This study has investigated the effect of rheumatoid factor and anti-cyclic citrullinated peptide positivity on drug survival of abatacept in patients with

Anti-citrullinated protein antibodies (ACPA) have been suggested to have a potential role in both bone loss and pain in rheumatoid arthritis (RA), based on studies in vitro and in animal models. Here we addressed if anti-cyclic citrullinated (anti-CCP) antibodies were associated with osteopenia or pain in patients with RA, at the time for diagnosis. Baseline data from the BARFOT (Better Anti-Rheumatic PharmacOTherapy) cohort, which consists of patients with RA with a disease duration of 1 year or less, were analyzed. To be included, they should have been assessed by anti-CCP, dual-energy X-ray absorptiometry (DEXA) of lumbar spine and hip, and/or digital X-ray radiogrammetry (DXR) of the metacarpal bones. Osteopenia was defined as a z-score | − 1 SD. Pain VAS | 40 mm, was defined as patient unacceptable pain. Multiple logistic regression analyses were performed to assess whether anti-CCP was independently associated with osteopenia or unacceptable pain. Of the 657 patients, 65% were women, 58% were

Objective: To investigate the dynamics of IgG1 and IgG4 anti-citrullinated protein antibodies (ACPA) subclasses during anti-TNF treatment in patients with rheumatoid arthritis (RA).. Methods: IgG, IgG1 and IgG4 ACPA levels were determined by ELISA on citrullinated fibrinogen (ACF) and IgG1:IgG4 ACPA ratios were calculated. A pilot study was performed in 28 ACF positive patients treated with infliximab for one year. Confirmation of the results was obtained using a cohort of 180 consecutive patients treated with adalimumab for 28 weeks.. Results: The median reduction in ACF levels was 31% for total IgG, 29% for IgG1, 40% for IgG4 and 22% for the IgG4:IgG1 ACF ratio in the infliximab cohort. In the adalimumab treated patients, ACF levels declined 14% for total IgG and IgG1, and 36% for IgG4 ACF; the IgG4:IgG1 ratio was reduced by 24% (all percentage values P , 0.05). The decrease in antibody levels was correlated with the clinical response; EULAR good responders had the greatest decline in antibody ...

Background Patients with rheumatoid arthritis (RA) have a high risk of cardiovascular mortality, which is further increased in presence of anti-citrullinated protein antibodies (ACPA). Recently, ACPA were unexpectedly detected in a cohort of patients with coronary artery disease (CAD) in the absence of RA. However, it is unknown if ACPA are consistently present in different cohorts of CAD patients, and if ACPA presence affects the course of cardiovascular disease in these patients. The purpose of this study was to assess the relationship between ACPA and long-term outcomes (including mortality) in patients with ST-elevation myocardial infarction (STEMI) in the absence of RA. ...

TY - JOUR. T1 - Anti-citrullinated protein antibody titre as a predictor of abatacept treatment persistence in patients with rheumatoid arthritis. T2 - a prospective cohort study in Japan. AU - Endo, Y.. AU - Koga, T.. AU - Kawashiri, S. Y.. AU - Morimoto, S.. AU - Nishino, A.. AU - Okamoto, M.. AU - Eguchi, M.. AU - Tsuji, S.. AU - Takatani, A.. AU - Shimizu, T.. AU - Sumiyoshi, R.. AU - Igawa, T.. AU - Iwamoto, N.. AU - Ichinose, K.. AU - Tamai, M.. AU - Nakamura, H.. AU - Origuchi, T.. AU - Ueki, Y.. AU - Yoshitama, T.. AU - Eiraku, N.. AU - Matsuoka, N.. AU - Okada, A.. AU - Fujikawa, K.. AU - Hamada, H.. AU - Tsuru, T.. AU - Nagano, S.. AU - Arinobu, Y.. AU - Hidaka, T.. AU - Tada, Y.. AU - Kawakami, A.. N1 - Funding Information: The authors wish to thank the patients and medical staff for their contributions to the study.. PY - 2020/1/2. Y1 - 2020/1/2. N2 - Objective: Successful rheumatoid arthritis (RA) outcome depends on treatment efficacy in the early stages of the disease and its ...

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The aim of this study was to evaluate secretory antibodies to citrullinated proteins (ACPA) in plasma and immunoglobulin (Ig)A ACPA in saliva from patients with rheumatoid arthritis (RA) and their unaffected first-degree relatives (FDRs). Patients with RA (n = 194) and first-degree relatives unaffected by RA (n = 191) were recruited for analysis of secretory antibodies to second-generation cyclic citrullinated peptides (anti-CCP) in plasma. From a subpopulation (25 RA patients, 21 first-degree relatives and 11 controls), saliva samples were obtained for IgA anti-CCP analysis. The presence of secretory ACPA was compared between subject categories, and related to genetic and environmental risk factors. Secretory ACPA occurred in 37 (19%) plasma samples from patients with RA, but only in two (1%) of FDRs. IgA ACPA in saliva was found in three of 25 (12%) patients with RA, but not in any of the 21 FDRs (, 5%). No significant associations were seen between the presence of secretory ACPA and SE or ...

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Calreticulin (CRT) and citrullinated (citCRT) are implicated in rheumatoid arthritis (RA) pathology. citCRT binds to RA shared epitopes (SE) on HLA-DR molecules with high affinity and triggers pro-inflammatory events in adjacent cells. The aim of the study was to detect the presence of citCRT prior to developing RA and evaluate if citCT is a target for autoantibodies in RA cohorts with and without lung disease. Antibodies were assessed by ELISA against native CRT, citCRT and general protein citrullination, in sera from 50 RA patients without lung disease, 122 bronchiectasis (BR) patients, 52 bronchiectasis patients with RA (BRRA), 87 asthma patients and 77 healthy controls (HC). Serum citCRT was detected by immunoblotting and mass spectrometry. Genomic DNA was genotyped for HLA-DRB1 alleles. Patients were assessed for DAS28, rheumatoid factor, and anti-cyclic citrullinated peptide antibodies. Extracellular citCRT was detected in BR patients sera prior to them developing RA. A citCRT SE binding ...

