Circular RNA vaccine in disease prevention and treatment

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Sept. 11, 2023

Abstract CircRNAs are a class of single-stranded RNAs with covalently linked head-to-tail topology. In the decades since its initial discovery, their biogenesis, regulation, and function have rapidly disclosed, permitting better understanding adoption them as new tools for medical applications. With development biotechnology molecular medicine, artificial circRNAs been engineered novel vaccines disease treatment prevention. Unlike linear mRNA vaccine which applications were limited by instability, inefficiency, innate immunogenicity, circRNA incorporate internal ribosome entry sites (IRESs) open reading frame (ORF) provides an improved approach to RNA-based vaccination safety, stability, simplicity manufacture, scalability. However, at early stage, optimization, delivery require further evaluation. this review, we comprehensively describe vaccine, including history superiority. We also summarize discuss current methodological research preparation, design, synthesis, purification. Finally, highlight options potential in diseases Considering unique high low protein/peptide-coding capacity special closed-loop construction, circRNA-based therapeutic platforms may superior application prospects broad range diseases.

Language: Английский

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The RANK–RANKL–OPG System: A Multifaceted Regulator of Homeostasis, Immunity, and Cancer

Medicina, Journal Year: 2023, Volume and Issue: 59(10), P. 1752 - 1752

Published: Sept. 30, 2023

The RANK-RANKL-OPG system is a complex signaling pathway that plays critical role in bone metabolism, mammary epithelial cell development, immune function, and cancer. RANKL ligand binds to RANK, receptor expressed on osteoclasts, dendritic cells, T other cells. promotes osteoclast differentiation activation, which leads resorption. OPG decoy inhibits its signaling. In cancer expression often increased, can lead increased resorption the development of metastases. RANKL-neutralizing antibodies, such as denosumab, have been shown be effective treatment skeletal-related events, including osteoporosis or metastases, This review will provide comprehensive overview functions cancer, together with potential therapeutic implications RANK-RANKL for management.

Language: Английский

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Medication-Related Osteonecrosis of the Jaw – 2024 Update

Oral Health & Dental Science, Journal Year: 2024, Volume and Issue: 8(1)

Published: Feb. 29, 2024

As the global number of patients with osteoporosis and malignant diseases such as breast cancer, multiple myeloma, prostate cancer increases every year, there is an associated rise in use antiangiogenic medications antiresorptive medications. With increasing frequencies medications, increase medication-related osteonecrosis jaw (MRONJ) cases reported from patients. MRONJ has emerged a significant comorbidity treated antiangiogenics or high doses potent agents, bisphosphonates (BPs) denosumab. first BP-treated who presented spectrum dental problems, including delayed wound healing following extraction oral surgery, exposed bone, soft tissue infection inflammation, anesthesia, paresthesia, odontalgia, sinus pain, aching bone pain mandible, which continues to be source problems for dentists, physicians, today. A secondary have also been osteoporotic receiving The American Association Oral Maxillofacial Surgeons (AAOMS) established diagnostic standards based on pharmacological history, clinical signs, radiographic findings. However, expertise knowledge base evolve, revisions refinements pathogenesis treatment strategies are necessary reflect current research status disease correctly. This review highlights scientific information identify summarize preventative measures, interventions reading impact this debiliating disorders.

Language: Английский

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Low molecular weight 35 kDa hyaluronan fragment HA35 in the treatment of bone metastasis pain: A case report

Medicine, Journal Year: 2024, Volume and Issue: 103(31), P. e39145 - e39145

Published: Aug. 2, 2024

Rationale: Late-stage cancer patients often experience severe pain due to bone metastasis, caused by structural damage and cancer-induced inflammation. Hyaluronan, known alleviate blocking the TRVP1 calcium channel, faces limitations its high molecular weight. However, 35 kDa low weight hyaluronan fragment (HA35) have shown promise in relieving various pains, including cancer-related pain. Nonetheless, evidence regarding their efficacy metastasis remains scarce. Patients concerns: A 52-year-old female with a rectal malignant tumor multiple secondary tumors sacrum lungs, accompanied Despite undergoing radiotherapy, her relief was unsatisfactory. Before treatment HA35, numerical rating scale score 10, severely affecting sleep, appetite, daily activities. Diagnoses: The patient diagnosed metastases, presenting symptoms such as sacral pain, anal lower limb anterior abdominal Sacral indicated clear diagnosis of Interventions: Treatment involved subcutaneous injection into deep fat tissue layer abdomen. 100 mg/5 mL HA35 administered once abdomen, subsequent injections repeated every 3 days. Outcomes: Following 1 injection, patient’s decreased 6 points within 20 minutes, providing 40% relief. After 40 further dropped 4 points, 60% 50 injections, consistently controlled at around points. Lessons subsections: Subcutaneous effectively alleviates resistant conventional treatments. Additionally, it helps anxiety fatigue, improves diet thereby offering crucial palliative care for advanced patients.

