Self-adaptive pyroptosis-responsive nanoliposomes block pyroptosis in autoimmune inflammatory diseases.

Nanoliposomes have a broad range of applications in the treatment of autoimmune inflammatory diseases because of their ability to considerably enhance drug transport. For their clinical application, nanoliposomes must be able to realize on-demand release of drugs at disease sites to maximize drug-delivery efficacy and minimize side effects. Therefore, responsive drug-release strategies for inflammation treatment have been explored; however, no specific design has been realized for a responsive drug-delivery system based on pyroptosis-related inflammation. Herein, we report a pioneering strategy for self-adaptive pyroptosis-responsive liposomes (R8-cardiolipin-containing nanoliposomes encapsulating dimethyl fumarate, RC-NL@DMF) that precisely release encapsulated anti-pyroptotic drugs into pyroptotic cells. The activated key pyroptotic protein, the N-terminal domain of gasdermin E, selectively integrates with the cardiolipin of liposomes, thus forming pores for controlled drug release, pyroptosis, and inflammation inhibition. Therefore, RC-NL@DMF exhibited effective therapeutic efficacies to alleviate autoimmune inflammatory damages in zymosan-induced arthritis mice and dextran sulfate sodium-induced inflammatory bowel disease mice. Our novel approach holds great promise for self-adaptive pyroptosis-responsive on-demand drug delivery, suppressing pyroptosis and treating autoimmune inflammatory diseases.

Delayed adverse events following COVID-19 vaccination in patients with systemic sclerosis and other autoimmune diseases: a substudy of the COVAD-2 cohort.

Data on short-term safety of COVID-19 vaccination in patients with systemic sclerosis (SSc) were explored previously in the first COVID-19 vaccination in autoimmune diseases (COVAD) survey conducted in 2021. However, delayed adverse events (ADEs) (occurring > 7 days post-vaccination) are poorly characterized in these patients with SSc. In this study, we analysed delayed COVID-19 vaccine-related ADEs among patients with SSc, other systemic autoimmune and inflammatory disorders (SAIDs) and healthy controls (HCs) using data from the second COVAD study conducted in 2022. The COVAD-2 study was a cross-sectional, patient self-reported global e-survey conducted from February to June 2022. Data on demographics, SSc/SAID disease characteristics, COVID-19 infection history, and vaccination details including delayed ADEs as defined by the Centre for Disease Control were captured and analysed. Among 17,612 respondents, 10,041 participants fully vaccinated against COVID-19 were included for analysis. Of these, 2.6% (n = 258) had SSc, 63.7% other SAIDs, and 33.7% were HCs. BNT162b2 Pfizer (69.4%) was the most administered vaccine, followed by MRNA-1273 Moderna (32.25%) and ChadOx1 nCOV-19 Oxford/AstraZeneca (12.4%) vaccines. Among patients with SSc, 18.9% reported minor, while 8.5% experienced major delayed ADEs, and 4.6% reported hospitalization. These frequencies were comparable to those of the ADEs reported by other patients with SAIDs and HCs. However, patients with SSc reported a higher frequency of difficulty in breathing than HCs [OR 2.3 (1.0-5.1), p = 0.042]. Patients with diffuse cutaneous SSc experienced minor ADEs [OR 2.1 (1.1-4.4), p = 0.036] and specifically fatigue more frequently [OR 3.9 (1.3-11.7), p = 0.015] than those with limited cutaneous SSc. Systemic sclerosis patients with concomitant myositis reported myalgia more frequently [OR 3.4 (1.1-10.7), p = 0.035], while those with thyroid disorders were more prone to report a higher frequency of joint pain [OR 5.5 (1.5-20.2), p = 0.009] and dizziness [OR 5.9 (1.3-27.6), p = 0.024] than patients with SSc alone. A diagnosis of SSc did not confer a higher risk of delayed post-COVID-19 vaccine-related ADEs overall compared with other SAIDs and HCs. However, the diffuse cutaneous phenotype and coexisting autoimmune conditions including myositis and thyroid disease may increase the risk of minor ADEs. These patients may benefit from pre-vaccination counselling, close monitoring, and early initiation of appropriate care in the post-COVID-19 vaccination period.

Golimumab for Polyarticular Juvenile Idiopathic Arthritis and Psoriatic Arthritis: Pharmacologic and Clinical Considerations.

