Silencing

Hypoxia, largely triggered by global warming and water contamination, has become an environmental issue of great concern, posing a great threat to aquatic ecosystem. As one of the world's most economically important fish, rainbow trout (Oncorhynchus mykiss) is extremely intolerant of hypoxic environments, however, little is known about the roles of non-coding RNAs (ncRNAs) in the response of rainbow trout to hypoxia stress. Herein, effects of moderate (Tm12L) and severe hypoxia for 12 h (Ts12L) and 12 h reoxygenation on histology, biochemical parameters (antioxidant, metabolism and immunity) and transcriptome (lncRNA, miRNA and mRNA) in rainbow trout liver were investigated...

The treatment of primary central nervous system (CNS) tumors is challenging due to the blood-brain barrier and complex mutational profiles, which is associated with low survival rates. However, recent studies have identified common mutations in gliomas (IDH-WT and mutant, WHO grades II-IV; with grade IV tumors referred to as glioblastomas; GBMs). These mutations drive epigenetic changes, leading to promoter methylation at the NAPRT gene locus, which encodes an enzyme involved in generating NAD+. Importantly, NAPRT-silencing introduces a therapeutic vulnerability to inhibitors targeting another NAD+ biogenesis enzyme, NAMPT, rationalizing a treatment for these malignancies...

Overactivation of the transforming growth factor-β (TGFβ) signaling in Duchenne muscular dystrophy (DMD) is a major hallmark of disease progression, leading to fibrosis and muscle dysfunction. Here, we investigated the role of SETDB1 (SET domain, bifurcated 1), a histone lysine methyltransferase involved in muscle differentiation. Our data show that, following TGFβ induction, SETDB1 accumulates in the nuclei of healthy myotubes while being already present in the nuclei of DMD myotubes where TGFβ signaling is constitutively activated...

Pancreatic ductal adenocarcinoma (PDAC) carries a dismal prognosis due to therapeutic resistance. We show that PDAC cells undergo global epigenetic reprogramming to acquire chemoresistance, a process that is driven at least in part by protein arginine methyltransferase 1 (PRMT1). Genetic or pharmacological PRMT1 inhibition impairs adaptive epigenetic reprogramming and delays acquired resistance to gemcitabine and other common chemo drugs. Mechanistically, gemcitabine treatment induces translocation of PRMT1 into the nucleus, where its enzymatic activity limits the assembly of chromatin-bound MAFF/BACH1 transcriptional complexes...

A growing body of research has confirmed the involvement of circular RNAs (circRNAs) in the regulation of intervertebral disc degeneration (IDD) progression. However, the underlying molecular networks remain largely elusive. This study aimed to explore whether a novel circRNA, named circKIAA0564, affects nucleus pulposus (NP) cell injury and to elucidate its molecular mechanism. Both in vivo and in vitro IDD models were established, and the expression patterns of circKIAA0564/miR-424-5p/lysine demethylase 4a (KDM4A) were evaluated through quantitative reverse transcription PCR and Western blot analysis...

Glial cells constitute nearly half of the mammalian nervous system's cellular composition. The glia in C. elegans perform majority of tasks comparable to those conducted by their mammalian equivalents. The cephalic sheath (CEPsh) glia, which are known to be the counterparts of mammalian astrocytes, are enriched with two nuclear hormone receptors (NHRs)-NHR-210 and NHR-231. This unique enrichment makes the CEPsh glia and these NHRs intriguing subjects of study concerning neuronal health. We endeavored to assess the role of these NHRs in neurodegenerative diseases and related functional processes, using transgenic C...

Nox1 signaling is a causal key element in arterial hypertension. Recently, we identified protein disulfide isomerase A1 (PDI) as a novel regulatory protein that regulates Nox1 signaling in VSMCs. Spontaneously hypertensive rats (SHR) have increased levels of PDI in mesenteric resistance arteries compared with Wistar controls; however, its consequences remain unclear. Herein, we investigated the role of PDI in mediating Nox1 transcriptional upregulation and its effects on vascular dysfunction in hypertension...

Osteoarthritis (OA) is the main cause of cartilage damage and disability. This study explored the biological function of S-phase kinase-associated protein 2 (SKP2) and Kruppel-like factor 11 (KLF11) in OA progression and its underlying mechanisms. C28/I2 chondrocytes were stimulated with IL-1β to mimic OA in vitro. We found that SKP2, Jumonji domain-containing protein D3 (JMJD3), and Notch receptor 1 (NOTCH1) were upregulated, while KLF11 was downregulated in IL-1β-stimulated chondrocytes. SKP2/JMJD3 silencing or KLF11 overexpression repressed apoptosis and extracellular matrix (ECM) degradation in chondrocytes...

BACKGROUND: Ssmall-interfering RNA (siRNA) targeting hepatic AGT (angiotensinogen) mRNA depletes AGT, lowering blood pressure for up to 6 months. However, certain situations may require a rapid angiotensin increase. The reverse siRNA silencing, RVR technology is a potential approach to counteract siRNA effects. METHODS: Spontaneously hypertensive rats received 10 mg/kg AGT siRNA, and 3 weeks later were given AGT-RVR (1, 10, or 20 mg/kg). One week after AGT-RVR dosing, a redose of AGT siRNA assessed its post-AGT-RVR effectiveness for 2 weeks...