TY - JOUR. T1 - Chemical modification and structure-activity relationships of pyripyropenes. 2. 1,11-cyclic analogs. AU - Obata, Rika. AU - Sunazuka, Toshiaki. AU - Kato, Yumiko. AU - Tomoda, Hiroshi. AU - Harigaya, Yoshihiro. AU - Omura, Satoshi. PY - 1996/1/1. Y1 - 1996/1/1. N2 - A series of 1,11-cyclic analogs of pyripyropene A were prepared. Replacement of the 1,11-acyl groups of pyripyropenes with 1,11-cyclic acetals effectively improved in vitro acyl CoA:cholesterol acyltransferase (ACAT) inhibitory activity. Especially noteworthy is benzylidene acetal analog 35, the most potent inhibitor (IC50 = 5.6 nM) among the derivatives prepared so far, which showed 16 times more potent inhibitory activity than pyripyropene A.. AB - A series of 1,11-cyclic analogs of pyripyropene A were prepared. Replacement of the 1,11-acyl groups of pyripyropenes with 1,11-cyclic acetals effectively improved in vitro acyl CoA:cholesterol acyltransferase (ACAT) inhibitory activity. Especially noteworthy is ...

Anti-cyclic citrullinated peptide (anti-CCP) antibodies are considered to be a marker of rheumatoid arthritis (RA). However, limited and controversial reports concern this problem in children with juvenile idiopathic arthritis (JIA). Objective: To access the prevalence and diagnostic value of...

High-frequency color Doppler ultrasonography together with anti-cyclic citrullinated peptide antibody testing may allow for earlier diagnosis of rheumatoid arthritis.

The presence or absence of antibodies to citrullinated peptides/proteins (ACPA) is an important parameter that helps a clinician set a diagnosis of early rheumatoid arthritis and, hence, initiate treatment. There are several commercial tests available to measure ACPA levels, although it can be difficult to decide what the best test for a given clinical question is. We analyzed literature data in which the diagnostic and other properties of various ACPA tests are compared. The results show that for diagnostic purposes the CCP2 test has the highest specificity, the highest sensitivity in stratified studies and the highest positive predictive value. For the prediction of future joint destruction the CCP2, MCV, and CCP3 tests may be used. The ability to predict the likelihood of not achieving sustained disease-modifying antirheumatic drug-free remission was highest for the CCP2 test. Finally, the levels of anti-CCP2 and anti-CCP3 (and possibly anti-mutated citrullinated vimentin) in rheumatoid arthritis

People who had What are the Cures For Rheumatoid Arthritis Chemotherapy Wiki often times have a heightened erythrocyte deposit charge and also M Responsive Peptids, which often may indicate a good your seditious system in your body. Additional popular body reports check out rheumatoid consideration and also anti-cyclic citrullinated peptide antibodies. A family doctor might would suggest Back button Ray of light for helping track any development with rheumatoid arthritis on your own predisposed joints throughout time. MRI and also sonography reports can really help physician assess any severity of the infection inside your body.. ...

Those with Mild Can You Die From Rheumatoid Arthritis Side Effects Blog often times have a heightened erythrocyte deposit pace and even Chemical Responsive Proteins, which unfortunately might point to the the -inflammatory procedure while in the body. Many other prevalent maintain assessments check out rheumatic point along with anti-cyclic citrullinated peptide antibodies. A medical professional might highly recommend Ten Re to observe the actual progress associated with rheumatoid arthritis in your own joint parts across time. MRI along with ultrasound assessments can certainly help your physician determine the actual harshness of the condition within your body.. ...

There is currently no biochemical test for detection of early-stage osteoarthritis (eOA). Tests for early-stage rheumatoid arthritis (eRA) such as rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibodies require refinement to improve clinical utility. We developed robust mass spectrometric methods to quantify citrullinated protein (CP) and free hydroxyproline in body fluids. We detected CP in the plasma of healthy subjects and surprisingly found that CP was increased in both patients with eOA and eRA whereas anti-CCP antibodies were predominantly present in eRA. A 4-class diagnostic algorithm combining plasma/serum CP, anti-CCP antibody and hydroxyproline applied to a cohort gave specific and sensitive detection and discrimination of eOA, eRA, other non-RA inflammatory joint diseases and good skeletal health. This provides a first-in-class plasma/serum-based biochemical assay for diagnosis and type discrimination of early-stage arthritis to facilitate improved treatment and patient

The use of cyclic peptides in one-bead-one-compound libraries is limited by difficulties in sequencing hit compounds. Lacking a free N-terminal amine, such peptides cannot be sequenced by the Edman degradation approach, and complex fragmentation patterns are obtained by tandem mass spectrometry. To overcome this problem, we designed an alternative approach introducing a methionine residue within the macrocycle and as a linker to allow simultaneous ring-opening and release from the resin upon treatment with cyanogen bromide. The methionine linker was inverted relative to the peptide chain to allow the synthesis of cyclic peptides anchored by a lysine side chain and to avoid the presence of two C-terminal homoserine lactones on the released linear peptides. After MALDI-TOF MS/MS analysis, the peptides released from a single bead were sequenced manually and with a de novo sequencing software. The strategy described herein is compatible with commonly used amino acids and allows sequencing of cyclic ...

0084] Further, diagnostic markers according to an embodiment of the present disclosure may include one or more of: 1,25 dihydroxy-vitamin D, 17-Hydroxyprogesterone, 25-hydroxy-vitamin D, Antineutrophil Cytoplasmic Antibodies, 5-Hydroxy Tryptamine, 5-hydroxyindoleacetic acid, Acetoacetate, Activated Partial Thromboplastin Time, Adrenocorticotropic Hormone, Alanine aminotransferase, Alanine transaminase, Albumin, Albumin-to-Creatinine ratio, Albumin/Globulin ratio, Alcohol, Aldolase, Aldosterone, Aldosterone and plasma renin activity, Aldosterone and Renin, Alkaline Phosphatase, Allergen-specific IgE, Alpha tryptase, Alpha-1 Antitrypsin, Alpha-fetoprotein, Alpha1-antitrypsin, Alzheimer biomarkers (including Tau protein and Amyloid Beta 42 peptides), Amylase, ANCA Antibodies, ANCA/MPO/PR3 Antibodies, Angiotensin-Converting Enzyme, Anti-citrulline antibody, anti-cyclic citrullinated peptide antibody, Anti-retroviral drug resistance testing, anti-ribonucleoprotein, anti-Sjogrens Syndrome A, ...

