Therapy Of Inflammatory Diseases Research Articles

Advancing inflammatory skin disease therapy: Sustained tofacitinib release via electrospun fiber dressings

Inflammatory skin diseases are typically managed with semi-solid formulations such as creams and ointments. These treatments often fail to remain on the skin for long, as they can be easily wiped off by clothing, necessitating frequent reapplication throughout the day and resulting in poor patient adherence. Therefore, this study sought to fabricate an electrospun dressing as an alternative dosage form that provides a sustained release of the anti-inflammatory agent tofacitinib over three days. In this study, three types of electrospun fiber dressings – uniaxial, coaxial, and layer-by-layer – were produced and examined for their morphological, mechanical, and release characteristics. In addition to a comprehensive characterization, another objective was to analyze the drug permeation behavior from these fiber dressings on porcine skin, comparing their performance to that of a tofacitinib cream. The layer-by-layer system notably exhibited a delayed drug release, while the uniaxial and coaxial systems demonstrated an initial burst release. However, the permeation studies revealed no significant differences between these systems, underscoring the necessity of conducting such studies – a crucial aspect often overlooked in research on electrospun fiber dressings. Overall, this study highlights the potential of electrospun, drug-loaded dressings for the treatment of inflammatory skin diseases.

The Impact of the CB2 Cannabinoid Receptor in Inflammatory Diseases: An Update.

The emergence of inflammatory diseases is a heavy burden on modern societies. Cannabis has been used for several millennia to treat inflammatory disorders such as rheumatism or gout. Since the characterization of cannabinoid receptors, CB1 and CB2, the potential of cannabinoid pharmacotherapy in inflammatory conditions has received great interest. Several studies have identified the importance of these receptors in immune cell migration and in the production of inflammatory mediators. As the presence of the CB2 receptor was documented to be more predominant in immune cells, several pharmacological agonists and antagonists have been designed to treat inflammation. To better define the potential of the CB2 receptor, three online databases, PubMed, Google Scholar and clinicaltrial.gov, were searched without language restriction. The full texts of articles presenting data on the endocannabinoid system, the CB2 receptor and its role in modulating inflammation in vitro, in animal models and in the context of clinical trials were reviewed. Finally, we discuss the clinical potential of the latest cannabinoid-based therapies in inflammatory diseases.

Macrophages: Balancing Inflammation and Homeostasis in Health and Disease

Abstract: Inflammation is crucial for maintaining tissue homeostasis and responding to insults, yet dysregulated inflammation can lead to various diseases. Macrophages, central to the immune system, play key roles in initiating, regulating, and resolving inflammation. This review provides an overview of macrophage functions, including activation mechanisms, recruitment to inflamed tissues, interactions with other immune cells and mediators, and their roles in phagocytosis, clearance of apoptotic cells and debris, and secretion of anti-inflammatory cytokines. Additionally, it discusses macrophage-induced regulatory T-cell formation, the impact of pro-inflammatory and anti-inflammatory cytokines on macrophage behavior, and the influence of microbial products and pathogen-associated molecular patterns (PAMPs) on macrophage function. The review also identifies targeting macrophages as a promising strategy for managing inflammatory diseases while acknowledging challenges such as macrophage heterogeneity, limitations of in vitro models, and incomplete understanding of regulatory mechanisms. Finally, it suggests areas for further research, including identifying specific macrophage subsets, understanding macrophage plasticity, exploring resolution signaling pathways, and investigating the role of metabolism and microenvironmental cues in macrophage function, aiming to pave the way for more effective macrophage-targeted therapies in inflammatory diseases.

Agonistic anti-DCIR antibody inhibits ITAM-mediated inflammatory signaling and promotes immune resolution.

