Osteogenic CpG Oligodeoxynucleotide, iSN40, Inhibits Osteoclastogenesis in a TLR9-Dependent Manner DOI Creative Commons

R. Ikeda,

Chihaya Kimura,

Yuma Nihashi

et al.

Life, Journal Year: 2024, Volume and Issue: 14(12), P. 1572 - 1572

Published: Nov. 30, 2024

A CpG oligodeoxynucleotide (CpG-ODN), iSN40, was originally identified as promoting the mineralization and differentiation of osteoblasts, independent Toll-like receptor 9 (TLR9). Since ODNs are often recognized by TLR9 inhibit osteoclastogenesis, this study investigated dependence anti-osteoclastogenic effect iSN40 to validate its potential an osteoporosis drug. The murine monocyte/macrophage cell line RAW264.7 treated with activator nuclear factor-κB ligand (RANKL) induce osteoclast differentiation, then on quantified tartrate-resistant acid phosphatase (TRAP) staining real-time RT-PCR. completely inhibited RANKL-induced into TRAP+ multinucleated osteoclasts suppressing osteoclastogenic genes inducing anti-/non-osteoclastogenic genes. Treatment a inhibitor, E6446, or mutation in motif abolished intracellular uptake iSN40. These results demonstrate that is subcellularly internalized via motif, modulates RANKL-dependent gene expression, ultimately inhibits osteoclastogenesis. Finally, confirmed osteoclastogenesis cells cocultured osteoblast MC3T3-E1, presenting model bone remodeling. This demonstrates which exerts both pro-osteogenic effects, may be promising nucleic drug for osteoporosis.

Language: Английский

The application of aptamers in the repair of bone, nerve, and vascular tissues DOI

Yu-Wei Hsu,

Le Ma,

Yue Tang

et al.

Journal of Materials Chemistry B, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Aptamers represent a distinct category of short nucleotide sequences or peptide molecules characterized by their ability to bind specific targets with high precision. These are predominantly synthesized through SELEX (Systematic Evolution Ligands Exponential Enrichment) technology. Recent findings indicate that aptamers may have significant applications in regenerative medicine, particularly the domain tissue repair. In comparison other bioactive agents, exhibit superior specificity and affinity, more readily accessible, can be chemically modified, thereby presenting promising avenue for functionalization engineering materials repair applications. This review delineates properties examines methodologies advancements related aptamer-functionalized hydrogels, nanoparticles, electrospun materials. It categorizes four primary functions repair, namely regeneration, delivery systems, anti-inflammatory actions, pro-coagulation effects. Furthermore, explores utilization bone, nerve, vascular tissues, highlighting mechanisms which facilitate growth role transporting substances promote Lastly, addresses future prospects challenges associated application offering novel insights directions further research this domain.

Language: Английский

Citations

1
RNA-based therapies in liver metabolic diseases DOI Creative Commons
Antonio Fontanellas, Pedro Berraondo, F Urigo

et al.

Gut, Journal Year: 2025, Volume and Issue: unknown, P. gutjnl - 331742

Published: Feb. 23, 2025

RNA-based therapeutics have rapidly emerged over the past decade, offering a new class of medicines that differ significantly from conventional drugs. These therapies can be programmed to target or restore defective genes, allowing for more personalised treatments and reducing side effects. Notably, RNA made significant progress in treatment genetic liver diseases, exemplified by small interfering hereditary transthyretin amyloidosis, which use liver-targeting strategies such as GalNAc conjugation improve efficacy safety. gene-editing technologies, base editor prime clustered regularly interspaced short palindromic repeats systems, also show promise with their ability minimise genomic rearrangements cancer risk. While offer high precision, challenges remain optimising delivery methods ensuring long-term safety efficacy. Lipid nanoparticle-mRNA therapeutics, particularly protein replacement rare gained support preclinical successes. Compared viral gene therapies, mRNA present safer profile reduced risks integration oncogene activation. However, clinical trials, especially face limitations sample sizes observation periods. Further studies, including non-human primates, will essential refining trial designs. Despite potential, costs pose challenge require cost–utility models guide pricing accessibility. Here, we discuss fundamental aspects showcase most relevant developments metabolic diseases.

