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Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the joints and it affects over 18 million people worldwide. Despite the availability of a variety of potent drugs for RA, over 30–40 percent of patients fail to achieve adequate remission, and many patients suffer from systemic adverse effects. Thus, there is an urgent need for a joint-targeted drug delivery system. Nanotechnology-based drug delivery methods offer a promising resource that is largely untapped for RA. Using the T cell-driven rat adjuvant-induced arthritis (AA) model of human RA, we developed a peptide-targeted liposomal drug delivery system for arthritis therapy. It was based on a novel joint-homing peptide ART-2 to guide liposomes entrapping dexamethasone (Dex) to arthritic joints of rats, and this approach was more effective in suppressing arthritis than the unpackaged (free) drug. To de-risk the translation of our innovative drug delivery technology to RA patients, we undertook the validation of ART-2-liposomal delivery in a genetically and mechanistically distinct arthritis model in mice, the collagen antibody-induced arthritis (CAIA) model. Using live imaging for tissue distribution of liposomes in vivo, immunohistochemistry of paws for cellular binding of ART-2, and liposomal Dex delivery, our results fully validated the key findings of the rat model, namely, preferential homing of peptide-functionalized liposomes to arthritic joints compared to healthy joints, and higher efficacy of liposomal Dex than free Dex. These results offer a proof-of-concept for the benefits of targeted drug delivery to the joints and its potential translation to RA patients. [ABSTRACT FROM AUTHOR]

Liposomes and other types of nanoparticles are increasingly being explored for drug delivery in a variety of diseases. There is an impetus in the field to exploit different types of ligands to functionalize nanoparticles to guide them to the diseased site. Most of this work has been conducted in the cancer field, with relatively much less information from autoimmune diseases, such as rheumatoid arthritis (RA). Furthermore, in RA, many drugs are self-administered by patients subcutaneously (SC). In this context, we have examined the attributes of liposomes functionalized with a novel joint-homing peptide (denoted ART-1) for arthritis therapy using the SC route. This peptide was previously identified following phage peptide library screening in the rat adjuvant arthritis (AA) model. Our results show a distinct effect of this peptide ligand on increasing the zeta potential of liposomes. Furthermore, liposomes injected SC into arthritic rats showed preferential homing to arthritic joints, following a migration profile in vivo similar to that of intravenously injected liposomes, except for a less steep decline after the peak. Finally, liposomal dexamethasone administered SC was more effective than the unpackaged (free) drug in suppressing arthritis progression in rats. We suggest that with suitable modifications, this SC liposomal treatment modality can be adapted for human RA therapy. [ABSTRACT FROM AUTHOR]

Inflammation is an integral part of autoimmune diseases, which are caused by dysregulation of the immune system. This dysregulation involves an imbalance between pro-inflammatory versus anti-inflammatory mediators. These mediators include various cytokines and chemokines; defined subsets of T helper/T regulatory cells, M1/M2 macrophages, activating/tolerogenic dendritic cells, and antibody-producing/regulatory B cells. Despite the availability of many anti-inflammatory/immunomodulatory drugs, the severe adverse reactions associated with their long-term use and often their high costs are impediments in effectively controlling the disease process. Accordingly, suitable alternatives are being sought for these conventional drugs. Natural products offer promising adjuncts/alternatives in this regard. The availability of specific compounds isolated from dietary/medicinal plant extracts have permitted rigorous studies on their disease-modulating activities and the mechanisms involved therein. Here, we describe the basic characteristics, mechanisms of action, and preventive/therapeutic applications of 5 well-characterized natural product compounds (Resveratrol, Curcumin, Boswellic acids, Epigallocatechin-3-gallate, and Triptolide). These compounds have been tested extensively in animal models of autoimmunity as well as in limited clinical trials in patients having the corresponding diseases. We have focused our description on predominantly T cell-mediated diseases, such as rheumatoid arthritis, multiple sclerosis, Type 1 diabetes, ulcerative colitis, and psoriasis. [ABSTRACT FROM AUTHOR]

Objective and design: Multiple sclerosis (MS) is a debilitating autoimmune disease involving immune dysregulation of the pathogenic T helper 17 (Th17) versus protective T regulatory (Treg) cell subsets, besides other cellular aberrations. Studies on the mechanisms underlying these changes have unraveled the involvement of mitogen-activated protein kinase (MAPK) pathway in the disease process. We describe here a gene expression- and bioinformatics-based study showing that celastrol, a natural triterpenoid, acting via MAPK pathway regulates the downstream genes encoding serum/glucocorticoid regulated kinase 1 (SGK1), which plays a vital role in Th17/Treg differentiation, and brain-derived neurotrophic factor (BDNF), which is a neurotrophic factor, thereby offering protection against experimental autoimmune encephalomyelitis (EAE) in mice.Methods: We first tested the gene expression profile of splenocytes of EAE mice in response to the disease-related antigen, myelin oligodendrocyte glycoprotein (MOG), and then examined the effect of celastrol on that profile.Results: Interestingly, celastrol reversed the expression of many MOG-induced genes involved in inflammation and immune pathology. The MAPK pathway involving p38MAPK and ERK was identified as one of the mediators of celastrol action. It involved suppression of SGK1 but upregulation of BDNF, which then contributed to protection against EAE.Conclusion: Our results not only provide novel insights into disease pathogenesis, but also offer promising therapeutic targets for MS. [ABSTRACT FROM AUTHOR]

Pro-inflammatory cytokines promote autoimmune inflammation and tissue damage, while anti-inflammatory cytokines help resolve inflammation and facilitate tissue repair. Over the past few decades, this general feature of cytokine-mediated events has offered a broad framework to comprehend the pathogenesis of autoimmune and other immune-mediated diseases, and to successfully develop therapeutic approaches for diseases such as rheumatoid arthritis (RA). Anti-tumor necrosis factor-α (TNF-α) therapy is a testimony in support of this endeavor. However, many patients with RA fail to respond to this or other biologics, and some patients may suffer unexpected aggravation of arthritic inflammation or other autoimmune effects. These observations combined with rapid advancements in immunology in regard to newer cytokines and T cell subsets have enforced a re-evaluation of the perceived pathogenic attribute of the pro-inflammatory cytokines. Studies conducted by others and us in experimental models of arthritis involving direct administration of IFN-γ or TNF-α; in vivo neutralization of the cytokine; the use of animals deficient in the cytokine or its receptor; and the impact of the cytokine or anti-cytokine therapy on defined T cell subsets have revealed paradoxical anti-inflammatory and immunoregulatory attributes of these two cytokines. Similar studies in other models of autoimmunity as well as limited studies in arthritis patients have also unveiled the disease-protective effects of these pro-inflammatory cytokines. A major mechanism in this regard is the altered balance between the pathogenic T helper 17 (Th17) and protective T regulatory (Treg) cells in favor of the latter. However, it is essential to consider that this aspect of the pro-inflammatory cytokines is context-dependent such that the dose and timing of intervention, the experimental model of the disease under study, and the differences in individual responsiveness can influence the final outcomes. Nevertheless, the realization that pro-inflammatory cytokines can also be immunoregulatory offers a new perspective in fully understanding the pathogenesis of autoimmune diseases and in designing better therapies for controlling them. [ABSTRACT FROM AUTHOR]