Language: Английский

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Recent Advances in Promoting Bone Regeneration in Type 2 Diabetes Using Drug Delivery Vehicles and Vehicle‐Free Therapeutics

Advanced Therapeutics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 12, 2025

Abstract The incidence of type 2 diabetes (T2DM) increases significantly worldwide. Due to consistent hyperglycemia, insulin resistance, and chronic inflammation, T2DM patients encounter osteoporosis induced osteoporotic fracture risks. Antidiabetic drugs have been traditional therapies that seek control blood glucose, balance bone metabolism, favor systemic immunosuppression. However, such impact quality its nano‐scale features in the long‐term. Today, biomedical experts are continuously advancing drug delivery tools for local osteo‐immunomodulatory agents T2DM. It is demonstrated bioavailability release profile determine osteoconductivity outcomes therapeutics. This review focuses on introducing currently used vehicles fabrication techniques biomaterial‐based systems thoroughly examined. Furthermore, feasibility potential factors contributing bioactive surveyed. extent vivo responses described context current research examples. Targeted signaling mechanisms also assessed detail elucidate activated healing routes.

Language: Английский

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The Role of Osteoprotegerin in Breast Cancer: Genetic Variations, Tumorigenic Pathways, and Therapeutic Potential

Cancers, Journal Year: 2025, Volume and Issue: 17(3), P. 337 - 337

Published: Jan. 21, 2025

Introduction: Osteoprotegerin (OPG), encoded by the TNFRSF11B gene, is linked to development of breast cancer via several pathways, including interactions with receptor activator nuclear factor-κB (RANK) ligands, apoptosis-inducing proteins like TRAIL, and genetic variations such as single nucleotide polymorphisms (SNPs), directly altering gene expression. This review aims investigate role OPG expression in cancer. Methods: A comprehensive literature search was conducted using PubMed Medline, Google Scholar, ScienceDirect. Only full-text English publications from inception September 2024 were included. Results: Studies have demonstrated that certain SNPs specifically rs3102735 rs2073618, are a higher risk development. Additionally, OPG’s function TRAIL decoy may inhibit death cells. Furthermore, serum its BRCA mutations being investigated for their potential influence on progression. found promotes tumorigenesis enhancing cell proliferation, angiogenesis, aneuploidy normal mammary epithelial Moreover, mediates tumor-promoting effects interleukin-1 beta serve biomarker risk, particularly BRCA1 mutation carriers, through dysregulated RANK signaling. Lastly, use recombinant mouse models has been exert anti-tumor effects. Conclusions: In this review, examined. multifaceted exerts TNF-related ligand (TRAIL), modulation pro-tumorigenic microenvironment survival, metastasis. dual tumor suppressor promoter serves possible therapeutic target enhance apoptosis, limit bone metastasis, modulate microenvironment. Whilst much now known, further studies necessary fully delineate OPG.

Language: Английский

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Incidence of Hypercalcemia and Vertebral Fractures Following Denosumab Withdrawal in Lung Cancer Patients: A Longitudinal Cohort Study

Journal of Bone Metabolism, Journal Year: 2025, Volume and Issue: 32(1), P. 38 - 48

Published: Feb. 28, 2025

Background: Bone-target agents (BTAs), including denosumab (DMAb), are one of the bone metastasis treatments that should continue indefinitely. However, BTAs may be interrupted in some cases. In osteoporosis, DMAb withdrawal causes a rebound effect characterized by an increased turnover with spine fractures and hypercalcemia; evidence oncology is lacking. Methods: This study aimed to identify amongst lung cancer patients treated for metastases between January 2020 December 2021. Patients who discontinued were included. Encounter notes, radiological laboratory findings comprehensively reviewed. Results: Thirty included median follow-up 21 months (interquartile range [IQR], 10-30) after discontinuation. Bisphosphonates administered before starting 7 (23.3%) 4 cases (13.3%). Three withdrawal-related hypercalcemia 3 following cessation identified 5 (16.7%), all them females age was 65 years old (IQR, 65-70). No statistical difference duration or number injections found developing compared others (binary logistic regression, <i>p</i>=0.688 <i>p</i>=0.938, respectively). Conclusions: bony-metastatic cancer, especially post-menopausal women, at risk calcium abnormalities discontinuation, suggesting also present oncological setting. A close careful monitoring during discontinuation necessary.

