Green synthesis of silver nanoparticle using pollen extract from Tetragonisca angustula a stingless bee.

This study explores the green synthesis of silver nanoparticles (AgNPs) using a methanolic extract of fermented pollen from Tetragonisca angustula, a species of stingless bees. The AgNPs exhibit spherical morphology, low charge values, and suspension stability, with their unique composition attributed to elements from the pollen extract. Antioxidant assays show comparable activity between the pollen extract and AgNPs, emphasizing the retention of antioxidant effects. The synthesized AgNPs demonstrate antimicrobial activity against multidrug-resistant bacteria, highlighting their potential in combating bacterial resistance. The AgNPs exhibit no toxic effects on Drosophila melanogaster and even enhance the hatching rate of eggs. The study underscores the innovative use of stingless bee pollen extract in green synthesis, offering insights into the varied applications of AgNPs in biomedicine.

Satellite DNAs, heterochromatin, and sex chromosomes of the wattled jacana (Charadriiformes; Jacanidae): a species with highly rearranged karyotype.

Charadriiformes, which comprises shorebirds and their relatives, is one of the most diverse avian orders, with over 390 species showing a wide range of karyotypes. Here, we isolated and characterized the whole collection of satellite DNAs (satDNAs) at both molecular and cytogenetic levels of one of its representative species, named the wattled jacana (Jacana jacana), a species that contains a typical ZZ/ZW sex chromosome system and a highly rearranged karyotype. In addition, we also investigate the in situ location of telomeric and microsatellite repeats. A small catalog of 11 satDNAs was identified that typically accumulated on microchromosomes and on the W chromosome. The latter also showed a significant accumulation of telomeric signals, being (GA)10 the only microsatellite with positive hybridization signals among all the 16 tested ones. These current findings contribute to our understanding of the genomic organization of repetitive DNAs in a bird species with high degree of chromosomal reorganization contrary to the majority of bird species that have stable karyotypes.

Satellitome Analysis in the Southern Lapwing (Vanellus chilensis) Genome: Implications for SatDNA Evolution in Charadriiform Birds.

Vanellus (Charadriidae; Charadriiformes) comprises around 20 species commonly referred to as lapwings. In this study, by integrating cytogenetic and genomic approaches, we assessed the satellite DNA (satDNA) composition of one typical species, Vanellus chilensis, with a highly conserved karyotype. We additionally underlined its role in the evolution, structure, and differentiation process of the present ZW sex chromosome system. Seven distinct satellite DNA families were identified within its genome, accumulating on the centromeres, microchromosomes, and the W chromosome. However, these identified satellite DNA families were not found in two other Charadriiformes members, namely Jacana jacana and Calidris canutus. The hybridization of microsatellite sequences revealed the presence of a few repetitive sequences in V. chilensis, with only two out of sixteen displaying positive hybridization signals. Overall, our results contribute to understanding the genomic organization and satDNA evolution in Charadriiform birds.

What is known about the effects of vitamin D in neuropsychiatric lupus?

Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect several organs and systems. The central and/or peripheral nervous system can suffer from complications known as neuropsychiatric lupus (NPSLE). Studies have associated the manifestations of SLE or NPSLE with vitamin D deficiency. It has been shown that hypovitaminosis D can lead to cognition deficits and cerebral hypoperfusion in patients with NPSLE. In this review article, we will address the main features related to vitamin D supplementation or serum vitamin D levels with neuropsychiatric manifestations, either in patients or in animal models of NPSLE.

Transitioning from static to suspension culture system for large-scale production of xeno-free extracellular vesicles derived from mesenchymal stromal cells.

Extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) have shown increasing therapeutic potential in the last years. However, large production of EV is required for therapeutic purposes. Thereby, scaling up MSC cultivation in bioreactors is essential to allow culture parameters monitoring. In this study, we reported the establishment of a scalable bioprocess to produce MSC-EV in suspension cultures using spinner flasks and human collagen-coated microcarriers (3D culture system). We compared the EV production in this 3D culture system with the standard static culture using T-flasks (2D culture system). The EV produced in both systems were characterized and quantify by western blotting and nanoparticle tracking analysis. The presence of the typical protein markers CD9, CD63, and CD81 was confirmed by western blotting analyses for EV produced in both culture systems. The cell fold-increase was 5.7-fold for the 3D culture system and 4.6-fold for the 2D culture system, signifying a fold-change of 1.2 (calculated as the ratio of fold-increase 3D to fold-increase 2D). Furthermore, it should be noted that the total cell production in the spinner flask cultures was 4.8 times higher than that in T-flask cultures. The total cell production in the spinner flask cultures was 5.2-fold higher than that in T-flask cultures. While the EV specific production (particles/cell) in T-flask cultures (4.40 ± 1.21 × 108 particles/mL, p < 0.05) was higher compared to spinner flask cultures (2.10 ± 0.04 × 108 particles/mL, p < 0.05), the spinner flask culture system offers scalability, making it capable of producing enough MSC-EV at a large scale for clinical applications. Therefore, we concluded that 3D culture system evaluated here serves as an efficient transitional platform that enables the scaling up of MSC-EV production for therapeutic purposes by utilizing stirred tank bioreactors and maintaining xeno-free conditions.

Antioxidant and anti-Alzheimer's potential of Tetragonisca angustula (Jataí) stingless bee pollen.

Alzheimer's disease (AD) is considered the leading cause of dementia in the elderly worldwide. It results in progressive memory loss and impairment of cognitive and motor skills, leading to a high degree of disability and dependence. The development of AD is associated with the accumulation of senile plaques in the brain, caused by the amyloidogenic pathway of the disease. Several genetic and biochemical events are linked to AD development, with oxidative stress being one of them. Due to the scarcity of drugs aimed at treating AD, antioxidant compounds are increasingly studied as therapeutic targets for the disease. In this study, we investigate the antioxidant and anti-Alzheimer potential of the Tetragonisca angustula (Jataí) pollen extract in a Drosophila melanogaster Alzheimer's model. For this purpose, we utilized a D. melanogaster AD-like model, which expresses genes related to the amyloidogenic pathway of Alzheimer's disease. We explored the floral origin of the collected pollen, conducted phytochemical prospecting, and evaluated its antioxidant capacity in vitro. In vivo experiments involved assessing the survival and climbing ability of the D. melanogaster AD-like model with various concentrations of the pollen extract. Our findings revealed that the pollen extract of Tetragonisca angustula exhibits a significant antioxidant response and high concentrations of important phytochemicals, such as flavonoids and polyphenols. Furthermore, it enhanced the survival rate of D. melanogaster, and across all concentrations tested, it improved the climbing ability of the flies after 15 days of treatment with methanolic pollen extract. Additionally, the pollen extract reduced the neurodegeneration index in histopathological analysis. Thus, our study demonstrates the potential of Tetragonisca angustula pollen as an important subject for further investigation, aiming to isolate molecules that could potentially serve as therapeutic targets for Alzheimer's disease.

The Perception of the Body Condition of Cats and Dogs by French Pet Owners and the Factors Influencing Underestimation.

Managing pet obesity relies heavily on the active involvement of owners; however, a key challenge arises from misperceptions about their own pet's body condition. Given evolving societal dynamics like the body positivity movement, understanding owners' perceptions is increasingly pivotal. To evaluate the differences in owners' perception, this study compared the use of verbal and visual body condition score scales versus the established nine-point body condition score system. The factors linked to underestimation were further specifically investigated. Owners of healthy adult dogs and cats attending vaccination consultations in Veterinary Hospitals in France between 2020 and 2022 were recruited. They were required to assess their pets' body condition initially using an oral description and then with the nine-point BCS visual scale. Their assessments were then compared with the BCS determined by veterinary health care personnel, considered the primary investigator. A total of 304 dogs and 270 cats were included in the study. It was observed that 27% of dog owners and 24% of cat owners underestimated their pets' body condition. Among dog and cat owners, factors associated with the underestimation of body condition were the pets' overweight status and having children. This discovery emphasizes the need for a holistic One Health approach that prioritizes the health and well-being of both humans and their pets. When it comes to pet owners evaluating their pets' body condition, underestimation proved to be the predominant misperception. Addressing this issue requires comprehensive education to empower owners to recognize and comprehend their pets' overweight status, a critical step for the overall well-being of companion animals.