Cholesterol homeostasis relies on an intricate network of cellular processes whose deregulation in response to Western type high-fat/cholesterol diets can lead to several life-threatening pathologies. Significant advances have been made in resolving the molecular identity and regulatory function of transcription factors sensitive to fat, cholesterol, or bile acids, but whether body senses the presence of both fat and cholesterol simultaneously is not known. Assessing the impact of a high-fat/cholesterol load, rather than an individual component alone, on cholesterol homeostasis is more physiologically relevant because Western diets deliver both fat and cholesterol at the same time. Moreover, dietary fat and dietary cholesterol are reported to act synergistically to impair liver cholesterol homeostasis. A key insight into the role of protein kinase C-β (PKCβ) in hepatic adaptation to high-fat/cholesterol diets was gained recently through the use of knockout mice. The emerging evidence indicates that PKCβ is an important regulator of cholesterol homeostasis that ensures normal adaptation to high-fat/cholesterol intake. Consistent with this function, high-fat/cholesterol diets induce PKCβ expression and signaling in the intestine and liver, while systemic PKCβ deficiency promotes accumulation of cholesterol in the liver and bile. PKCβ disruption results in profound dysregulation of hepatic cholesterol and bile homeostasis and imparts sensitivity to cholesterol gallstone formation. The available results support involvement of a two-pronged mechanism by which intestine and liver PKCβ signaling converge on liver ERK1/2 to dictate diet-induced cholesterol and bile acid homeostasis. Collectively, PKCβ is an integrator of dietary fat/cholesterol signal and mediates changes to cholesterol homeostasis. [ABSTRACT FROM AUTHOR]

• Autoimmune diseases are a major global health problem. • Several advances have been made in the pathogenesis and treatment of autoimmunity. • Eight leading experts have presented their work and perspectives. [ABSTRACT FROM AUTHOR]

Natural plant products have been used for centuries for health maintenance and treatment of a variety of diseases in various traditional systems of medicine in Egypt and other African countries, India, China, and other countries around the world. Over the past several decades, the popularity of herbal and other natural products has gradually increased in many western countries. Despite the increasing popularity of natural products, both the public and the professionals are skeptical about the use of these products. Reasons for this skepticism include, but are not limited to, the lack of proper documentation about the source and formulations used; standardization of the composition, batch-to-batch consistency, documented safety of herbal products; and information about the mechanisms of action of these products. The 1st Euro-MediterraneanWorkshop: Natural Products in Health and Diseases was organized by the Euro-Mediterranean Association of Life Sciences (EMALS) and various other local organizations to review and discuss the above-mentioned strengths and limitations of the use of natural products. The aim of this workshop was to share best practices and expertise about natural products, and to identify opportunities for collaboration among researchers, health professionals, and business personnel in a productive atmosphere. [ABSTRACT FROM AUTHOR]

Cytokines serve as key mediators of inflammation and tissue damage in a variety of immune–mediated disorders. The induction, progression, and resolution of inflammation in such disorders are characterized by a dynamic balance between both the pro-inflammatory and anti-inflammatory cytokines as well as the pathogenic and protective T cell subsets. Over the past two decades, the roles of the interleukin-17 (IL-17) /IL-23 axis and the T helper 17 (Th17)/ T regulatory (Treg) cell balance in the pathogenesis of autoimmunity and other inflammatory diseases have extensively been analyzed, and their significance validated. However, these studies, coupled with others devoted to well-established Th1/Th2 cytokines, have unraveled some challenging issues including the dual action of cytokines and the plasticity of T cell subsets. Nevertheless, major positive advances have also been made regarding cytokines and T cell subsets as therapeutic targets/agents. In this special issue, “Cytokines in Immune Pathology and Therapy,” leading experts have shared their research work and perspectives on the roles of cytokines in the development and control of immune-mediated diseases. An outline of 14 articles in the first volume is presented here. The second volume will follow soon. [ABSTRACT FROM AUTHOR]

There is currently a global epidemic of obesity as a result of recent changes in lifestyle. Excess body fat deposition is caused by an imbalance between energy intake and energy expenditure due to interactions between genetic and environmental factors. The signals and biological mechanisms that trigger fat accumulation by disrupting energy homeostasis are not well understood. There is considerable evidence now supporting a possible role of protein kinase C beta (PKCβ) in energy homeostasis. This review highlights recent findings on the role of PKCβ activation in the genesis and progression of obesity, and of PKCβ repression in mediating the beneficial effects of physical exercise. Available data support a model in which adipose PKCβ activation is among the initiating events that disrupt mitochondrial function through interaction with p66 shc and amplify fat accumulation and adipose dysfunction, with systemic consequences. Manipulation of PKCβ levels, activity, or signaling could provide a therapeutic approach to combat obesity and associated metabolic disorders. [ABSTRACT FROM AUTHOR]

