Результаты поиска

CKD-5, a novel pan-histone deacetylase inhibitor, synergistically enhances the efficacy of sorafenib for hepatocellular carcinoma.

BackgroundHistone deacetylase inhibitors (HDACIs) have distinctive epigenetic targets involved in hepatocarcinogenesis and chemoresistance. A recent phase I/II study reported the possibility of HDACI as a chemosensitizer in sorafenib-resistant patients. In this study, we evaluated whether CKD-5, a novel pan-HDACI, can potentiate the efficacy of sorafenib.MethodsThe anticancer effect of CKD-5 with and without sorafenib was evaluated in vitro using an MTS assay with human HCC cells (SNU-3058 and SNU-761) under both normoxic and hypoxic conditions. Microarray analysis was performed to investigate

The use of RNA-based treatments in the field of cancer immunotherapy.

Over the past several decades, mRNA vaccines have evolved from a theoretical concept to a clinical reality. These vaccines offer several advantages over traditional vaccine techniques, including their high potency, rapid development, low-cost manufacturing, and safe administration. However, until recently, concerns over the instability and inefficient distribution of mRNA in vivo have limited their utility. Fortunately, recent technological advancements have mostly resolved these concerns, resulting in the development of numerous mRNA vaccination platforms for infectious diseases and various t

Characteristics of registered clinical trials assessing treatments for COVID-19: a cross-sectional analysis.

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has prompted many initiatives to identify safe and efficacious treatments, yet little is known regarding where early efforts have focused. We aimed to characterise registered clinical trials assessing drugs or plasma treatments for COVID-19. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional analysis of clinical trials for the treatment of COVID-19 that were registered in the USA or in countries contributing to the WHO's International Clinical Trials Registry Platform. Relevant trial entries of drugs or plasma were downloaded on 26 M

The Proliferative and Apoptotic Landscape of Basal-like Breast Cancer.

Basal-like breast cancer (BLBC) is an aggressive molecular subtype that represents up to 15% of breast cancers. It occurs in younger patients, and typically shows rapid development of locoregional and distant metastasis, resulting in a relatively high mortality rate. Its defining features are that it is positive for basal cytokeratins and, epidermal growth factor receptor and/or c-Kit. Problematically, it is typically negative for the estrogen receptor and human epidermal growth factor receptor 2 (HER2), which means that it is unsuitable for either hormone therapy or targeted HER2 therapy. As

Transcript-Targeted Therapy Based on RNA Interference and Antisense Oligonucleotides: Current Applications and Novel Molecular Targets.

The development of novel target therapies based on the use of RNA interference (RNAi) and antisense oligonucleotides (ASOs) is growing in an exponential way, challenging the chance for the treatment of the genetic diseases and cancer by hitting selectively targeted RNA in a sequence-dependent manner. Multiple opportunities are taking shape, able to remove defective protein by silencing RNA (e.g., Inclisiran targets mRNA of protein PCSK9, permitting a longer half-life of LDL receptors in heterozygous familial hypercholesteremia), by arresting mRNA translation (i.e., Fomivirsen that binds to UL1

Circular RNAs as Trojan horses of leukaemia: A promising path to cancer precision medicine.

Аннотация не предоставлена источником. Откройте карточку для перехода к публикации.

Совпадение в полном тексте источника
… The consequence of these R‐loops was site‐specific pausing of RNA polymerase II, inhibition of the proteasome, increased DNA breakage at these sites and three‐dimensional rearrangement of the genome bringing the MLL and fusion genes into closer proximity (Figure 1 ). …

Autoantibodies as Biomarker and Therapeutic Target in Systemic Sclerosis.

Systemic sclerosis (SSc) is a rare connective tissue disorder characterized by immune dysregulation evoking the pathophysiological triad of inflammation, fibrosis and vasculopathy. In SSc, several alterations in the B-cell compartment have been described, leading to polyclonal B-cell hyperreactivity, hypergammaglobulinemia and autoantibody production. Autoreactive B cells and autoantibodies promote and maintain pathologic mechanisms. In addition, autoantibodies in SSc are important biomarkers for predicting clinical phenotype and disease progression. Autoreactive B cells and autoantibodies rep

Ferret coronavirus-associated diseases.

A novel coronavirus of ferrets was first described in 1993. This coronavirus caused an enteric disease called epizootic catarrhal enteritis (ECE). Recently, a ferret systemic coronavirus (FRSCV)-associated disease was discovered. This new systemic disease resembles the dry form of feline infectious peritonitis (FIP) and has been reported in the United States and Europe. This article addresses the clinical signs, pathology, pathogenesis, diagnosis, treatment, and prevention of this ferret FIP-like disease.