DC inhibitory receptor (DCIR) is a C-type lectin receptor selectively expressed on myeloid cells, including monocytes, macrophages, DCs, and neutrophils. Its role in immune regulation has been implicated in murine models and human genome-wide association studies, suggesting defective DCIR function associates with increased susceptibility to autoimmune diseases such as rheumatoid arthritis, lupus, and Sjögren's syndrome. However, little is known about the mechanisms underlying DCIR activation to dampen inflammation. Here, we developed anti-DCIR agonistic antibodies that promote phosphorylation on DCIR's immunoreceptor tyrosine-based inhibitory motifs and recruitment of SH2 containing protein tyrosine phosphatase-2 for reducing inflammation. We also explored the inflammation resolution by depleting DCIR+ cells with antibodies. Utilizing a human DCIR-knock-in mouse model, we validated the antiinflammatory properties of the agonistic anti-DCIR antibody in experimental peritonitis and colitis. These findings provide critical evidence for targeting DCIR to develop transformative therapies for inflammatory diseases.

Symptomatic therapy for acute infectious and inflammatory diseases of the pharynx

Symptomatic therapy for acute infectious and inflammatory diseases of the pharynx

Low Intensity Renal Ultrasound Exposure Reduces Systemic Inflammation Induced by LPS Challenge in Mice

Low-intensity pulsed ultrasound (LIPUS), a procedure historically used to stimulate bone healing and tissue repair, activates the splenic cholinergic anti-inflammatory pathway and ultimately reduces circulating and tissue-specific pro-inflammatory cytokine release if applied to the kidney prior to renal ischemia/reperfusion injury. We questioned whether LIPUS would be effective in reducing the inflammatory response to lipopolysaccharide (LPS) if exposure occurred as pre- or post-treatment. We hypothesized that LIPUS exposure before an LPS challenge would suppress the subsequent inflammatory response in mice, and that LIPUS exposure after an LPS challenge would be similarly beneficial. Female C57BL/6J mice were randomized into Saline, LPS, LPS/Pre-treatment and LPS/Post-treatment groups at 15 weeks of age. Pre-treated mice were subjected to 20-minute LIPUS exposure while under anesthesia for five consecutive days. On the 6th day, mice were injected with LPS (1 mg/kg dissolved in saline, IP) or saline (100 μL). One hour after LPS injection, post-treated mice were exposed to LIPUS for 20 min. Three hours after LPS or saline injection, all mice were humanely euthanized, and plasma, spleen and kidney were harvested for analysis of proinflammatory cytokines associated with the response to LPS. LPS significantly increased plasma TNF-α (280±37 vs. 0.07±0.00 pg/mL), plasma IL-6 (96124±6688 vs. 425±181 pg/mL), splenic IL-6 (0.77±0.16 vs. 0.17±0.04 pg/μg of protein), and renal cortical IL-6 (0.50±0.07 vs. 0.01±0.00 pg/μg of protein) compared to saline-treated mice (all p<0.05). LIPUS pre-treatment significantly reduced plasma TNF-α (183±15 pg/mL) and plasma IL-6 (63656±8441 pg/mL), without altering splenic and renal cytokines in LPS-treated mice. LIPUS post-treatment lowered plasma IL-6 (47432 ± 1182 pg/mL). In conclusion, five days of LIPUS exposure prior to an LPS challenge effectively reduced circulating inflammatory mediators, while a single LIPUS exposure after an LPS challenge also successfully reduced systemic IL-6. These findings demonstrate the potential in using LIPUS as a therapeutic strategy for quelling acute inflammatory responses and warrant further investigation of its use as a therapy for chronic inflammatory diseases. Studies funded by Department of Defense (LR210096) for KWM. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Interleukin 17 as a central component of the pathogenesis of pain associated with immunoinflammatory process: A new “target” of pharmacotherapy