R1984 --> 704.2 --> The ongoing epidemic of obesity and its associated comorbidities has increased the demand for novel therapeutics targeted toward modulating appetite and/or energy metabolism. The search for clinically useful drugs has thus far met with limited success, and therefore the identification of novel potential targets remains of great interest. We previously showed that mice with systemic PKCβ depletion displayed many of the features one would desire in individuals treated with an ideal antiobesity drug; increase in lean body mass and elevated metabolic rate contributing to prevention of diet‐induced adiposity, hepatic steatosis, and insulin resistance (Hepatology 49:1525, 2009; J. Lipid Res. 286:22795, 2011). Even depletion of hepatocyte‐specific PKCβ recapitulated many of the bebeficial features of whole‐body knockout mice (Mol. Metab. 44:e101133, 2021; JCI Insight 6:e149023, 2021). Our results provide compelling evidence that PKCβ is an important therapeutic target for treatment of obesity and related metabolic complications. An alternative strategy to genetic manipulation of PKCβ expression is the chronic use of selective inhibitors to resolve obesity, or reverse obesity, or both. About 25 years ago, it was reported that a small, orally available molecule, called ruboxistaurin, (also known as LY333,531) reported to potently and selectively inhibited PKCβ. This inhibitor displayed kinetics consistent with direct competition for ATP binding to PKCβ. This selectivity fueled several randomized clinical trials of ruboxstaurin to resolve chronic diabetic microvascular complications such as neuropathy, retinopathy, and macular oedema. Although the mechanism through which hyperglycemia results in vascular dysfunction has not been well established, but the in vivo and in vitro preclinical evidence suggested that hyperglycemia‐induced activation of PKCβ might underlie the development of these microvascular diseases into chronic diabetic complications. To the best of our knowledge, primary outcomes were never achieved in any of the trials and ruboxistaurin has not been approved from the U. S. Food and Drug Administration. Considering that targeting PKCβ outside of the conserved ATP site may be an effective strategy to achieve greater selectivity and potency, we hereby describe screening of already known and newly synthesized bisindolylmaleimides and their derivatives to evaluate whether these chemicals inhibit PKCβ with similar or higher potency than ruboxistaurin. These chemicals were also used to evaluate inhibition of PKCβ vs PKCα. We identified INST3399 as the most potent inhibitor of PKCβ in the basal state, being about 5‐times more potent than ruboxistaurin and more than 100‐fold selectivity for PKCβ versus PKCα. INST3399 is also several orders of magnitude more selective for inhibition of PKCβ in comparison to other ATP dependent kinases. INST3399 appears to inhibit PKCβ by a mechanism different from ruboxistaurin. As expected, INST3399 prevented diet‐induced obesity and hepatic steatosis. This has clear implications for the treatment of metabolic conditions with excessive PKCβ activity. Further studies are in progress to assess the therapeutic efficacy of this compound in reversing obesity. [ABSTRACT FROM AUTHOR]

B-cell receptor (BCR) signaling is essential for normal B-cell development, selection, survival, proliferation, and differentiation into antibody-secreting cells. Similarly, this pathway plays a key role in the pathogenesis of multiple B-cell malignancies. Genetic and pharmacological approaches have established an important role for the Spleen tyrosine kinase (Syk), Bruton's tyrosine kinase (Btk), and phosphatidylinositol 3-kinase isoform p110delta (PI3Kδ) in coupling the BCR and other BCRs to B-cell survival, migration, and activation. In the past few years, several small-molecule inhibitory drugs that target PI3Kδ, Btk, and Syk have been developed and shown to have efficacy in clinical trials for the treatment of several types of B-cell malignancies. Emerging preclinical data have also shown a critical role of BCR signaling in the activation and function of self-reactive B cells that contribute to autoimmune diseases. Because BCR signaling plays a major role in both B-cell-mediated autoimmune inflammation and B-cell malignancies, inhibition of this pathway may represent a promising new strategy for treating these diseases. This review summarizes recent achievements in the mechanism of action, pharmacological properties, and clinical activity and toxicity of these BCR signaling inhibitors, with a focus on their emerging role in treating lymphoid malignancies and autoimmune disorders. [ABSTRACT FROM AUTHOR]

Summary: Introduction: The aim of this study was to assess the efficacy of dissection of radial forearm flap in a superficial plan above the deep fascia to prevent donor site problems. Patients and methods: Eighteen radial forearm flaps were used for orofacial reconstruction: 11 suprafascial flaps and seven infrafascial flaps. We compared in the two groups: flap failure, graft success, tendon adhesions, sensory nerve damage at donor site. Results: We observed one case of flap failure in the infrafascial group and one case in the suprafascial group. With suprafascial elevation flap technique, we noted 100% of grafts integration without tendon adhesion. In infrafascial elevation flap technique, four out of seven patients had delayed healing. Discussion: The suprafascial dissection of free radial forearm flap creates a superior graft recipient bed ensuring early and complete successful graft. [Copyright &y& Elsevier]

Abstract: Heat-shock proteins (Hsps) are among the most highly conserved and immunogenic proteins shared by microbial agents and mammals. Under physiological conditions, the ubiquitously distributed Hsps maintain the integrity and function of other cellular proteins when cells are exposed to stressful stimuli. However, owing to their conserved nature and stress inducibility, Hsps may become targets of immune response. The T cells and/or antibodies induced by a microbial Hsp may crossreact with the corresponding mammalian Hsp (molecular mimicry) and trigger an autoimmune response, which if unchecked can lead to immune pathology and clinical manifestations. Furthermore, enhanced expression of Hsp under stress can unveil previously hidden antigenic determinants that can initiate and perpetuate autoimmune reactivity. Also, the innate immune mechanisms activated by an Hsp can reinforce and even direct the type of adaptive immune response to that protein. Hsps have been implicated in the induction and propagation of autoimmunity in several diseases, including rheumatoid arthritis, atherosclerosis and type 1 diabetes. However, Hsps possess immunoregulatory attributes as well and therefore, are being exploited for immunomodulation of various immune-mediated disorders. [Copyright &y& Elsevier]

Abstract: The pro-inflammatory cytokines play a critical role in the initiation and propagation of autoimmune arthritis and many other disorders resulting from a dysregulated self-directed immune response. These cytokines influence the interplay among the cellular, immunological and biochemical mediators of inflammation at multiple levels. Regulation of the pro-inflammatory activity of these cytokines is generally perceived to be mediated by the anti-inflammatory and immunosuppressive cytokines such as IL-4, IL-10, or TGF-β. However, increasing evidence is accumulating in support of the regulatory attributes of the pro-inflammatory cytokines themselves, in studies conducted in animal models of diabetes, multiple sclerosis, uveitis, and lupus. The results of our recent studies have shown that the pro-inflammatory cytokines, TNF-α and IFN-γ, can suppress arthritic inflammation in rats, and also contribute to resistance against arthritis. These results are of paramount significance not only in fully understanding the pathogenesis of autoimmune arthritis, but also in anticipating the full ramifications of the in vivo neutralization of the pro-inflammatory cytokines, including that for therapeutic purposes. [Copyright &y& Elsevier]

Heat-shock proteins (hsps) are highly conserved and immunogenic, and they are generally perceived to be attractive initiators or targets of a pathogenic immune response, and as such, have been implicated in the pathogenesis of autoimmune arthritis. However, studies in animal models and arthritis patients have unraveled the disease-regulating attributes of self-hsp65. We propose that the self-hsp65 induces a protective and beneficial immune response because of its ubiquitous distribution, stress inducibility and participation in tolerogenic processes. By contrast, the foreign hsp65 that does not influence the above processes and that resides admixed with microbial ligands for innate receptors generates an inflammatory pathogenic response. The regulatory properties of self-hsps need be fully explored and might be used for therapeutic purposes. [Copyright &y& Elsevier]

