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Pediatric Rheumatology Online Journal Mar 2024Systemic juvenile idiopathic arthritis (sJIA) is a severe form of juvenile arthritis that is characterized by chronic joint inflammation and systemic symptoms such as...
BACKGROUND
Systemic juvenile idiopathic arthritis (sJIA) is a severe form of juvenile arthritis that is characterized by chronic joint inflammation and systemic symptoms such as fever, rash, and organ involvement. Anti-IL-6 receptor monoclonal antibody tocilizumab is an effective treatment. However, some patients still experience persisting or recurrent symptoms and the real-world effectiveness of canakinumab in Chinese patients with sJIA has never been reported. Therefore, this study aimed to assess the efficacy and safety of canakinumab in Chinese patients with sJIA using real-world data.
METHODS
We conducted a retrospective study on children with active sJIA. Clinical features, laboratory data, corticosteroid dosage, and adverse events (AEs) were collected at baseline and at 4, 8, 12, and 24 weeks after initiating canakinumab treatment.
RESULTS
Seven female and four male patients were included in the study. All patients had previously been treated with tocilizumab and were administered canakinumab for 12.4 ± 3.4 months. Notably, significant improvements were observed in both clinical signs and symptoms as well as laboratory indicators. Four children under corticosteroid treatment were able to successfully discontinue their corticosteroid therapy: one at week 4, two at week 12, and one at week 24. Notably, there was a significant reduction in the number of tender and swollen joints (P = 0.0059) as well as the systemic juvenile arthritis disease activity score (P < 0.0001). The most common AE was infection, but no patients experienced serious AEs. No cases of macrophage activation syndrome or death were reported during the follow-up period.
CONCLUSIONS
Canakinumab was found to be potentially efficacious and safe in Chinese patients with sJIA. No new AEs were observed with canakinumab treatment.
Topics: Child; Humans; Male; Female; Arthritis, Juvenile; Antibodies, Monoclonal; Retrospective Studies; Adrenal Cortex Hormones; Antibodies, Monoclonal, Humanized
PubMed: 38504360
DOI: 10.1186/s12969-024-00974-4 -
Arthritis Research & Therapy Mar 2024To evaluate long-term outcomes and prognostic factors in patients with juvenile idiopathic arthritis (JIA), presenting as oligoarthritis, who received IAC as the first...
BACKGROUND
To evaluate long-term outcomes and prognostic factors in patients with juvenile idiopathic arthritis (JIA), presenting as oligoarthritis, who received IAC as the first treatment for their disease.
METHODS
We conducted retrospective study at the University Children's Hospital Ljubljana, Slovenia, from January 2015 to May 2023 in children with JIA, clinically presenting as oligoarthritis receiving intra-articular corticosteroid injection (IAC) as the initial treatment. Patient and treatment data were collected, and the outcomes were categorized into three groups based on the later need for therapy: no therapy needed, only additional IAC needed and systemic therapy needed. The last group was further divided based on the requirement of bDMARD. Log-rank (Mantel-Cox) survival analyses compared different outcome groups.
RESULTS
We included 109 patients with JIA, presenting as oligoarthritis (63% female), who were first treated with IAC. The mean age at IAC was 8.0 years, with a 4.3-year follow-up. Notably, 38.5% of patients did not require additional therapy post-IAC, whereas 15.5% required only additional IAC. Systemic therapy, mainly methotrexate (MTX), was necessary for 45.9% of patients, initiated in average 7.8 months post-IAC. Biologic therapy was initiated in 22% in average 2.2 years post-IAC. Number of injected joints correlated with the need for biologics. At the last follow-up, 88.9% had inactive disease. ANA positivity (P = 0.049, chi square 3.89) and HLA B27 antigen presence (P = 0.050, chi square 3.85) were associated with the need for systemic therapy. A subgroup of children older than 8 years, ANA and HLA B27 negative required significantly less systemic (25.8%) and biologic therapy (9.6%) compared to other patients (p = 0.050, chi square 3.77).
CONCLUSION
Almost 40% of children with oligoarticular JIA requiring IAC did not progress to chronic disease. Younger age, ANA positivity, and HLA B27 presence were predictive factors for systemic therapy, while the number of injected joints predicted the future need for biologic therapy.
