Evidence of Silencing of Intestinal Inflammatory and Immune Transcripts Following Induction of Joint Inflammation DOI Open Access
Meghan M. Moran, Jun Li, Quan Shen

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 17, 2024

ABSTRACT Disrupted intestinal epithelial barrier function has been proposed to be integral rheumatoid arthritis (RA) progression and pathogenesis. To further define the molecular pathways in synovial inflammation response of tissues, we have used a rat model mono-joint inflammatory arthritis, induced by intra-articular injection Complete Freund’s adjuvant (CFA). The predominant single into knee joint resulted rapid reproducible formation fibrotic myeloid-infiltrated pannus. Our aim was determine how including proximal distal ileum colon, responded changes synovium temporally coordinated manner comparing their transcriptomic landscapes using RNASeq analyses. We confirmed timeline swelling measurement, increased fluid levels bikunin (a component both acute phase protein pre-alpha-inhibitor inter-alpha-inhibitor) demonstrated self-correcting trabecular cortical bone CFA challenge. Intestine-specific responses were monitored 16S microbiome amplicon sequencing, histopathology for mucus layer integrity, immune cell immunohistochemistry. present data that shows tissue displays an allostatic region specific. primarily with secretion silencing T-cell specific pathways, whereas colon showed transient upregulation macrophages, broader suppression related metabolic pathway transcripts. Interestingly, many neuropathways activated early but then suppressed later colon. There only insignificant fecal composition or post-CFA administration. In summary, our show first time following induction minimal microbiome. results help clarify tissues stresses accompany pathogenesis diseases.

Language: Английский

Circadian Regulation of Bone Remodeling DOI Open Access
Nobuaki Kikyo

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(9), P. 4717 - 4717

Published: April 26, 2024

Adult bones are continuously remodeled by the balance between bone resorption osteoclasts and subsequent formation osteoblasts. Many studies have provided molecular evidence that remodeling is under control of circadian rhythms. Circadian fluctuations been reported in serum urine levels turnover markers, such as digested collagen fragments alkaline phosphatase. Additionally, expressions over a quarter all transcripts show rhythmicity, including genes encoding master transcription factors for osteoblastogenesis osteoclastogenesis, osteogenic cytokines, signaling pathway proteins. Serum calcium, phosphate, parathyroid hormone, calcitonin also display rhythmicity. Finally, osteoblast- osteoclast-specific knockout mice targeting core regulator gene Bmal1 disrupted remodeling, although results not always consistent. Despite these studies, however, establishing direct link rhythms vivo remains major challenge. It nearly impossible to repeatedly collect materials from human subjects while following changes. In addition, differences regulation diurnal humans nocturnal mice, main model organism, remain unclear. Filling knowledge gap could reveal novel regulatory mechanisms underlying many disorders osteoporosis, genetic diseases, fracture healing. This an important question basic understanding how cell differentiation progresses influence cyclically fluctuating environments.

Language: Английский

Citations

12
The role of circadian clock in regulating cell functions: implications for diseases DOI Creative Commons

Yanke Lin,

Liangliang He, Yuting Cai

et al.

MedComm, Journal Year: 2024, Volume and Issue: 5(3)

Published: March 1, 2024

Abstract The circadian clock system orchestrates daily behavioral and physiological rhythms, facilitating adaptation to environmental internal oscillations. Disruptions in rhythms have been linked increased susceptibility various diseases can exacerbate existing conditions. This review delves into the intricate regulation of diurnal gene expression cell function by clocks across diverse tissues. . Specifically, we explore rhythmicity expressions, behaviors, functions both immune non‐immune cells, elucidating regulatory effects mechanisms imposed clocks. A detailed discussion is centered on complex regulating key cellular signaling pathways. We further diseases, with a focus inflammatory cancers, systemic diseases. By highlighting intimate interplay between especially through clock‐controlled function, this contributes development novel disease intervention strategies. enhanced understanding holds significant promise for design targeted therapies that exploit improved treatment efficacy.