Language: Английский

Citations

1
Use of Mesenchymal Stem Cell-Targeting 3WJ Nanoparticles and Reported Specific Delivery of Anti-miRNA 138 to Treat Osteoporosis DOI Creative Commons
Liangliang Xu, Xiangzhong Liu, Jian Chen

et al.

ACS Omega, Journal Year: 2025, Volume and Issue: unknown

Published: March 4, 2025

Purpose: Locked nucleic acid (LNA)-modified anti-microRNAs have been demonstrated to target mesenchymal stem cells (MSCs) treat bone diseases. However, the "off-target" effect limits its clinical application. Methods: We selected specific aptamer M4 of MSCs and employed three-way junction (3WJ) as core scaffold construct nanoparticles (3WJ-M4-LNA) for delivery anti-miRNA 138. Results: Our results suggested that 3WJ-M4-LNA nanoparticles, not 3WJ-M4 or 3WJ-LNA, can specifically deliver MSCs, resulting in significant inhibition miRNA 138 expression. experiment further confirmed promote MSCs' osteogenic differentiation by activating ERK1/2 pathway. In vivo, promoted formation improved microarchitecture rabbit osteoporosis models. Conclusions: These indicate 3WJ could develop a therapeutic strategy osteoporosis.

Language: Английский

Citations

0
Recent advances and prospects of nanoparticle-based drug delivery for diabetic ocular complications DOI Creative Commons
Siqi Wang, Hongyu Yang, Jiaying Zheng

et al.

Theranostics, Journal Year: 2025, Volume and Issue: 15(8), P. 3551 - 3570

Published: Feb. 25, 2025

Diabetes mellitus (DM) is a chronic metabolic disorder that significantly affects various organ systems. The systemic effects of DM lead to numerous complications, with ocular manifestations being particular concern due their severity and impact on quality life. Hyperglycemia-induced damage often results in range lesions, including diabetic retinopathy (DR), keratopathy, cataracts, glaucoma. These conditions impose considerable physical discomfort patients place substantial economic burden healthcare advent nanotechnology has facilitated the development innovative therapeutic strategies for managing complications. This review highlights several common complications associated DM, focusing pathogenesis treatment strategies. Emphasis placed applications potential treating

Language: Английский

Citations

0
Replication Features of SARS-CoV-2 and Advantages of Targeting S Protein with Aptamers to Block Viral Entry DOI Creative Commons
Jun Zheng,

Qiuxia Pang,

Zhaoying Fu

et al.

ACS Omega, Journal Year: 2025, Volume and Issue: unknown

Published: April 21, 2025

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a virus of the coronaviridae family. The enters cell through binding to corresponding receptor angiotensin-converting enzyme (ACE2) on host membrane with spike protein (S protein) its envelope; thus, we can design inhibitors that bind S block entry into cells. Aptamers are single stranded DNA or RNA molecules form specific three-dimensional structures and their target high affinity specificity thus promising candidates for inhibitors. This paper reviews replication cycle mechanisms SARS-CoV-2 as well preparation principle characteristics aptamers, features discussion advantages using aptamers prevent from infecting cells, finally summarizes research progress in protein-blocking aptamers.

Language: Английский

Citations

0
Chemical Insights into Oligonucleotide–Protein Binding for Therapeutic Applications DOI
Shalini Gupta, Abhishek Gupta, Mandira Mukherjee

et al.

Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: May 7, 2025

Plasma protein binding is an important determinant in the clinical success of oligonucleotide-based drugs. Optimal oligonucleotide critical to its tissue distribution and retention by preventing renal excretion. This property can be modulated through suitable chemical modifications depending on backbone achieve a balanced pharmacokinetic profile minimize off-target effects. The macromolecular structure leads dynamic characteristics as compared small-molecule-based drugs, which are not associated with additional barriers such intracellular delivery. perspective provides insight into diverse plasma interactions various classes oligonucleotides explores strategies for modulating these interactions. Furthermore, we have discussed different methods quantification along correlation chemistry therapeutic outcomes FDA-approved oligonucleotides.

