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Abstract Rheumatic joints have an altered cartilage turnover. Cartilage intermediate layer protein 1 (CILP-1) is secreted from articular chondrocytes and deposited into the cartilage extracellular matrix. We developed an immunoassay targeting a Matrix Metalloproteinase (MMP)-generated neo-epitope of CILP-1, named CILP-M. Human articular cartilage was cleaved with proteolytic enzymes and CILP-M levels were measured. We also quantified CILP-M in two studies from patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and osteoarthritis (OA) and explored the monitoring and prognostic potential of CILP-M in TNF-α inhibitory treatment and modified Stoke AS Spine Score (mSASSS) progression. CILP-M was generated by MMP-1, -8 and -12. In the discovery study, CILP-M was significantly higher in patients with RA, AS and OA than healthy donors (p 0.95 (p 0.90 (p

Objective To explore the potential of a panel of ECM remodelling markers as endotyping tools for axial spondyloarthritis (axSpA) by separating patients into subtypes and investigate how they differ among each other in disease activity scores and response to treatment with adalimumab.Methods In three axSpA studies, a panel of 14 blood-based ECM biomarkers related to formation of collagen (PRO-C2, PRO-C3, PRO-C6), degradation of collagen by metalloproteinases (C1M, C2M, T2CM, C3M, C4M, C6M, C10C), matrix metalloproteinase (MMP)-degraded prolargin (PROM), MMP-degraded and citrullinated vimentin (VICM), basement membrane turnover (PRO-C4) and neutrophil activity (CPa9-HNE) were assessed to enable patient clustering (endotyping). MASH (n=41) was a cross-sectional study, while Adalimumab in Axial Spondyloarthritis study (ASIM,n=45) and Danish Multicenter Study of Adalimumab in Spondyloarthritis (DANISH, n=49) were randomised, double-blind placebo-controlled trials of adalimumab versus placebo every other week for 6 or 12 weeks, respectively, followed by active treatment. Biomarker data were log-transformed, standardised by mean centering and scaled by the SD prior to principal component analysis and K-means clustering.Results Based on all three studies, we identified two orthogonal dimensions reflecting: (1) inflammation and neutrophil activity (driven by C1M and CPa9-HNE) and (2) collagen turnover (driven by PRO-C2). Three endotypes were identified: high inflammation endotype (Endotype1), low inflammation endotype (Endotype 2) and high collagen turnover endotype (Endotype3). Endotype1 showed higher disease activity (Ankylosing Spondylitis Disease Activity Score (ASDAS)) at baseline compared with Endotype2 and Endotype3 and higher percentage of patients responding to adalimumab based on ASDAS clinical improvement at week 24. Endotype3 showed higher percentage of patients with 50% improvement in Bath Ankylosing Spondylitis Disease Activity Index response at week 24 compared with Endotype2.Conclusion These endotypes differ in their tissue remodelling profile and may in the future have utility for patient stratification and treatment tailoring.

Abstract Objective To investigate if extracellular matrix (ECM) blood-based biomarkers reflect the pharmacodynamic effect and response to TNF-α inhibitor therapy (adalimumab, ADA), in patients with axial spondyloarthritis (axSpA). Methods We investigated ECM biomarkers in two randomized, double-blind, placebo-controlled trials of axSpA patients (DANISH and ASIM, n = 52 and n = 49, respectively) receiving ADA 40 mg or placebo every other week for 12 and 6 weeks, respectively, and thereafter ADA to week 48. Serum concentrations of degraded type I (C1M), II (C2M, T2CM), III (C3M), IV (C4M), VI (C6M), type X (C10C) collagen; metabolite of C-reactive protein (CRPM), prolargin (PROM), citrullinated vimentin (VICM), calprotectin (CPa9-HNE); and formation of type II (PRO‑C2), III (PRO‑C3), and VI (PRO‑C6) turnover of type IV collagen (PRO-C4) were measured at baseline and weeks 6 or 12, 24, and 48. The pharmacodynamic effect and treatment response to ADA was evaluated by linear mixed models, and correlations between biomarkers and clinical scores were assessed by Spearman’s correlation. Results C1M, C3M, C4M, C6M, CRP, PRO-C4, and CPa9-HNE levels declined after 6 or 12 weeks in patients receiving ADA compared to placebo (all p