Modern pathogenetic therapy of inflammatory rheumatic diseases (IRD) is aimed not only at reducing disease activity (although achieving remission and low disease activity remains the main goal of treatment), but also at eliminating as quickly and completely as possible the main symptoms that cause a decrease in the quality of life of patients. Particular importance is attached to effective control of chronic pain – the main and most distressing manifestation of IRD. To solve this problem, the pathogenesis of chronic pain in IRD continues to be actively studied, aimed at finding new ”targets” of pharmacotherapy. Thus, the role of central sensitization (CS) and comorbid fibromyalgia in the formation of clinical manifestations of IRD is now clearly proven. Signs of CS, depending on the instrument of its detection, are determined in 20–40% of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (AxSpA).Interleukin (IL) 17 plays a fundamental role in the development of chronic pain in IIRD. This cytokine takes a leading position in the development of the ”cytokine cascade”, inducing the synthesis of various cytokines and chemokines, as well as chemotaxis and activation of neutrophils and T cells. Induction of synthesis of inflammatory mediators (including prostaglandin E2) determines the role of IL-17 in activation of nociceptors and their sensitization. IL-17 also takes an active part in neuroimmune interactions by activating glia cells and affecting receptors present on the membrane of neurons of the posterior horns of the spinal cord. This defines the role of IL-17 as one of the inductors of CS development. Pharmacologic blockade of IL-17 is a known pathway to suppress the activity of IIRPs such as PsA and AxSpA. However, this mechanism also allows for significant effects on chronic pain. In particular, the IL-17 inhibitor ixekizumab has shown high analgesic potential in a series of studies in PsA and AxSpA (SPIRIT-P1 and SPIRIT-P2, COAST V and COAST W). It is important to note that this drug demonstrated a very rapid analgesic effect: pain intensity was significantly reduced already 7 days after the first injection. These data suggest a specific effect of ixekizumab on the nociceptive system, independent of the anti-inflammatory effect. This fact allows us to consider ixekizumab as a drug of choice for the treatment of patients with PsA and AxSpA who experience severe pain and have signs of CS and fibromyalgia.

Rapid Selenoprotein Activation by Selenium Nanoparticles to Suppresses Osteoclastogenesis and Pathological Bone Loss.

Osteoclast hyperactivation stands as a significant pathological factor contributing to the emergence of bone disorders driven by heightened oxidative stress levels. The modulation of the redox balance to scavenge reactive oxygen species (ROS) emerges as a viable approach in addressing this concern. Selenoproteins, characterized by selenocysteine (SeCys2) as the active center, are crucial for selenium-based antioxidative stress therapy for inflammatory diseases. This study reveals that surface-active elemental selenium (Se) nanoparticles, particularly those derived from lentinan (LNT-Se), exhibit enhanced cellular accumulation and accelerated metabolism to SeCys2, the primary active Se form in biological systems. Consequently, LNT-Se demonstrates significant inhibition of RANKL-induced osteoclastogenesis and osteoclastic activity when compared to alternative Se species. Furthermore, in vivo studies underscore the superior therapeutic efficacy of LNT-Se over SeCys2, potentially attributable to the enhanced stability and safety profile of LNT-Se. Specifically, LNT-Se effectively modulates the expression of the selenoprotein GPx1, thereby exerting regulatory control over macrophage polarization, osteoclast activity inhibition, and the prevention of CIA/OVX-induced osteolysis. In summary, these results suggest that the prompt activation of selenoproteins by Se nanoparticles serves to suppress osteoclastogenesis and pathological bone loss by upregulating GPx1 to re-polarize macrophages. Moreover, the utilization of bioactive Se species presents a promising avenue for effectively managing bone disorders, with considerable potential for clinical translation. This article is protected by copyright. All rights reserved.

