Preliminary Phytochemical Screening and Proximate Analyses of Leaf Extracts of Newbouldia laevis (Boundary Tree)

This work is designed to enrich the available scientific data on the phytochemistry and nutrient content of N. laevis leaves. The method of cold maceration was used in the extraction by serial exhaustive extraction method. The phytochemical screening of Newbouldia laevis was using through controlled experiment. Qualitative phytochemical screening and proximate analyses of Newbouldia laevis was studied using extracts of n-hexane, ethyl acetate, acetone and methanol which were obtained extract from powdered plant part. The extracts were subjected to qualitative phytochemical screening using standard procedure and the results shows that all the phytochemicals screened for were revealed in various leaf extracts. Alkaloids and flavonoids are present in all the extracts except ethyl acetate that did not show the presence of alkaloids. Only phlobatannins and tannins were absent in all the extract, steroid is present only in acetone. The proximate analysis revealed the nutritional composition of Newbouldia laevis to be 6.03% of moisture, 7.96% of ash, 9.81% of crude protein, 16.50% of fat, 33.40%. The diversity of phytochemical present suggested that N. laevis could serve as a source of drugs. Keywords: Newbouldia laevis, phytochemistry, Nutrient

Imaging Findings in Patients with Immune Checkpoint Inhibitor-Induced Arthritis

Immune checkpoint inhibitor (ICI)-induced arthritis is an increasingly recognized adverse event in patients with oncologic disease during immunotherapy. Four patterns are well described, including rheumatoid arthritis (RA)-like, polymyalgia rheumatica (PMR)-like, psoriatic arthritis (PsA)-like, and oligo-monoarthritis, among others. Despite better clinical recognition of these syndromes, information about the main imaging findings is limited. Methods: We conducted a retrospective observational study including all adult patients referred to the Rheumatology Department of a single-center due to ICI-induced arthritis who underwent imaging studies [ultrasound (US), magnetic resonance imaging (MRI), and (18)F-FDG PET/CT)] between January 2017 and January 2022. Results: Nineteen patients with ICI-induced arthritis with at least one diagnostic imaging assessment were identified (15 US, 4 MRI, 2 (18)F-FDG PET/CT). Most patients were male (84.2%), with a median age at inclusion of 73 years. The main underlying diagnoses for ICI treatment were melanoma in five cases. The distribution of ICI-induced arthritis was as follows: PMR-like (5, 26.2%), RA-like (4, 21.1%), PsA-like (4, 21.1%), and others (6, 31.6%). All RA-like patients had US findings indistinguishable from conventional RA patients. In addition, 3/5 (60%) of PMR-like patients had significant involvement of the hands and wrists. Abnormal findings on MRI or PET-CT were reported by clinical symptoms. No erosions or myofascitis were seen. Conclusions: ICI-induced arthritis patients present inflammatory patterns on imaging studies similar to conventional inflammatory arthropathies, and therefore these syndromes should be followed carefully and treated according to these findings

The synovial and blood monocyte DNA methylomes mirror prognosis, evolution and treatment in early arthritis

Identifying predictive biomarkers at early stages of early inflammatory arthritis is crucial for starting appropriate therapies to avoid poor outcomes. Monocytes and macrophages, largely associated with arthritis, are contributors and sensors of inflammation through epigenetic modifications. In this study, we investigated associations between clinical features and DNA methylation in blood and synovial fluid (SF) monocytes in a prospective cohort of early inflammatory arthritis patients. Undifferentiated arthritis (UA) blood monocyte DNA methylation profiles exhibited significant alterations in comparison with those from healthy donors. We identified additional differences both in blood and SF monocytes after comparing UA patients grouped by their future outcomes, good versus poor. Patient profiles in subsequent visits revealed a reversion towards a healthy level in both groups, those requiring disease-modifying antirheumatic drugs (DMARDs) and those that remitted spontaneously. Changes in disease activity between visits also impacted DNA methylation, partially concomitant in the SF of UA and in blood monocytes of rheumatoid arthritis patients. Epigenetic similarities between arthritis types allow a common prediction of disease activity. Our results constitute a resource of DNA methylation-based biomarkers of poor prognosis, disease activity and treatment efficacy in early untreated UA patients for the personalized clinical management of early inflammatory arthritis patients

The synovial and blood monocyte DNA methylomes mirror prognosis, evolution, and treatment in early arthritis

Identifying predictive biomarkers at early stages of inflammatory arthritis is crucial for starting appropriate therapies to avoid poor outcomes. Monocytes (MOs) and macrophages, largely associated with arthritis, are contributors and sensors of inflammation through epigenetic modifications. In this study, we investigated associations between clinical features and DNA methylation in blood and synovial fluid (SF) MOs in a prospective cohort of patients with early inflammatory arthritis. DNA methylation profiles of undifferentiated arthritis (UA) blood MOs exhibited marked alterations in comparison with those from healthy donors. We identified additional differences both in blood and SF MOs after comparing patients with UA grouped by their future outcomes, i.e., good versus poor. Patient profiles in subsequent visits revealed a reversion toward a healthy level in both groups, those requiring disease-modifying antirheumatic drugs and those who remitted spontaneously. Changes in disease activity between visits also affected DNA methylation, which was partially concomitant in the SF of UA and in blood MOs of patients with rheumatoid arthritis. Epigenetic similarities between arthritis types allow a common prediction of disease activity. Our results constitute a resource of DNA methylation-based biomarkers of poor prognosis, disease activity, and treatment efficacy for the personalized clinical management of early inflammatory arthritis.We thank CERCA Programme/Generalitat de Catalunya and the Josep Carreras Foundation for institutional support. The authors thank all the patients who graciously donated their time and samples to further arthritis research. We are also thankful to Núria Sapena, Marta Bassas, and Cristina González, nurses from the outpatient clinic of the Department of Rheumatology, for their help in the management of biologic samples. This research was funded by Fondo de Investigación en Salud (FIS) grant PI17/00993 from the Institute of Health Carlos III (ISCIII) (to JDC); by grants SAF2017-88086-R and PID2020-117212RB-I00 / AEI / 10.13038/501100011033) from the Spanish Ministry of Science and Innovation (MICINN) (to EB); and by the Thematic Networks for Cooperative Research (RETICS) grant provided by ISCII, Research Network for Inflammation and Rheumatic Diseases (RIER) RD16/0012/0013, cofinanced by the European Fund for Regional Development’s (FEDER) Una manera de hacer Europa program (to JDC and EB).Peer reviewe