Background: Myocardial Infarction carries a significant morbidity, psychological effects, and financial constraints for the patient and the family when it occurs at young age. However there is limited data on the clinical features of young adults with AMI in Egypt and the Middle Eastern region. We therefore sought to investigate the clinical profile, risk factors and angiographic variables of this age group in Egypt. Aim of the Work: To determine the clinical profile and prevalence of different risk factors including Cigarette Smoking, Tramadol use, Cannabis smoking, HDL & LDL levels, stressful lifestyle and bad sleeping habits in Egyptian patients presented with Myocardial Infarction for the first time at age ≥ 45 years. Methods: We conducted a cross sectional observational study on 106 consecutive patients aged ≤ 45 years admitted with 1st time myocardial infarction in the period between February 2018 and August 2018 at Ain Shams University, Egypt. Clinical, and Angiographic variables were recorded from all patients. Results: Out of 1207 patients admitted with 1st time MI, 106 were young that gave a prevalence of 8.8% in our center. Out of 106 patients, 101 were male. Mean age was 39.19 yrs. 71 patients had ST elevation myocardial infarction (MI) (67%) and 35 had non ST elevation MI (33%). Anterior wall MI was present in 49 patients (46.2%), inferior wall MI in 20 patients (18.9%) and lateral wall MI in 2 patients (1.9%). 93 patients (88%) were smokers, 31 patients (29.2%) were Tramadol users, 43 patients(40.6%) smoked cannabis, 50 patients (47.2%) had bad sleeping habits, 29 patients (27.4%) had high stress levels, 37 patients (34.9%) were hypertensive, 22 patients were diabetic (20.8%). Family history of CAD was present in 20 (18.9%) patients. Low High-density lipoprotein (HDL) was seen in 47 patients (44.3%), and high Low-density lipoprotein in 20 patients (18.9%). LAD was involved in 56% of patients, with a significant association between Tramadol use and LAD involvement. We found significant association between both Tramadol use and Cannabis smoking and the presence of Heavy thrombus burden in Coronary Angiography. Conclusion: AMI in the young almost exclusively occurs in male, Anterior wall MI is most common, with LAD being involved in around half of patients. Smoking, hypertension, low HDL, Tramadol use, Cannabis smoking, and bad sleeping habits are the major risk factors. Tramadol use was associated with significant affection of LAD. Tramadol use and Cannabis smoking were associated with high thrombus burden on coronary angiograph. [ABSTRACT FROM AUTHOR]

In this opinion, we propose that the hierarchy of antigenic determinants within self-antigens is the major influence in molding the potentially autoreactive T-cell repertoire. The well processed and presented determinants constitute a ‘dominant self’, whereas the poorly processed and/or presented determinants will be invisible to T cells and comprise a ‘cryptic self’, which we consider a fundamental cornerstone of a theory of autoimmunity. It accounts for the large repertoire of self-reactive clones because a similar hierarchy is established in the thymus and controls positive and negative selection. Furthermore, this residual T-cell repertoire, largely directed against cryptic determinants, will contain some T cells with sufficient affinity for MHC and antigen that enables them to respond under inflammatory conditions, thus facilitating presentation of previously cryptic determinants. [Copyright &y& Elsevier]

Substrate-based sirtuin inhibitors target bacterial genome and RNA and provide a promising approach to address bacterial resistance issues, if cellular internalisation can be achieved. We designed N -trifluoroacetyl lysine and N -thioacetyl lysine peptides (KP 13 , KP 15 and KP 24) as inhibitors of bacterial sirtuins and their cell-penetrating peptide conjugates Tat KP 13 , Tat KP 15 and Tat KP 24. The conjugated peptides were successfully internalised and showed signs of bacterial transcription inhibition resulting in enhanced antibacterial potency against model Gram negative and Gram positive pathogens. Synergistic activity in combination with streptomycin and polymyxin B has also been established. These peptides were effective in inhibiting biofilm formation and eradicating preformed biofilms. Morphological analysis using both SEM and TEM showed bacterial membrane disruption. Calcein dye leakage analysis established the selectivity of these peptides to bacterial membranes. This study documents the first report of the application of substrate-based sirtuin inhibitors as antimicrobial therapeutics. [Display omitted] • First report of substrate-based sirtuin inhibitors as antimicrobials. • Tat-conjugates cause bacterial transcription inhibition. • Synergistic activity with known antibiotics established. [ABSTRACT FROM AUTHOR]

Reports on the selective and reversible chemical modification of mucin-like ligand that alters the mechanical properties of its bond with L-selectin. How interactions between adhesion molecules on two different cells differ from interactions between receptors and soluble ligands in that the adhesion molecule interaction (bond) are often subjected to force; The role of L-selectin; Findings.

Focuses on the role of cell adhesion molecules called L-selectins in binding carbohydrate ligands and in promoting interaction between leukocytes and the vessel wall in vascular shear flow. High molecular strengths of selectin-ligand bonds; Shear threshold requirement for L-selectin in the prevention of inappropriate aggregation of leukocytes.

Examines the role of CD34 in mediating lymphocyte tethering and rolling under in vitro flow conditions and determines its contribution relative to other components in the peripheral node addressin (PNAd) complex. High endothelial venules; Lymphocyte homing or recirculation.

Determinant spreading has been implicated in the pathogenesis of certain autoimmune diseases in animal models. We have observed that during the course of adjuvant arthritis (AA) in the Lewis rat, there is 'diversification' of response to the bacterial 65-kDa heat shock protein (Bhsp65) towards its carboxy-terminal determinants (BCTD). Strikingly, pretreatment of naive Lewis rats with BCTD affords significant protection from AA. Our preliminary studies indicate that the diversification of response to BCTD in the Lewis rat is probably triggered in vivo by the induction and enhanced processing of self(rat0 hsp65. Thus, the self hsp65-directed T-cell responses appear to be involved in mediating natural remission from acute inflammatory arthritis induced by a foreign antigen, Mycobacterium tuberculosis. This this first report describing that the new T-cell specificities arising during the course of an autoimmune disease are regulatory/protective rather than pathogenic. Moreover, our results suggest that a final common mechanism involving BCTD might be recruited by other rat strains which either are resistant to AA (WKY rats) or whose susceptibility to AA is modulated significantly by microbial flora (Fisher rats). The results of this study would contribute significantly to understanding of the pathogenesis of human rheumatoid arthritis, and in devising new therapeutic strategies for this disease. [ABSTRACT FROM AUTHOR]

Studies the role of endothelin (ET) receptors in thrombin-induced modulation of vascular tone. Contribution of ET-1 to the increase in nitric oxide production; Significance of ET receptor activation; Thrombin-induced relaxation during pretreatment with endothelin receptor antagonists.

Evaluates the role of endothelin (ET) receptors in thrombin-induced modulation of vascular tone by direct measurement of ET-1 and ET receptor-coupled nitric oxide release and developed isometric tension in thrombin-treated aortic rings. Vascular contraction and reagents; ET receptor desensitization; Synthesis and release of ET-1.