Recommendations for topical antimicrobial therapy of inflammatory diseases of the middle ear based on the results of evidence-based clinical study

Introduction. In conditions of widespread resistance of pathogens to traditional antimicrobial drugs, active attention is paid to the development of topical antimicrobial drugs for the effective treatment of inflammatory pathology of the middle ear.Aim. To study the efficacy and safety of a new dosage form of the drug Dioxydin® (2.5 mg/ml ear drops) in the treatment of patients with acute purulent otitis media and exacerbation of chronic purulent otitis media in comparison with ear drops containing 0.3% ciprofloxacin solution.Materials and methods. A multicenter randomized comparative clinical trial included adults with acute purulent otitis media or exacerbation of chronic purulent otitis media and during 6 face-to-face visits (days 1st, 3rd, 6th, 9th, as well as a therapy completion visit and a follow-up visit), the effect of drugs was evaluated according to examination, otoscopy, microbiological and audiometric examinations. Safety was assessed by the frequency of adverse events and the results of blood, urine tests and vital signs.Results. The achievement of the primary criteria was evaluated among 164 participants randomized into 2 groups: the proportion of patients with no indications for systemic antibacterial therapy at Visit 2 and with no ear pain at Visit 4, Dioxydin® ear drops had no less effectiveness than the comparison drug (64.6 and 89.9% versus 68.3 and 87.3%, respectively). In terms of the frequency of elimination of the pathogen and improvement of air conduction, the compared drugs also had no statistically significant differences, and according to some secondary criteria, Dioxydin® significantly exceeded 0.3% ciprofloxacin solution (the proportion of patients with a pronounced decrease in pain and congestion in the ear, as well as hyperemia of the eardrum). According to the safety criteria, the compared drugs had no significant differences.Conclusions. The results of the study confirmed the high efficacy and safety of Dioxydin® ear drops in the treatment of otitis media in adults.

Nanoparticle-Mediated Multiple Modulation of Bone Microenvironment To Tackle Osteoarthritis.

Development of nanomedicines that can collaboratively scavenge reactive oxygen species (ROS) and inhibit inflammatory cytokines, along with osteogenesis promotion, is essential for efficient osteoarthritis (OA) treatment. Herein, we report the design of a ROS-responsive nanomedicine formulation based on fibronectin (FN)-coated polymer nanoparticles (NPs) loaded with azabisdimethylphoaphonate-terminated phosphorus dendrimers (G4-TBP). The constructed G4-TBP NPs-FN with a size of 268 nm are stable under physiological conditions, can be specifically taken up by macrophages through the FN-mediated targeting, and can be dissociated in the oxidative inflammatory microenvironment. The G4-TBP NPs-FN loaded with G4-TBP dendrimer having intrinsic anti-inflammatory property and FN having both anti-inflammatory and antioxidative properties display integrated functions of ROS scavenging, hypoxia attenuation, and macrophage M2 polarization, thus protecting macrophages from apoptosis and creating designed bone immune microenvironment for stem cell osteogenic differentiation. These characteristics of the G4-TBP NPs-FN lead to their effective treatment of an OA model in vivo to reduce pathological changes of joints including synovitis inhibition and cartilage matrix degradation and simultaneously promote osteogenic differentiation for bone repair. The developed nanomedicine formulation combining the advantages of both bioactive phosphorus dendrimers and FN to treat OA may be developed for immunomodulatory therapy of different inflammatory diseases.

