Antisense anti-inflammatory

Contemporary treatments for osteoarthritis (OA) pursue only to alleviate the pain caused by the illness. Discovering disease-modifying osteoarthritis drugs (DMOADs) that can induce the repair and regeneration of articular tissues would be of substantial usefulness. The purpose of this manuscript is to review the contemporary role of DMOADs in managing OA. A narrative literature review on the subject, exploring the Cochrane Library and PubMed (MEDLINE) was performed. It was encountered that many publications have analyzed the impact of several DMOAD methods, including anti-cytokine therapy (tanezumab, AMG 108, adalimumab, etanercept, anakinra), enzyme inhibitors (M6495, doxycycline, cindunistat, PG-116800), growth factors (bone morphogenetic protein-7, sprifermin), gene therapy (micro ribonucleic acids, antisense oligonucleotides), peptides (calcitonin) and others (SM04690, senolitic, transient receptor potential vanilloid 4, neural EGFL-like 1, TPCA-1, tofacitinib, lorecivivint and quercitrin)...

BACKGROUND/AIMS: Resveratrol (RSV) is a natural polyphenol with strong biological activity that confers a measure of protection against the development of inflammatory bowel disease (IBD), and the long noncoding RNA (lncRNA) antisense non-coding RNA in the INK4 locus (ANRIL) is closely related to inflammation. The present study determined whether resveratrol attenuated IBD by regulating ANRIL and its specific molecular mechanism. METHODS: In vivo model of IBD was induced by dextran sulfate sodium (DSS)...

Neuropathic pain is the most difficult-to-treat pain syndrome in multiple sclerosis. Evidence relates neuropathic pain to demyelination, which often originates from unresolved neuroinflammation or altered immune response. Posttranscriptional regulation of gene expression might play a fundamental role in the regulation of these processes. The ELAV RNA-binding proteins HuR and HuD are involved in the promotion of inflammatory phenomena and in neuronal development and maintenance, respectively. Thus, the aim of this study was to investigate the role of HuR and HuD in demyelination-associated neuropathic pain in the mouse experimental autoimmune encephalomyelitis (EAE) model...

BACKGROUND: Metabolic syndrome (Mets) is a common metabolic disorder in which hypoadiponectinemia is one of the consequences for the body caused by inflammation, and vitamin D may help improve inflammatory symptoms. LncRNAs (long non-coding RNA) play several different regulatory roles in the body. The goal of this study was to see how adding vitamin D to milk affected the levels of adiponectin and inflammatory lncRNAs in the serum of people with Mets. METHODS: This clinical trial was conducted on staff and students between the ages of 30 and 50 at Mashhad University of Medical Sciences and met the International Diabetes Federation's criteria for Mets...

Colorectal cancer (CRC) is a common gastrointestinal malignancy with high morbidity and fatality. Chemotherapy, as traditional therapy for CRC, has exerted well antitumor effect and greatly improved the survival of CRC patients. Nevertheless, chemoresistance is one of the major problems during chemotherapy for CRC and significantly limits the efficacy of the treatment and influences the prognosis of patients. To overcome chemoresistance in CRC, many strategies are being investigated. Here, we review the common and novel measures to combat the resistance, including drug repurposing (nonsteroidal anti-inflammatory drugs, metformin, dichloroacetate, enalapril, ivermectin, bazedoxifene, melatonin, and S-adenosylmethionine), gene therapy (ribozymes, RNAi, CRISPR/Cas9, epigenetic therapy, antisense oligonucleotides, and noncoding RNAs), protein inhibitor (EFGR inhibitor, S1PR2 inhibitor, and DNA methyltransferase inhibitor), natural herbal compounds (polyphenols, terpenoids, quinones, alkaloids, and sterols), new drug delivery system (nanocarriers, liposomes, exosomes, and hydrogels), and combination therapy...

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers, with high mortality and recurrence rate. In this study, we generated a human immune system mouse model by transplanting human peripheral blood mononuclear cells into NSG-B2m mice followed by xenografting AsPC-1 cells, after which we assessed the role of transforming growth factor-β2 (TGF-β2) in T-cell-mediated anti-tumor immunity. We observed that inhibiting the TGF-β2 production by TGF-β2 antisense oligonucleotide (TASO) combined with IL-2 delays pancreatic cancer growth...