Abstract Extracellular matrix (ECM) remodeling of the skin is a continuous process necessary for maintaining tissue homeostasis. Type VI collagen (COL6) is characterized as a beaded filament, located in the dermal ECM, where COL6-α6-chain has been demonstrated upregulated in atopic dermatitis. The aim of this study was to develop and validate a competitive ELISA, targeting the N-terminal of COL6-α6-chain, named C6A6, and evaluate its associations with the dermatological condition’s atopic dermatitis, psoriasis, hidradenitis suppurativa, systemic lupus erythematosus, systemic sclerosis, urticaria, vitiligo, and cutaneous malignant melanoma in comparison, to healthy controls. A monoclonal antibody was raised and employed in an ELISA assay. The assay was developed, technically validated, and evaluated in two independent patient cohorts. Cohort 1 showed C6A6 was significantly elevated in patients with atopic dermatitis (p

Abstract Background Axial spondyloarthritis (axSpA) is a common chronic inflammatory disease, associated with extracellular matrix (ECM) remodeling of the cartilage, bone, and connective tissues. The primary symptom of axSpA is back pain, caused by inflammation. However, there is a medical need to truly identify patients with axSpA from other subjects with buttock or low back pain attributable to other reasons. We aimed to investigate circulating biomarkers of ECM/inflammation (MMP-degraded type I (C1M), II (C2M, T2CM), III (C3M), IV (C4M), VI (C6M), and X (C10C, COL10NC) collagens, CRPM, PROM and VICM) and ECM formation of type II (PRO-C2), III (PRO-C3), IV (PRO-C4), and VI (PRO-C6) collagens as potential biomarkers to identify patients with axSpA. Methods We measured biomarkers from a cross-sectional study with 204 participants by enzyme-linked immunosorbent assay (ELISA). The study included axSpA patients (N = 41), women with postpartum buttock/pelvic pain (N = 46), disc herniation (N = 25), and a group of healthy subjects (including women without postpartum pelvic pain (N = 14), subjects with various types of physical strain (cleaning staff (N = 26) long-distance runners (N = 23)), and healthy men (N = 29)). Differences between the groups were calculated by ANCOVA and AUC, while Spearman’s correlations were performed with ECM biomarkers and clinical scores. Results Patients with axSpA expressed significantly higher levels of C1M, C4M, and VICM (p < 0.05-p < 0.0001) compared to all the non-axSpA control groups. Further, C6M and PRO-C4 were significantly higher in patients with axSpA (both p < 0.0001) compared to women with postpartum pelvic pain and healthy subjects, whereas PRO-C3 was significantly lower compared to healthy subjects (p = 0.01). The best ECM common biomarker to differentiate between axSpA and the non-axSpA control groups was PRO-C4 (AUC ≥ 0.75; specificity ≥ 0.79, sensitivity = 0.65). Mild correlations were observed between collagen turnover and inflammation biomarkers and CRP and MRI (ρ ≥ 0.3; p < 0.05-p < 0.001). Conclusions Biomarkers of type I, IV, and VI collagen and biomarkers of inflammation showed an altered turnover in patients with axSpA compared with the non-axSpA control groups. Such biomarkers may be useful in combination with MRI or independently to separate patients with axSpA from other back pain conditions.