0077] Further, diagnostic markers according to an embodiment of the present disclosure may include one or more of: 1,25 dihydroxy-vitamin D, 17-Hydroxyprogesterone, 25-hydroxy-vitamin D, Antineutrophil Cytoplasmic Antibodies, 5-Hydroxy Tryptamine, 5-hydroxyindoleacetic acid, Acetoacetate, Activated Partial Thromboplastin Time, Adrenocorticotropic Hormone, Alanine aminotransferase, Alanine transaminase, Albumin, Albumin-to-Creatinine ratio, Albumin/Globulin ratio, Alcohol, Aldolase, Aldosterone, Aldosterone and plasma renin activity, Aldosterone and Renin, Alkaline Phosphatase, Allergen-specific IgE, Alpha tryptase, Alpha-1 Antitrypsin, Alpha-fetoprotein, Alpha1-antitrypsin, Alzheimer biomarkers (including Tau protein and Amyloid Beta 42 peptides), Amylase, ANCA Antibodies, ANCA/MPO/PR3 Antibodies, Angiotensin-Converting Enzyme, Anti-citrulline antibody, anti-cyclic citrullinated peptide antibody, Anti-retroviral drug resistance testing, anti-ribonucleoprotein, anti-Sjogrens Syndrome A, ...

RESULTS: 19.5% of plasmablast-derived antibodies from CCP-positive RA patients, but none from the CCP-negative RA patient or healthy controls, specifically recognized citrullinated antigens. The immunoglobulin genes encoding these ACPAs were highly mutated with increased replacement/silent mutation ratios, suggesting the involvement of active antigen selection in ACPA generation. Interestingly, 63% of the ACPAs cross-reacted with OMAs and/or citrullinated enolase from P. gingivalis. The reactivity of ACPAs against citrullinated proteins from P. gingivalis was confirmed by immuno blot and mass spectrometry. Furthermore, germ-line reversions of some ACPAs completely eliminated their reactivity to citrullinated human antigens but retained their reactivity to P. gingivalis ...

Bottromycin is a macrocyclic peptide with antibiotic activity. It was first discovered in 1957 as a natural product isolated from Streptomyces bottropensis. It has been shown to inhibit methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE) among other Gram-positive bacteria and mycoplasma. Bottromycin is structurally distinct from both vancomycin, a glycopeptide antibiotic, and methicillin, a beta-lactam antibiotic. Bottromycin binds to the A site of the ribosome and blocks the binding of aminoacyl-tRNA, therefore inhibiting bacterial protein synthesis. Although bottromycin exhibits antibacterial activity in vitro, it has not yet been developed as a clinical antibiotic, potentially due to its poor stability in blood plasma. To increase its stability in vivo, some bottromycin derivatives have been explored. The structure of bottromycin contains a macrocyclic amidine as well as a thiazole ring. The absolute stereochemistry at several chiral centers has been ...

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this test finds immune system chemicals, called antibodies, that target ccp (cyclic citrullinated peptide), which is present in about 60% to 70% of people with rheumatoid arthritis (ra). you could hav

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Results. In all, 4177 NHW and 292 AA JIA cases from the CARRA Registry and 212 NHW and 71 AA cases from Emory were analyzed. AA subjects more often had rheumatoid factor (RF)-positive polyarthritis in both the CARRA (13.4% vs 4.7%, p = 5.3 × 10−7) and the Emory (26.8% vs 6.1%, p = 1.1 × 10−5) cohorts. AA children had positive tests for RF and cyclic citrullinated peptide antibodies (CCP) more frequently, but oligoarticular or early onset antinuclear antibody (ANA)-positive JIA less frequently in both cohorts. AA children were older at onset in both cohorts and this difference persisted after excluding RF-positive polyarthritis in the CARRA Registry (median age 8.5 vs 5.0 yrs, p = 1.4 × 10−8). ...

Here we describe the identification of the marine depsipeptide sansalvamide A as an inhibitor of MCV topoisomerase. Sansalvamide A inhibited the initial DNA binding by MCV topoisomerase and, consequently, formation of covalent protein-DNA complexes, but did not inhibit religation by the covalent protein-DNA intermediate. This work provides a starting point for possible development of depsipeptide inhibitors for treating MCV infection.. Cyclic peptides such as sansalvamide A are a potent class of naturally occurring bioactive molecules. The immunosuppressant drug cyclosporin is a cyclic peptide secondary metabolite produced by the fungusCylindrocarpon lucidum (Borel et al., 1976). Bacitracin and polymyxin, also cyclic peptides of microbial origin, are in use as topical antibiotic agents (Strohl, 1997). Marine invertebrates are also prolific producers of bioactive cyclic peptides, including the antiviral and cytotoxic molecule didemnin B (Rinehart et al., 1988), the thrombin inhibitor ...

Citrullinated peptide dendritic cell immunotherapy in HLA risk genotype-positive rheumatoid arthritis patients Journal Articles Refereed ...

Objectives Dendritic cell immunoreceptor (polymorphisms were associated with anti-citrullinated proteins antibodies (ACPA)-unfavorable rheumatoid arthritis (RA) in Swedish Caucasians. out association analysis of rs2377422 polymorphisms with DCIR mRNA expression levels. Results rs2377422 was found to be significantly associated with ACPA -unfavorable RA in Han Chinese (OR 1.92, 95% CI 1.27C2.90, rs2377422 as a risk factor for ACPA-negative RA across distinct ethnic groups (ORoverall?=?1.17, 95% CI 1.06C1.30, mRNA expression level, i.e. RA-risk CC genotype exhibit a significant increase in the expression of DCIR (rs2377422 and RA in non-Caucasian populations and confirm the influence of polymorphisms on RA susceptibility, especially on ACPA-negative RA. Introduction Rheumatoid arthritis (RA) is usually a common autoimmune disease, characterized by chronic inflammation and progressive destruction in the joints. Although the pathogenesis of RA remains poorly comprehended, it is widely accepted that ...

This study is investigating whether the somatostatin analogue Lanreotide slows progression of polycystic kidney and liver disease in autosomal dominant

Jaspamide (jasplakinolide; NSC-613009) is a cyclodepsipeptide that has antitumor activity. Concentration-dependent increases in rhythmic beating rate were noted at 6 h of treatment, followed by dose-dependent decreases after 6 and 72 hours exposure. The toxic effects of jaspamide were compared with that of the known cardiotoxicant mitoxantrone, and confirmed by multiparameter fluorescence imaging analysis. These results support the hypothesis that the toxicity observed in rats and dogs is due to toxic effects of jaspamide on cardiomyocytes. (Crews et al., 1986) has been extensively investigated as a potential cancer therapeutic agent. Jaspamide exhibits antitumor activity in multiple in vitro tumor models for prostate and breast carcinomas and acute myeloid leukemia (Takeuchi et al., 1998; Bubley et al., 1996; Stingl et al., 1992; Fabian et al., 1995). Jaspamide inhibits the growth of prostate carcinoma PC-3 cells by disrupting the actin cytoskeleton (Senderowicz et al., 1995) and acts as a ...

