weight load, but studies have increasingly shown that OA is an inflammation-mediated metabolic disease. The current existing evidence suggests that OA is associated with obesity-related chronic inflammation as well as abnormal lipid metabolism in obesity, such as fatty acids (FA) and triglycerides. Adiponectin, a cytokine secreted by adipose tissue, can affect the progression of OA by regulating obesity-related inflammatory factors. However, the specific molecular mechanism has not been fully elucidated. According to previous research, adiponectin can promote the metabolism of FA and triglycerides, which indicates that it is a potential protective factor for OA through many mechanisms. This article aims to review the mechanisms of chronic inflammation, FA and triglycerides in OA, as well as the potential mechanisms of adiponectin in regulating chronic inflammation and promoting FA and triglyceride metabolism. Therefore, adiponectin may have a protective effect on obesity-related OA, which could provide new insight into adiponectin and the related mechanisms in OA.

Synthesis, characterization and antimicrobial activity of selenium nanoparticles with Clitoria ternatea on oral pathogens

Background: Selenium nanoparticles have been studied for possible therapeutic effects in a variety of oxidative stress and inflammation-mediated diseases such as arthritis, cancer, diabetes, nephropathy, as well as antimicrobial properties. Clitoria ternatea is a perennial herbaceous plant which has been documented for its antimicrobial properties that are beneficial to human health. Therefore, this study was designed to synthesize, characterize and investigate the synergistic antimicrobial activity of selenium nanoparticles with Clitoria ternatea on oral pathogens. Materials and method: Green synthesis of selenium nanoparticles was achieved by a simple biological procedure using the reducing power of Clitoria ternatea flower extract. The synthesized nanoparticles were characterized using UV-vis-spectroscopy and Transmission Electron Microscopy. The antimicrobial activity was assessed using agar well diffusion method against strains of S.aureus, S.mutans, E.faecalis and C.albicans. Results: The synthesised nanoparticles showed potential antimicrobial activity against strains of gram positive bacteria especially against S.aureus where 35 mm of inhibitory activity was observed. They also showed enhanced antifungal property as compared to the control.

Component-Resolved Diagnosis for Endotyping Patients with Chronic Rhinosinusitis with Nasal Polyps

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a predominantly type 2 inflammation-mediated disease of the nasal mucosa and paranasal sinuses that often coexists with asthma. The role of atopy in the development and severity of CRSwNP is still a controversial issue. Objective: The aim of our study was to propose a systematic allergy workup to identify atopic patients in the context of CRSwNP and to characterize their allergen sensitization profile (sources/molecules). Methods: Patients with a diagnosis of CRSwNP (n = 97) were studied in the otorhinolaryngologist and allergy settings. Demographic and clinical data were collected for each patient. Different allergen sensitization profiles (sources/molecules) were evaluated in atopic CRSwNP patients by using component-resolved diagnosis (CRD). Results: In our cohort of patients, the CRSwNP was frequently diagnosed during adulthood with significant impact on health-related quality of life. Asthma and atopy were the most common comorbidities with a prevalence of asthma in the atopic group. In CRSwNP patients sensitized to grass pollens and/or to house dust mites, the CRD analysis revealed a prevalence of sensitization to species-specific allergens of Phleum pratense (Phl p1, Phl p2, and Phl p5) or Dermatophagoides pteronyssinus (Der p1 and Der p2) rather than to cross-reactive ones. Conclusion: To define the allergen sensitization profile in atopic CRSwNP patients by CRD, it may be useful to better characterize type 2 inflammation, thus providing a personalized endotype-driven treatment.

What's Race Got to Do With It? CRP Levels in Immune Mediated Skin Diseases: Considerations for Hidradenitis Suppurativa.

Currently, there is a lack of racial/ethnic heterogeneity in research databases, exposing a systematic issue in studies exploring inflammation-mediated diseases, such as hidradenitis suppurativa (HS). HS is a chronic inflammatory skin condition that disrupts normal structure and functioning of terminal hair follicles, resulting in the formation of recurrent abscesses, nodules, and sinus tracts within intertriginous regions. Studies have described higher serum levels of inflammation-mediated C-reactive protein (CRP) in patients with HS, a disease that predominantly affects skin of color (SOC) populations. Herein, we explore the role of CRP levels in the context of HS disease presentation, management, and psychosocial implications in SOC patients to determine existing disparities in research studies.