Language: Английский

Citations

0
Recent advances in surface plasmon resonance for the detection of ovarian cancer biomarkers: a thorough review DOI
Shahnam Valizadeh Shahbazlou, Somayeh Vandghanooni, Bahareh Dabirmanesh

et al.

Microchimica Acta, Journal Year: 2024, Volume and Issue: 191(11)

Published: Oct. 9, 2024

Language: Английский

Citations

1
Developing point-of-care diagnosis using electrochemical biosensor: Mosquito-borne disease DOI

Muhammad Fadlan Raihan,

Ni Luh Wulan Septiani, Gilang Gumilar

et al.

Sensors and Actuators Reports, Journal Year: 2024, Volume and Issue: 9, P. 100261 - 100261

Published: Dec. 2, 2024

Language: Английский

Citations

1
Screening and Characterization of DNA Aptamers for the Anti-<em>Klebsiella pneumoniae </em>Omp X Protein by the SELEX Method DOI Open Access

Zhenxing Fan,

Baihai Huang,

Lei He

et al.

Published: July 11, 2024

Klebsiella pneumoniae (KP) is an important gram-negative zoonotic conditional pathogen. It can infect humans and a variety of farm animals, leading to infections such as pneumonia, meningitis even sepsis. thereby posing significant threat public health. OmpX acts virulence protein that participate in bacterial pathogenesis, mediates adhesion invasion epithelial cells, involved adaptation the osmotic pressure external environment. In this study, MBs-SELEX was used main strategy for screening aptamers. Omp X target A counter-screening target. qPCR flow cytometry were determine nature specificity obtained aptamers protein. The analysis showed among aptamers, three Apt-1, Apt-2 Apt-3, selected with Kd values 62.50 nM, 22.05 nM 7.9 respectively. addition, total internal reflection fluorescence microscopy (TIRFM) characterization KP complex specific FITC-labeled (FITC-Apt-3) AuNCs. complexes characterized by observing blue fluorescent dots from AuNCs green overlapping presence. These results suggest specifically bind bacteria, forming complexes. Furthermore, vitro demonstrated Apt-3 inhibited growth, having most inhibitory effect. selectively recognize membrane proteins, disrupting cell formation effectively inhibiting growth. Aptamers have potential mechanism inhibit

Language: Английский

Citations

0
Osteogenic CpG oligodeoxynucleotide, iSN40, inhibits osteoclastogenesis in a TLR9-dependent manner DOI Creative Commons

R. Ikeda,

Chihaya Kimura,

Yuma Nihashi

et al.

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

Published: Sept. 2, 2024

Abstract A CpG oligodeoxynucleotide (CpG-ODN), iSN40 (5’-GGA ACG ATC CTC AAG CTT-3’), was originally identified to promote osteoblast differentiation independent of Toll-like receptor 9 (TLR9). While CpG-ODNs are generally known be recognized by TLR9 and inhibit osteoclasto-genesis. This study investigated the anti-osteoclastogenic effect iSN40. The murine mono-cyte/macrophage cell line RAW264.7 treated with activator nuclear factor-κB ligand (RANKL) induce osteoclast differentiation, effects on formation were quantified tartrate-resistant acid phosphatase (TRAP) staining real-time RT-PCR. completely inhibited RANKL-induced into TRAP + multinucleated osteoclasts suppressing osteoclastogenic genes ( Nfatc1, Ctsk , Dcstamp ) inducing anti-/non-osteoclasto-genic Irf8, Adgre1 Il1b ). Treatment a inhibitor, E6446, or mutation in motif abolished intracellular uptake These results demonstrate that is internalized subcellularly, via its motif, modulates RANKL-dependent gene expression, ultimately inhibits formation. Computational simulation structure also suggested importance superficial for function. Finally, confirmed osteoclastogenesis cells cocultured MC3T3-E1, which model bone remodeling. demonstrates iSN40, exerts both pro-osteogenic effects, may promising nucleic drug osteoporosis.

Language: Английский

Citations

0