Trypanosoma cruzi P21 recombinant protein modulates Toxoplasma gondii infection in different experimental models of the human maternal-fetal interface.

Introduction: Toxoplasma gondii is the etiologic agent of toxoplasmosis, a disease that affects about one-third of the human population. Most infected individuals are asymptomatic, but severe cases can occur such as in congenital transmission, which can be aggravated in individuals infected with other pathogens, such as HIV-positive pregnant women. However, it is unknown whether infection by other pathogens, such as Trypanosoma cruzi, the etiologic agent of Chagas disease, as well as one of its proteins, P21, could aggravate T. gondii infection. Methods: In this sense, we aimed to investigate the impact of T. cruzi and recombinant P21 (rP21) on T. gondii infection in BeWo cells and human placental explants. Results: Our results showed that T. cruzi infection, as well as rP21, increases invasion and decreases intracellular proliferation of T. gondii in BeWo cells. The increase in invasion promoted by rP21 is dependent on its binding to CXCR4 and the actin cytoskeleton polymerization, while the decrease in proliferation is due to an arrest in the S/M phase in the parasite cell cycle, as well as interleukin (IL)-6 upregulation and IL-8 downmodulation. On the other hand, in human placental villi, rP21 can either increase or decrease T. gondii proliferation, whereas T. cruzi infection increases T. gondii proliferation. This increase can be explained by the induction of an anti-inflammatory environment through an increase in IL-4 and a decrease in IL-6, IL-8, macrophage migration inhibitory factor (MIF), and tumor necrosis factor (TNF)-α production. Discussion: In conclusion, in situations of coinfection, the presence of T. cruzi may favor the congenital transmission of T. gondii, highlighting the importance of neonatal screening for both diseases, as well as the importance of studies with P21 as a future therapeutic target for the treatment of Chagas disease, since it can also favor T. gondii infection.

A novel program of infiltrative control in astrocytomas: ADAM23 depletion promotes cell invasion by activating γ-secretase complex.

Background: Infiltration is a life-threatening growth pattern in malignant astrocytomas and a significant cause of therapy resistance. It results in the tumor cell spreading deeply into the surrounding brain tissue, fostering tumor recurrence and making complete surgical resection impossible. We need to thoroughly understand the mechanisms underlying diffuse infiltration to develop effective therapies. Methods: We integrated in vitro and in vivo functional assays, RNA sequencing, clinical, and expression information from public data sets to investigate the role of ADAM23 expression coupling astrocytoma's growth and motility. Results: ADAM23 downregulation resulted in increased infiltration, reduced tumor growth, and improved overall survival in astrocytomas. Additionally, we show that ADAM23 deficiency induces γ-secretase (GS) complex activity, contributing to the production and deposition of the Amyloid-ß and release of NICD. Finally, GS ablation in ADAM23-low astrocytomas induced a significant inhibitory effect on the invasive programs. Conclusions: Our findings reveal a role for ADAM23 in regulating the balance between cell proliferation and invasiveness in astrocytoma cells, proposing GS inhibition as a therapeutic option in ADAM23 low-expressing astrocytomas.

NanoLC-EI-MS: Perspectives in Biochemical Analysis.

