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The c9,t11‐conjugated linoleic acid (CLA), which is the minor polyunsaturated fatty acid (PUFA) naturally present in butter, has gained attention due to its important preventive effect against breast cancer in vitro. In this paper, the enrichment of c9,t11‐CLA from butter was optimized and the preventive effect of dietary c9,t11‐CLA against breast cancer in vivo was investigated. Results showed that the concentration of c9,t11‐CLA increased more than 10 times via a one‐step urea complexation. Furthermore, the dietary c9,t11‐CLA showed obvious preventive effect against breast cancer in decreasing the tumor weight and volume, and reducing the tumor incidence up to 50%. In addition, the expression of progesterone receptor and Ki‐67 decreased significantly with the treatment of c9,t11‐CLA. In conclusion, the dietary c9,t11‐CLA enriched from butter showed a preventive effect against breast cancer in vivo via the inhibition of the hormonal receptor and cell proliferation. Practical applications: This paper provided new insight into the preparation of specific c9,t11‐CLA isomer. It can be enriched from butter in large‐scale with low‐cost by urea complexation. Meanwhile, the enriched dietary c9,t11‐CLA can be further processed into cancer prevention functional foods. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a chronic inflammatory disease with a high prevalence and canceration rate. The immune disorder is one of the recognized mechanisms. Acupuncture is widely used to treat patients with IBD. In recent years, an increasing number of studies have proven the effectiveness of acupuncture in the treatment of IBD, and some progress has been made in the mechanism. In this paper, we reviewed the studies related to acupuncture for IBD and focused on the immunomodulatory mechanism. We found that acupuncture could regulate the innate and adaptive immunity of IBD patients in many ways. Acupuncture exerts innate immunomodulatory effects by regulating intestinal epithelial barrier, toll-like receptors, NLRP3 inflammasomes, oxidative stress, and endoplasmic reticulum stress and exerts adaptive immunomodulation by regulating the balance of Th17/Treg and Th1/Th2 cells. In addition, acupuncture can also regulate intestinal flora. [ABSTRACT FROM AUTHOR]

Tumor is the most serious threat to human beings. Although war against cancer has been launched over forty years, cancer treatment is still far away from being satisfactory. Immunotherapy, especially checkpoint blockade immunotherapy, is a rising star that shows a promising future. To fulfill the requirement of depleting primary tumor and inhibiting tumor metastasis and recurrence, many researchers combined checkpoint blockade immunotherapy with other treatment strategies to extend the treatment outcome. Photodynamic therapy could induce immunogenic cell death, and checkpoint blockade could further accelerate the immunity; therefore, combining these two strategies publishes many papers. Additionally, photothermal therapy and immunotherapy were also utilized for combining with checkpoint blockade, which were also reviewed in this paper. Furthermore, antibodies, siRNA, and small molecule inhibitors are developed to block the checkpoint; therefore, we categorized the papers into three sections, combination nanoparticles with checkpoint blockade antibody, combination nanoparticles with checkpoint blockade siRNA, and combination nanoparticles with small molecule checkpoint inhibitors, and related researches were summarized. In conclusion, the combination nanoparticle with checkpoint blockade cancer immunity is a promising direction that may fulfill the requirement of cancer treatment. [ABSTRACT FROM AUTHOR]

Identifying the interactions of the drug-target is central to the cognate areas including drug discovery and drug reposition. Although the high-throughput biotechnologies have made tremendous progress, the indispensable clinical trials remain to be expensive, laborious, and intricate. Therefore, a convenient and reliable computer-aided method has become the focus on inferring drug-target interactions (DTIs). In this research, we propose a novel computational model integrating a pyramid histogram of oriented gradients (PHOG), Position-Specific Scoring Matrix (PSSM), and rotation forest (RF) classifier for identifying DTIs. Specifically, protein primary sequences are first converted into PSSMs to describe the potential biological evolution information. After that, PHOG is employed to mine the highly representative features of PSSM from multiple pyramid levels, and the complete describers of drug-target pairs are generated by combining the molecular substructure fingerprints and PHOG features. Finally, we feed the complete describers into the RF classifier for effective prediction. The experiments of 5-fold Cross-Validations (CV) yield mean accuracies of 88.96%, 86.37%, 82.88%, and 76.92% on four golden standard data sets (enzyme, ion channel, G protein-coupled receptors (GPCRs), and nuclear receptor, respectively). Moreover, the paper also conducts the state-of-art light gradient boosting machine (LGBM) and support vector machine (SVM) to further verify the performance of the proposed model. The experimental outcomes substantiate that the established model is feasible and reliable to predict DTIs. There is an excellent prospect that our model is capable of predicting DTIs as an efficient tool on a large scale. [ABSTRACT FROM AUTHOR]