Cell-derived exosomes have opened new horizons in modern therapy for advanced drug delivery and therapeutic applications, due to their key features such as low immunogenicity, high physicochemical stability, capacity to penetrate into tissues, and the innate capacity to communicate with other cells over long distances. Exosome-based liquid biopsy has been potentially used for the diagnosis and prognosis of a range of disorders. Exosomes deliver therapeutic agents, including immunological modulators, therapeutic drugs, and antisense oligonucleotides to certain targets, and can be used as vaccines, though their clinical application is still far from reality...

A colloidal synthesis' proof-of-concept based on the Bligh-Dyer emulsion inversion method was designed for integrating into lipid nanoparticles (LNPs) cell-permeating DNA antisense oligonucleotides (ASOs), also known as GapmeRs (GRs), for mRNA interference. The GR@LNPs were formulated to target brain border-associated macrophages (BAMs) as a central nervous system (CNS) therapy platform for silencing neuroinflammation-related genes. We specifically aim at inhibiting the expression of the gene encoding for lipocalin-type prostaglandin D synthase (L-PGDS), an anti-inflammatory enzyme expressed in BAMs, whose level of expression is altered in neuropsychopathologies such as depression and schizophrenia...

Despite wide recognition as a disease of pandemic proportions, effective treatments for nonalcoholic fatty liver disease (NAFLD) remain elusive. Most of the current clinical programs aim to reduce hepatic fat accumulation and, thus, prevent downstream inflammation and fibrosis. To date, this therapeutic approach has helped identify a potential disconnect between steatosis reduction and disease resolution. Mounting preclinical evidence indicates liver inflammation may play a major role in steatosis development and fibrosis but has not garnered the same clinical representation...

Cyclosporine A (CSA) is an immunosuppressive drug that has improved transplant survival rates. However, its use is often limited because it is thought to be linked to the development of chronic kidney disease after kidney transplants. This study aimed to investigate the protective effects and underlying mechanisms of physiological unconjugated (UC) hyperbilirubinemia mediated by UGT1A1 antisense oligonucleotide in a mouse model of CsA-induced chronic kidney disease, and match these with that of chitosan (CH) as a natural chelator against kidney injury...

OBJECTIVE: While the upregulation of cytochrome P450 family 24 subfamily A member 1 (CYP24A1) gene expression has been reported in colon cancer, its role in tumorigenesis remains largely unknown. In this study, we aimed to investigate the involvement of CYP24A1 in Wnt pathway regulation via the nuclear factor kappa B (NF-κB) pathway. METHODS: The human colon cancer cell lines HCT-116 and Caco-2 were subjected to stimulation with interleukin-6 (IL-6) as well as tumor necrosis factor alpha (TNF-α), with subsequent treatment using the NF-κB pathway-specific inhibitor ammonium pyrrolidinedithiocarbamate (PDTC)...

Following injury the kidney undergoes a repair process, which results in replacement of the injured tissue with little evidence of damage. However, repetitive injuries or inability of the kidney to stop the repair process result in abnormal deposition of extracellular matrix (ECM) components leading to fibrosis and organ dysfunction. The synthesis/degradation of ECM components is finely regulated by several factors, including discoidin domain receptors (DDRs). These are receptor tyrosine kinases that are activated by collagens...

Objective To investigate whether long non-coding RNA-HOX transcript antisense intergenic RNA (lncRNA-HOTAIR) regulates the inflammatory response of sepsis by targeting microRNA miR-1-3p. Methods 0.5 μg/mL lipopolysaccharide (LPS) was used to induce cardiomyocytes of H9c2 rats to establish a septic cardiomyocyte injury model. H9c2 cells were divided into control group, LPS group, and LPS combined with HOTAIR small interfering RNA negative control (si-NC) group, LPS combined with HOTAIR small interfering RNA (si-HOTAIR) group, LPS combined with miR-1-3p negative control (miR-NC) group, LPS combined with miR-1-3p group, LPS combined with si-HOTAIR and miR-1-3p inhibitor negative (anti-miR-NC) group, and LPS combined with siHOTAIR and anti-miR-1-3p group...