Psoriatic arthritis is a chronic debilitating autoimmune condition, and when diagnosed in patients before the age of eighteen, it is considered pediatric polyarticular juvenile idiopathic arthritis. Monoarticular or polyarticular psoriatic arthritis can be distinguished from other arthropathies by its unique cutaneous manifestations. With numerous treatments already in clinical practice, there are numerous options for treatment. The current literature indicates an elevated level of tumor necrosis factor is present in the epidermis of patients with psoriatic arthritis when compared with the general population. For this reason, anti-tumor necrosis factor therapies have become a hallmark option for psoriatic arthritis patients. Golimumab, a human monoclonal antibody tumor necrosis factor-alpha (TNF-a) receptor antagonist, was chosen as the focus therapy for this investigation. The mechanism of action behind anti-tumor necrosis factor-alpha blockers involves the binding of human TNF-a soluble and transmembrane proteins to competitively inhibit TNF-a from binding to its cellular receptors. The present investigation evaluated current treatment options available for both juvenile- and adult-onset psoriatic arthritis and compared them with the efficacy seen with golimumab use. Pediatric patients included children ages 2-17, while adult populations included adults 18-83 years old. The Food and Drug Administration has approved golimumab for the treatment of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis, and polyarticular juvenile idiopathic arthritis. The results of four different studies reporting on the therapeutic effects and adverse events of golimumab use in psoriatic arthritis, juvenile psoriatic arthritis, juvenile idiopathic arthritis, and juvenile polyarticular arthritis were used for comparison. The meta-analysis referenced studies including children ages 2-17 with no reference mentioning children less than age 2. Based on the results of each study, it can be concluded that golimumab, a human monoclonal antibody that prevents the activation of cellular inflammatory reactions when it binds to the TNF-a receptor, is an effective option for patients with active psoriatic arthritis and psoriatic juvenile idiopathic arthritis and for patients who are no longer responding to their current treatment with adalimumab. Each study also reported minimal adverse events associated with golimumab use, and the drug can be safely used in the pediatric population.

Ras family signaling pathway in immunopathogenesis of inflammatory rheumatic diseases.

The Ras (rat sarcoma virus) is a GTP-binding protein that is considered one of the important members of the Ras-GTPase superfamily. The Ras involves several pathways in the cell that include proliferation, migration, survival, differentiation, and fibrosis. Abnormalities in the expression level and activation of the Ras family signaling pathway and its downstream kinases such as Raf/MEK/ERK1-2 contribute to the pathogenic mechanisms of rheumatic diseases including immune system dysregulation, inflammation, and fibrosis in systemic sclerosis (SSc); destruction and inflammation of synovial tissue in rheumatoid arthritis (RA); and autoantibody production and immune complexes formation in systemic lupus erythematosus (SLE); and enhance osteoblast differentiation and ossification during skeletal formation in ankylosing spondylitis (AS). In this review, the basic biology, signaling of Ras, and abnormalities in this pathway in rheumatic diseases including SSc, RA, AS, and SLE will be discussed.

Guselkumab, a Novel Monoclonal Antibody Inhibitor of the p19 Subunit of IL-23, for Psoriatic Arthritis and Plaque Psoriasis: A Review of Its Mechanism, Use, and Clinical Effectiveness.

Psoriatic arthritis and plaque psoriasis are autoimmune conditions affecting multiple organs, including the skin. The pathophysiology and etiology of these conditions are not fully understood; however, numerous factors are believed to play a critical role, including genetics and environmental risk factors. Furthermore, research suggests the IL-23/IL-17 pathway partially mediates these diseases. Once the IL-23 receptor is bound and activated, two subunits, p19, and p40, act through different signaling pathways. Ultimately, inflammation is produced through the effector molecule, IL-17, other cytokines, and tumor necrosis factor (TNF). Traditionally, these chronic conditions have been treated with TNF-α inhibitors and methotrexate, a dihydrofolate reductase inhibitor. Although successful in inhibiting the immune system, these drugs can have many adverse effects due to their broad targets. In recent years, more targeted therapy has become popular. Guselkumab is a monoclonal antibody that inhibits the p19 subunit of IL-23. It has been FDA-approved to treat both plaque psoriasis and psoriatic arthritis. Clinical trials showing guselkumab's efficacy have been promising, even showing improvement in symptoms of plaque psoriasis patients resistant to adalimumab, a TNF-α inhibitor. Guselkumab has also been shown to be well tolerated with a similar safety profile as other biologics inhibiting the immune system. In addition to its efficacy in treating plaque psoriasis and psoriatic arthritis, the mechanism of action offers a targeted approach that may minimize the broad immunosuppressive effects often associated with traditional therapies, providing a potential advantage in the long-term management of these autoimmune conditions.