Reports on platelet-mediated lymphocyte delivery to high endothelial venules. Ability of circulating lymphocytes to initiate rolling along endothelial venules; Binding of activated platelets to circulating lymphocytes.

Background: Malnutrition and suboptimal food intake are common concerns among chronic kidney disease (CKD) patients. Medical nutrition therapy plays a significant role in ensuring the well-being of CKD patients undergoing maintenance hemodialysis (MHD). The present study explored the dietary intake and quality of life (QOL) of CKD patients on MHD. Materials and Methods: Adult CKD patients (n = 107, >20 years, 72% male) on MHD were conveniently selected from dialysis centers across India. This cross-sectional exploratory study elicited information on general profile, height, dry body weight, biochemical parameters, food intake, and QOL of the patients. Nutrient intake was compared with Kidney Disease Outcomes Quality Initiative (KDOQI) Guidelines. Results: The average energy and protein intake per kg body weight was below the recommendations (energy ~21 kcal/kg vs. 30-35 kcal/kg body weight and protein ~0.7g/kg vs. 1-1.2 g/kg body weight). Majority of them (>75%) had inadequate energy and protein intake. The sodium intake of the participants (3109.42 ± 1012.31 mg) was higher than the suggested limit. The energy and protein intake/kg ideal body weight of female patients was significantly higher than male patients (p < 0.05). Overall, their QOL was satisfactory. However, nearly half of them (47%) reported moderate-level problem in the pain and discomfort dimension. Conclusion: Patients were not meeting the recommendations especially for energy and protein. Patient-specific customized nutrition counseling along with routine nutrition assessment, follow-up of patients and continued nutrition education, and motivation and support from the medical care team, especially the dietitian is needed for better dietary compliance and overall improvement of QOL. [ABSTRACT FROM AUTHOR]

Background: Excessive production of IgE plays a major role in the pathology of food allergy. In an attempt to identify anti‐IgE natural products, Arctium Lappa was one of the most effective herbs among approximately 300 screened medicinal herbs. However, little is known about its anti‐IgE compounds. Objective: To identify compounds from Arctium Lappa for targeted therapy on IgE production and explore their underlying mechanisms. Methods: Liquid‐liquid extraction and column chromatographic methods were used to purify the compounds. IgE inhibitory effects were determined on IgE‐producing human myeloma U266 cells, peanut‐allergic murine model and PBMCs from food‐allergic patients. Genes involved in IgE inhibition in PBMCs were studied by RNA sequencing. Results: The main compounds isolated were identified as arctiin and arctigenin. Both compounds significantly inhibited IgE production in U266 cells, with arctigenin the most potent (IC50=5.09μg/mL). Arctigenin (at a dose of 13 mg/kg) markedly reduced peanut‐specific IgE levels, blocked hypothermia and histamine release in a peanut‐allergic mouse model. Arctigenin also significantly reduced IgE production and Th2 cytokines (IL‐5, IL‐13) by PBMCs. We found 479 differentially expressed genes in PBMCs with arctigenin treatment (p <.001 and fold‑change ≥1.5), involving 24 gene ontology terms (p <.001, FDR <0.05); cell division was the most significant. Eleven genes including UBE2C and BCL6 were validated by qPCR. Conclusion: Arctigenin markedly inhibited IgE production in U266 cells, peanut‐allergic murine model and PBMCs from allergic patients by down‐regulating cell division, cell cycle‐related genes and up‐regulating anti‐inflammatory factors. [ABSTRACT FROM AUTHOR]

Eczema is a complex chronic inflammatory skin disease impacted by environmental factors, infections, immune disorders, and deficiencies in skin barrier function. Shi Zhen Tea (SZT), derived from traditional Chinese medicine Xiao-Feng-San, has shown to be an effective integrative therapy for treating skin lesions, itching, and sleeping loss, and it facilitates reduction of topical steroid and antihistamine use in pediatric and adult patients with severe eczema. Yet, its active compounds and therapeutic mechanisms have not been elucidated. In this study, we sought to investigate the active compounds and molecular mechanisms of SZT in treating eczema using systems pharmacology and in silico docking analysis. SZT is composed of 4 medicinal herbs, Baizhu (Atractylodis macrocephalae rhizome), Jingjie (Schizonepetae herba), Kushen (Sophorae flavescentis radix), and Niubangzi (Arctii fructus). We first identified 51 active compounds from SZT and their 81 potential molecular targets by high-throughput computational analysis, from which we identified 4 major pathways including Th17 cell differentiation, metabolic pathways, pathways in cancer, and the PI3K-Akt signaling pathway. Through network analysis of the compound-target pathway, we identified hub molecular targets within these pathways including carbonic anhydrase II (CA2), peroxisome proliferator activated receptor γ (PPAR γ), retinoid X receptor α (RXRA), and vitamin D receptor (VDR). We further identified top 5 compounds including cynarine, stigmasterin, kushenol, β-sitosterol, and (24S)-24-propylcholesta-5-ene-3β-ol as putative key active compounds on the basis of their molecular docking scores with identified hub target proteins. Our study provides an insight into the therapeutic mechanism underlying multiscale benefits of SZT for eczema and paves the way for developing new and potentially more effective eczema therapies. [ABSTRACT FROM AUTHOR]

• Environment plays a significant role in the pathogenesis of autoimmune arthritis. • 'Hygiene hypothesis' suggests inverse relationship between infection and autoimmunity. • Gut microbiota is critical for Th17/Treg balance and protection against autoimmunity. • Many functional attributes of microbiota are mediated via microbial metabolites. • Gut dysbiosis can be re-set in part via pre-/pro-biotics and fecal transplantation. Observations in patients with autoimmune diseases and studies in animal models of autoimmunity have revealed that external environmental factors including exposure to microbes and the state of the host gut microbiota can influence susceptibility to autoimmunity and subsequent disease development. Mechanisms underlying these outcomes continue to be elucidated. These include deviation of the cytokine response and imbalance between pathogenic versus regulatory T cell subsets. Furthermore, specific commensal organisms are associated with enhanced severity of arthritis in susceptible individuals, while exposure to certain microbes or helminths can afford protection against this disease. In addition, the role of metabolites (e.g., short-chain fatty acids, tryptophan catabolites), produced either by the microbes themselves or from their action on dietary products, in modulation of arthritis is increasingly being realized. In this context, re-setting of the microbial dysbiosis in RA using prebiotics, probiotics, or fecal microbial transplant is emerging as a promising approach for the prevention and treatment of arthritis. It is hoped that advances in defining the interplay between gut microbiota, dietary products, and bioactive metabolites would help in the development of therapeutic regimen customized for the needs of individual patients in the near future. [ABSTRACT FROM AUTHOR]