Background: Tumor microenvironment (TME) is one of the most important factors in tumor aggressiveness, with an active exchange between tumor and other TME-associated cells that promotes metastasis. The tumor-inhibitory effect of resveratrol on colorectal cancer (CRC) cells has been frequently reported. However, whether resveratrol can specifically suppress TME-induced CRC invasion via β1-integrin receptors has not been fully elucidated yet. Methods: Two CRC cell lines (HCT116, RKO) were cultured in multicellular, pro-inflammatory 3D-alginate TME cultures (containing fibroblasts, T-lymphocytes) to investigate the role of β1-integrin receptors in the anti-invasive and anti-metastatic effect of resveratrol by antisense oligonucleotides (ASO)...

OBJECTIVE: miR-148a-3p (miR-148a) is a hepatic and immune-enriched microRNA (miRNA) that regulates macrophage-related lipoprotein metabolism, cholesterol homeostasis, and inflammation. The contribution of miR-148a-3p to the progression of atherosclerosis is unknown. In this study, we determined whether miR-148a silencing mitigated atherogenesis in APOBTG Apobec-/- Ldlr+/- mice. METHODS: APOBTG Apobec-/- Ldlr+/- mice were fed a typical Western-style diet for 22 weeks and injected with a nontargeting locked nucleic acid (LNA; LNA control) or miR-148a LNA (LNA 148a) for the last 10 weeks...

Constitutive heterochromatin is responsible for genome repression of DNA enriched in repetitive sequences, telomeres, and centromeres. During physiological and pathological premature aging, heterochromatin homeostasis is profoundly compromised. Here, we showed that LINE-1 ( Long Interspersed Nuclear Element-1; L1 ) RNA accumulation was an early event in both typical and atypical human progeroid syndromes. L1 RNA negatively regulated the enzymatic activity of the histone-lysine N -methyltransferase SUV39H1 (suppression of variegation 3-9 homolog 1), resulting in heterochromatin loss and onset of senescent phenotypes in vitro...

Monocytes are key players in innate immunity, with their ability to regulate inflammatory responses and combat invading pathogens. There is a growing body of evidence indicating that long non-coding RNA (lncRNA) participate in various cellular biological processes, including the innate immune response. The immunoregulatory properties of numerous lncRNAs discovered in monocytes remain largely unexplored. Here, by RNA sequencing, we identified a lncRNA JHDM1D-AS1, which was upregulated in blood monocytes obtained from patients with sepsis relative to healthy controls...

Even though macrophages have the potential to harm tissues through excessive release of inflammatory mediators, they play protective roles to maintain tissue integrity. In this study, we hypothesized that lysophosphatidylcholine (LPC), via G2A and A2B receptors, puts brakes on macrophages by the induction of adenosine release which could contribute to termination of inflammation. Mechanistically, LPC-induced PGE2 production followed by the activation of cAMP/protein kinase A (PKA) pathway which results in the activation of LKB1/AMPK signaling pathway leading to increasing Mg2+ influx concomitantly with an increase in mitochondrial membrane potential (MMP, Δψm ) and ATP production...

Apolipoprotein C-III (apoC-III) is a critical regulator of triglyceride metabolism and correlates positively with hypertriglyceridemia and cardiovascular disease (CVD). It remains unclear if therapeutic apoC-III lowering reduces CVD risk and if the CVD correlation depends on the lipid-lowering or antiinflammatory properties. We determined the impact of interventional apoC-III lowering on atherogenesis using an apoC-III antisense oligonucleotide (ASO) in 2 hypertriglyceridemic mouse models where the intervention lowers plasma triglycerides and in a third lipid-refractory model...

Drug-induced kidney injury has historically been associated with renal tubule injury related to small molecule pharmaceuticals such as nonsteroidal anti-inflammatory drugs, antineoplastic agents, or antibiotics, but as a greater number of alternative classes of medicines such as biotherapeutics, molecular-targeted antineoplastic drugs, chimeric antigen receptor T-cell therapies, antibody-drug conjugates, oligonucleotide therapies, or other immunomodulatory drugs come to market, the presentation of drug-induced nephrotoxicity is changing...