Galectin-3 has been suggested as a pro-inflammatory mediator in animal arthritis and rheumatoid arthritis (RA). We aimed to study the serum level of galectin-3 in patients with newly diagnosed RA and associations with disease profile, Magnetic resonance imaging (MRI) findings and seromarkers of synovial matrix inflammation. One hundred and sixty DMARD naïve patients newly diagnosed with RA were included (CIMESTRA study). Clinical, serological and imaging data were recorded before treatment and at 6 weeks, 3 and 12 months. Galectin-3 and hyaluronan (HYA) were measured by ELISA (R&D and Corgenix, USA), and the N-terminal propeptide of type III collagen (PIIINP) by radioimmunoassay (Orion Diagnostica, Finland). One hundred and nineteen, 87 and 60 blood donors served as controls for galectin-3, HYA and PIIINP, respectively. Baseline galectin-3 was significantly elevated in anti-CCP positive (4.2 μg/l IQR [3.6;6.1]) patients as compared with anti-CCP negatives (4.0 μg/l [2.6;4.9], P = 0.05) and ...

Caspofungin acetate was found in Pediatrics Central. Pediatrics Central™ is an all-in-one application that puts valuable medical information, via your mobile device or the web, in the hands of clinicians treating infants, children, and adolescents.

Increased cardiovascular risk has been associated with high levels of serum antibodies to citrullinated proteins (ACPA) in patients with rheumatoid arthritis (RA). Citrullination is part of many chronic inflammatory processes and we therefore investi

The endo aryl-aryl and aryl-alkyl ether bonds exist in a number of biologically important macrocyclic natural products, such as vancomycin family glycopeptide antibiotics (1, 2, 3), antitumor series...

This unit outlines methods for identifying cyclic peptides that inhibit protein-protein interactions. Proteins of interest are cloned into a two-hybrid system engineered to operate in reverse, allowing the disruption of a protein complex to be coupled to cell growth. Cyclic peptide libraries are gen …

Introduction: The presence of a new autoantibody system, anti-carbamylated protein (anti-CarP) antibodies, has been identified in rheumatoid arthritis (RA). The presence of anti-CarP antibodies was evaluated in samples taken from individuals who subsequently developed RA before and after onset of symptoms and related to previously analysed antibodies against citrullinated peptides (ACPA specificities) and anti-CCP2. Methods: A total of 252 individuals, with 423 samples from before onset of symptoms of RA, and 197 population controls were identified as donors to the Medical Biobank of Northern Sweden; 192 of them were also sampled at the time of diagnosis. All samples were analysed for anti-CarP IgG and anti-CCP2 antibodies using ELISAs. Ten different antibody reactivities against citrullinated antigens (ACPA specificities) were analysed using a custom-made microarray based on the ImmunoCAP ISAC system (Phadia). Results: The concentration of anti-CarP antibodies was significantly increased in the ...

The substrate scope of fluorinase enzyme mediated transhalogenation reactions is extended. Substrate tolerance allows a peptide cargo to be tethered to a 5-chloro-5-deoxynucleoside substrate for transhalogenation by the enzyme to a 5-fluoro-5-deoxynucleoside. The reaction is successfully extended from that previously reported for a monomeric cyclic peptide (cRGD) to cargoes of dendritic scaffolds carrying two and four cyclic peptide motifs. The RGD peptide sequence is known to bind upregulated αVβ3 integrin motifs on the surface of cancer cells and it is demonstrated that the fluorinated products have a higher affinity to αVβ3 integrin than their monomeric counterparts. Extending the strategy to radiolabelling of the peptide cargoes by tagging the peptides with [18F]fluoride was only moderately successful due to the poor water solubility of these higher order peptide scaffolds although the strategy holds promise for peptide constructs with improved solubility ...

Top Quality 99% Ramoplanin CAS : 76168-82-6 Ramoplanin Chinese name: Remolanin Ramoplanin Chinese Synonyms: Remolanin; Remolanin Complex Ramoplanin English name: Ramoplanin Ramoplanin English synonym: Ramoplanin; A 16686; A 16686A; Antibiotic A...

HDACi are showing promise in the clinic as anticancer agents, particularly for the treatment of hematologic malignancies (1-3). A large number of HDACi have been synthesized or purified from natural sources and there are clear differences in the chemical composition of the different compounds and their relative affinities for different class I, II, and IV HDACs (1, 15, 16). Although HDACi have variously been shown to induce tumor cell apoptosis, inhibit cell cycle progression, augment antitumor immune responses, or suppress angiogenesis depending on the tumor cell type, concentration of HDACi used, or cellular context of the experiment, very few comparative studies aimed at identifying different molecular or biological activities of structurally diverse HDACi have been done to identify subtle yet potentially important unique activities of the different compounds.. Herein, we have directly compared the apoptotic activities of the cyclic tetrapeptide romidepsin with the hydroxamic acid oxamflatin ...

Abstract. The integrin family is a group of transmembrane glycoprotein comprised of 19 α- and 8 β-subunits that are expressed in 25 different α/β heterodimeric combinations on the cell surface. Integrins play critical roles in many physiological processes, including cell attachment, proliferation, bone remodeling, and wound healing. Integrins also contribute to pathological events such as thrombosis, atherosclerosis, tumor invasion, angiogenesis and metastasis, infection by pathogenic microorganisms, and immune dysfunction. Among 25 members of the integrin family, the αvβ3 is studied most extensively for its role of tumor growth, progression and angiogenesis. In contrast, the αIIbβ3 is expressed exclusively on platelets, facilitates the intercellular bidirectional signaling (inside-out and outside-in) and allows the aggregation of platelets during vascular injury. The αIIbβ3 plays an important role in thrombosis by its activation and binding to fibrinogen especially in arterial ...