Although LC-MS with atmospheric pressure ionization (API) sources is the primary technique used in modern bioanalytical studies, electron ionization mass spectrometry (EI-MS) can provide some substantial advantages over it. EI-MS is a matrix effect-free technique that provides reproducible and comparable mass spectra, serving as a compound fingerprint for easy identification through automated comparison with spectral libraries. Leveraging EI-MS in biochemical studies can yield critical analytical benefits for targeted and untargeted analyses. However, to fully utilize EI-MS for heavy and non-volatile molecules, a new technology that enables the coupling of liquid chromatography with EI-MS is needed. Recent advancements in nanoLC have addressed the compatibility issues between LC and EI-MS, and innovative interfacing strategies such as Direct-EI, liquid electron ionization (LEI), and Cold-EI have extended the application of EI-MS beyond the determination of volatile organic molecules. This review provides an overview of the latest developments in nanoLC-EI-MS interfacing technologies, discussing their scope and limitations. Additionally, selected examples of nanoLC-EI-MS applications in the field of biochemical analysis are presented, highlighting the potential prospects and benefits that the establishment of this technique can bring to this field.

Erosion-inhibiting and enamel rehardening effects of different types of saliva.

OBJECTIVES: The objective of this study was to assess the effects of in situ saliva compared to in vitro human saliva, with or without mucin, on inhibiting erosion and promoting enamel rehardening. DESIGN: Bovine enamel blocks were randomly distributed into groups (n = 23): Gsitu (human saliva in situ), Gvitro (collected human saliva) and GvitroM (collected human saliva with mucin). The enamel blocks underwent a 2-hour period for the formation of salivary pellicle, based on the assigned groups. Subsequently, they were subjected to three erosive cycles, each of them consisting of an erosive challenge (immersion in 0.65 % citric acid, pH 3.5, 1 min) and saliva exposure (immersion in situ or in vitro saliva for 2 h). Microhardness measurements were performed at each cycle, after each experimental step (erosive challenge and exposure to saliva). RESULTS: After the first demineralization, in vitro saliva groups presented greater hardness loss, with no statistical difference between GVitroM and GVitro. After the third erosive demineralization the in situ saliva resulted in less hardness loss compared to the first demineralization. In relation to surface hardness recovery, there was no difference among types of saliva but there was a decrease in hardness as the cycles progressed. CONCLUSION: Saliva groups had different behaviors between the first and third demineralization, being similar after the third cycle in terms of hardness loss. Regarding hardness recovery, all saliva promoted enamel gain, but there was a gradual decrease with the progression of the cycles.

The overshadowed role of electron ionization-mass spectrometry in analytical biotechnology.

Target and untargeted analysis of several compounds are crucial methods in important areas such as omics sciences. Gas chromatography coupled to mass spectrometry (GC-MS) is widely used for volatile and thermally stable compounds. In this case, the electron ionization technique (EI) is preferable as it produces highly fragmented and reproducible spectra comparable to spectral libraries. However, only a fraction of target compounds is analyzable by GC without chemical derivatization. Therefore, liquid chromatography (LC) coupled with MS is the most used technique. Contrary to EI, electrospray ionization does not produce reproducible spectra. That is why researchers have been working on interfaces between LC and EI-MS to bridge the gap between those techniques. This short review will discuss advancements, applications, and perspectives on biotechnological analysis.

Microextraction by packed sorbent of N-nitrosamines from Losartan tablets using a high-throughput robot platform followed by liquid chromatography-tandem mass spectrometry.