Language: Английский

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Combination treatment with anti-RANKL and antibiotics for preventing joint destruction in septic arthritis

JCI Insight, Journal Year: 2025, Volume and Issue: 10(6)

Published: March 11, 2025

Septic arthritis, the most severe joint disease, is frequently caused by Staphylococcus aureus (S. aureus). A substantial proportion of patients with septic arthritis experience poor outcomes, often necessitating replacement surgery. Here, we show that monocyte depletion confers full protection against bone erosion in a mouse model. In infected synovium, Ly6Chi monocytes exhibited increased expression osteoclastogenesis-related molecules, including CCR2, c-Fms, and RANK. S. lipoproteins induced elevated levels RANKL, MCSF, CCL2 joints, synovial fibroblasts identified as major RANKL producer. Anti-RANKL treatment prevented destruction both local hematogenous murine models. Importantly, combining anti-RANKL antibiotics provided robust damage. Our results indicate infiltration transformation into bone-destructive, osteoclast-like cells are key mechanisms arthritis. Combining antibiotic therapy represents promising this devastating disease.

Language: Английский

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An update on the pharmacotherapy of osteoporosis

Expert Opinion on Pharmacotherapy, Journal Year: 2025, Volume and Issue: unknown

Published: April 3, 2025

Osteoporosis is a chronic metabolic bone disease characterized by progressive loss and structural deterioration, increasing fracture risk morbidity. As the global population ages, its incidence rising, underscoring urgent need for more effective prevention treatment strategies. This review synthesizes latest evidence guidelines from leading international societies, establishing contemporary framework osteoporosis pharmacotherapy. It emphasizes best practices explores future directions in optimization prevention. To optimize outcomes, enhancing early detection, refining strategies, prioritizing patient-centered care are essential. Improving diagnosis through increased use of mineral density (BMD) assessments identifying secondary causes critical steps to addressing underdiagnosis, particularly men. Pharmacotherapies play vital role management; while bisphosphonates serve as cost-effective first-line treatment, Denosumab anabolic agents like Teriparatide Romosozumab essential alternatives high-risk patients. Future management emphasize advancing strategies novel drug targets innovative delivery systems, alongside personalized medicine approaches considering individual genetic comorbidity profiles. Enhanced adherence further research into combination therapies monitoring tools crucial improving ultimately reducing fragility burden worldwide.

Language: Английский

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The genetic architecture of bone metastases: unveiling the role of epigenetic and genetic modifications in drug resistance

Cancer Drug Resistance, Journal Year: 2025, Volume and Issue: unknown

Published: April 22, 2025

Bone metastases represent frequent and severe complications in various cancers, notably impacting prognosis quality of life. This review article delves into the genetic epigenetic mechanisms underpinning drug resistance bone metastases, a key challenge effective cancer treatment. The development can manifest as either intrinsic or acquired, with heterogeneity playing pivotal role. Intrinsic is often due to pre-existing mutations, while acquired evolves through alterations during These include mutations driver genes like TP53 RB1, modifications such DNA methylation histone changes, pathway alterations, involving RANK-RANKL signaling PI3K/AKT/mTOR cascade. Recent studies underline significance tumor microenvironment fostering resistance, components cancer-associated fibroblasts hypoxia crucial roles. interactions between metastatic cells facilitate survival proliferation drug-resistant clones. highlights necessity understanding these complex develop targeted therapies that overcome improve treatment outcomes. Current therapeutic strategies future directions are discussed, emphasizing integration genomic profiling interventions managing metastases. evolving landscape research, including application next-generation sequencing CRISPR technology, offers promising avenues for novel more strategies. comprehensive exploration aims provide insights molecular intricacies paving way improved clinical management patient care.

Language: Английский

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