Abstract Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the synovial tissue of the joints. Inadequately controlled disease may cause severe joint damage and deformity. Currently, the anti-arthritic drugs are given systemically, and therefore, they are widely distributed to other organs that are not the intended therapeutic targets. Accordingly, using a particular dose/regimen of a drug to achieve an effective local concentration of the drug in arthritic joints may lead to expected adverse effects involving other organs. Thus, improved methods of drug delivery are needed for arthritis therapy. One attractive approach is the targeting of a systemically administered drug to the inflamed joints. We describe here a prototypic drug delivery system using a novel peptide ligand denoted as ART-1. We previously reported ART-1 (=ADK) as a peptide that preferentially homes to the inflamed joints of arthritic rats and binds to synovial endothelial cells. We tested the ART-1-coated liposomes encapsulating a fluorescent compound for binding to activated endothelial cells in vitro and homing to arthritic joints in vivo, compared to control liposomes lacking the ART-1 coating. Similar liposomes but encapsulating an immunomodulatory cytokine interleukin-27 (ART-1-IL-27 liposomes) were tested for their anti-arthritic activity compared with control liposomes. ART-1-displaying liposomes showed better binding to endothelial cells as well as in vivo homing to arthritic joints compared to control liposomes. Furthermore, ART-1-IL-27 liposomes, when intravenously injected to arthritic rats after the onset of arthritis, were more effective in suppressing disease progression than control-IL-27 liposomes lacking ART-1 or free IL-27 at an equivalent dose of IL-27. In addition, ART-1-directed liposomal IL-27 had a better safety profile than undirected liposomal IL-27 or free IL-27, thereby offering an improved therapeutic index for IL-27 therapy. These results provide a proof-of concept for the use of a novel joint-homing peptide for targeted delivery of drugs including biologics or small molecule compounds to arthritic joints with enhanced efficacy and reduced systemic exposure. This targeted therapy platform may be suitable for use in RA patients. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]

Although aging is associated with progressive adiposity and a decline in liver function, the underlying molecular mechanisms and metabolic interplay are incompletely understood. Here, we demonstrate that aging induces hepatic protein kinase Cbeta (PKCβ) expression, while hepatocyte PKCβ deficiency (PKCβHep−/−) in mice significantly attenuates obesity in aged mice fed a high-fat diet. Compared with control PKCβfl/fl mice, PKCβHep−/− mice showed elevated energy expenditure with augmentation of oxygen consumption and carbon dioxide production which was dependent on β3-adrenergic receptor signaling, thereby favoring negative energy balance. This effect was accompanied by induction of thermogenic genes in brown adipose tissue (BAT) and increased BAT respiratory capacity, as well as a shift to oxidative muscle fiber type with an improved mitochondrial function, thereby enhancing oxidative capacity of thermogenic tissues. Furthermore, in PKCβHep−/− mice, we determined that PKCβ overexpression in the liver mitigated elevated expression of thermogenic genes in BAT. In conclusion, our study thus establishes hepatocyte PKCβ induction as a critical component of pathophysiological energy metabolism by promoting progressive hepatic and extrahepatic metabolic derangements in energy homeostasis, contributing to late-onset obesity. These findings have potential implications for augmenting thermogenesis as a means of combating aging-induced obesity. [ABSTRACT FROM AUTHOR]

Introduction: Various materials are used to improve the longevity of the dental implants. In our study, we assessed the marginal bone loss around dental implants after implantation with platelet-rich plasma. Materials and Methods: We conducted a prospective clinical study among 200 subjects who were grouped equally as those with and without the application of PRF in the implantation. The radiographic and clinical features for the marginal bone loss were assessed and compared keeping P < 0.05 as statistically significant. Results: We observed no significant variation between the groups for the mobility, bleeding on probing, plaque index, and marginal bone loss. Conclusion: We can conclude that the application of PRP concentrate did not significantly affect the marginal bone loss in the dental implantation. [ABSTRACT FROM AUTHOR]

Hydatid cyst is a common name for the larval stage of a tapeworm species of Echinococcus granulosus, which is transmitted from animals to humans via the fecal–oral route. Hydatid cysts predominantly affect the liver (75%), followed by the lung (15%), and they can affect many organs in the human body. Medical imaging modalities are the keystone for the diagnosis of hydatid cysts with high sensitivity and specificity. Ultrasound imaging with high resolution is the first choice for diagnosis, differential diagnosis, staging, establishing a role in interventional management, and follow-up, and it can differentiate Type I hydatid cysts from simple liver cysts. Unenhanced computed tomography (CT) is indicated where or when an ultrasound is unsatisfactory, such as with chest or brain hydatid cysts, when detecting calcification, and in obese patients. Magnetic resonance imaging (MRI) is superior for demonstrating cyst wall defects, biliary communication, neural involvement, and differentiating hydatid cysts from simple cysts using diffusion-weighted imaging (DWI) sequences. According to the phase of growth, hydatid cysts occur in different sizes and shapes, which may mimic benign or malignant neoplasms and may create diagnostic challenges in some cases. Hydatid cysts can mimic simple cysts, choledochal cysts, Caroli's disease, or mesenchymal hamartomas of the liver. They can mimic lung cystic lesions, mycetoma, blood clots, Rasmussen aneurysms, and even lung carcinomas. Differential diagnosis can be difficult for arachnoid cysts, porencephalic cysts, pyogenic abscesses, and even cystic tumors of the brain, and can create diagnostic dilemmas in the musculoskeletal system. [ABSTRACT FROM AUTHOR]

Cerebral palsy is the most common cause of developing neuro-motor disability in children, in many cases, the triggering cause remaining unknown. Quadriplegia is the most severe spastic cerebral palsy, characterized by severe mental retardation and bi-pyramidal syndrome. The purpose of this paper was to demonstrate the importance of knowing the risk factors and the psychosomatic ones, determining to what extent they influence the functional evolution in patients diagnosed with spastic quadriplegia. 23 children diagnosed with spastic quadriplegia were included in the study, being aged between 1 year and half and 12 years. Patients were assessed at baseline (T1), at one year (T2) and after two years at the end of the study (T3). Patients received a comprehensive rehabilitation program for the motor and sensory deficits throughout the study. Initially, a comprehensive evaluation (etiopathogenic, clinical and functional) that started from a thorough medical history of children (the older ones), was conducted but chose parents to identify the risk factors, and a complete physical exam. At each assessment, joint and muscle balance was conducted. To assess functionality, the gross motor function classification systems (GMFCS) and manual ability (MACS) were used. Many risk factors that were classified according to the timeline in prenatal factors, perinatal and postnatal, were identified from a thorough history. A direct correlation was noticed between the decrease of coarse functionality and manual ability, both initially and in dynamic and low APGAR scores, low gestational age, low birth weight and a higher body mass index of the mother. A direct link was observed between the gross motor function and the manual ability. A significant improvement in the MACS score was noticed in patients with a better GMFCS score. [ABSTRACT FROM AUTHOR]