The type II collagen C-terminal pro-peptide is one of the most abundant polypeptides in cartilage. The purpose of this study was to develop a competitive chemiluminescence enzyme-linked immunosorbent assay, CALC2, targeting this pro-peptide as a marker of cartilage formation. Technical assay parameters were evaluated. CALC2 level was measured after in vitro cleavage of recombinant type II collagen with bone morphogenetic protein-1 (BMP-1) and treatment of ex vivo human osteoarthritis (OA) cartilage explant model (HEX) with insulin-like growth factor-1 (IGF-1). Serum CALC2 levels were assessed in 18 patients with rheumatoid arthritis (RA), 19 patients with ankylosing spondylitis (AS), and 18 age- and sex-matched controls in cohort 1 and 8 patients with OA and 14 age- and sex-matched controls in cohort 2. Type II collagen cleavage with BMP-1 increased the CALC2 level. IGF-1 treatment increased the CALC2 levels in HEX compared with the untreated explants (p < 0.05). Results were confirmed using Western blot analysis. CALC2 levels were decreased in the patients with RA and AS compared with the healthy controls (p = 0.01 and p = 0.02, respectively). These findings indicate that CALC2 may be a novel biomarker of type II collagen formation. However, further preclinical and clinical studies are required to validate these findings.

No contexto da engenharia de barragens mundial, o estudo do comportamento dos rejeitos de mineração vem sendo muito fomentado. No Brasil, um país com alta produção mineradora, a preocupação com o comportamento dos rejeitos ganhou ênfase após os desastres recentes. Uma das maneiras de analisar o comportamento destes materiais é por meio de ensaios de laboratório, sendo o equipamento de Simple Shear, uma ferramenta robusta para análises com o princípio das deformações planas. Este trabalho objetivou a reprodução de comportamento de um rejeito de mineração de bauxita a partir de modelagem numérica utilizando a versão estudantil do software ABAQUS®. Utilizou-se o modelo constitutivo CamClay Modificado para o material e comparou-se os resultados obtidos com os resultados experimentais apresentados por Gonçalves (2021) para as tensões confinantes efetivas de 50 e 100 kPa. O modelo apresentou boa adequação, convergindo para a tensão de confinamento efetiva média.

Bryophytes are the earliest plant group on Earth. They are a fundamental component of many ecosystems around the World. Some of their main roles are related to soil development, water retention, and biogeochemical cycling. Bryophytes include liverworts, hornworts, and mosses. The sequencing of chloroplast and mitochondria genomes has been useful to elucidate the taxonomy of this heterogeneous plant group. To date, despite their ecological importance only 41 mosses mitogenomes have been deposited in the GenBank. Here, the complete mitochondria genome sequence of Pseudocrossidium replicatum, a moss of the Pottiaceae family isolated in Tlaxcala, Mexico, is reported. The mitochondrial genome size of P. replicatum comprises 105,495 bp and contains the groups of genes described for other bryophytes mitogenomes. Our phylogenetic analysis shows that during the evolution of the mosses’ mitogenome, nad7, rps4, rpl16, and rpl10 genes were lost independently in several lineages. The complete mitogenome sequence reported here would be a useful tool for our comprehension of the evolutionary and population genetics of this group of plants.

Las hormonas vegetales son moléculas señalizadoras que se localizan en los diferentes tejidos de una planta y en cantidades específicas de acuerdo al proceso que regulan. Los cambios en la concentración y distribución de las hormonas vegetales modulan el desarrollo y las respuestas al estrés biótico y abiótico. La autofagia, que significa autodigestión, es un mecanismo que degrada los componentes dañados o tóxicos que surgen del metabolismo, con la finalidad de reciclarlos y mantener la salud de la célula. En este proceso se forman vesículas de doble membrana llamadas autofagosomas, las cuales encierran la carga dañada o no deseada, que posteriormente se deposita para su degradación en la vacuola de donde la célula recupera aminoácidos, lípidos y proteínas. Se ha observado una confluencia entre las hormonas vegetales y la autofagia durante el desarrollo y el crecimiento, la senescencia y la muerte celular programada. En esta revisión repasamos los avances en la comprensión del papel de las hormonas vegetales involucradas en la modulación de la autofagia en las plantas.