In this paper, we sought to explore the relationship between apolipoprotein AV (APOAV) overexpression and insulin resistance in hepatocytes. The insulin-resistant HepG2 cell model was constructed, and then, APOAV-overexpressed HepG2 cells (B-M) were induced by infecting with a recombinant adenovirus vector. Microarray data were developed from B-M samples compared with negative controls (A-con), and the microarray data were analyzed by bioinformatic methods. APOAV-overexpression induced 313 upregulated genes and 563 downregulated ones in B-M sample. The differentially expressed genes (DEGs) were significantly classified in fat digestion and absorption pathway. Protein-protein interaction network was constructed, and AGTR1 (angiotensin II receptor type 1) and P2RY2 (purinergic receptor P2Y, G-protein coupled 2) were found to be the significant nodes closely related with G-protein related signaling. Additionally, overexpression of APOAV could change the expression of Glut4 and release the insulin resistance of hepatic cells. Thus, APOAV overexpression may prevent the insulin resistance in liver cells by mediating the genes such as AGTR1 and P2RY2. [ABSTRACT FROM AUTHOR]

The body's autoimmune process is involved in the development of Graves' disease (GD), which is manifested by an overactive thyroid gland. In some patients, autoreactive inflammatory reactions contribute to the development of symptoms such as thyroid ophthalmopathy, and the subsequent signs and symptoms are derived from the expansion of orbital adipose tissue and edema of extraocular muscles within the orbit. The autoimmune process, production of antibodies against self-antigens such as TSH receptor (TSHR) and IGF-1 receptor (IGF-1R), inflammatory infiltration, and accumulation of glycosaminoglycans (GAG) lead to edematous-infiltrative changes in periocular tissues. As a consequence, edema exophthalmos develops. Orbital fibroblasts seem to play a crucial role in orbital inflammation, tissue expansion, remodeling, and fibrosis because of their proliferative activity as well as their capacity to differentiate into adipocytes and myofibroblasts and production of GAG. In this paper, based on the available medical literature, the immunological mechanism of GO pathogenesis has been summarized. Particular attention was paid to the role of orbital fibroblasts and putative autoantigens. A deeper understanding of the pathomechanism of the disease and the involvement of immunological processes may give rise to the introduction of new, effective, and safe methods of treatment or monitoring of the disease activity. [ABSTRACT FROM AUTHOR]

Objective. To explore the effect of C-phycocyanin (C-PC) on voiding behavior and histological changes in cyclophosphamide- (CYP-) induced cystitis in mice. Methods. Sixty female mice were included. The mice in the C-PC group received C-PC (25 mg/kg, twice, i.p.) and then CYP (200 mg/kg, i.p.) two hours later, while the mice in the CYP group only received the equivalent CYP. Saline was injected in the mice in the control group. A voided stain on paper (VSOP) test was conducted to analyze the micturition. The bladders were harvested for histological evaluation and measurements of inflammatory factors. Results. C-PC reduced the micturition frequency in the mice with CYP-induced cystitis. The bladder/body weight ratio and edema were remarkably higher in the CYP group compared to the C-PC group. C-PC suppressed the expressions of COX-2, PGE2, and EP4 (prostaglandin E receptor 4) according to the ELISA assay. Immunohistochemical staining also indicated that C-PC reduced the expressions of COX-2 in urothelium and EP4 in smooth muscles. Conclusions. C-PC relieved symptoms associated with CYP-induced cystitis in mice by inhibiting bladder inflammation through COX-2 and EP4 expression. [ABSTRACT FROM AUTHOR]