The T helper (Th) cell subsets are characterized by the type of cytokines produced and the master transcription factor expressed. Th1 cells participate in cell-mediated immunity, whereas Th2 cells promote humoral immunity. Furthermore, the two subsets can control each other. Thereby, Th1–Th2 balance offered a key paradigm in understanding the induction and regulation of immune pathology in autoimmune and other diseases. However, over the past decade, Th17 cells producing interleukin-17 (IL-17) have emerged as the major pathogenic T cell subset in many pathological conditions that were previously attributed to Th1 cells. In addition, the role of CD4 + CD25 + T regulatory cells (Treg) in controlling the activity of Th17 and other T cell subsets has increasingly been realized. Thereby, examination of the Th17/Treg balance in the course of autoimmune diseases has significantly advanced our understanding of the pathogenesis of these disorders. The differentiation of Th17 and Treg cells from naïve T cells is inter-related and controlled in part by the cytokine milieu. For example, transforming growth factor β (TGFβ) is required for Treg induction, whereas the same cytokine in the presence of IL-6 (or IL-1) promotes the differentiation of Th17. Furthermore, IL-23 plays a role in the maintenance of Th17. Accordingly, novel therapeutic approaches are being developed to target IL-23/IL-17 as well as to modulate the Th17/Treg balance in favor of immune regulation to control autoimmunity. [ABSTRACT FROM AUTHOR]

Psychosocial aspects related to home hemodialysis (HD) play an important role in the success of home HD programs. Once patients commence HD at home, unique psychosocial issues related to patient and care partner burden can emerge. Proactive professional support, peer support, respite care, travel support, and financial support from the home HD health care team must be a priority for patient care. If the psychosocial aspects are not proactively addressed, patients receiving HD at home may return to in-center HD and the program may struggle as a result. This review provides a psychosocial guide for new start-up home HD programs. [ABSTRACT FROM AUTHOR]

Psychosocial aspects related to home hemodialysis ( HD) play an important role in the success of home HD programs. Once patients commence HD at home, unique psychosocial issues related to patient and care partner burden can emerge. Proactive professional support, peer support, respite care, travel support, and financial support from the home HD health care team must be a priority for patient care. If the psychosocial aspects are not proactively addressed, patients receiving HD at home may return to in-center HD and the program may struggle as a result. This review provides a psychosocial guide for new start-up home HD programs. [ABSTRACT FROM AUTHOR]

Susceptibility to autoimmunity is determined by multiple factors. Defining the contribution of the quantitative versus qualitative aspects of antigen-directed immune responses as well as the factors influencing target organ susceptibility is vital to advancing the understanding of the pathogenesis of autoimmunity. In a series of studies, we have addressed these issues using the adjuvant-induced arthritis (AA) model of human rheumatoid arthritis (RA). Lewis rats are susceptible to AA following immunization with heat-killed Mycobacterium tuberculosis H37Ra, whereas Wistar-Kyoto (WKY) rats of the same MHC (major histocompatibility complex) haplotype are resistant. Comparative studies on these and other susceptible/resistant rodent strains have offered interesting insights into differential cytokine responses in the face of comparable T cell proliferative response to the disease relevant antigens. Study of the cytokine kinetics have also permitted validation of the disease-protective versus disease- aggravating effects of specific cytokines by treatment of rats/mice with those cytokines at different phases of the disease. In regard to the target organ attributes, the migration of arthritogenic leukocytes into the joints; the expression of mediators of inflammation, angiogenesis, and tissue damage; the role of vascular permeability; and the characteristics of vascular endothelial cells have been examined. Further, various inhibitors of angiogenesis are effective in suppressing arthritis. Taken together, the differential cytokine responses and unique attributes of the target organ have revealed novel aspects of disease susceptibility and joint damage in AA. The translation of this basic research in animal models to RA patients would not only advance our understanding of the disease process, but also offer novel avenues for immunomodulation of this disease. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the synovial joints leading to bone and cartilage damage. Untreated inflammatory arthritis can result in severe deformities and disability. The use of anti-inflammatory agents and biologies has been the mainstay of treatment of RA. However, the prolonged use of such agents may lead to severe adverse reactions. In addition, many of these drugs are quite expensive. These limitations have necessitated the search for newer therapeutic agents for RA. Natural plant products offer a promising resource forpotential antiarthritic agents. We describe here the cellular and soluble mediators of inflammation-induced bone damage (osteoimmunology) in arthritis. We also elaborate upon various herbal products that possess antiarthritic activity, particularly mentioning the specific target molecules. As the use of natural product supplements by RA patients is increasing, this paper presents timely and useful information about the mechanism of action of promising herbal products that can inhibit the progression of inflammation and bone damage in the course of arthritis. [ABSTRACT FROM AUTHOR]

Abstract: Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the joints. The prolonged use of non-steroidal anti-inflammatory drugs and other newer drugs is associated with severe adverse reactions. Therefore, there is a need for newer anti-arthritic agents. Celastrol, a bioactive component of the Chinese herb Celastrus, possesses anti-arthritic activity as tested in the adjuvant arthritis (AA) model of rheumatoid arthritis (RA). However, the mechanism of action of Celastrol has not been fully defined. We reasoned that microarray analysis of the lymphoid cells of Celastrol-treated arthritic animals might provide vital clues in this regard. We isolated total RNA of the draining lymph node cells (LNCs) of Celastrol-treated (Tc) and vehicle-treated (Tp) arthritic Lewis rats that were restimulated in vitro with the disease-related antigen, mycobacterial heat-shock protein 65 (Bhsp65), and tested it using microarray gene chips. Also tested was RNA from LNCs of control arthritic rats just before any treatment (T0). Seventy six genes involved in various biological functions were differentially regulated by Bhsp65 in LNCs of Tp group, and 19 genes among them were shared by the Tc group. Furthermore, a group of 14 genes was unique to Tc. When Tc and Tp were compared, many of the Bhsp65-induced genes were related to the immune cells, cellular proliferation and inflammatory responses. Our results revealed 10 differentially expressed genes and 14 pathways that constituted the “Celastrol Signature”. Our results would help identify novel targets for RA therapy. [Copyright &y& Elsevier]