Targeting Eukaryotic Elongation Factor 1A: How Small-Molecule Inhibitors Suppress Tumor Growth via Diverse Pathways.

Eukaryotic elongation factor 1A (eEF1A), the second most abundant intracellular protein, not only plays a key role in peptide elongation, but is also capable of numerous moonlighting functions. Within malignant cells, eEF1A is by no means a neutral bystander but instead actively participates in oncogenic transformations via a myriad of molecular pathways. Thus far, a broad range of small-molecule inhibitors have been identified, which, despite their structural diversity, suppress tumor growth by targeting eEF1A. Interestingly, just as eEF1A enables its oncogenic potential far beyond boosting p

Совпадение в полном тексте источника
… Treatment with metarrestin induces marked nucleolar segregation and reduces Pol I occupancy at rDNA promoters without broadly affecting RNA polymerase II transcription or causing DNA damage, distinguishing it from classical genotoxic agents. …

Novel Interleukin-6 Inducible Gene PDZ-Binding Kinase Promotes Tumor Growth of Multiple Myeloma Cells.

[Figure: see text] Multiple myeloma (MM) remains an intractable hematological malignancy, despite recent advances in anti-MM drugs. Here, we show that role of PDZ binding kinase (PBK) in MM tumor growth. We identified that interleukin-6 (IL-6) readily increases PBK expression. Kaplan-Meier analysis showed that the MM patients with higher expression of PBK have a significant shorter survival time compared with those with moderate/lower expression of PBK. Knockout of PBK dramatically suppressed in vivo tumor growth in MM cells, while genome editing of PBK changing from asparagine to serine subst

CAR-T cell therapy for treatment-refractory rheumatic autoimmune diseases: a systematic review of clinical outcomes and safety profiles.

OBJECTIVES: Current therapeutic paradigms for treatment-refractory rheumatic diseases rely on chronic immunosuppression with variable efficacy and potential for cumulative toxicity. We systematically synthesised evidence on the clinical efficacy, safety and durability of chimeric antigen receptor T-cell (CAR-T) therapy in autoimmune rheumatic diseases. METHODS: We conducted a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO: CRD42025641602). Five databases were searched from inception to February 2025 for primary studies inves

The Multiple Roles of Microrna-223 in Regulating Bone Metabolism.

Bone metabolism is a lifelong process for maintaining skeletal system homeostasis, which is regulated by bone-resorbing osteoclasts and bone-forming osteoblasts. Aberrant differentiation of osteoclasts and osteoblasts leads to imbalanced bone metabolism, resulting in ossification and osteolysis diseases. MicroRNAs (miRNAs) are pivotal factors in regulating bone metabolism via post-transcriptional inhibition of target genes. Recent studies have revealed that miR-223 exerts multiple effects on bone metabolism, especially in the processes of osteoclast and osteoblasts differentiation. In this rev

Совпадение в полном тексте источника
… MiRNA genes are transcribed by RNA polymerase II to form primary miRNA (pri-miRNA) [ 22 ]. Nuclear pri-miRNA is processed to precursor miRNA (pre-miRNA), comprising 70 nucleotides, through the action of the RNase III enzyme, Drosha, and is exported from the nucleus [ 23 ]. … MicroRNA genes are transcribed by RNA polymerase II EMBO J. 2004 23 4051 4060 10.1038/sj.emboj.7600385 15372072 PMC524334 23. Lee Y. Ahn C. Han J. Choi H. Kim J. Yim J. Lee J. Provost P. Radmark O. Kim S. Kim V.N. …

miRNAs and lncRNAs as Novel Therapeutic Targets to Improve Cancer Immunotherapy.

Immunotherapy is presently one of the most promising areas of investigation and development for the treatment of cancer. While immune checkpoint-blocking monoclonal antibodies and chimeric antigen receptor (CAR) T-cell-based therapy have recently provided in some cases valuable therapeutic options, the goal of cure has not yet been achieved for most malignancies and more efforts are urgently needed. Noncoding RNAs (ncRNA), including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), regulate several biological processes via selective targeting of crucial molecular signaling pathways. Recent

Совпадение в полном тексте источника
… They are transcribed by RNA polymerase II (Pol II) in primary miRNA transcripts (pri-mRNAs) and then converted by the endonuclease DROSHA and its cofactor DGCR8 in pre-miRNA transcripts [ 11 ]. …

Genetic Therapy and Molecular Targeted Therapy in Oncology: Safety, Pharmacovigilance, and Perspectives for Research and Clinical Practice.