Coronavirus disease 2019 vaccination uptake and hesitancy among Polish patients with inborn errors of immunity, autoinflammatory syndromes, and rheumatic diseases: A multicenter survey.

Data regarding the willingness of patients affected by inborn errors of immunity to accept vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are limited. Therefore, this study assessed SARS-CoV-2 vaccination coverage and hesitancy in immunodeficient patients by surveying adults with primary immune deficiencies and autoinflammatory and rheumatic diseases on biologic therapy. The study was conducted from September 20, 2021, to January 22, 2022, when the primary coronavirus disease 2019 (COVID-19) vaccinations were available to all adults in Poland. We included 207 participants consecutively recruited from five referral centers (57% female; median age: 42.6 [range: 18-76, standard deviation ± 14.70] years). Overall, 55% (n = 114), 17% (n = 36), and 28% (n = 57) of the patients had primary immune deficiencies, autoinflammatory diseases, and rheumatic diseases, respectively. Among the entire cohort, 168 patients (81%) were vaccinated, and 82% were willing to receive a booster dose. Patients with autoinflammatory diseases had the highest vaccination rate (94.4%). A strong conviction that it was the correct decision (72%), fear of getting COVID-19 (38%), and expert opinions (34%) influenced the decision to vaccinate. Among the unvaccinated patients, 33.3% had primary or vocational education (p <0.001). Furthermore, only 33% believed they were at risk of a severe course of COVID-19 (p = 0.014), and 10% believed in vaccine efficacy (p <0.001). They also doubted the safety of the vaccine (p <0.001) and feared a post-vaccination flare of their disease (p <0.001). Half of the unvaccinated respondents declared that they would consider changing their decision. Vaccination coverage in immunodeficient patients was higher than in the general Polish population. However, the hesitant patients doubted the vaccine's safety, feared a post-vaccination disease flare, and had primary or vocational education. Therefore, vaccination promotion activities should stress personal safety and the low risk of disease flares due to vaccination. Furthermore, all evidence must be communicated in patient-friendly terms.

Early onset of immune-mediated diseases in minority ethnic groups in the UK.

BACKGROUND: The prevalence of some immune-mediated diseases (IMDs) shows distinct differences between populations of different ethnicities. The aim of this study was to determine if the age at diagnosis of common IMDs also differed between different ethnic groups in the UK, suggestive of distinct influences of ethnicity on disease pathogenesis. METHODS: This was a population-based retrospective primary care study. Linear regression provided unadjusted and adjusted estimates of age at diagnosis for common IMDs within the following ethnic groups: White, South Asian, African-Caribbean and Mixed-race/Other. Potential disease risk confounders in the association between ethnicity and diagnosis age including sex, smoking, body mass index and social deprivation (Townsend quintiles) were adjusted for. The analysis was replicated using data from UK Biobank (UKB). RESULTS: After adjusting for risk confounders, we observed that individuals from South Asian, African-Caribbean and Mixed-race/Other ethnicities were diagnosed with IMDs at a significantly younger age than their White counterparts for almost all IMDs. The difference in the diagnosis age (ranging from 2 to 30 years earlier) varied for each disease and by ethnicity. For example, rheumatoid arthritis was diagnosed at age 49, 48 and 47 years in individuals of African-Caribbean, South Asian and Mixed-race/Other ethnicities respectively, compared to 56 years in White ethnicities. The earlier diagnosis of most IMDs observed was validated in UKB although with a smaller effect size. CONCLUSION: Individuals from non-White ethnic groups in the UK had an earlier age at diagnosis for several IMDs than White adults.

Treating Autoimmune Inflammatory Diseases with an siERN1-Nanoprodrug That Mediates Macrophage Polarization and Blocks Toll-like Receptor Signaling.

