Therapy Of Inflammatory Diseases Research Articles

Advances in Targeted Therapies for Inflammatory Diseases and Cancer: Exploring Cellular Mechanisms and Therapeutic Strategies

Advances in Targeted Therapies for Inflammatory Diseases and Cancer: Exploring Cellular Mechanisms and Therapeutic Strategies

Interleukin 17 as a central component of the pathogenesis of pain associated with immunoinflammatory process: А 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.

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.

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.

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.

Characterization of the MT-2 Treg-like cell line in the presence and absence of forkhead box P3 (FOXP3).

CD4+ forkhead box P3 (FOXP3)+ regulatory T cells (Tregs) are essential in maintaining immune tolerance and suppressing excessive immune responses. Tregs also contribute to tissue repair processes distinct from their roles in immune suppression. For these reasons, Tregs are candidates for targeted therapies for inflammatory and autoimmune diseases, and in diseases where tissue damage occurs. MT-2 cells, an immortalized Treg-like cell line, offer a model to study Treg biology and their therapeutic potential. In the present study, we use clustered regularly interspaced palindromic repeats (CRISPR)-mediated knockdown of FOXP3 in MT-2 cells to understand the transcriptional and functional changes that occur when FOXP3 is lost and to compare MT-2 cells with primary human Tregs. We demonstrate that loss of FOXP3 affects the transcriptome of MT-2 cells and that FOXP3's potential downstream targets include a wide range of transcripts that participate in the cell cycle, promote growth and contribute to inflammatory processes, but do not wholly simulate previously reported human primary Treg transcriptional changes in the absence of FOXP3. We also demonstrate that FOXP3 regulates cell cycling and proliferation, expression of molecules crucial to Treg function and MT-2 cell-suppressive activities. Thus, MT-2 cells offer opportunities to address regulatory T-cell functions in vitro.

ECCO Grant Analysis of the tolerogenic role of the liver in controlling intestinal inflammation

Abstract Background and Aims There is a close anatomical connection between the liver and the intestine. This connection is further highlighted by the association between Primary Sclerosing Cholangitis (PSC) and Inflammatory Bowel Disease (IBD). Interestingly, PSC-associated IBD (PSC/IBD) presents with milder colitis symptoms compared to Crohn's disease and Ulcerative Colitis. We hypothesize that PSC has a protective impact on IBD, which is mediated by Foxp3+ regulatory T cells. This hypothesis is supported by our preliminary data. However, the mechanism by which PSC induces tolerance in the intestine remains unknown and answering this question is the aim of this proposal. Methods In Objective 1, we will test the hypothesis that changes in the intestinal microbiota mediate the protective effects of PSC on IBD. We will compare the intestinal microbiota in patients with PSC/IBD and IBD. This analysis will be complemented by functional experiments. Specifically, we aim to engraft germ-free wild type (WT) mice with fecal microbiota from PSC/IBD and IBD patients, as well as from Mdr2-deficient and WT mice. In these mouse models, we will analyze the effect of the microbiota on effector and regulatory T cells and on colitis susceptibility. In Objective 2, we will test whether changes in the composition of bile acids mediate the protective effects of PSC on IBD. To test this, we will deliver specific bile acids identified by us into Il10-deficient mice and analyze their impact on colitis severity and the intestinal T cell repertoire. Moreover, we will decipher how those bile acids impact the intestinal microbiota. Using in vitro assays, we will further test the direct effect of specific bile acids on T cell differentiation. Anticipated Impact Finally, our long-term aim is to understand how the liver induces immunological tolerance in the intestine. This knowledge could pave the way for new targeted therapies for inflammatory diseases.

Understanding T lymphocytes inner workings to harness therapeutic potential

Understanding T lymphocytes inner workings to harness therapeutic potential Leslie J. Berg, PhD from the University of Colorado, Anschutz School of Medicine, sheds light on understanding the inner workings of T lymphocytes to harness their therapeutic potential. In the past two decades, we have witnessed the powerful impact of years of research to uncover the mechanisms regulating our immune responses to infections. This research has revealed opportunities to harness our immune systems to fight cancers, leading to many therapies for autoimmune and inflammatory diseases. The prevalence and impact of these treatments are highlighted by their descriptor, ‘immunotherapies’, now a common word familiar to the broader public. At the heart of this research is studying immune cells, including lymphocytes and myeloid cells, that implement our immune responses to pathogens, cancers, and self-tissues.