The development of a fast, cost-effective, and efficient microextraction by packed sorbent setup was achieved by combining affordable laboratory-repackable devices of microextraction with a high-throughput cartesian robot. This setup was evaluated for the development of an analytical method to determine N-nitrosamines in losartan tablets. N-nitrosamines pose a significant concern in the pharmaceutical market due to their carcinogenic risk, necessitating their control and quantification in pharmaceutical products. The parameters influencing the performance of this sample preparation for N-nitrosamines were investigated through both univariate and multivariate experiments. Microextractions were performed using just 5.0 mg of carboxylic acid-modified polystyrene divinylbenzene copolymer as the extraction phase. Under the optimized conditions, the automated setup enabled the simultaneous treatment of six samples in less than 20 min, providing reliable analytical confidence for the proposed application. The analytical performance of the automated high-throughput microextraction by the packed sorbent method was evaluated using a matrix-matching calibration. Quantification was performed using ultra-high-performance liquid chromatography-tandem mass spectrometry with chemical ionization at atmospheric pressure. The method exhibited limits of detection as low as 50 ng/g, good linearity, and satisfactory intra-day (1.38-18.76) and inter-day (2.66-20.08) precision. Additionally, the method showed accuracy ranging from 80% to 136% for these impurities in pharmaceutical formulations.

Cytogenetics Meets Genomics: Cytotaxonomy and Genomic Relationships among Color Variants of the Asian Arowana Scleropages formosus.

Scleropages formosus (Osteoglossiformes, Teleostei) represents one of the most valued ornamental fishes, yet it is critically endangered due to overexploitation and habitat destruction. This species encompasses three major color groups that naturally occur in allopatric populations, but the evolutionary and taxonomic relationships of S. formosus color varieties remain uncertain. Here, we utilized a range of molecular cytogenetic techniques to characterize the karyotypes of five S. formosus color phenotypes, which correspond to naturally occurring variants: the red ones (Super Red); the golden ones (Golden Crossback and Highback Golden); the green ones (Asian Green and Yellow Tail Silver). Additionally, we describe the satellitome of S. formosus (Highback Golden) by applying a high-throughput sequencing technology. All color phenotypes possessed the same karyotype structure 2n = 50 (8m/sm + 42st/a) and distribution of SatDNAs, but different chromosomal locations of rDNAs, which were involved in a chromosome size polymorphism. Our results show indications of population genetic structure and microstructure differences in karyotypes of the color phenotypes. However, the findings do not clearly back up the hypothesis that there are discrete lineages or evolutionary units among the color phenotypes of S. formosus, but another case of interspecific chromosome stasis cannot be excluded.

Morphofunctional parameters, physical fitness and musculoskeletal symptoms in cooperative recyclers.

Introduction: Members of solid waste recycling cooperatives are exposed to serious conditions and complications in their everyday life, which makes them likely to present poor quality of life and unfavorable health conditions in their work environment. Objectives: To evaluate morphofunctional parameters, physical fitness, and musculoskeletal symptoms of workers at solid waste recycling cooperatives in Maringá, state of Paraná, Brazil. Methods: This was a quantitative, cross-sectional, descriptive study. Data were collected from 60 cooperative members of both sexes linked to the Popular and Solidarity Recycling Association of Maringá. Participants underwent a medical screening at the cooperative, involving anamnesis, pulmonary and cardiac auscultation, and blood pressure measurement. In a second moment, they underwent physical assessment in the laboratory, using instruments for physical tests and questionnaires. Results: There was a predominance of females in the sample (54%), with a mean age of 41.82±12.03 years, and most participants did not practice physical activity (70%). With regard to body composition, women had the highest body mass index (28.29±6.61 kg/m2); as for the variables physical and aerobic fitness, men showed better scores than women (p < 0.05). In relation to musculoskeletal symptoms, most participants complained of lower back pain (56.66%). Conclusions: Although the results for anthropometric variables are within normal standards in most cooperative members, most of them present with musculoskeletal symptoms and do not practice physical activity, which can have negative implications in their health conditions in the medium and long term.