The clinical application of small interfering RNA (siRNA) drugs provides promising opportunities to develop treatment strategies for autoimmune inflammatory diseases. In this study, siRNAs targeting the endoplasmic reticulum to nucleus signaling 1 (ERN1) gene (siERN1) were screened. Two cationic polymers, polyethylenimine (PEI) and poly(ß-amino amine) (PBAA), which can improve the efficiency of the siRNA transfection, were used as siERN1 delivery carriers. They were implemented to construct a nanodrug delivery system with macrophage-targeting ability and dual responsiveness for the treatment of autoimmune inflammatory diseases. In terms of the mechanism, siERN1 can regulate the intracellular calcium ion concentration by interfering with the function of inositol 1,4,5-trisphosphate receptor 1/3 (IP3R1/3) and thus inducing M2 polarization of macrophages. Furthermore, siERN1-nanoprodrug [FA (folic acid)-PEG-R(RKKRRQRRR)-NPs(ss-PBAA-PEI)@siERN1] acts as a conductor of macrophage polarization by controlling the calcium ion concentration and is an inhibitor of MyD88-dependent Toll-like receptor signaling. The results revealed that the FA-PEG-R-NPs@siERN1 has universal biocompatibility, long-term drug release responsiveness, superior targeting properties, and therapeutic effects in mouse collagen-induced arthritis and inflammatory bowel disease models. In conclusion, this study reveals a potential strategy to treat autoimmune inflammatory disorders.

Impact of Biological Therapies on the Immune Response after Pneumococcal Vaccination in Patients with Autoimmune Inflammatory Diseases.

Patients with different autoimmune inflammatory diseases (AIID) on biological therapy are at risk of pneumococcal disease. Adults with inflammatory arthropathies, connective tissue diseases, psoriasis, or inflammatory bowel disease on biological therapy such as anti-TNFα, rituximab, tocilizumab, abatacept, or anakinra were included in this study. Patients completed a protocol combining the pneumococcal vaccines PCV13 and PPV23. Immune response against pneumococcal serotypes 1, 3, 7F, 14, 19A, and 19F were assessed evaluating functional antibodies by an opsonophagocytosis killing assay (OPKA). In this study, 182 patients with AIID completed the sequential vaccination protocol. Patients on etanercept tended to achieve OPKA titers against a larger number of serotypes than the rest of patients on other biological therapies, while adalimumab was associated to a lower number of serotypes with OPKA titers. Rituximab was not associated with a worse response when compared with the rest of biological agents. Not glucocorticoids, nor synthetic disease-modifying antirheumatic drugs, interfered with the immune response. OPKA titers against serotype 3 which is one of the most prevalent, was obtained in 44% of patients, increasing up to 58% in those on etanercept. Hence, almost 50% of patients on biological therapy achieved functional antibodies after the administration of a complete pneumococcal vaccination protocol.

Respuesta serológica en pacientes con enfermedades inflamatorias autoinmunes tras la vacunación de la gripe: resultados del estudio RIER / Serological response to influenza vaccine in patients with autoimmune inflammatory diseases: Results of RIER study

Introducción: Los pacientes con enfermedades autoinmunes inflamatorias (EAII) en tratamiento biológico deben recibir la vacunación antigripal anualmente.ObjetivoEstudiar si la respuesta serológica a la vacuna antigripal en pacientes con EAII con tratamiento biológico es diferente de la obtenida en enfermos en tratamiento con fármacos modificadores de la enfermedad (FAME) sintéticos y de la conseguida en sujetos sanos.MétodosSe diseñó un estudio de cohortes en el que se incluyeron pacientes con EAII, 68 tratados con biológicos (grupo biológicos) y 46 con tratamiento con FAME sintéticos (grupo FAME), así como 48 personas sanas. Todos recibieron la vacuna antigripal 2015-2016. Se midieron, mediante ELISA, los títulos de anticuerpos (Ac) frente a los antígenos (Ag) A y B, antes y después de la vacunación.ResultadosTras la vacunación, el 88,24% de los enfermos del grupo biológicos, el 71,74% del grupo FAME y el 89,58% de las personas sanas fueron seropositivos frente al Ag A, mientras que el 42,65% del grupo biológicos, el 41,30% del grupo FAME y el 54,17% de las personas sanas fueron seropositivos frente al Ag B. No hubo diferencias significativas entre los grupos.ConclusionesEn nuestro estudio, el tratamiento biológico no se asoció a una peor respuesta serológica. (AU)

Background: Influenza vaccine is recommended for patients with autoimmune inflammatory diseases (AIID) on biological therapy.ObjectiveTo evaluate whether serological response to Influenza vaccine obtained in patients on biological therapy is similar to that achieved in patients on synthetic disease-modifying anti-rheumatic drugs (DMARDs) and that obtained in healthy controls.MethodsWe designed a cohort study in which patients with AIID, 68 on biological therapy and 46 on synthetic DMARDs, as well as 48 healthy controls, were included and vaccinated during the 2015-2016 influenza season. ELISA was used to measure Influenza antigen (Ag) A and B antibodies, before and after vaccination.ResultsAfter vaccination, 88.24% of patients on biologics, 71.74% of those on synthetic DMARDs and 89.58% of healthy controls, presented detectable antibodies against antigen A, while 42.65% of subjects on biologics, 41.30% of those on DMARDs and 54.17% of healthy subjects were seropositive against Ag B. We did not find statistical differences.ConclusionsIn our study, biological therapy is not associated with worse serological response. (AU)