BACKGROUND: It remains unclear whether BPIV3 infection leads to stress granules formation and whether G3BP1 plays a role in this process and in viral replication. This study aims to clarify the association between BPIV3 and stress granules, explore the effect of G3BP1 on BPIV3 replication, and provide significant insights into the mechanisms by which BPIV3 evades the host's antiviral immunity to support its own survival. METHODS: Here, we use Immunofluorescence staining to observe the effect of BPIV3 infection on the assembly of stress granules...

Posttraumatic osteoarthritis (PTOA) patients are often diagnosed by X-ray imaging at a middle-late stage when drug interventions are less effective. Early PTOA is characterized by overexpressed matrix metalloprotease 13 (MMP13). Herein, we constructed an integrated diagnosis and treatment micelle modified with MMP13 enzyme-detachable, cyanine 5 (Cy5)-containing PEG, black hole quencher-3 (BHQ3), and cRGD ligands and loaded with siRNA silencing MMP13 (siM13), namely ERMs@siM13. ERMs@siM13 could be cleaved by MMP13 in the diseased cartilage tissues to detach the PEG shell, causing cRGD exposure...

In this editorial we comment on the article by Wei et al , published in the recent issue of the World Journal of Clinical Oncology . The authors investigated the role of Transmembrane 9 superfamily member 1 (TM9SF1) protein in bladder cancer (BC) carcinogenesis. Lentiviral vectors were used to achieve silencing or overexpression of TM9SF1 gene in three BC cell lines. These cell lines were then subject to cell counting kit 8, wound-healing assay, transwell assay, and flow cytometry. Proliferation, migration, and invasion of BC cells were increased in cell lines subjected to TM9SF1 overexpression...

Cardiovascular thrombotic events have long been a perplexing factor in clinical settings, influencing patient prognoses significantly. Ultrasound-mediated acoustic therapy, an innovative thrombolytic treatment method known for its high efficiency, non-invasiveness, safety, and convenience, has demonstrated promising potential for clinical applications and has gradually become a focal point in cardiovascular thrombotic disease research. The current challenge lies in the technical complexities of preparing ultrasound-responsive carriers with thrombus-targeting capabilities and high thrombolytic efficiency...

Promotion of public health is one of the most important benefits of ecosystems. Nevertheless, the relationship between ecosystems and social health' needs is not well understood. Therefore, a study was done to investigate the potential of natural (forests and rangelands) and artificial (urban parks and gardens) ecosystems in ensuring the five dimensions of public health (i.e. physical, mental, spiritual, social and environmental) in the social systems (urban and rural societies). Therefore, 47 health indicators were used in order to relate different ecosystems and social' needs to five dimensions of public health through questionnaire...

Parkinson's disease (PD) is a severe neurodegenerative disease associated with the loss of dopaminergic (DA) neurons in the substantia nigra (SN). Although its pathogenesis remains unclear, microglia-mediated neuroinflammation significantly contributes to the development of PD. Here we showed that the sine oculis homeobox (SIX) homologue family transcription factors SIX2 exerted significant effects on neuroinflammation. The SIX2 protein, which is silenced during development, was reactivated in lipopolysaccharide (LPS)-treated microglia...

Mutations in the RNA splicing factor gene SF3B1 are common across hematologic and solid cancers and result in widespread alterations in splicing, yet there is currently no therapeutic means to correct this mis-splicing. Here, we utilize synthetic introns uniquely responsive to mutant SF3B1 to identify trans factors required for aberrant mutant SF3B1 splicing activity. This revealed the G-patch domain-containing protein GPATCH8 as required for mutant SF3B1-induced splicing alterations and impaired hematopoiesis...

Breast cancer (BC) has been the focus of numerous studies aimed at identifying novel biological markers for its early detection. PIWI-interacting RNAs (piRNAs), a subset of small non-coding RNAs, have emerged as potential markers due to their aberrant expression in various cancers. PiRNAs have recently gained attention due to their aberrant expression in various cancers, including BC. PiRNAs, exhibit diverse biological activities, such as epigenetic regulation of gene and protein expression and their association with cell proliferation and metastasis has been well-established...

Light-driven modulation of neuronal activity at high spatial-temporal resolution is becoming of high interest in neuroscience. In addition to optogenetics, nongenetic membrane-targeted nanomachines that alter the electrical state of the neuronal membranes are in demand. Here, we engineered and characterized a photoswitchable conjugated compound (BV-1) that spontaneously partitions into the neuronal membrane and undergoes a charge transfer upon light stimulation. The activity of primary neurons is not affected in the dark, whereas millisecond light pulses of cyan light induce a progressive decrease in membrane resistance and an increase in inward current matched to a progressive depolarization and action potential firing...

BACKGROUND: Acute kidney injury (AKI) is common in hospitalized patients and is associated with high mortality. Inflammation plays a key role in the pathophysiology of AKI. Long non-coding RNAs (lncRNAs) are increasingly recognized as regulators of the inflammatory and immune response, but its role in AKI remains unclear. METHODS: We explored the role of lncRNA Neat1 in (1) a cross-sectional and a longitudinal cohort of AKI in human; (2) three murine models of septic and aseptic AKI and (3) cultured C1...

Noise from firearms is well known to be harmful to human hearing. This problem has been addressed by various military units through the use of muzzle suppressors. However, as suppressor technology has advanced, shooters report hearing the mechanical action of gas-operated semi-automatic rifles (ArmaLite Rifle Model 15 style aka AR-15) as being louder than the suppressed muzzle noise. This study aims to evaluate if harmful noise is present in the shooter's ear, even when impulse noise emanating from the muzzle is suppressed...