Regional Antibiotic Resistance of the Main Uropathogens

The most important reason for the increase in mortality from infectious factors on the planet is the acquisition of resistance to antibacterial agents by microflora. Therefore, modern guidelines for the treatment of human infectious diseases recommend considering the regional sensitivity of the microflora when choosing an antibiotic. The treatment of infectious lesions of the urinary system is no exception, the disease of which is annually included in the list of the most frequent reasons for increasing the «burden of disease» on the planet. Therefore, the study of the microbial landscape of uropathogenic flora and its sensitivity to modern antibiotics in the Ukrainian population will contribute to increasing the effectiveness of treatment, especially empirical treatment, and reducing the antibiotic resistance of local uropathogens. The objective: optimization of the therapy of infectious and inflammatory diseases of the urinary system by considering the sensitivity of the main regional uropathogens to antibacterial agents. Materials and methods. Bacteriological research was carried out on 545 urine samples of symptomatic inpatients and outpatients aged 19 to 95 years, in whom pathological changes in urine sediment were determined during the examination. According to the sex distribution, women predominated in both groups in the ratio of 1.6:1 and 3.8:1, respectively. Identification of causative agents and their properties, as well as sensitivity to antibiotics, was carried out according to the standardized methods of domestic and international guidelines. The growth of microflora with the number of colony-forming units in 1 ml ≥ 104 (CFU/ml) was considered clinically significant. Statistical analysis was carried out with the help of the statistical package EZR v. 1.50. The critical level of significance is 0.05. Results. In urine samples obtained from patients of a multidisciplinary hospital, 81.7% of identified microorganisms were Escherichia coli (31.5%), Enterococcus faecalis (17.2%), Klebsiella spp. (16.2%), Candida albicans (6.6%), Acinetobacter species (5.6%) and Staphylococcus aureus (4.6%). In the outpatient group of patients, 92.1% of uropathogens were Escherichia coli (52.3%), Klebsiella spp. (13.6%), Staphylococcus aureus (13.6%), Enterococcus faecalis (8.0%) and Enterobacter sрp. (4.6%). In the spectrum of pathogens of infectious and inflammatory diseases of the urinary system, the role of microorganisms that form a capsule (Klebsiella spp., Acinetobacter sрp.) has been increasing in recent years: among the uropathogens in examined inpatients in 2013 (n=122) and 2022 (n=108) proportion of Klebsiella spp. increased, respectively, from 14.8% to 37%; and the proportion of Acinetobacter sрp. from 2.8% to 3.3%. The majority of uropathogens identified from the urine of patients of a multidisciplinary somatic hospital, in contrast to the outpatient group, was characterized by polyresistance to the action of antibacterial agents. Escherichia coli and Klebsiella spp. were sensitive only to fosfomycin and carbapenems, and Enterococcus faecalis – to fosfomycin, amoxicillin clavulonate, ampicillin sulbactam, vancomycin, meropenem and linezolid. Acinetobacter sрp. was insensitive to all antibiotics used in the study. The growth of fungi of the genus Candida albicans was inhibited by the main antifungal drugs of the «access» category – fluconazole, itraconazole, and ketoconazole, with a tendency toward a gradual increase in resistance, which was indicated by a significant number of moderately sensitive strains – 35, 25, and 10%, respectively. Conclusions. The spectrum of uropathogenic flora in patients of a multidisciplinary hospital is characterized by greater diversity and a more frequent combination of several types of microorganisms in one patient compared to the outpatient group. The most common causative agents of infectious and inflammatory diseases of the urinary tract in the Kyiv region are polyresistant strains of Escherichia coli, Enterococcus faecalis and Klebsiella spp. In the spectrum of pathogens of infectious and inflammatory diseases of the urinary system, the role of microorganisms that form a capsule (Klebsiella spp., Acinetobacter sрp.) has been increasing in recent years. Therefore, we are witnessing the evolutionary success of the protective mechanism of capsule formation, which is related, among other things, to the phenomenon of Bacterial Quorum Sensing in microorganisms and the formation of biofilms. Implementation of the obtained results of the study of regional sensitivity of uropathogens to antibacterial agents in medical practice will improve the results of treatment of infectious and inflammatory urological pathology and prevent the growth of antibiotic resistance of the local flora.