Serological response to influenza vaccine in patients with autoimmune inflammatory diseases: Results of RIER study. / Respuesta serológica en pacientes con enfermedades inflamatorias autoinmunes tras la vacunación de la gripe: resultados del estudio RIER.

BACKGROUND: Influenza vaccine is recommended for patients with autoimmune inflammatory diseases (AIID) on biological therapy. OBJECTIVE: To evaluate whether serological response to Influenza vaccine obtained in patients on biological therapy is similar to that achieved in patients on synthetic disease-modifying anti-rheumatic drugs (DMARDs) and that obtained in healthy controls. METHODS: We designed a cohort study in which patients with AIID, 68 on biological therapy and 46 on synthetic DMARDs, as well as 48 healthy controls, were included and vaccinated during the 2015-2016 influenza season. ELISA was used to measure Influenza antigen (Ag) A and B antibodies, before and after vaccination. RESULTS: After vaccination, 88.24% of patients on biologics, 71.74% of those on synthetic DMARDs and 89.58% of healthy controls, presented detectable antibodies against antigen A, while 42.65% of subjects on biologics, 41.30% of those on DMARDs and 54.17% of healthy subjects were seropositive against Ag B. We did not find statistical differences. CONCLUSIONS: In our study, biological therapy is not associated with worse serological response.

Allosteric inhibitors of the STAT3 signaling pathway.

Over-expression and/or hyperactivation of signal transducer and activator of transcription 3 (STAT3) signaling are found in various human diseases, including cancer, autoimmune disorders, and inflammatory diseases. Therefore, STAT3 represents a highly promising therapeutic target for the treatment of these diseases. However, the traditional orthosteric inhibitors of STAT3 exhibit limited clinical efficacy, with low selectivity, numerous side effects, and emerging acquired resistance. Allosteric inhibitors targeting STAT3 or its upstream molecules have emerged as a promising approach to overcome these barriers. In this review, we summarize the recent advances in the development of these inhibitors as well as their applications.

Antibody responses to influenza vaccine in patients on biological therapy: Results of RIER cohort study.

BACKGROUND AND OBJECTIVES: Influenza vaccine is recommended for patients with autoimmune inflammatory rheumatic diseases who receive biological therapy. To evaluate if biological therapy impairs immunization after seasonal influenza vaccine. MATERIAL AND METHODS: Patients with inflammatory arthopathies, psoriasis, inflammatory bowel disease or connective tissue diseases who were receiving or were going to initiate biological therapy were included and vaccinated during 2014-2015 influenza season. ELISA was used to measure influenza antigen A and B antibodies, before and after vaccination. Demographic parameters, diagnosis and kind of treatment were recorded and their influence on the final serological status against influenza was studied. RESULTS: 253 subjects were analyzed. After vaccination, 77% of participants presented detectable antibodies against antigen A and 50.6% of them had detectable antibodies against antigen B. Final seropositivity rate against antigen B antibodies increased from baseline (50.6% vs 43.5%, p<0.001). Anti-TNF drugs were associated with better response and rituximab with the worst (79.2% vs 55.0% for final seropositivity against antigen A, p=0.020). Vaccine response in the rituximab group tended to improve when the interval between the drug administration and the vaccination was at least 12 weeks (seropositivity rate 80.0% in those with the longer interval vs 25.0% in the other group, p=0.054). CONCLUSIONS: Among the patients on biological therapy vaccinated against influenza, anti-TNF therapy was identified as a predictive factor of final seropositivity. Rituximab presented a lower rate of final seropositivity, which could be increased with an accurate administration schedule.

Drugs for Autoimmune Inflammatory Diseases: From Small Molecule Compounds to Anti-TNF Biologics.