Language: Английский

Citations

11
Complex gene-dependent and-independent mechanisms control daily rhythms of hematopoietic cells DOI Open Access
Francesca Sciarra, Edoardo Franceschini, Gabriella Palmieri

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2025, Volume and Issue: 183, P. 117803 - 117803

Published: Jan. 2, 2025

Language: Английский

Citations

1
Melatonin from Plants: Going Beyond Traditional Central Nervous System Targeting—A Comprehensive Review of Its Unusual Health Benefits DOI Creative Commons
Lucas Fornari Laurindo,

Otávio Augusto Garcia Simili,

Adriano Cressoni Araújo

et al.

Biology, Journal Year: 2025, Volume and Issue: 14(2), P. 143 - 143

Published: Jan. 30, 2025

Melatonin is indispensable for the homeostasis of plants and animals. In humans, it can help prevent or be an adjuvant treatment several diseases mainly related to immune system, inflammation, oxidative stress. Moreover, a melatonin-rich diet linked health benefits, such as regulation circadian rhythm, immunological epilepsy control, delaying aging process, diminishing hormones cancer. This review aimed show effects melatonin in beyond its traditional use. The results showed present scavenging free radicals, reducing inflammatory cytokines, modulating system. improve insulin resistance, blood pressure, LDL-c, adipose tissue mass, adhesion molecules, endothelial impairment, plaque formation. These result neuro- cardioprotection, improvement liver diseases, rheumatoid arthritis, dermatitis, COVID-19, polycystic ovaries, sepsis. We conclude that plant benefit patients with many besides sleep problems neurodegeneration. Plant may more cost-effective fewer adverse events than synthetic. However, clinical trials should performed adequate doses, formulation, time.

Language: Английский

Citations

0
Advances in nanodelivery systems based on apoptosis strategies for enhanced rheumatoid arthritis therapy DOI
Zongquan Zhang, Yilin Liu, Xiaoya Liang

et al.

Acta Biomaterialia, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

0
A Time Adjustable Pulsatile Release System of Ketoprofen by Combination of Floating Drug Delivery and a Novel Natural Pulsatile Polymer DOI

R. R. N. Sailaja,

L Lavanya,

Kalyani K. Naga.

et al.

Asian Journal of Research in Pharmaceutical Sciences, Journal Year: 2025, Volume and Issue: unknown, P. 13 - 19

Published: March 7, 2025

Back ground: Rheumatoid atritis is an inflammatory diesease related to joints and its symptoms worsen in the early morning. The aim of current work was formulate evaluate pulsatile drug release Ketoprofen tablets by both natural synthetic polymers get a required lag time o for at which arthritis worsen. Methods: A gum prepared from delonix regia seeds used release. Peanut husk powder as floating polymer. Direct compression method prepare Core tablets. were coated with gum, HPMC ethylcellulose timed These improve time. Compression evaluated hardness, friability, time, percent Results: shown adequate pharmaceutical properties. core (F3, F4) dehydrated banana superdisintegrant disintegrated within 20sec. layer has improved burst 80% after 4hrs. Conclusion: formulation contain super disintegrant disintegrates 30sec Delonix alone fro concluded that mucilage potential applications delivery.

Language: Английский

Citations

0
Disulfide bond-based oxidation-responsive triptolide-loaded nanodrug for inflammation-targeted treatment of collagen-induced arthritis DOI

Huahui Zeng,

Man Li, Zhirong Wang

et al.

Applied Materials Today, Journal Year: 2024, Volume and Issue: 40, P. 102350 - 102350

Published: Aug. 2, 2024

Language: Английский

Citations

3
The circadian regulator PER1 promotes cell reprogramming by inhibiting inflammatory signaling from macrophages DOI Creative Commons
Nobuko Katoku-Kikyo, Seunghyun Lim, Ce Yuan

et al.