Inflammation-Targeted Drug Delivery Strategies via Albumin-Based Systems.

Albumin, being the most abundant serum protein, has the potential to significantly enhance the physicochemical properties of therapeutic payloads, thereby improving their pharmacological effects. Apart from its passive transport via the enhanced permeability and retention effect, albumin can actively accumulate in tumor microenvironments or inflammatory tissues via receptor-mediated processes. This unique property makes albumin a promising scaffold for targeted drug delivery. This review focuses on exploring different delivery strategies that combine albumin with drug payloads to achieve targeted therapy for inflammatory diseases. Also, albumin-derived therapeutic products on the market or undergoing clinical trials in the past decade have been summarized to gain insight into the future development of albumin-based drug delivery systems. Given the involvement of inflammation in numerous diseases, drug delivery systems utilizing albumin demonstrate remarkable advantages, including enhanced properties, improved in vivo behavior and efficacy. Albumin-based drug delivery systems have been demonstrated in clinical trials, while more advanced strategies for improving the capacity of drug delivery systems with the help of albumin remain to be discovered. This could pave the way for biomedical applications in more effective and precise treatments.

Analytical Study of Dashamoolakatu Treyam Kvatha Churna

Aim: For the purpose of analyzing the active principle in the obtained extracts of the herbs, GC-MS is considered as an important tool. This study includes two techniques where the components is separated by Gas chromatography and the mass spectroscopy does the analysis of the active component. As a part of such an analytical aspect, Dashamoolakayu treyam Kvatha Churna is subjected to GC-MS to study their bioactive compounds. Methodology: 1g of sample was extracted with 10mL of methanol and was filtered through a syringe filter (Nylon 13 mm 0.2um) and injected to GCMS. The components of the oil were identified by comparison of their mass spectra with those of the spectrometer/ mass spectral database using NIST library (NIST -08 SPECTRAL DATA). The identifications were confirmed by comparison of the fragmentation pattern and their retention indices with those reported in the literature. Result: Result shows three peaks with R.T mins as 7.689, 7.964, 8.841 and the compounds are identified are α-Copaene (Tricyclo [4.4.0.02,7] dec-3-ene, 1,3-dimethyl- 8- (1-methylethyl)-, stereoisomer), Caryophyllene, Caryophyllene oxide with peak heights as 17768, 104199, 39458 respectively. Discussion: Identified components has antioxidant, Analgesic and anti-inflammatory activity and are used in the therapy of inflammatory diseases of the upper airways and also in the management of acute and chronic infectious and inflammatory diseases of different localization. Conclusion: Thus, this GC-MS study indicates the scientific validation of Dashamoolakatu treyam Kvatha Churna as a potent medicine as claimed by ayurvedic literature and practice.

Targeted therapies of inflammatory diseases with intracellularly gelated macrophages in mice and rats

Membrane-camouflaged nanomedicines often suffer from reduced efficacy caused by membrane protein disintegration and spatial disorder caused by separation and reassembly of membrane fragments during the coating process. Here we show that intracellularly gelated macrophages (GMs) preserve cell membrane structures, including protein content, integration and fluidity, as well as the membrane lipid order. Consequently, in our testing GMs act as cellular sponges to efficiently neutralize various inflammatory cytokines via receptor-ligand interactions, and serve as immune cell-like carriers to selectively bind inflammatory cells in culture medium, even under a flow condition. In a rat model of collagen-induced arthritis, GMs alleviate the joint injury, and suppress the overall arthritis severity. Upon intravenous injection, GMs efficiently accumulate in the inflammatory lungs of acute pneumonia mice for anti-inflammatory therapy. Conveniently, GMs are amenable to lyophilization and can be stored at ambient temperatures for at least 1 month without loss of integrity and bio-activity. This intracellular gelation technology provides a universal platform for targeted inflammation neutralization treatment.