Purpose: Currently only one‐third of patients treated for depression enjoy complete remission of their negative symptoms. This paper explores ketamine research as it applies to understanding and treating mood illnesses. Conclusions: Ketamine's rapid antidepressant effect implicates downstream signal transduction involving the spontaneous transmissions associated with ketamine's action at the NMDA receptor. Practice Implications: Better understanding of brain neuropathophysiology offers hope for symptom relief to those living with affective illness refractory to currently available medical management. [ABSTRACT FROM AUTHOR]

Background. The prevalence of hypertension in children increases rapidly. This paper is to investigate the association of vitamin A and serum 25(OH)D level with hypertension and to explore the risk factors of hypertension in children. Methods. 164 children (age: 6-12 years, females: 49.39%) were included in this case-control study. The serum vitamin A and serum 25(OH)D level, the transcription level of RARs and RXRs, 25(OH)D receptor, and the retinol acyltransferase (LRAT), an indicator of vitamin A storage function, were measured. Results. The serum vitamin A level in hypertensive subjects was not significantly different compared to control, but the serum 25(OH)D level was significantly lower in hypertensive subjects compared to control (38.22±12.00umol/L vs. 43.28±12.33 umol/L, P=0.02). The transcription levels of RARα, RARβ, and RARγ were not significantly different between the two groups; but the LRAT was lower in the hypertensive group than that in the control (P<0.001). Compared with control group, the level of 25(OH)D receptor was lower in hypertension children (P=0.003). Logistic regression model showed that LRAT, HDL, and breastfed duration were negatively associated with blood pressure, and waist circumference was positively associated with blood pressure. Conclusions. The LRAT, serum 25(OH)D, and 25(OH)D receptor were significantly associated with blood pressure level, and both breastfed and HDL-C were independent protective factors of blood pressure level in children. [ABSTRACT FROM AUTHOR]

Enteropathogenic and enterohaemorrhagic E scherichia coli ( EPEC/EHEC) manipulate many cell processes by injecting effector proteins from the bacteria into the host cell via a Type III secretion system. In this paper we report that the effector protein EspG disrupts recycling endosome function. In particular, we found that following transferrin binding and endocytosis EspG reduces recycling of the transferrin receptor ( TfR), the prototypical recycling protein, from an intracellular location to the cell surface, resulting in an accumulation of TfR within the cell. The surface levels of three receptors [ TfR, epidermal growth factor receptor ( EGFR) and β1 integrin] were tested and found to be reduced dependent on EspG translocation. Furthermore, disruption of recycling endosome function and the reduced surface presentation of receptors was dependent on the previously reported RabGAP activity and ARF binding ability of EspG. This paper therefore supports the previous hypothesis that EspG acts as an enzyme scaffold perturbing cell signalling events, in this case altering recycling endosome function and cell surface receptor levels during infection. [ABSTRACT FROM AUTHOR]

Glucocorticoids intake is the most common cause of secondary osteoporosis. Clinical studies have shown that 50% patients develop glucocorticoids-induced osteoporosis (GCIOP) after taking glucocorticoids for more than 6 months. Hydroxysafflor yellow A (HYA) is one main active ingredient in Carthamus tinctorius L. Previous studies have shown that HYA promoted bone marrow mesenchymal stem cells to differentiate into osteoblasts which promoted bone formation. Therefore, we speculated that HYA has a therapeutic effect on GCIOP. However, there is no in vivo evidence about the anti-GCIOP effect of HYA. In this paper, the effect of HYA (0.1, 1.0, and 10.0 μM) on bone formation in normal zebrafish was investigated firstly. Secondly, the reversal effect of HYA on GCIOP was also evaluated by zebrafish model. It is demonstrated that HYA not only promoted bone formation in normal zebrafish (compared to Control group), but also reversed glucocorticoid induced bone loss (compared to Prednisolone group) according to the intervention of HYA in upregulating the area of mineralized bones (p < 0.01), increasing cumulative optical density (p < 0.01), promoting bone formation related gene expression (AKP, Type I, Runx2, OPG, and OCN, p < 0.01), inhibiting bone resorption related gene expression (TRACP, p < 0.01), and elevating whole-body trace mineral elements (Ca, P, K, Mg, Zn, and Fe) levels (p < 0.01). In conclusion, HYA had the potential to prevent and heal GCIOP by promoting bone mineralization, osteoblasts viability, and bone collagen expression and inhibiting bone resorption. [ABSTRACT FROM AUTHOR]