Topics: Child; Humans; Female; Male; Arthritis, Juvenile; Follow-Up Studies; HLA-B27 Antigen; Retrospective Studies; Injections, Intra-Articular; Adrenal Cortex Hormones
PubMed: 38486285
DOI: 10.1186/s13075-024-03303-y -
Plants (Basel, Switzerland) Mar 2024Phase change refers to the process of maturation and transition from the juvenile to the adult stage. In response to this shift, certain species like chestnut lose the...
Phase change refers to the process of maturation and transition from the juvenile to the adult stage. In response to this shift, certain species like chestnut lose the ability to form adventitious roots, thereby hindering the successful micropropagation of adult plants. While auxin is the main hormone involved in adventitious root formation, other hormones, such as ethylene, are also thought to play a role in its induction and development. In this study, experiments were carried out to determine the effects of ethylene on the induction and growth of adventitious roots. The analysis was performed in two types of chestnut microshoots derived from the same tree, a juvenile-like line with a high rooting ability derived from basal shoots (P2BS) and a line derived from crown branches (P2CR) with low rooting responses. By means of the application of compounds to modify ethylene content or inhibit its signalling, the potential involvement of this hormone in the induction of adventitious roots was analysed. Our results show that ethylene can modify the rooting competence of mature shoots, while the response in juvenile material was barely affected. To further characterise the molecular reasons underlying this maturation-derived shift in behaviour, specific gene expression analyses were developed. The findings suggest that several mechanisms, including ethylene signalling, auxin transport and epigenetic modifications, relate to the modulation of the rooting ability of mature chestnut microshoots and their recalcitrant behaviour.
PubMed: 38475584
DOI: 10.3390/plants13050738 -
International Journal of Molecular... Feb 2024Mevalonate kinase (MevK) is an important enzyme in the mevalonate pathway that catalyzes the phosphorylation of mevalonate into phosphomevalonate and is involved in...
Mevalonate kinase (MevK) is an important enzyme in the mevalonate pathway that catalyzes the phosphorylation of mevalonate into phosphomevalonate and is involved in juvenile hormone biosynthesis. Herein, we present a structure model of MevK from the red flour beetle (MevK), which adopts a compact α/β conformation that can be divided into two parts: an N-terminal domain and a C-terminal domain. A narrow, deep cavity accommodating the substrate and cofactor was observed at the junction between the two domains of MevK. Computational simulation combined with site-directed mutagenesis and biochemical analyses allowed us to define the binding mode of MevK to cofactors and substrates. Moreover, MevK showed optimal enzyme activity at pH 8.0 and an optimal temperature of 40 °C for mevalonate as the substrate. The expression profiles and RNA interference of indicated its critical role in controlling juvenile hormone biosynthesis, as well as its participation in the production of other terpenoids in . These findings improve our understanding of the structural and biochemical features of insect Mevk and provide a structural basis for the design of MevK inhibitors.
Topics: Animals; Tribolium; Coleoptera; Mevalonic Acid; Juvenile Hormones; Phosphotransferases (Alcohol Group Acceptor)
PubMed: 38473803
DOI: 10.3390/ijms25052552 -
ELife Mar 2024Imidacloprid is a global health threat that severely poisons the economically and ecologically important honeybee pollinator, . However, its effects on developing bee...
Imidacloprid is a global health threat that severely poisons the economically and ecologically important honeybee pollinator, . However, its effects on developing bee larvae remain largely unexplored. Our pilot study showed that imidacloprid causes developmental delay in bee larvae, but the underlying toxicological mechanisms remain incompletely understood. In this study, we exposed bee larvae to imidacloprid at environmentally relevant concentrations of 0.7, 1.2, 3.1, and 377 ppb. There was a marked dose-dependent delay in larval development, characterized by reductions in body mass, width, and growth index. However, imidacloprid did not affect on larval survival and food consumption. The primary toxicological effects induced by elevated concentrations of imidacloprid (377 ppb) included inhibition of neural transmission gene expression, induction of oxidative stress, gut structural damage, and apoptosis, inhibition of developmental regulatory hormones and genes, suppression of gene expression levels involved in proteolysis, amino acid transport, protein synthesis, carbohydrate catabolism, oxidative phosphorylation, and glycolysis energy production. In addition, we found that the larvae may use antioxidant defenses and P450 detoxification mechanisms to mitigate the effects of imidacloprid. Ultimately, this study provides the first evidence that environmentally exposed imidacloprid can affect the growth and development of bee larvae by disrupting molting regulation and limiting the metabolism and utilization of dietary nutrients and energy. These findings have broader implications for studies assessing pesticide hazards in other juvenile animals.