The pseudomonal phytotoxin syringomycin Electronic, and related nonribosomal peptides, contain an L-genome suggests only 1 putative nonheme iron hydroxylase, AspH. of nonribosomal peptide (NRP) natural basic products. Phytopathogenic strains create a accurate amount of this kind of vegetable harmful toxins, which includes coronatine, syringomycins, phaseolotoxin, tabtoxin, and tagetitoxin (1-5). Syringomycins are people of a family group of related cyclic lipodepsipeptides that become plant harmful toxins by aggregating to create pores in vegetable cellular membranes to facilitate leave of nutrition. One hallmark of nonribosomal peptides may be the articles of non-proteinogenic amino acidity residues. Within the five known pseudomonal lipopeptides, syringomycin Electronic, cormycin A, pseudomycin B, syringostatin A and syringotoxin B theres a conserved C-terminal tripeptide moiety within the scaffold, made up of dehydrobutyrine7, -OH-Asp8, and 4-Cl-Thr9 (Shape 1a) (3, 6-9). This ...

Margo Haygood, Ph.D. has assisted in the development of a new approach using genetic pathways in cyanobacterial symbionts of marine ascidians to engineer the production of a new cyclic peptide.

The Department of Medicine is the largest department within the University of Rochester School of Medicine and Dentistry. It is made up of nearly 450 faculty members who are involved in patient care, research and education.

Disulfide bridges are an important structural element in many proteins and peptides. This brochure is a guideline how to plan and execute the synthesis of peptides with one or several disulfide bridges.

Increased expression of toll-like receptor 4 (TLR4) and its endogenous ligands, is characteristic of rheumatoid arthritis (RA) synovitis. In this study, we evaluated how these TLR4 ligands may drive pathogenic processes and whether the fine profiling of anti-citrullinated protein antibodies (ACPA) based on their target specificity might provide a simple means to predict therapeutic benefit when neutralizing TLR4 in this disease.. ...

Objective Production of anticitrullinated protein antibodies (ACPAs) is an important biomarker for rheumatoid arthritis (RA). We undertook this study to determine whether genetic factors (HLADRB1 alleles) are associated with extreme ACPA levels in individuals with ACPA-positive RA, and to ascertain whether there are any phenotypic characteristics associated with these subgroups of RA. Methods HLADRB1 allelic groups were genotyped in 1,073 ACPA-positive RA patients from the Swedish Epidemiological Investigation of Rheumatoid Arthritis study. We found that 283 patients (26.4%) had high ACPA levels (defined as ,1,500 units/ml using the Euro-Diagnostica anti-CCP2 test), while the rest of the patients had moderate ACPA levels and served as the comparison group. A replication group consisted of 235 RA patients. Results No significant differences in baseline disease activity were observed between patients with high and those with moderate ACPA levels. However, the HLADRB1*15 allele was associated with ...

Background/Purpose: Chikungunya (CKV) is a disease caused by an alphavirus, transmitted by mosquitoes of the genus Aedes. Is characterized by arthralgia, myalgia, arthritis and tenosynovitis.1 Anticyclic citrullinated peptide antibodies (ACPA) are considered specific markers of rheumatoid arthritis (RA). However ACPA have also been detected in patients with other types of chronic inflammatory rheumatism.2 The objective of this study is to investigate the positivity of ACPA in post-chikungunya arthritis.. Methods: This was a ambispective study, cross-sectional, with patients who were taken from the group comprised a total of 514 patients from the register of patients with musculoskeletal post-chikungunya infections in the rheumatology department of the Hospital Docente Padre Billini, from December 2013 to June 2017, 3 patients who met the classification criteria for reactive arthritis.4 at the Hospital Docente Padre Bilini, in the period December 2013 - June 2017. Inclusion criteria: Meet the ...

Cyclopeptide alkaloids are polyamidic, macrocyclic compounds, containing a 13-, 14-, or 15-membered ring. The ring system consists of a hydroxystyrylamine moiety, an amino acid, and a β-hydroxy amino acid; attached to the ring is a side chain, comprised of one or two more amino acid moieties. In vitro antiplasmodial activity was shown before for several compounds belonging to this class, and in this paper the antiplasmodial and cytotoxic activities of ten more cyclopeptide alkaloids are reported. Combining these results and the IC50 values that were reported by our group previously, a library consisting of 19 cyclopeptide alkaloids was created. A qualitative SAR (structure-activity relationship) study indicated that a 13-membered macrocyclic ring is preferable over a 14-membered one. Furthermore, the presence of a β-hydroxy proline moiety could correlate with higher antiplasmodial activity, and methoxylation (or, to a lesser extent, hydroxylation) of the styrylamine moiety could be important for

Introduction Anti-citrullinated protein antibodies (ACPAs) play an important role in rheumatoid arthritis (RA). Citrullinated proteins (CPs), which are produced by post-translational modification via...

OBJECTIVE: Anti-cyclic citrullinated peptide (CCP) antibodies have emerged as sensitive and specific serological markers of rheumatoid arthritis (RA). However, antibodies to several other citrulline-containing proteins, including citrullinated fibrin and vimentin, have been detected in patients with RA, suggesting that citrulline is an essential constituent of autoantigens for RA-specific autoantibodies. We examined the diagnostic performance of the newly developed anti-mutated citrullinated vimentin (MCV) antibody assay. METHODS: Concentrations of anti-MCV, anti-CCP2, and rheumatoid factors (RF) were determined in the sera of 237 individuals: 119 patients with RA and 118 controls, including patients with other rheumatic diseases and healthy subjects. Diagnostic properties were compared by receiver-operating characteristic curve analysis. RESULTS: Using manufacturers recommended cutoff values, sensitivity and specificity of anti-MCV antibodies were 75.6% and 91.5% in RA, compared to 66.4% and ...

In the present study, chronic administration of bosentan, an antagonist of both ETA and ETB receptors, had no significant effect on the systolic BP level reached after 6 weeks of L-NAME treatment, confirming the observation that acute (60 minutes) administration of the selective ETA receptor antagonist BQ-123 could not lower BP in rats treated for 3 weeks with an l-arginine analogue.21 However, the delay in the BP elevation occurring when bosentan was added to L-NAME would suggest that ET is involved in the early hypertensive response to the l-arginine analogue. This observation is in line with studies showing a blunted hypertensive effect of acute L-NAME administrations by ET receptor antagonists12 13 14 and provides experimental evidence to explain the discrepancy in the efficacy of ET receptor antagonists in acute and chronic L-NAME-induced hypertension.. Chronic administration of L-NAME leads to eutrophic remodeling of the basilar artery, as we previously reported.15 The structural ...