SLC25A3 negatively regulates NLRP3 inflammasome activation by restricting the function of NLRP3

The NACHT, leucine-rich repeat, and pyrin domains-containing protein 3 (collectively known as NLRP3) inflammasome activation plays a critical role in innate immune and pathogenic microorganism infections. However, excessive activation of NLRP3 inflammasome will lead to cellular inflammation and tissue damage, and naturally it must be precisely controlled in the host. Here, we discovered that solute carrier family 25 member 3 (SLC25A3), a mitochondrial phosphate carrier protein, plays an important role in negatively regulating NLRP3 inflammasome activation. We found that SLC25A3 could interact with NLRP3, overexpression of SLC25A3 and knockdown of SLC25A3 could regulate NLRP3 inflammasome activation, and the interaction of NLRP3 and SLC25A3 is significantly boosted in the mitochondria when the NLRP3 inflammasome is activated. Our detailed investigation demonstrated that the interaction between NLRP3 and SLC25A3 disrupted the interaction of NLRP3-NEK7, promoted ubiquitination of NLRP3, and negatively regulated NLRP3 inflammasome activation. Thus, these findings uncovered a new regulatory mechanism of NLRP3 inflammasome activation, which provides a new perspective for the therapy of NLRP3 inflammasome-associated inflammatory diseases.

The New Frontiers of Gene Therapy and Gene Editing in Inflammatory Diseases.

Inflammatory diseases are conditions characterized by abnormal and often excessive immune responses, leading to tissue and organ inflammation. The complexity of these disorders arises from the intricate interplay of genetic factors and immune responses, which challenges conventional therapeutic approaches. However, the field of genetic manipulation has sparked unprecedented optimism in addressing these complex disorders. This review aims to comprehensively explore the application of gene therapy and gene editing in the context of inflammatory diseases, offering solutions that range from correcting genetic defects to precise immune modulation. These therapies have exhibited remarkable potential in ameliorating symptoms, improving quality of life, and even achieving disease remission. As we delve into recent breakthroughs and therapeutic applications, we illustrate how these advancements offer novel and transformative solutions for conditions that have traditionally eluded conventional treatments. By examining successful case studies and preclinical research, we emphasize the favorable results and substantial transformative impacts that gene-based interventions have demonstrated in patients and animal models of inflammatory diseases such as chronic granulomatous disease, cryopyrin-associated syndromes, and adenosine deaminase 2 deficiency, as well as those of multifactorial origins such as arthropathies (osteoarthritis, rheumatoid arthritis) and inflammatory bowel disease. In conclusion, gene therapy and gene editing offer transformative opportunities to address the underlying causes of inflammatory diseases, ushering in a new era of precision medicine and providing hope for personalized, targeted treatments.

Intravenous cyclophosphamide therapy for patients with severe ocular inflammatory diseases who failed other immunomodulatory therapies

BackgroundOcular inflammatory diseases, including scleritis and uveitis, have been widely treated with immunomodulatory therapies (IMTs) as a steroid-sparing approach. Such strategy includes conventional therapies (antimetabolites, alkylating agents, and calcineurin inhibitors) as well as biologic agents like adalimumab, infliximab, rituximab, and tocilizumab. Cyclophosphamide (CP) is an alkylating agent and mainly inhibits the functioning of both T and B cells. Though known to have potential adverse events, including bone marrow suppression, hemorrhagic cystitis, and sterility, CP has been shown to be efficacious, especially in recalcitrant cases and when used intravenous (IV) for a limited period.Main findingsWe conducted a retrospective case-series to assess the safety and efficacy of CP therapy for patients with severe ocular inflammatory diseases who failed other IMTs. Medical records of 1295 patients who presented to the Uveitis Clinic at the Byers Eye Institute at Stanford between 2017 and 2022 were reviewed. Seven patients (10 eyes) who received CP therapy for ocular inflammatory diseases with at least one year of follow-up were included. The mean age of the patients (4 males, 3 females) was 61.6 ± 14.9 (43.0–89.0) years. Clinical diagnoses included necrotizing scleritis (5 eyes), peripheral ulcerative keratitis (2 eyes), orbital pseudotumor (1 eye), HLA-B27 associated panuveitis and retinal vasculitis (2 eyes). Ocular disease was idiopathic in 3 patients, and was associated with rheumatoid arthritis, IgG-4 sclerosing disease, dermatomyositis, and ankylosing spondylitis in 1 patient each. All the patients had history of previous IMT use including methotrexate (5), mycophenolate mofetil (3), azathioprine (1), tacrolimus (1), adalimumab (2), infliximab (4), and rituximab (1). The mean follow-up time was 34.4 ± 11.0 (13–45) months, and mean duration of CP therapy was 11.9 ± 8.8 (5–28) months. Remission was achieved in 5 patients (71.4%). Four patients (57.1%) experienced transient leukopenia (white blood cell count < 4000/mL).Short conclusionCP therapy can be considered a potentially effective and relatively safe therapeutic option for patients with severe ocular inflammatory diseases who failed other IMTs including biologics (TNFa and CD20 inhibitors).