Introdução: Os cooperados de reciclagem de resíduos sólidos são expostos a gravidades e complicações no seu dia a dia. Diante disso, é possível que apresentem uma má qualidade de vida e condições de saúde não favoráveis em seu âmbito de trabalho. Objetivos: Avaliar os parâmetros morfofuncionais, a aptidão física e os sintomas osteomusculares dos trabalhadores das cooperativas de reciclagem de resíduos sólidos de Maringá, no estado do Paraná. Métodos: Tratou-se de estudo quantitativo do tipo transversal descritivo. Foram coletados dados de 60 cooperados, de ambos os sexos, vinculados à Associação de Reciclagem Popular e Solidária de Maringá. Os participantes foram submetidos a uma triagem médica na cooperativa, envolvendo anamnese, ausculta pulmonar e cardíaca e mensuração da pressão arterial. Em um segundo momento, foram submetidos à avaliação física em laboratório, com a utilização de instrumentos para testes físicos e preenchimento de questionários. Resultados: Na amostra, houve predomínio do sexo feminino (54%), com média de idade de 41,82±12,03, e a maioria não praticava exercícios físicos (70%). Quanto à composição corporal, o sexo feminino apresentou maior índice de massa corporal (28,29±6,61 kg/m2); para as variáveis de aptidão física e aeróbia, o sexo masculino apresentou melhores escores em relação ao sexo feminino (p < 0,05). Em relação aos sintomas osteomusculares, a maioria relatou sintomas de dor na parte inferior das costas (56,66%). Conclusões: Apesar de os resultados das variáveis antropométricas da maioria dos cooperados encontrarem-se dentro dos padrões de normalidade, a maioria apresenta sintomas osteomusculares e não pratica atividades físicas, o que pode ter implicações negativas nas suas condições de saúde a médio e longo prazo.

A global synthesis of microplastic contamination in wild fish species: Challenges for conservation, implications for sustainability of wild fish stocks and future directions.

Research on the occurrence of microplastics in wild fish populations is a constantly growing area, requiring continuous reviews to properly keep up with the fast pace of publications and guide future work. This review analyses the scientific output of 260 field studies covering 1053 different fish taxa for the presence of microplastics. To date, microplastics have been recorded in 830 wild fish species, including 606 species of interest to commercial and subsistence fisheries. Among these, based on IUCN Red List status, 34 species are globally classified in one of the three threatened categories (Critically Endangered, Endangered or Vulnerable) and another 22 species were assessed as "Near Threatened". Of the species for which the IUCN Red List tracks population trend data, the fish species reported to have microplastics so far include 81 which are recorded as declining, 134 as stable and just 16 as increasing. This review highlights the potential implications of fish microplastic contamination to biodiversity conservation, sustainability of wild fish stocks, and human food safety and security. Finally, recommendations for future research are presented.

Is There a Relationship between Laser Therapy and Root Canal Cracks Formation? A Systematic Review.

Introduction: Crack formation has become an important issue for endodontists, as it can be decisive for the long-term prognosis of the endodontically treated tooth. Since the applicability of laser in endodontics has become frequent, this systematic review aimed to evaluate the association between laser therapy and the formation of cracks in the dentinal structure of the root canal. Materials and Methods: A search was performed in PubMed, Scopus, Web of Science, and Virtual Health Library, as well as in the gray literature, on September 24, 2021. Studies that evaluated the formation of cracks in human root dentin due to different types of lasers were included. The risk of bias was assessed following the modified version of the Consolidated Standards of Reporting Trials (CONSORT) checklist tool. A meta-analysis was performed to evaluate (i) the total number of crack incidences; (ii) complete crack formation; (iii) incomplete crack formation; (iv) intra-dentinal crack formation between ultrasonic tips and laser use. The mean difference was calculated with a 95% confidence interval in a fixed-effect model, the heterogeneity was tested using the I2 index with level of significance of 5%. Results: Of the 22 studies included in this review, 15 have shown that lasers can form cracks in root dentin, including those that performed baseline assessment of samples. The meta-analysis confirmed no difference in crack formation between ultrasonic tips and laser devices. Conclusions: Laser therapy has been gaining prominence in endodontics and that irradiation can form and propagate cracks in the dentinal structure of the root canal assessed by in vitro studies. This is a critical concern for endodontists as it affects the strength and longevity of the tooth. Future research is encouraged to seek the standardization of good methodological practices and achieve establishing parameters to minimize harmful effects of laser on dentin.