Alzheimer’s disease (AD) is a chronic and progressive neurodegenerative disorder and the pathogenesis of AD is poorly understood. G protein-coupled receptors (GPCRs) are involved in numerous key AD pathways and play a key role in the pathology of AD. To fully understand the pathogenesis of AD and design novel drug therapeutics, analyzing the connection between AD and GPCRs is of great importance. In this paper, we firstly build and analyze the AD-related pathway by consulting the KEGG pathway of AD and a mass of literature and collect 25 AD-related GPCRs for drug discovery. Then the ILbind and AutoDock Vina tools are integrated to find out potential drugs related to AD. According to the analysis of DUD-E dataset, we select five drugs, that is, Acarbose (ACR), Carvedilol (CVD), Digoxin (DGX), NADH (NAI), and Telmisartan (TLS), by sorting the ILbind scores (≥0.73). Then depending on their AutoDock Vina scores and pocket position information, the binding patterns of these five drugs are obtained. We analyze the regulation function of GPCRs in the metabolic network of AD based on the drug screen results, which may be helpful for the study of the off-target effect and the side effect of drugs. [ABSTRACT FROM AUTHOR]

The Locus Coeruleus (LC) is a small collection of noradrenergic neurons located in the pons. In the brain, noradrenaline (NE) is primarily produced by noradrenergic cell groups in the LC, which is the largest group of noradrenergic neurons in the central nervous system. Acupuncture, including the electroacupuncture which is a modified acupuncture method, is known to be effective in various kinds of diseases, and the involvement of noradrenergic system in the central nervous system has been reported by previous studies. However, on whether acupuncture can modulate the LC neuronal cells activities, results vary from studies to studies. In this paper, we included twelve articles, which observed the effect of acupuncture on the activities of LC in humans and animals. Our study shows that, among twelve included studies, six reported decrease of LC activities, whereas six showed increase of LC activities after acupuncture treatment. Although it is difficult to draw a firm conclusion, the authors suggest that the difference of frequencies may play an important role in the modulatory effect of acupuncture on LC. Further studies are needed to clarify the precise mechanism of acupuncture on LC, as it can lead to a new therapeutic method for various LC-NE related diseases. [ABSTRACT FROM AUTHOR]

Target selection is a key feature in cancer immunotherapy, a promising field in cancer research. In this respect, gangliosides, a broad family of structurally related glycolipids, were suggested as potential targets for cancer immunotherapy based on their higher abundance in tumors when compared with the matched normal tissues. GD2 is the first ganglioside proven to be an effective target antigen for cancer immunotherapy with the regulatory approval of dinutuximab, a chimeric anti-GD2 therapeutic antibody. Although the therapeutic efficacy of anti-GD2 monoclonal antibodies is well documented, neuropathic pain may limit its application. O-Acetyl-GD2, the O-acetylated-derivative of GD2, has recently received attention as novel antigen to target GD2-positive cancers. The present paper examines the role of O-acetyl-GD2 in tumor biology as well as the available preclinical data of anti-O-acetyl-GD2 monoclonal antibodies. A discussion on the relevance of O-acetyl-GD2 in chimeric antigen receptor T cell therapy development is also included. [ABSTRACT FROM AUTHOR]