Este artigo apresenta uma experiência de Educação Popular em Saúde para a doação de leite humano. Tem o objetivo de relatar a experiência acerca da promoção do aleitamento materno com nutrizes, para a doação de leite em uma Unidade Básica de Saúde (UBS), localizada no município do Rio de Janeiro. Apresenta todo o processo desde a capacitação dos profissionais da Unidade, os grupos educativos desenvolvidos com as nutrizes, a captação e seleção da doadora, assim como a coleta, a conservação, o transporte do leite doado até os bancos de leite humano. Todo esse processo ocorreu com valorização dos princípios da Educação Popular em Saúde, como amorosidade e valorização do saber da doadora. Dessa forma, percebeu-se que quanto mais se aumentava o vínculo das nutrizes com os profissionais da UBS, aumentava o número de doadoras e também de leite humano doado.

Na extensão universitária busca-se integrar o saber científico ao saber popular. O presente texto tem o objetivo de descrever as experiências vivenciadas no projeto "Educação em Saúde no Projeto Pescar". A metodologia utilizada foi de abordagem qualitativa, com a descrição do relato da experiência sobre a participação de um grupo de acadêmicos extensionistas do curso de Enfermagem no Projeto Pescar, desenvolvido em parceria com a Universidade e a Usina Gerdau Cosigua. Os resultados apontam que a extensão universitária possibilitou um espaço para ensino-aprendizagem, tanto para os acadêmicos de enfermagem quanto para os adolescentes inseridos no projeto. Conclui que a educação em saúde realizada por meio da extensão, enquanto espaço de formação voltada para o cuidado e como produção de conhecimento, auxilia o indivíduo a realizar escolhas inteligentes, tomada de decisões, mudanças no estilo de vida, para alcançar qualidade e cidadania, independente de condições econômicas sociais existentes.

Bacillus thuringiensis produces crystal toxins known as Cry that are highly selective against important agricultural and human health-related insect pests. Cry proteins are pore-forming toxins that interact with specific receptors in the midgut cell membrane of susceptible larvae making pores that cause osmotic shock, leading finally to insect death. In the case of pore-forming toxins that are specific to mammalian cells, death responses at low doses may induce apoptosis or pyroptosis, depending on the cell type. The death mechanism induced by Cry toxins in insect midgut cells is poorly understood. Here, we analyze the caspases expression by RT-PCR analysis, showing that the initial response of Manduca sexta midgut cells after low dose of Cry1Ab toxin administration involves a fast and transient accumulation of caspase-1 mRNA, suggesting that pyroptosis was activated by Cry1Ab toxin as an initial response but was repressed later. In contrast, caspase-3 mRNA requires a longer period of time of toxin exposure to be activated but presents a sustained activation, suggesting that apoptosis may be a cell death mechanism induced also at low dose of toxin.

Abstract Mosses in conjunction with hornworts and liverworts are collectively referred to as bryophytes. These seedless, nonvascular plants are the closest extant relatives of early terrestrial plants and their study is essential to understand the evolutionary first steps of land plants. Here we report the complete chloroplast (cp) genome sequence of Pseudocrossidium replicatum, a moss belonging to the Pottiaceae family that is common in the central highlands of Mexico, in South America, in southern USA, and in Kenia. The cp genome (plastome) of P. replicatum is 123,512 bp in size, comprising inverted repeats of 9,886 bp and single-copy regions of 85,146 bp (LSC) and 18,594 bp (SSC). The plastome encodes 82 different proteins, 31 different tRNAs, and 4 different rRNAs. Phylogenetic analysis using 16 cp protein-coding genes demonstrated that P. replicatum is closely related to Syntrichia ruralis, and the most basal mosses are Takakia lepidozioides followed by Sphagnum palustre. Our analysis indicates that during the evolution of the mosses’ plastome, eight genes were lost. The complete plastome sequence reported here can be useful in evolutionary and population genetics.