PLoS Biology, Journal Year: 2023, Volume and Issue: 21(12), P. e3002419 - e3002419

Published: Dec. 4, 2023

Circadian regulation of gene expression is prevalent and plays critical roles in cell differentiation. However, its the reprogramming differentiated cells remain largely unknown. Here, we found that one master circadian regulators PER1 promoted virus-mediated mouse embryonic fibroblasts (MEFs) to induced neurons (iNs) pluripotent stem (iPSCs). Unexpectedly, achieved this by repressing inflammatory activation contaminating macrophages MEF culture, rather than directly modulating reprogrammability MEFs. More specifically, transduced viruses activated genes macrophages, such as Tnf encoding TNFα, central an autocrine activator macrophages. TNFα inhibited iN reprogramming, whereas a inhibitor connecting responses reprogramming. In addition, were proliferate mature non-macrophage serving feeders, which also supported up-regulation without virus transduction. Furthermore, 2 repressed regulator making dependent on time-of-day Similar results obtained with iPSC suggesting wide occurrence macrophage-mediated inhibition This study uncovers mechanistic links between bystander rhythms, are particularly relevant vivo organoid formation incorporating immune cells.

Language: Английский

Citations

7
Engineered self-regulating macrophages for targeted anti-inflammatory drug delivery DOI Creative Commons
Molly Klimak,

Amanda Cimino,

Kristin L. Lenz

et al.

Arthritis Research & Therapy, Journal Year: 2024, Volume and Issue: 26(1)

Published: Nov. 6, 2024

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by increased levels of inflammation that primarily manifests in the joints. Macrophages act as key drivers for progression RA, contributing to perpetuation chronic and dysregulation pro-inflammatory cytokines such interleukin 1 (IL-1). The goal this study was develop macrophage-based cell therapy biologic drug delivery an autoregulated manner. For proof-of-concept, we developed "smart" macrophages mitigate effects IL-1 delivering its inhibitor, receptor antagonist (IL-1Ra). Bone marrow-derived were lentivirally transduced with synthetic gene circuit uses NF-κB inducible promoter upstream either Il1rn or firefly luciferase transgenes. Two types joint like cells utilized examine therapeutic protection vitro, miPSCs derived cartilage isolated primary mouse synovial fibroblasts while K/BxN model RA vivo protection. These engineered able repeatably produce IL-1Ra could successfully inflammatory activation co-culture both tissue-engineered constructs fibroblasts. Following injection vivo, homed sites mitigated severity RA. findings demonstrate successful development possess ability controlled, production based on signaling via pathway cytokine applications other diseases. This system provides proof concept immune self-regulating systems range

Language: Английский

Citations

2
Melanogenesis Is Directly Affected by Metabolites of Melatonin in Human Melanoma Cells DOI Open Access

Jack K. S. Möller,

Kinga Linowiecka, Maciej Gagat

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(19), P. 14947 - 14947

Published: Oct. 6, 2023

Melatonin (N-acetyl-5-methoxytryptamine, MEL), its kynurenic (N1-acetyl-N2-formyl-5-methoxykynurenine, AFMK) and indolic derivatives (6-hydroxymelatonin, 6(OH)MEL 5-methoxytryptamine, 5-MT) are endogenously produced in human epidermis. Melatonin, by the pineal gland, brain peripheral organs, displays a diversity of physiological functions including anti-inflammatory, immunomodulatory, anti-tumor capacities. Herein, we assessed their regulatory effect on melanogenesis using amelanotic (A375, Sk-Mel-28) highly pigmented (MNT-1, melanotic) melanoma cell lines. We discovered that subjected compounds decrease downstream pathway melanin synthesis causing significant drop cyclic adenosine monophosphate (cAMP) level, microphthalmia-associated transcription factor (MITF) resultant collapse tyrosinase (TYR) activity, content comparatively to N-phenylthiourea (PTU, positive control). observed reduction pigment melanosomes visualized transmission electron microscopy. Finally, role G-protein-coupled seven-transmembrane-domain receptors. Obtained results revealed nonselective MT1 MT2 receptor antagonist (luzindole) or selective (4-P-PDOT) did not affect dysregulation indicating receptor-independent mechanism. Our findings, together with current state art, provide convenient experimental model study complex relationship between metabolites melatonin control pigmentation serving as future rationale strategy for targeted therapies melanoma-affected patients.

Language: Английский

Citations

4