This paper investigates the protective effect of interleukin-1 receptor antagonist (IL-1Ra) released from hyaluronic acid chitosan (HA-CS) microspheres in a controlled manner on IL-1β-induced inflammation and apoptosis in chondrocytes. The IL-1Ra release kinetics was characterized by an initial burst release, which was reduced to a linear release over eight days. Chondrocytes were stimulated with 10 ng/ml IL-1β and subsequently incubated with HA-CS-IL-1Ra microspheres. The cell viability was decreased by IL-1β, which was attenuated by HA-CS-IL-1Ra microspheres as indicated by an MTT assay. ELISA showed that HA-CS-IL-1Ra microspheres inhibited IL-1β-induced inflammation by attenuating increases in NO2- and prostaglandin E2 levels as well as increase in glycosaminoglycan release. A terminal deoxyribonucleotide transferase deoxyuridine triphosphate nick-end labeling assay revealed that the IL-1β-induced chondrocyte apoptosis was decreased by HA-CS-IL-1Ra microspheres. Moreover, HA-CS-IL-1Ra microspheres blocked IL-1β-induced chondrocyte apoptosis by increasing B-cell lymphoma 2 (Bcl-2) and decreasing Bcl-2-associated X protein and caspase-3 expressions at mRNA and protein levels, as indicated by reverse-transcription quantitative polymerase chain reaction and western blot analysis, respectively. The results of the present study indicated that HA-CS-IL-1Ra microspheres as a controlled release system of IL-1Ra possess potential anti-inflammatory and antiapoptotic properties in rat chondrocytes due to their ability to regulate inflammatory factors and apoptosis associated genes. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is one of the major metabolic disorders that is currently threatening the world. DM is seen associated with obesity and diabetic retinopathy (DR). In the present paper we tried to evaluate the relationship between the three aliments at the gene level and further performed the molecular docking to identify the common drug for all the three diseases. We have adopted several software programs such as Phenopedia, VennViewer, and CDOCKER to accomplish the objective. Our results revealed six genes that commonly associated and are involved in the signalling pathway. Furthermore, evaluation of common gene association from the selected set of genes projected the presence of SIRT1 in all the three aliments. Therefore, we targeted protein 4KXQ which was produced from the gene SIRT1 and challenged it with eight phytochemicals, adopting the CDOCKER. C1 compound has displayed highest -CDOCKER energy and -CDOCKER interaction energy of 43.6905 and 43.3953, respectively. Therefore, this compound is regarded as the most potential lead molecule. [ABSTRACT FROM AUTHOR]

P2Y1 receptor (P2Y1R), which belongs to G protein-coupled receptors (GPCRs), is an important target in ADP-induced platelet aggregation. The crystal structure of P2Y1R has been solved recently, which revealed orthosteric and allosteric ligand-binding sites with the details of ligand-protein binding modes. And it suggests that P2Y1R antagonists, which recognize two distinct sites, could potentially provide an efficacious and safe antithrombotic profile. In present paper, 2D similarity search, pharmacophore based screening, and molecular docking were used to explore the potential natural P2Y1R antagonists. 2D similarity search was used to classify orthosteric and allosteric antagonists of P2Y1R. Based on the result, pharmacophore models were constructed and validated by the test set. Optimal models were selected to discover potential P2Y1R antagonists of orthosteric and allosteric sites from Traditional Chinese Medicine (TCM). And the hits were filtered by Lipinski’s rule. Then molecular docking was used to refine the results of pharmacophore based screening and analyze the binding mode of the hits and P2Y1R. Finally, two orthosteric and one allosteric potential compounds were obtained, which might be used in future P2Y1R antagonists design. This work provides a reliable guide for discovering natural P2Y1R antagonists acting on two distinct sites from TCM. [ABSTRACT FROM AUTHOR]

The ongoing epidemics of metabolic diseases and increase in the older population have increased the incidences of neurodegenerative diseases. Evidence from murine and cell line models has implicated calcineurin-nuclear factor of activated T-lymphocytes (NFAT) signaling pathway, a Ca2+/calmodulin-dependent major proinflammatory pathway, in the pathogenesis of these diseases. Neurotoxins such as amyloid-β, tau protein, and α-synuclein trigger abnormal calcineurin/NFAT signaling activities. Additionally increased activities of endogenous regulators of calcineurin like plasma membrane Ca2+-ATPase (PMCA) and regulator of calcineurin 1 (RCAN1) also cause neuronal and glial loss and related functional alterations, in neurodegenerative diseases, psychotic disorders, epilepsy, and traumatic brain and spinal cord injuries. Treatment with calcineurin/NFAT inhibitors induces some degree of neuroprotection and decreased reactive gliosis in the central and peripheral nervous system. In this paper, we summarize and discuss the current understanding of the roles of calcineurin/NFAT signaling in physiology and pathologies of the adult and developing nervous system, with an emphasis on recent reports and cutting-edge findings. Calcineurin/NFAT signaling is known for its critical roles in the developing and adult nervous system. Its role in physiological and pathological processes is still controversial. However, available data suggest that its beneficial and detrimental effects are context-dependent. In view of recent reports calcineurin/NFAT signaling is likely to serve as a potential therapeutic target for neurodegenerative diseases and conditions. This review further highlights the need to characterize better all factors determining the outcome of calcineurin/NFAT signaling in diseases and the downstream targets mediating the beneficial and detrimental effects. [ABSTRACT FROM AUTHOR]