Paediatric indications and dosing guidance for advanced targeted treatments in Australia.

As with adults, paediatric patients may benefit from a number of advanced targeted therapies for inflammatory skin disease. This brief report aims to be an accessible reference tool with respect to regulatory approval and reimbursement of these treatments within Australia.

Dynamics of changes in the microflora of the oral fluid after the removal of lower wisdom teeth against the background of antibiotic therapy and phage therapy

The purpose of our study was to study the effectiveness of the drug «Sextafag» as a therapeutic and prophylactic agent after the removal of impacted lower third molars.Recently, there has been a large number of patients with antibiotic resistance, so it is to find an alternative to traditional antibiotic therapy. This article examines the qualitative and quantitative composition of the oral microbiota after removal of impacted lower wisdom teeth. We studied the dynamics of changes in microflora during antibacterial treatment and phage therapy. The data obtained confirm the clinical and bacteriological effectiveness of oral phage therapy for inflammatory diseases in dental practice and can serve as the basis for the development of a new algorithm for the use of bacteriophages in the treatment of purulent-inflammatory diseases of the oral cavity.

Caffeic acid-grafted chitooligosaccharides downregulate MAPK and NF-kB in RAW264.7 cells.

Chitooligosaccharide (COS) is a derivative of chitosan, which is a natural macromolecular compound. COS has been shown effects in an inflammatory response. Recent reports show that COS derivatives have enhanced anti-inflammatory activity by inhibiting intracellular signals. Evaluation of the anti-inflammatory effect of caffeic acid conjugated COS chain (CA-COS) was performed in this study. The effects of CA-COS on the inflammatory response were demonstrated in lipopolysaccharide-stimulated RAW264.7 macrophages. The results showed that CA-COS inhibited nitric oxide (NO) production and downregulated the gene expression of nitric oxide synthase (iNOS), and cytokines such as tumor necrosis factor-alpha (TNF-α), IL-1β, and IL-6 without cytotoxic effect. In addition, western blot analysis showed that CA-COS inhibits the protein expression of iNOS and nuclear factor kappa B (NF-kB), including p50 and p65, and mitogen-activated protein kinase (MAPK) signaling pathways. Collectively, these results provide clear evidence for the anti-inflammatory mechanism of CA-COS that show great potential as a novel agent for the prevention and therapy of inflammatory diseases.

Targeted therapy for immune mediated skin diseases. What should a dermatologist know?

BackgroundMolecularly targeted therapies, such as monoclonal antibodies (mAbs) and Janus Kinase inhibitors (JAKis), have emerged as essential tools in the treatment of dermatological diseases. These therapies modulate the immune system through specific signaling pathways, providing effective alternatives to traditional systemic immunosuppressive agents. This review aims to provide an updated summary of targeted immune therapies for inflammatory skin diseases, considering their pathophysiology, efficacy, dosage, and safety profiles. MethodsThe review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A systematic search was conducted on PubMed over the past 10 years, focusing on randomized clinical trials, case reports, and case series related to targeted immune therapies in dermatology. Eligibility criteria were applied, and data were extracted from each study, including citation data, study design, and results. ResultsWe identified 1360 non-duplicate articles with the initial search strategy. Title and abstract review excluded 1150, while a full-text review excluded an additional 50 articles. The review included 143 studies published between 2012 and 2022, highlighting 39 drugs currently under investigation or in use for managing inflammatory skin diseases. Study limitationsThe heterogeneity of summarized information limits this review. Some recommendations originated from data from clinical trials, while others relied on retrospective analyses and small case series. Recommendations will likely be updated as new results emerge. ConclusionTargeted therapies have revolutionized the treatment of chronic skin diseases, offering new options for patients unresponsive to standard treatments. Paradoxical reactions are rarely observed. Further studies are needed to fully understand the mechanisms and nature of these therapies. Overall, targeted immune therapies in dermatology represent a promising development, significantly improving the quality of life for patients with chronic inflammatory skin diseases.