Is GRP78 (Glucose-regulated protein 78) a prognostic biomarker in differents types of cancer? A systematic review and meta-analysis.

GRP78 is a chaperone with anti-apoptotic function associated with aggressive tumors. This systematic review aimed to evaluate GRP78 expression in cancer and its relation to prognosis outcomes. This review was conducted in different databases searching for human cancer studies assessing GRP78 immunohistochemical levels on tissue samples. A total of 98 manuscripts were included. In 62% of the studies, GRP78 was associated with a worse prognosis. A meta-analysis included 29 studies that detected a significantly higher expression of GRP78 in cancer tissues (RR= 2.35, 95% CI 1.75-3.15) compared to control. A meta-analysis of 3 and 5-years Overall Survival revealed an increased risk of death for tumors with high expression of GRP78 (RR=1.36, 95%CI 1.16-1,59, I2 = 57%) and (RR=1.65, 95%CI 1.22-2.21, I2 =64%), respectively. GRP78 is an important prognostic biomarker for different types of cancer and a promising therapeutic target.

Age and sex drive differential behavioral and neuroimmune phenotypes during postoperative pain.

Surgical procedures in the geriatric population are steadily increasing, driven by improved healthcare technologies and longer lifespans. However, effective postoperative pain treatments are lacking, and this diminishes quality of life and recovery. Here we present one of the first preclinical studies to pursue sex- and age-specific differences in postoperative neuroimmune phenotypes and pain. We found that aged males, but not females, had a delayed onset of mechanical hypersensitivity post-surgery and faster resolution than young counterparts. This sex-specific age effect was accompanied by decreased paw innervation and increased local inflammation. Additionally, we find evidence of an age-dependent decrease in hyperalgesic priming and perioperative changes in nociceptor populations and spinal microglia in the aged. These findings suggest that impaired neuronal function and maladaptive inflammatory mechanisms influence postoperative pain development in advanced age. Elucidation of these neuroimmune phenotypes across age and sex enables the development of novel therapies that can be tailored for improved pain relief.

A Review of Metabolomic Profiling in Rheumatoid Arthritis: Bringing New Insights in Disease Pathogenesis, Treatment and Comorbidities.

Metabolomic analysis provides a wealth of information that can be predictive of distinctive phenotypes of pathogenic processes and has been applied to better understand disease development. Rheumatoid arthritis (RA) is an autoimmune disease with the establishment of chronic synovial inflammation that affects joints and peripheral tissues such as skeletal muscle and bone. There is a lack of useful disease biomarkers to track disease activity, drug response and follow-up in RA. In this review, we describe potential metabolic biomarkers that might be helpful in the study of RA pathogenesis, drug response and risk of comorbidities. TMAO (choline and trimethylamine oxide) and TCA (tricarboxylic acid) cycle products have been suggested to modulate metabolic profiles during the early stages of RA and are present systemically, which is a relevant characteristic for biomarkers. Moreover, the analysis of lipids such as cholesterol, FFAs and PUFAs may provide important information before disease onset to predict disease activity and treatment response. Regarding therapeutics, TNF inhibitors may increase the levels of tryptophan, valine, lysine, creatinine and alanine, whereas JAK/STAT inhibitors may modulate exclusively fatty acids. These observations indicate that different disease modifying antirheumatic drugs have specific metabolic profiles and can reveal differences between responders and non-responders. In terms of comorbidities, physical impairment represented by higher fatigue scores and muscle wasting has been associated with an increase in urea cycle, FFAs, tocopherols and BCAAs. In conclusion, synovial fluid, blood and urine samples from RA patients seem to provide critical information about the metabolic profile related to drug response, disease activity and comorbidities.