Topics: Bees; Animals; Larva; Molting; Pilot Projects; Energy Metabolism; Nutrients; Neonicotinoids; Nitro Compounds
PubMed: 38466325
DOI: 10.7554/eLife.88772 -
PeerJ 2024The soldier caste is one of the most distinguished castes inside the termite colony. The mechanism of soldier caste differentiation has mainly been studied at the...
The soldier caste is one of the most distinguished castes inside the termite colony. The mechanism of soldier caste differentiation has mainly been studied at the transcriptional level, but the function of microRNAs (miRNAs) in soldier caste differentiation is seldom studied. In this study, the workers of Shiraki were treated with methoprene, a juvenile hormone analog which can induce workers to transform into soldiers. The miRNomes of the methoprene-treated workers and the controls were sequenced. Then, the differentially expressed miRNAs (DEmiRs) were corrected with the differentially expressed genes DEGs to construct the DEmiR-DEG regulatory network. Afterwards, the DEmiR-regulated DEGs were subjected to GO enrichment and KEGG enrichment analysis. A total of 1,324 miRNAs were identified, among which 116 miRNAs were screened as DEmiRs between the methoprene-treated group and the control group. A total of 4,433 DEmiR-DEG pairs were obtained. No GO term was recognized as significant in the cellular component, molecular function, or biological process categories. The KEGG enrichment analysis of the DEmiR-regulated DEGs showed that the ribosome biogenesis in eukaryotes and circadian rhythm-fly pathways were enriched. This study demonstrates that DEmiRs and DEGs form a complex network regulating soldier caste differentiation in termites.
Topics: Animals; Isoptera; Methoprene; Circadian Rhythm; Control Groups; MicroRNAs
PubMed: 38436016
DOI: 10.7717/peerj.16843 -
Life (Basel, Switzerland) Jan 2024Light is an indispensable factor in the healthy growth of living organisms, and alterations in the photoperiod can have consequences for body homeostasis. The eyestalk...
Light is an indispensable factor in the healthy growth of living organisms, and alterations in the photoperiod can have consequences for body homeostasis. The eyestalk is a photosensitive organ that secretes various hormones to regulate the Chinese mitten crab (). However, the photoperiod-dependent eyestalk patterns of gene expression that may underlie changes in body homeostasis are unknown. In this study, we investigated the molecular mechanisms involved in eyestalk transcriptomic responses in under different photoperiod regimes on days 2, 4, and 6. The photoperiods tested were 12, 24, and 0 h light/day. In total, we obtained 110, 958, 348 clean datasets and detected 1809 differentially expressed genes (DEGs). Genes involved in the crustacean hyperglycemic hormone superfamily and juvenile hormones were observed, which play important roles in gonadal development, growth, and immunity in and may also be involved in photoperiod adaptation. In addition, the MAPK signaling pathway was the only signaling pathway identified in the continuous light group but was absent in the continuous darkness group. We suggest that the MAPK pathway is highly responsive to light input during the subjective night and insensitive to light during the middle of the subjective day. These results provide insight into the molecular mechanisms underlying the effects of photoperiod on the immune regulation of .
PubMed: 38398718
DOI: 10.3390/life14020209 -
Journal of the American Mosquito... Mar 2024Understanding the influence of salinity on the efficacy of mosquito larvicides in brackish water habitats is crucial for effective salt-marsh Aedes taeniorhynchus...
Understanding the influence of salinity on the efficacy of mosquito larvicides in brackish water habitats is crucial for effective salt-marsh Aedes taeniorhynchus control. This study investigated the interactive effects of salinity on the toxicity of 3 commonly used mosquito larvicides: Bacillus thuringiensis israelensis (VectoBac® 12AS), spinosad (Natular® SC), and S-methoprene (Altosid® 12AS) against Ae. taeniorhynchus larvae. Four salinity levels (0 ppt [parts per thousand], 8 ppt, 16 ppt, and 32 ppt) were tested in laboratory bioassays. The results revealed distinct responses of these larvicides to varying salinity levels. VectoBac 12AS displayed consistent efficacy across all salinity levels, indicating its suitability for brackish water habitats. In contrast, Natular 2EC exhibited increased effectiveness with higher salinity, making it a preferable choice for saline environments. Altosid 12AS showed its highest efficacy in freshwater, with reduced effectiveness as salinity increased. These findings underscore the need to consider salinity levels when selecting and applying mosquito larvicides in diverse aquatic habitats. Understanding the complex interplay between salinity and larvicide performance is essential for optimizing mosquito control strategies and mitigating mosquito-borne diseases in various environments.