The impressive advances in the knowledge of biomarkers and molecular targets has enabled significant progress in drug therapy for crucial diseases such as cancer. Specific areas of pharmacology have contributed to these therapeutic outcomes-mainly targeted therapy, immunomodulatory therapy, and gene therapy. This review focuses on the pharmacological profiles of these therapeutic classes and intends, on the one hand, to provide a systematic definition and, on the other, to highlight some aspects related to pharmacovigilance, namely the monitoring of safety and the identification of potential t

Early administration of remdesivir plus convalescent plasma therapy is effective to treat COVID-19 pneumonia in B-cell depleted patients with hematological malignancies.

Patients with hematological malignancies (HMs) are at a higher risk of developing severe form and protracted course of COVID-19 disease. We investigated whether the combination of viral replication inhibition with remdesivir and administration of anti-SARS-CoV-2 immunoglobulins with convalescent plasma (CP) therapy might be sufficient to treat B-cell-depleted patients with COVID-19. We enrolled 20 consecutive patients with various HMs with profound B-cell lymphopenia and COVID-19 pneumonia between December 2020 and May 2021. All patients demonstrated undetectable baseline anti-SARS-CoV-2 immun

Aptamers: Potential Diagnostic and Therapeutic Agents for Blood Diseases.

Aptamers are RNA/DNA oligonucleotide molecules that specifically bind to a targeted complementary molecule. As potential recognition elements with promising diagnostic and therapeutic applications, aptamers, such as monoclonal antibodies, could provide many treatment and diagnostic options for blood diseases. Aptamers present several superior features over antibodies, including a simple in vitro selection and production, ease of modification and conjugation, high stability, and low immunogenicity. Emerging as promising alternatives to antibodies, aptamers could overcome the present limitations

Exploring Nanoherbal Paraboea leuserensis as a Therapeutic Agent in Traumatic Brain Injury: In Silico, and In Vivo Approaches.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a pathogen that causes various infections and exhibits antibiotic resistance and virulence factors, requiring alternative therapies. This study aimed to evaluate the effects of nanocurcumin on gene expression of S. aureus isolates from burn wounds in Iraqi patients, focusing on inhibiting resistance and virulence genes. METHODS: From March 2023 to May 2024, burn wound samples from Iraqi patients yielded 110 S. aureus isolates. Identification was conducted by Gram staining, biochemical assays, and culture techniques. Fifty isola

MicroRNAs in Aseptic Loosening of Prosthesis: Pathophysiology and Potential Therapeutic Approaches.

OBJECTIVES: Aseptic loosening (AL) is one of the leading causes of total joint arthroplasty (TJA) revision. Discovering the roles of microRNAs (miRNA/miR) in ontogenesis and osteolysis has attracted more attention to diagnosing and treating bone disorders. This review aimed to summarize miRNA biogenesis and describe the involvement of miRNAs in AL of implants. METHODS: A detailed search was carried out on scientific search engines, including Google Scholar, Web of Science, and PubMed, to find appropriate papers related to subjects. The search process was performed using the following keywords

Совпадение в полном тексте источника
… These clusters usually have similar seed regions and encode miRNAs of the same family. 15 In general, the biogenesis of miRNA can be grouped into canonical and non-canonical pathways; the canonical biogenesis process of miRNAs starts when RNA polymerase II (pol II) encodes miRNA genes long primary to … MicroRNA genes are transcribed by RNA polymerase II. EMBO J. 2004;23(20):4051–60. doi: 10.1038/sj.emboj.7600385. 17. Medley JC, Panzade G, Zinovyeva AY. microRNA strand selection: Unwinding the rules. Wiley Interdiscip Rev RNA. 2021;12(3):e1627. doi: 10.1002/wrna.1627. 18. …

Transcriptome Analysis Reveals Altered Inflammatory Pathway in an Inducible Glial Cell Model of Myotonic Dystrophy Type 1.

Myotonic dystrophy type 1 (DM1), the most frequent inherited muscular dystrophy in adults, is caused by the CTG repeat expansion in the 3'UTR of the DMPK gene. Mutant DMPK RNA accumulates in nuclear foci altering diverse cellular functions including alternative splicing regulation. DM1 is a multisystemic condition, with debilitating central nervous system alterations. Although a defective neuroglia communication has been described as a contributor of the brain pathology in DM1, the specific cellular and molecular events potentially affected in glia cells have not been totally recognized. Thus,

An Overview of Advances in Rare Cancer Diagnosis and Treatment.

Cancer stands as the leading global cause of mortality, with rare cancer comprising 230 distinct subtypes characterized by infrequent incidence. Despite the inherent challenges in addressing the diagnosis and treatment of rare cancers due to their low occurrence rates, several biomedical breakthroughs have led to significant advancement in both areas. This review provides a comprehensive overview of state-of-the-art diagnostic techniques that encompass new-generation sequencing and multi-omics, coupled with the integration of artificial intelligence and machine learning, that have revolutioniz