Peculiarities of treatment of dermatitis in young children

The skin of children of the first years of life has a number of structural and physiological features that determine the development of inflammatory process and clinical picture of the disease. Inflammatory skin diseases such as atopic dermatitis and allergic contact dermatitis are common in children in the first two years of life. Atopic dermatitis (AD) develops in individuals with hereditary predisposition, has a chronic recurrent course, is characterized by itching, typical morphology and localization of lesions. The prevalence of atopic dermatitis is up to 20%. Contact allergic dermatitis develops on the background of monovalent sensitization, the prevalence is about 16.5%. The clinical picture depends on the severity of the inflammatory reaction and the duration of the disease. The main goal of treatment of allergodermatoses is to stop the signs of inflammation, subjective symptoms. External therapy of inflammatory skin diseases consists in the prescription of topical glucocorticosteroids. When choosing the means of external therapy, it is necessary to take into account the age of the patient, the degree of severity of the inflammatory process, localization of lesions, pharmacokinetics of the active substance and other factors. The article describes clinical cases of treatment of atopic dermatitis, contact allergic dermatitis in patients of the first two years of life using methylprednisolone aceponate with ceramides in the form of cream, ointment. High efficacy and safety of topical corticosteroids in infants in combination with emollients has been shown to rapidly reduce the intensity of inflammation and subjective symptoms.

Pathogenesis-Guided Rational Engineering of Nanotherapies for the Targeted Treatment of Abdominal Aortic Aneurysm by Inhibiting Neutrophilic Inflammation.

Abdominal aortic aneurysm (AAA) remains a fatal disease in the elderly. Currently, no drugs can be clinically used for AAA therapy. Considering the pivotal role of neutrophils in the pathogenesis of AAA, herein we propose the targeted therapy of AAA by site-specifically regulating neutrophilic inflammation. Based on a luminol-conjugated α-cyclodextrin material (LaCD), intrinsically anti-inflammatory nanoparticles (NPs) were engineered by simple nanoprecipitation, which were examined as a nanotherapy (defined as LaCD NP). After efficient accumulation in the aneurysmal aorta and localization in pathologically relevant inflammatory cells in rats with CaCl2-induced AAA, LaCD NP significantly alleviated AAA progression, as implicated by the decreased aortic expansion, suppressed elastin degradation, inhibited calcification, and improved structural integrity of the abdominal aorta. By functionalizing LaCD NP with alendronate, a calcification-targeting moiety, the in vivo aneurysmal targeting capability of LaCD NP was considerably enhanced, thereby affording significantly potentiated therapeutic outcomes in AAA rats. Mechanistically, LaCD NP can effectively inhibit neutrophil-mediated inflammatory responses in the aneurysmal aorta. Particularly, LaCD NP potently attenuated the formation of neutrophil extracellular traps (NETs), thereby suppressing NETs-mediated pro-inflammatory events and NETosis-associated negative effects responsible for AAA progression. Consequently, we demonstrated the effectiveness and underlying mechanisms of anti-NETosis nanotherapies for the targeted treatment of AAA. Our findings provide promising insights into discovering precision therapies for AAA and other inflammatory vascular diseases.