An analysis of 11 crystal structures of cyclic dipeptides so far reported in the literature is made, with main reference to the internal parameters of these molecules. Preferred conformations of the side chains of cyclic dipeptides with different α-amino acid residues have been studied by classical energy calculations. The possible conformations of the DKP ring are also studied. The significance of the non-bonded interaction in deciding the pathway for conformational change has also been investigated. The agreement between theoretical results and experimental observations is quite good, both with respect to the conformation of these molecules as well as the enthalpy difference as estimated from n.m.r. studies between different conformers.. ...

TY - JOUR. T1 - Erosive arthropathy. T2 - Clinical variance in lupus erythematosus and associated with anti-CCP case series and review of the literature. AU - Martinez, Jose Bernardo. AU - Valero, Jenny Soraida. AU - Bautista, Alain J.. AU - Restrepo, Jose Felix. AU - Matteson, Eric Lawrence. AU - Rondon, Frederico. AU - Iglesias-Gamarra, Antonio. PY - 2007/1. Y1 - 2007/1. N2 - Objective: To describe the occurrence of erosive arthropathy in systemic lupus erythematosus (SLE) and its relationship to anti-CCP antibodies. Methods: Retrospective medical record review of a case series of five female patients with SLE and erosive arthropathies. Results: The initial disease presentation in all patients was a polyarthritis. Anti-CCP antibodies were detected in 4 out of 5 (80%) patients, 2 of whom had a positive rheumatoid factor. Conclusion: Erosive arthritis was strongly associated with the presence of anti-CCP antibodies in these patients with SLE, who presented with polyarthritis. Anti-CCP in ...

Aim: Detection of Anti-CCP antibodies in rheumatoid arthritis patients using Automated Microreader and Gen5 Software for analysis and data processing. Material and method: Total of 776 blood samples from inflammatory arthritis patients were obtained. Statistical analysis for positive and negative results was calculated and test values were compared. Results: Anti-CCP test was found positive (>25U/ml) in 32,8% of blood samples. The all positive test results were in rheumatoid arthritis patients with 95% specificity. Negative test results was found in 67,2% of blood samples that were drawn from all IgM RF negative individuals, reactive arthritis and osteoarthritis patients as well as in some end-stage rheumatoid arthritis disease. Mean value of positive results was very high: 599,62 U/ml. Conclusion: The anti-CCP test is highly specific test in Rheumatoid arthritis. The positive test in early undifferentiated inflammatory polyarthritis provides new laboratory diagnostic inflammatory marker and ...

Aspergillosis remains to be a life-threatening complication in immunocompromised patients. However, Aspergillus infection can be observed in non-immunocompromised individuals in rare cases. We report a case of liver aspergilloma in a chronic aplastic anemia patient under relatively intact immune status. Therapeutic strategy for this rare condition was extensively discussed and caspofungin acetate single agent first-line therapy was applied after careful consideration. Encouraging clinical and radiologic improvements were achieved in response to the antifungal salvage. Our long-term follow-up study also revealed a favorable prognosis. Based on this experience, we suggest caspofungin acetate as first-line therapy for treatment plans of liver aspergilloma.

Specific blood tests can help diagnose rheumatoid arthritis, but arent accurate in everyone.. About half of all people with rheumatoid arthritis have a positive rheumatoid factor present in their blood when the disease starts, but about one in 20 people without rheumatoid arthritis also tests positive.. An antibody test known as anti-CCP (anti-cyclic citrullinated peptide) is available. People who test positive for anti-CCP are very likely to develop rheumatoid arthritis, but not everybody found to have rheumatoid arthritis has this antibody.. Those who test positive for both rheumatoid factor and anti-CCP may be more likely to have severe rheumatoid arthritis requiring higher levels of treatment.. ...

TY - JOUR. T1 - A randomized phase II trial of trimetrexate or didemnin B for the treatment of metastatic or recurrent squamous carcinoma of the uterine cervix. T2 - A Southwest Oncology Group trial. AU - Weiss, Geoffrey R.. AU - Liu, P. Y.. AU - OSullivan, Janet. AU - Alberts, David S.. AU - Brown, Thomas D.. AU - Neefe, John R.. AU - Hutchins, Laura F.. PY - 1992/6. Y1 - 1992/6. N2 - Patients with measurable metastatic or recurrent squamous carcinoma of the uterine cervix who had failed prior surgery or radiation therapy were enrolled on this randomized phase II study. Twenty-seven eligible patients were assigned to receive didemnin B at either 2.6 mg/m2 iv every 28 days (sixteen patients) or at 5.6 mg/m2 (eleven patients). Sixteen patients were assigned to receive 12 mg/m2/day iv trimetrexate for 5 days, repeated every 21 days. Toxicity for didemnin B was characterized by nausea and vomiting (78% of patients), anemia (59%), mild diarrhea (11%), and episodic hypersensitivity (three patients). ...

Testing for certain antibodies in the blood may alert physicians to the development of rheumatoid arthritis (RA) years before physical symptoms appear. A study, the results of which were published in the October 2003 issue of Arthritis and Rheumatism, found that one third of people with RA had antibodies?anti?cyclic citrullinated peptide (CCP) antibodies?in their blood long before they ever felt the first symptoms of the disease. Presently, physicians diagnose RA based on symptoms and the presence of rheumatoid factor in the blood. ?The anti-CCP test may help us detect patients who have early rheumatoid arthritis better than rheumatoid factor, and it may also predict patients who have more progressive disease,? said Clifton O. Bingham III, MD, director of the Seligman Center for Advanced Therapeutics at NYU-Hospital for Joint Disease (New York City). In the latest study, researchers reviewed data from the Northern Sweden Health and Disease Study and the Maternity cohorts of Northern Sweden. They ...

Diagnosing RA: Blood Tests. If RA is suspected, your doctor may order blood tests to check for markers of inflammation in the body. Other common tests are for rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP), which is present in most people with RA.. Diagnosing RA: Imaging Tests. X-rays are helpful in diagnosing RA and to provide a baseline for comparison later as the disease progresses. An MRI or ultrasound may also be done to help detect joint damage and inflammation.. Treating RA. There is no known cure for RA. The goal of treatment is to reduce joint inflammation and pain, prevent joint damage, and maximize joint function. Aggressive treatment should be started as early as possible. Treatment includes a combination of medication and exercises to strengthen supporting muscles around the joints. Treatment may also include surgery. Treatment is tailored to the individual, taking into account their age, affected joints, and the progression of the disease.. RA ...