MHC molecule plays a key role in immunology, and the molecule binding reaction with peptide is an important prerequisite for T cell immunity induced. MHC II molecules do not have conserved residues, so they appear as open grooves. As a consequence, this will increase the difficulty in predicting MHC II molecules binding peptides. In this paper, we aim to propose a novel prediction method for MHC II molecules binding peptides. First, we calculate sequence similarity and structural similarity between different MHC II molecules. Then, we reorder pseudosequences according to descending similarity values and use a weight calculation formula to calculate new pocket profiles. Finally, we use three scoring functions to predict binding cores and evaluate the accuracy of prediction to judge performance of each scoring function. In the experiment, we set a parameter α in the weight formula. By changing α value, we can observe different performances of each scoring function. We compare our method with the best function to some popular prediction methods and ultimately find that our method outperforms them in identifying binding cores of HLA-DR molecules. [ABSTRACT FROM AUTHOR]

Oncotype Dx Breast Cancer Assay is a 21-gene assay used in estrogen receptor ( ER)-positive breast cancer to predict benefit from chemotherapy (CT). Tumors are placed into one of three risk categories based on their recurrence score ( RS). This paper explores the impact of tumor histopathologic features and Oncotype Dx RS on the treatment plan for invasive lobular carcinoma ( ILC). Invasive lobular carcinoma cases submitted for Oncotype Dx testing were identified from a clinical data base. The histopathologic and immunohistochemical features and RS subcategory of each tumor, and treatment regimen and medical oncologic assessments of each patient were reviewed. A total of 135 cases of ILC had RS testing, which represented 15% of all ILC diagnosed at the institution over the time period. 80% of ILC was of the classical subtype and all tumors were ER positive and human epidermal growth factor receptor 2 (HER-2) negative by immunohistochemistry. Sixty three percent of cases were low risk ( LR), 35.5% were intermediate risk ( IR) and 1.5% were high risk ( HR). Both HR cases were pleomorphic ILC. Sixty eight percent of classical ILC had a LR score, while 70% of pleomorphic ILC had an IR score. Patients in the IR category were significantly more likely to undergo CT than patients in the LR category (54% versus 18%; p < 0.0001). In the LR category, those undergoing CT were significantly younger and more likely to have positive lymph nodes (p < 0.05). Qualitative analysis of medical oncologic assessments showed that RS played a role in decision-making on CT in 74% of cases overall. At our institution, Oncotype Dx RS currently plays a role in the management of a proportion of ILC and impacts on treatment decisions. [ABSTRACT FROM AUTHOR]

Interferons, as the first line of defense against the viral infection, play an important role in innate immune responses. Type III interferon (IFN-λ) was a newly identified member of IFN family, which plays IFN-like antiviral activity. Towards a better understanding of the type III interferon system in birds, type III interferon lambda receptor (IFNLR1) was first identified in the Chinese goose. In this paper, we had cloned 1952 bp for goose IFNLR1 (goIFNLR1), including an ORF of 1539 bp, encoding a 512-amino acid protein with a 20 aa predict signal peptide at its N terminal and a 23 aa transmembrane region. The predicted amino acid sequence of goIFNLR1 has 90%, 73%, and 34% identity with duck IFNLR1 (predicted sequence), chicken IFNLR1, and human IFNLR1, respectively. And the age-related tissue distribution of goIFNLR1 was identified by Real Time quantitative PCR (RT-qPCR), we found that the goIFNLR1 has a mainly expression in epithelium-rich tissues similar to other species’, such as small intestinal, lung, liver, and stomach. Moreover, a relatively high expression of goIFNLR1 was also observed in the secondary immune tissues (harderian gland and cecal tonsil). The identification and tissue distribution of goIFNLR1 will facilitate further study of the role of IFN-λ in goose antiviral defense. [ABSTRACT FROM AUTHOR]