Although initially described as an anti-tumor mediator, tumor necrosis factor-alpha (TNF) is generally considered as the master pro-inflammatory cytokine. It plays a crucial role in the pathogenesis of inflammatory diseases, such as rheumatoid arthritis (RA), inflammatory bowel disease, ankylosing spondylitis (AS), and psoriasis. Consequently, anti-TNF therapy has become mainstay treatment for autoimmune diseases. Historically, anti-inflammatory agents were developed before the identification of TNF. Salicylates, the active components of Willow spp., were identified in the mid-19th century for the alleviation of pain, fever, and inflammatory responses. Study of this naturally occurring compound led to the discovery of aspirin, which was followed by the development of non-steroidal anti-inflammatory drugs (NSAIDs) due to the chemical advances in the 19th-20th centuries. Initially, the most of NSAIDs were organic acid, but the non-acidic compounds were also identified as NSAIDs. Although effective in the treatment of inflammatory diseases, NSAIDs have some undesirable and adverse effect, such as ulcers, kidney injury, and bleeding in the gastrointestinal tract. In the past two decades, anti-TNF biologics were developed. Drugs belong to this class include soluble TNF receptor 2 fusion protein and anti-TNF antibodies. The introduction of anti-TNF therapeutics has revolutionized the management of autoimmune diseases, such as RA, psoriatic arthritis (PsA), plaque psoriasis (PP), AS, CD and ulcerative colitis (UC). Nevertheless, up to 40% of patients have no response to anti-TNF treatment. Furthermore, this treatment is associated with some adverse effects such as increased risk of infection, and even triggered the de novo development of autoimmune diseases. Such harmful effect of anti-TNF treatment is likely caused by the global inhibition of TNF biological functions. Therefore, specific inhibition of TNF receptor (TNFR1 or TNFR2) may represent a safer and more effective treatment, as proposed by some recent studies. In this review article, the historical development of anti-inflammatory drugs after World War II as briefly described above will be reviewed and analyzed. The future trend in the development of novel TNF receptor-targeting therapeutics will be discussed in the context of latest progress in the research of TNF biology.

Regulation of Interleukin-17 Production.

Innate immunity represents the first line of host defense against extracellular infections. Timely initiation of inflammatory responses to invading pathogens confers host the ability to prevent, restrict, and eliminate microorganisms and further trigger adaptive immunity to provide extended eradication of the pathogens as well as long-term protection of the host from recurrent infections. During this process, various types of cytokines are required for efficient immune responses, and interleukin 17 (IL-17) is one of them. The IL-17 family of cytokines bridges innate and adaptive immune responses and play an essential role in defining the Th17 cell lineage differentiation and function. Th17 cells have pivotal roles in protecting the host against extracellular pathogens as well as in promoting inflammatory pathology in autoimmune diseases. Strict regulation of the IL-17 family of cytokines at different levels ensures appropriate controls of their abilities to shape immune responses. This chapter provides the recent progress in the field of IL-17 studies for the understanding of the regulatory mechanisms in the expression and signaling of the IL-17 family cytokines. IL-17A (IL-17) is the most well-studied member in this family, while information on the other members is relatively sketchy. Thus, we mainly focus on the study of IL-17A.

Embelin and Its Role in Chronic Diseases.

Embelia ribes Burm of Myrsinaceae family has been widely used as an herb in the traditional medicine of India. Embelin is an active component extracted from the fruits of Embelia ribes. It has a wide spectrum of biological activities and is not toxic at low dose. This review focuses on the physical-chemical properties and bioactivities of Embelin, as well as its effects on chronic diseases such as tumors, autoimmune inflammatory diseases, parasitic infections, microbial infections, diabetes, obesity, and cardio-cerebral vascular diseases. The underlying mechanisms of the effects are also discussed. As a multiple-targeted therapeutic agent, Embelin has the potential to be used widely for the treatment of a variety of chronic diseases, including malignant tumors.

Stress Dose Steroids: Myths and Perioperative Medicine.

Perioperative medication management for patients with systemic autoimmune inflammatory diseases has focused on strategies to improve outcomes and mitigate risks. The emphasis has been to minimize the risk of infection associated with most antirheumatic medications, while attempting to avoid flares of disease precipitated by medication withdrawal. Management of glucocorticoids in the perioperative period has been based on an assumption that supraphysiologic increases in dose were always necessary to avoid hypotension and shock in glucocorticoid treated patients, and alternative strategies were rarely considered despite the known infectious, metabolic, and wound healing risks associated with glucocorticoid administration. This paper will review current recommendations for perioperative glucocorticoid administration for glucocorticoid treated patients with systemic inflammatory autoimmune diseases and discuss glucocorticoid physiology to analyze the basis for these recommendations and consider alternative perioperative management strategies.