Publications Resulting from Studies Utilizing CLEAR Data and Samples. June, 2011. CLEAR Published manuscripts. 1) Hughes LB, Moreland LW, and Bridges SL Jr. Genetic influences on rheumatoid arthritis in African-Americans. Immunol Res 26/1-3;15-26, 2002. 2) Bridges SL, Jr., Hughes LB, Mikuls TF, Howard G, Tiwari HK, Alarcón GS, Moreland LW, for CLEAR Investigators. Early rheumatoid arthritis in African-Americans: The CLEAR registry. Clin Exp Rheum, 21 (Suppl 31):S138-S145, 2003. 3) Mikuls TR, Saag KG, Curtis J, Bridges SL Jr., Alarcón GS, Westfall AO, Lim SS, Smith EA, Jonas BL, Moreland LW, and the CLEAR Investigators. The prevalence of osteoporosis and osteopenia among African Americans with early rheumatoid arthritis: the impact of ethnic-specific normative data. J Natl Med Assoc 97(8):1155-60, 2005. 4) Mikuls TR, Holers VM, Parrish L, Kuhn KA, Conn DL, Gilkeson G, Smith EA, Kamen DL, Jonas BL, Callahan LF, Alarcon GS, Howard G, Moreland LW, Bridges SL Jr. Anti-cyclic citrullinated peptide ...

Purification of MCV-ACPAs. Samples of serum with very high ACPA response (,1,000 IU/ml) were obtained from 3 RA patients presenting at the Department of Medicine 3 of the University Clinic of Erlangen. ACPA activity was detected with a commercially available ELISA for detection of antibodies against citrullinated vimentin (Orgentec Diagnostika).. Recombinant MCV was conjugated to CNBr-sepharose (GE Healthcare) (1 mg protein/ml equilibrated sepharose) according to the manufacturers instructions and stored at 4°C in PBS with 0.1% BSA. Prior to affinity purification of ACPAs, IgG was purified by affinity chromatography on a protein A column (GE Healthcare). Eluted IgG fractions were immediately neutralized with 1:10 volume of 1 M Tris-buffer (pH 8.0) and dialyzed against PBS (pH 7.2). Each purified IgG fraction was applied to a separate citrullinated vimentin affinity column (1 ml matrix per serum sample) and incubated for 2 hours at 4°C, rotating end over end. The column was washed with 0.5 M ...

Objective To evaluate the contribution of the SPP1 rs11439060 and rs9138 polymorphisms, previously reported as autoimmune risk variants, in the RA genetic background according to anti-citrullinated protein antibodies (ACPAs) status of RA individuals. Methods We analyzed a total of 11,715 RA cases and 26,493 controls from 9 independent cohorts, all individuals were genotyped or had imputed genotypes for SPP1 rs11439060 and rs9138. The effect of the SPP1 rs11439060 and rs9138 risk-allele combination on OPN expression in macrophages and OPN serum levels was investigated. Results We provide evidence for a distinct contribution of SPP1 to RA susceptibility according to ACPA status: the combination of ≥ 3 SPP1 rs11439060 and rs9138 common alleles was associated mainly with ACPA negativity (P = 1.29x10-5, ORACPA-negative 1.257 1.135-1.394) and less with ACPA positivity (P = 0.0148, ORACPA-positive 1.072 1.014-1.134]). The odds ratios between these subgroups (i.e., ACPA-positive and -negative)

Introduction The finding of antinuclear antibody (ANA) positivity in a wholesome individual is usually of unknown significance and generally is benign. Outcomes Overall, ANA amounts are considerably higher in females than in men which association retains in patients using the autoimmune illnesses lupus and arthritis rheumatoid (RA) aswell as in healthful controls (HC). Age group was not considerably connected with ANA amounts and the raised ANA values cannot be described by higher IgG amounts. Another autoantibody, anti- cyclic citrullinated peptide (CCP), didnt present gender dimorphism in arthritis rheumatoid (RA) or healthful people. The autoantigen array demonstrated significant elevations of various other autoantibodies in high ANA HCs. A few of these autoantibodies had been aimed to antigens in others and epidermis had been linked to autoimmune circumstances of kidney, joints or thyroid. Gene appearance analyses showed a larger prevalence of considerably upregulated genes in HCs with ...

Despite recent therapeutic advances the prognosis of heart failure remains poor. Recent research suggests that heart failure is a heterogeneous syndrome and that many patients have stimulating auto-antibodies directed against the second extracellular loop of the β1 adrenergic receptor (β1EC2). In a human-analogous rat model such antibodies cause myocyte damage and heart failure. Here we used this model to test a novel antibody-directed strategy aiming to prevent and/or treat antibody-induced cardiomyopathy. To generate heart failure, we immunised n = 76/114 rats with a fusion protein containing the human β1EC2 (amino-acids 195-225) every 4 weeks; n = 38/114 rats were control-injected with 0.9% NaCl. Intravenous application of a novel cyclic peptide mimicking β1EC2 (β1EC2-CP, 1.0 mg/kg every 4 weeks) or administration of the β1-blocker bisoprolol (15 mg/kg/day orally) was initiated either 6 weeks (cardiac function still normal, prevention-study, n = 24 (16 treated vs. 8 untreated)) or 8.5 months

X-MOL提供的期刊论文更新，Journal of Natural Products--Pagoamide A, a Cyclic Depsipeptide Isolated from a Cultured Marine Chlorophyte, Derbesia sp., Using MS/MS-Based Molecular Networking.，Yueying Li,Hao-Bing Yu,Yi Zhang,Tiago Leao,Evgenia Glukhov,Marsha L Pierce,Chen Zhang,Hyunwoo Kim,Huanru Henry Mao,Fang Fang,Garrison W Cottrell,Thomas F Murray,Lena Gerwick,Huashi Guan,William H Gerwick

The present study analyzed the clinical, radiographic, and immunologic features of a series of 71 RA patients along a 9-year interval. As a group, there was progressive deterioration in functional capacity and in joint structure. The serum levels of APF and anti-CCP antibodies tended to remain stable while serum levels of rheumatoid factor increased along the 9-year interval. There was no consistent association of autoantibody status at baseline with rate of joint destruction along the 9-year interval. The outcome measure for evaluation of disease severity was the rate of joint destruction as measured by the progression in Sharp index. Therefore, we calculated the difference in Sharp index between the end and the beginning of the study for each patient and tested the correlation of this parameter with the autoantibody status at the beginning of the study. No statistically significant correlation between the baseline autoantibody status and the rate of joint destruction was observed. When a ...