Abstract: Rheumatoid arthritis (RA) is a chronic debilitating disease characterized by synovial inflammation, damage to cartilage and bone, and deformities of the joints. Several drugs possessing anti-inflammatory and immunomodulatory properties are being used in the conventional (allopathic) system of medicine to treat RA. However, the long-term use of these drugs is associated with harmful side effects. Therefore, newer drugs with low or no toxicity for the treatment of RA are actively being sought. Interestingly, several herbs demonstrate anti-inflammatory and anti-arthritic activity. In this review, we describe the role of the major biochemical and molecular mediators in the pathogenesis of RA, and highlight the sites of action of herbal medicinal products that have anti-arthritic activity. With the rapidly increasing use of CAM products by patients with RA and other inflammation-related disorders, our review presents timely information validating the scientific rationale for the use of natural therapeutic products. [ABSTRACT FROM AUTHOR]

Abstract: Studies on the precursors of Nummulites gizehensis group and Nummulites partschi group from the Eocene of Egypt has permitted the identification of seven species. Two of these, namely Nummulites rushdisaidi n.sp. and Nummulites qenaensis n.sp. are new. This study suggests that the group might have evolved polyphyletically since the early Ypresian with more marked diversification during the Middle Eocene and attained maximum test size during Bartonian (Nummulites lyelli). This group has been studied in stratigraphic sequence, taking into consideration their geographic distribution. Some known Ypresian precursors such as Nummulites delaharpei and Nummulites mariettei (topotypes) and Nummulites rollandi are also described and illustrated for the first time. During the evolution, retrogenesis was noticed with species evolving from lax to tightly coiled whorls in microspheric forms, whilst the megalospheric forms become progressively lax internally and tighter externally, or vice versa. In addition, duplication of the spiral was noticed in N. qenaensis n.sp. Also, reflexive coiling expressing change in the course of the septa in the outer whorls has been noticed during the ontogeny in N. rollandi. [Copyright &y& Elsevier]

Abstract: Heat-shock proteins (Hsps) have been invoked in the pathogenesis of a variety of autoimmune diseases. The mycobacterial heat-shock protein 65 (Bhsp65) has been studied extensively as one of the antigenic triggers of autoimmunity in experimental models of, as well as patients with, rheumatoid arthritis. As Hsps are highly conserved and immunogenic, it is generally anticipated that self Hsps might serve as the endogenous targets of the immune response initiated by the homologous foreign Hsps. Contrary to this expectation, studies in the rat adjuvant arthritis (AA) model have revealed that priming of the self (rat) hsp65 (Rhsp65)-directed T cells in the Lewis rat leads to protection against AA instead of disease induction or aggravation. The arthritis-protective attribute of the self hsp65 is also evident following spontaneous priming of the anti-Rhsp65 T cells during the natural course of AA. Furthermore, immunization of rats with human hsp60, or with Bhsp65 peptides that are crossreactive with the corresponding self hsp65 peptides, leads to protection against AA. Importantly, high levels of T cell reactivity against self hsp60 in patients with juvenile idiopathic arthritis positively correlate with a favorable outcome of the disease. Thus, immune response against self hsp65 in autoimmune arthritis is protective rather than being pathogenic. [Copyright &y& Elsevier]

Until recently, autoimmune disease research has primarily been focused on elucidating the role of the adaptive immune system. In the past decade or so, the role of the innate immune system in the pathogenesis of autoimmunity has increasingly been realized. Recent findings have elucidated paradigm-shifting concepts, for example, the implications of "trained immunity" and a dysbiotic microbiome in the susceptibility of predisposed individuals to clinical autoimmunity. In addition, the application of modern technologies such as the quantum dot (Qdot) system and 'Omics' (e.g., genomics, proteomics, and metabolomics) data-processing tools has proven fruitful in revisiting mechanisms underlying autoimmune pathogenesis and in identifying novel therapeutic targets. This review highlights recent findings discussed at the American Autoimmune Related Disease Association (AARDA) 2019 colloquium. The findings covering autoimmune diseases and autoinflammatory diseases illustrate how new developments in common innate immune pathways can contribute to the better understanding and management of these immune-mediated disorders. • The role of the innate immune system in the pathogenesis of autoimmunity is increasingly being realized. • 'Trained immunity' or 'innate immune memory' is a paradigm-shifting concept with broad applications. • Environmental factors, including host-resident microbiota, have a profound effect on autoimmunity • Common innate immune pathways can be targeted for the management of both autoimmune and autoinflammatory diseases. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic autoimmune disease of the joints affecting about 0.3–1% of the population in different countries. About 50–60 percent of RA patients respond to presently used drugs. Moreover, the current biomarkers for RA have inherent limitations. Consequently, there is a need for additional, new biomarkers for monitoring disease activity and responsiveness to therapy of RA patients. We examined the micro-RNA (miRNA) profile of immune (lymphoid) cells of arthritic Lewis rats and arthritic rats treated with celastrol, a natural triterpenoid. Experimental and bioinformatics analyses revealed 8 miRNAs (miR-22, miR-27a, miR-96, miR-142, miR-223, miR-296, miR-298, and miR-451) and their target genes in functional pathways important for RA pathogenesis. Interestingly, 6 of them (miR-22, miR-27a, miR-96, miR-142, miR-223, and miR-296) were further modulated by celastrol treatment. Interestingly, serum levels of miR-142, miR-155, and miR-223 were higher in arthritic versus control rats, whereas miR-212 showed increased expression in celastrol-treated rats compared with arthritic rats or control rats. This is the first study on comprehensive miRNA expression profiling in the adjuvant-induced arthritis (AA) model and it also has revealed new miRNA targets for celastrol in arthritis. We suggest that subsets of the above miRNAs may serve as novel biomarkers of disease activity and therapeutic response in arthritis. [ABSTRACT FROM AUTHOR]

Arishtas and asavas are self-generated herbal fermentations of traditional system and are considered as unique and valuable therapeutics in ayurveda. The objective of the present study was to determine the antibacterial and anthelmintic activity of four fermented ayurvedic herbal formulations namely Vidangarishta, Chandanasava, Pippalyasava and Kanakasava. The antibacterial activity of herbal formulations was tested against bacteria namely Staphylococcus aureus and Escherichia coli in liquid nutrient media. S. aureus has shown more susceptibility than E. coli. Among formulations tested, Vidangarishta caused inhibition of E. coli to more extent followed by Kanakasava, Pippalyasava and Chandanasava. Inhibition of S. aureus was higher in case of Vidangarishta followed by Kanakasava, Chandanasava and Pipalyasava. The anthelmintic assay was performed on adult Indian earthworm Pheretima pasthuma due to its anatomical and physiological resemblance with the intestinal roundworm parasites of human beings. The formulations have shown a dose-dependent paralysis and death of worms. Among formulations, Vidangarishta was shown more effective in causing paralysis and death of worms in shorter period of time followed by Kanakasava, Pippalyasava and Chandanasava. The consumption of formulations could be useful against pathogenic bacteria and helminths in addition to the ailments for which they are recommended. [ABSTRACT FROM AUTHOR]