Topics: Animals; Aedes; Methoprene; Salinity; Bacillus thuringiensis; Larva; Ochlerotatus
PubMed: 38369954
DOI: 10.2987/23-7151 -
The Science of the Total Environment Apr 2024Pentabromodiphenyl ether (BDE-99) and bisphenol A (BPA) are synthetic organic compounds present in several daily use products. Due to their physicochemical properties,...
Pentabromodiphenyl ether (BDE-99) and bisphenol A (BPA) are synthetic organic compounds present in several daily use products. Due to their physicochemical properties, they are ubiquitously present in aquatic ecosystems and considered highly persistent. Recent evidence has confirmed that both emerging compounds are toxic to humans and terrestrial mammals eliciting a wide range of detrimental effects at endocrine and immune levels. However, the ecotoxicological responses that they can trigger in vertebrate marine species have not yet been established. Hence, this study aimed to investigate the ecotoxicological responses of juvenile Sparus aurata upon chronic (28 days) dietary exposure to BDE-99 and BPA (alone and combined) following an integrated multi-biomarker approach that combined fitness indicators (Fulton's K and splenosomatic indexes) with endocrine [cortisol, 17β-estradiol (E2), 11-ketotestosterone (11-KT) concentrations] and immune (peroxidase and antiprotease activities) endpoints in fish plasma, and oxidative stress [superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST) activities, and lipid peroxidation (LPO)] endpoints in the fish spleen. The mixture of BDE-99 and BPA yielded the highest IBR index value in both plasma and spleen biomarkers, therefore, suggesting that the effects of these compounds are more severe when they act together. Endocrine biomarkers were the most responsive in the three contaminated treatments. Fitness indicators were not affected by the individual nor the interactive effects of BDE-99 and BPA. These findings highlight the relevance of accounting for the interactive effects of emerging chemical contaminants and integrating responses associated with distinct biological pathways when investigating their impacts on marine life, as such a multi-biomarker approach provides a broader, more realistic and adequate perspective of challenges faced by fish in a contaminated environment.
Topics: Animals; Humans; Sea Bream; Ecosystem; Oxidative Stress; Biomarkers; Mammals; Benzhydryl Compounds; Phenols; Halogenated Diphenyl Ethers
PubMed: 38365038
DOI: 10.1016/j.scitotenv.2024.170989 -
Insect Biochemistry and Molecular... Apr 2024Compounds classified as benzoylphenylurea (BPU), such as diflubenzuron (DFB), are used as insecticides. Although BPU disrupts molting by inhibiting chitin biosynthesis...
Compounds classified as benzoylphenylurea (BPU), such as diflubenzuron (DFB), are used as insecticides. Although BPU disrupts molting by inhibiting chitin biosynthesis and exhibits insecticidal activity, their exact mode of action remains unknown. Since epidermal cells proliferate and morphologically change from squamous to columnar cells during the early stages of insect molting, we speculate that a transition similar to that from epithelium to mesenchyme occurs and that BPU may inhibit this transition. Here, we addressed this possibility. We found that DFB decreases actin expression in insect cells (the tissue cultures of insect integument). Detailed analysis in Schneider S2 cells reveals that DFB inhibits the expression of actin isoforms (Act5C and Act42A) and the Drosophila ortholog of myocardin-related transcription factor (Mrtf), leading to cell growth suppression. Proteomics identified the Drosophila ortholog of prohibitin (Phb1D and Phb2E) as one of the DFB-binding proteins. DFB inhibits the interaction between Phb1D and Phb2E and induces mitochondrial dysfunction. The knock-down of Phb2E suppresses the expression of Act5C, Act42A, and Mrtf, leading to cell growth inhibition. Thus, the disruption of Phb function is a possible novel target of DFB.
Topics: Animals; Diflubenzuron; Actins; Insecticides; Drosophila
PubMed: 38342197
DOI: 10.1016/j.ibmb.2024.104088