This paper analyzes the main trend of the development of acquired immunodeficiency syndrome (AIDS) vaccines in recent years. Designing an HIV-1 vaccine that provides robust protection from HIV-1 infection remains a challenge despite many years of effort. Therefore, we describe the receptor binding domain of gp120 as a target for developing AIDS vaccines. And we recommend some measures that could induce efficiently and produce cross-reactive neutralizing antibodies with high binding affinity. Those measures may offer a new way of the research and development of the potent and broad AIDS vaccines. [ABSTRACT FROM AUTHOR]

Anthraquinones are a class of aromatic compounds with a 9,10-dioxoanthracene core. So far, 79 naturally occurring anthraquinones have been identified which include emodin, physcion, cascarin, catenarin, and rhein. A large body of literature has demonstrated that the naturally occurring anthraquinones possess a broad spectrum of bioactivities, such as cathartic, anticancer, antiinflammatory, antimicrobial, diuretic, vasorelaxing, and phytoestrogen activities, suggesting their possible clinical application in many diseases. Despite the advances that have been made in understanding the chemistry and biology of the anthraquinones in recent years, research into their mechanisms of action and therapeutic potential in autoimmune disorders is still at an early stage. In this paper, we briefly introduce the etiology of autoimmune diabetes, an autoimmune disorder that affects as many as 10 million worldwide, and the role of chemotaxis in autoimmune diabetes. We then outline the chemical structure and biological properties of the naturally occurring anthraquinones and their derivatives with an emphasis on recent findings about their immune regulation. We discuss the structure and activity relationship, mode of action, and therapeutic potential of the anthraquinones in autoimmune diabetes, including a new strategy for the use of the anthraquinones in autoimmune diabetes. [ABSTRACT FROM AUTHOR]

High titer of anti-β2-glycoprotein I antibodies (anti-β2GPI Ab) plays a pathogenic role in antiphospholipid syndrome (APS). Numerous studies have focused on the pathological mechanism in APS; however, little attention is paid to the immune mechanism of production of anti-β2GPI antibodies in APS. Our previous study demonstrated that Toll-like receptor 4 (TLR4) plays a vital role in the maturation of bone marrow-derived dendritic cells (BMDCs) from the mice immunized with human β2-glycoprotein I (β2GPI). TLR4 is required for the activation of B cells and the production of autoantibody in mice treated with β2GPI. However, TLR4 provides a third signal for B cell activation and then promotes B cells better receiving signals from both B cell antigen receptor (BCR) and CD40, thus promoting B cell activation, surface molecules expression, anti-β2GPI Ab production, and cytokines secretion and making B cell functioning like an antigen presenting cell (APC). At the same time, TLR4 also promotes B cells producing antibodies by upregulating the expression of B-cell activating factor (BAFF). In this paper, we aim to review the functions of TLR4 in B cell immune response and antibody production in autoimmune disease APS and try to find a new way for the prevention and treatment of APS. [ABSTRACT FROM AUTHOR]

Background. CD8+ T cells have putative roles in the regulation of adaptive immune responses during infection. The purpose of this paper is to compare the status of CD8+ T cells in Multiple Sclerosis (MS) and Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). Methods. This preliminary investigation comprised 23 CFS/ME patients, 11 untreated MS patients, and 30 nonfatigued controls. Whole blood samples were collected from participants, stained with monoclonal antibodies, and analysed on the flow cytometer. Using the following CD markers, CD27 and CD45RA (CD45 exon isoform 4), CD8+ T cells were divided into naïve, central memory (CM), effector memory CD45RA- (EM), and effector memory CD45RA+ (EMRA) cells. Results. Surface expressions of BTLA, CD127, and CD49/CD29 were increased on subsets of CD8+ T cells from MS patients. In the CFS/ME patients CD127 was significantly decreased on all subsets of CD8+ T cells in comparison to the nonfatigued controls. PSGL-1 was significantly reduced in the CFS/ME patients in comparison to the nonfatigued controls. Conclusions. The results suggest significant deficits in the expression of receptors and adhesion molecules on subsets of CD8+ T cells in both MS and CFS/ME patients. These deficits reported may contribute to the pathogenesis of these diseases. However, larger sample size is warranted to confirm and support these encouraging preliminary findings. [ABSTRACT FROM AUTHOR]