AureoGen Biosciences was incorporated on August 12, 2003. The companys business is focused on the development of novel chemistry and genetic engineering methodologies for the modification of cyclic peptide-based compounds. Historically, structural modifications required to convert a native cyclic peptide into a functional drug often involved complicated and expensive synthetic chemistry approaches. This hampered the development of many promising drug candidates. It also prevented optimization (such as reduction of side effects) of many existing drugs. AureoGen is taking advantage of recent advances in medicinal chemistry to develop novel approaches that allow efficient, cost-effective modification, optimization, and production of cyclic peptide compounds. AureoGens chemistries allow many modifications (to cyclic peptides) to be introduced directly, without the need for the multiple synthesis steps, disassembly of the core ring structure, and re-synthesis of large portions of the molecule, that ...

PubMed journal article: Contrasting microcystin production and cyanobacterial population dynamics in two Planktothrix-dominated freshwater lakes. Download Prime PubMed App to iPhone, iPad, or Android

1. Jurisson SS, Lydon JD. Potential technetium small molecule radiopharmaceuticals. Chem Rev. 1999;99:2205-18 2. Anderson CJ, Welch MJ. Radiometal-labeled agents (non-technetium) for diagnostic imaging. Chem Rev. 1999;99:2219-34 3. Liu S, Edwards DS. 99mTc-labeled small peptides as diagnostic radiopharmaceuticals. Chem Rev. 1999;99:2235-68 4. Liu S, Edwards DS. Fundamentals of receptor-based diagnostic metalloradiopharmaceuticals. Top Curr Chem. 2002;222:259-78 5. Liu S. The role of coordination chemistry in the development of target-specific radiopharmaceuticals. Chem Soc Rev. 2004;33:445-61 6. Liu S, Edwards DS. Bifunctional chelators for therapeutic lanthanide radiopharmaceuticals. Bioconj Chem. 2001;12:7-34 7. Heppeler A, Froidevaux S, Eberle AN, Maecke HR. Receptor targeting for tumor localization and therapy with radiopeptides. Curr Med Chem. 2000;7:971-94 8. Kwekkeboom D, Krenning EP, de Jong M. Peptide receptor imaging and therapy. J Nucl Med. 2000;41:1704-13 9. Boerman OC, Oyen WJ, ...

Laboratory abnormalities in liver function tests have been seen in healthy volunteers and patients treated with caspofungin acetate. In some patients with serious underlying conditions who were receiving multiple concomitant medications along with caspofungin acetate, clinical hepatic abnormalities have also occurred. Isolated cases of significant hepatic dysfunction, hepatitis, or worsening hepatic failure have been reported in patients; a causal relationship to caspofungin acetate has not been established ...

New Cyclic Peptide and Bisindolyl Benzenoid Metabolites from the Sclerotia of Aspergillus sclerotiorum. Whyte, Authrine C.; Joshi, Biren K.; Gloer, James B.; Wicklow, Donald T.; Dowd, Patrick F. J. Nat. Prod., 63(7), 1006- ...

The tridecaptins are attractive antibiotic candidates, owing to their selective activity against Gram-negative bacteria and ease of preparation by solid-phase peptide synthesis (SPPS). However, it was recently discovered that the tridecaptins are hydrolytically cleaved by the D-peptidase TriF at the amide bond between D-Trp5 and Ser6, rendering them inactive.7 Although this is likely a self-protection mechanism, similar resistance mechanisms could develop in more pathogenic bacteria, rendering these DNRPs inactive. Macrocyclization is often an effective strategy to improve the stability of peptides towards peptidases.12 However, N to C cyclization, which is one of the most commonly used methods to cyclize peptides, is not appropriate for the tridecaptins. Firstly, they are N-acylated, making N to C cyclization more difficult. Secondly and most importantly, the lipid II-bound conformation of TriA1 places the N- and C-termini far apart as it wraps around lipid II on the cell membrane (Fig. 1B). ...

A graft polymer containing a cyclic structure comprised of a polymer containing a cyclic structure graft-modified with an unsaturated compound containing a polar group, having a graft ratio of 10 to 150 mol %, having a weight average molecular weight of 1,000 to 1,000,000, and having a gel content of not more than 0.1 wt % or having a ratio (Ha/La) of high molecular weight side area (Ha) and low molecular weight side area (La) divided by a vertical line suspended from a peak top of a differentiated elution profile measured by gel permeation chromatography to a baseline of not more than 1.6, a method of production of the same, and a curable composition containing that graft polymer containing a cyclic structure and a curing agent.

Professor Craiks research focuses on applications of cyclic peptides and toxins in drug design. He is the discoverer of the cyclotides, an ultrastable family of plant-derived cyclic peptides that have wide-ranging applications in medicine and agriculture and is known internationally for his work in peptide-based drug design. Recognised as the worlds leading authority on cyclotides, Professor Craik is regularly invited to speak at conferences across the globe. Professor Craik has successfully shown that he can turn peptides into orally active drugs. His team was the first to take a natural conotoxin (peptide from a cone snail) and reengineer it to make cyclic. He was able to create a pain killing peptide one hundred times more potent than gabapentin, the current gold standard painkiller on the market for chronic pain. The conotoxin drug was highly effective in animal trials and has the potential to have reduced side-effects compared to other analgesics.. The Craik Group has also helped to ...

Chitinase inhibitors have chemotherapeutic potential as fungicides, pesticides, and antiasthmatics. Argifin, a natural product cyclopentapeptide, competitively inhibits family 18 chitinases in the nanomolar to micromolar range and shows extensive substrate mimicry

Rheumatoid arthritis (RA) is an autoimmune disease characterized by symmetric polyarthritis, rheumatoid factor (RF) positivity, and bone erosions. Recently, research has been conducted on anti-citrull

Cumulatively, CIPPS researchers have published over 1800 publications, books and book chapters in the past 10 years. 310,000 Citations. CIPPS researchers have been cited over 310,000 times. ...

The present invention relates to new pyridine sulfonamide modulators of endothelin-A receptor, pharmaceutical compositions thereof, and methods of use thereof. |p||chemistry id=CHEM-US-00001 num=00