Impact of Comorbidities on Disease Activity, Patient Global Assessment, and Function in Psoriatic Arthritis: A Cross-Sectional Study

Abstract Introduction The aim of this study was to evaluate the impact of comorbidities on disease activity, patient’s impact of the disease, patient global assessment, and function in psoriatic arthritis (PsA). Methods Consecutive PsA patients were enrolled in this cross-sectional study. During the visit, the patients underwent a complete physical examination and clinical/laboratory data were collected, including type and number of comorbidities, recorded as simple comorbidity count (SCC). Disease activity was assessed using the Disease Activity Score for Psoriatic Arthritis (DAPSA) and the Minimal Disease Activity (MDA) was also evaluated. The Psoriatic Arthritis Impact of Disease (PsAID), the Health Assessment Questionnaire-Disability Index (HAQ-DI), and the Patient Global Assessment of disease activity (PtGA) were also collected. Results A total of 144 patients were enrolled. At least one comorbidity was registered in 104 (72.2%) patients. The SCC was associated with DAPSA (β = 1.48, p = 0.013), PsAID (β = 0.41, p < 0.01), HAQ-DI (β = 0.11, p < 0.01) and PtGA (β = 0.50, p < 0.01). The comorbidities that showed an impact on outcome measures were anxiety and fibromyalgia (FM). Anxiety showed an impact on DAPSA (β = 14.46, p < 0.001), PsAID (β = 1.98, p = 0.039) and HAQ-DI (β = 0.54, p = 0.036). FM showed an impact on DAPSA (β = 6.46, p = 0.025), PsAID (β = 2.88, p < 0.001), HAQ-DI (β = 0.70, p < 0.001), PtGA (β = 2.00, p = 0.014), and MDA (β = − 2.79, p = 0.01). The median PtGA value was different among patients with different numbers of comorbidities. Conclusions This study showed that comorbidities, either as a simple comorbidity count number or as single comorbidity, might have an impact on the main domains affecting PsA patients in real clinical practice

Characterization of Single-Tryptophan Mutants of Histidine-Containing Phosphocarrier Protein: Evidence for Local Rearrangements during Folding from High Concentrations of Denaturant

We have used site-directed mutagenesis in combination with a battery of biophysical techniques to probe the stability and folding behavior of a small globular protein, the histidine-containing phosphocarrier protein (HPr). Specifically, the four phenylalanine residues (2, 22, 29, and 48) of the wild-type protein were individually replaced by single tryptophans, thus introducing site-specific probes for monitoring the behavior of the protein. The folding of the tryptophan mutants was investigated by NMR, DSC, CD, intrinsic fluorescence, fluorescence anisotropy, and fluorescence quenching. The heat-induced denaturation of all four mutants, and the GdnHCl-induced unfolding curves of F2W, F29W, and F48W, can be fitted adequately to a two-state model, in agreement with the observations for the wild-type protein. The GdnHCl unfolding transitions of F22W, however, showed the accumulation of an intermediate state at low concentrations of denaturant. Kinetic refolding studies of F2W, F29W, and F48W showed a major single phase, independent of the probe used (CD, fluorescence, and fluorescence anisotropy) and similar to that of the wild-type protein. In contrast, F22W showed two phases in the fluorescence experiments corresponding to the two phases previously observed in ANS binding studies of the wild-type protein. Residue 22 was found from NMR studies to be part of the binding interface on HPr for ANS. These observations indicate that the second slow phase reflects a local, rather than a global, rearrangement from a well-structured highly nativelike intermediate state to the fully folded native state that has less hydrophobic surface exposed to the solvent. The detection of the second slow phase by the use of selective labeling of different regions of the protein with fluorophores illustrates the need for an integrated approach in order to understand the intricate details of the folding reactions of even the simplest proteins.

sj-docx-1-tab-10.1177_1759720X221114105 – Supplemental material for Plasma calprotectin as a biomarker of ultrasound synovitis in rheumatoid arthritis patients receiving IL-6 antagonists or JAK inhibitors

Supplemental material, sj-docx-1-tab-10.1177_1759720X221114105 for Plasma calprotectin as a biomarker of ultrasound synovitis in rheumatoid arthritis patients receiving IL-6 antagonists or JAK inhibitors by Beatriz Frade-Sosa, Andrés Ponce, José Inciarte-Mundo, Rosa Morlà, Viginia Ruiz-Esquide, Laura Macías, Ana Belen Azuaga, Julio Ramirez, Juan D. Cañete, Jordi Yague, Josep M. Auge, José A. Gomez-Puerta and Raimon Sanmarti in Therapeutic Advances in Musculoskeletal Disease</p