Targeting OGF/OGFR signal to mitigate doxorubicin-induced cardiotoxicity.

Enkephalins are reportedly correlated with heart function. However, their regulation in the heart remains unexplored. This study revealed a substantial increase in circulating levels of opioid growth factor (OGF) (also known as methionine enkephalin) and myocardial expression levels of both OGF and its receptor (OGFR) in subjects treated with doxorubicin (Dox).

An orally administered bacterial membrane protein nanodrug ameliorates doxorubicin cardiotoxicity through alleviating impaired intestinal barrier.

The cardiotoxicity caused by Dox chemotherapy represents a significant limitation to its clinical application and is a major cause of late death in patients undergoing chemotherapy. Currently, there are no effective treatments available. Our analysis of 295 clinical samples from 132 chemotherapy patients and 163 individuals undergoing physical examination revealed a strong positive correlation between intestinal barrier injury and the development of cardiotoxicity in chemotherapy patients.

Microbubble Biointerfacing by Regulation of the Platelet Membrane Surfactant Activity at the Gas-Liquid Interface for Acute Thrombosis Targeting.

Biointerfacing nanomaterials with cell membranes has been successful in the functionalization of nanoparticles or nanovesicles, but microbubble functionalization remains challenging due to the unique conformation of the lipid monolayer structure at the gas-liquid interface that provides insufficient surfactant activity. Here, we describe a strategy to rationally regulate the surfactant activity of platelet membrane vesicles by adjusting the ratio of proteins to lipids through fusion with synthetic phospholipids (i.e.

DNMT1 determines osteosarcoma cell resistance to apoptosis by associatively modulating DNA and mRNA cytosine-5 methylation.

Cellular apoptosis is a central mechanism leveraged by chemotherapy to treat human cancers. 5-Methylcytosine (m5C) modifications installed on both DNA and mRNA are documented to regulate apoptosis independently. However, the interplay or crosstalk between them in cellular apoptosis has not yet been explored.

Activating ryanodine receptor improves isoflurane-induced cognitive dysfunction.

Background: Postoperative cognitive dysfunction (POCD) is characterized by impaired learning and memory. 6 h duration isoflurane anesthesia is an important factor to induce POCD, and the dysfunction of ryanodine receptor (RyR) in the hippocampus may be involved in this process. We investigated the expression of RyR3 in the hippocampus of mice after 6-h duration isoflurane anesthesia, as well as the improvement of RyR receptor agonist caffeine on POCD mice, while attempting to identify the underlying molecular mechanism.

Circulating cardiac MicroRNAs safeguard against dilated cardiomyopathy.

Background: Cardiac-resident or -enriched microRNAs (miRNAs) could be released into the bloodstream becoming circulating cardiac miRNAs, which are increasingly recognized as non-invasive and accessible biomarkers of multiple heart diseases. However, dilated cardiomyopathy (DCM)-associated circulating miRNAs (DACMs) and their roles in DCM pathogenesis remain largely unexplored.

Methods: Two human cohorts, consisting of healthy individuals and DCM patients, were enrolled for serum miRNA sequencing (10 vs.

Association of Diabetes Mellitus with All-Cause and Cause-Specific Mortality among Patients with Metabolic-Dysfunction-Associated Fatty Liver Disease: A Longitudinal Cohort Study.

Background: Diabetes mellitus (DM) is a comorbidity commonly presenting with metabolic-dysfunction-associated fatty liver disease (MAFLD); however, few tests for interaction have been reported. Our target was to evaluate the prognostic implications of DM in patients with different forms of MAFLD.

Methods: Using data from the Third National Health and Nutrition Examination Survey (NHANES III) in the United States, we screened 14,797 participants aged 20-74 who received ultrasound examinations from 1988-1994.

Low expression of PEBP1P2 promotes metastasis of clear cell renal cell carcinoma by post-transcriptional regulation of PEBP1 and KLF13 mRNA.

Background: Pseudogenes play an essential role in tumor occurrence and progression. However, the functions and mechanisms of pseudogenes in clear cell renal cell carcinoma (ccRCC) remain largely elusive.

Methods: We quantified PEBP1P2 expression in ccRCC tissues and cells using fluorescence in situ hybridization and real-time PCR.

Inhibition of the integrated stress response reverses oxidative stress damage-induced postoperative cognitive dysfunction.

Postoperative cognitive dysfunction (POCD) is a common complication following anesthesia and surgery that might lead to a decline in learning and memory. Oxidative stress damage is one of the pathogenic mechanisms underlying POCD. Recent studies had shown that the integrated stress response (ISR) is closely related to oxidative stress.

Both SUMOylation and ubiquitination of TFE3 fusion protein regulated by androgen receptor are the potential target in the therapy of Xp11.2 translocation renal cell carcinoma.

Background: The aggressiveness of renal cell carcinoma (RCC) associated with Xp11.2 translocation/TFE3 gene fusion (Xp11.2 translocation RCC [Xp11.

Up-regulation of NMRK2 mediated by TFE3 fusions is the key for energy metabolism adaption of Xp11.2 translocation renal cell carcinoma.

Due to the inadequate awareness of Xp11.2 translocation renal cell carcinoma (Xp11.2 tRCC), its metabolic features have not been described.

Mitochondrial DNA methylation drift and postoperative delirium in mice.

Background: Mitochondrial dysfunction is linked to the etiopathogenesis of postoperative delirium (POD), which severely affects the prognosis of elderly patients undergoing surgery. The methylation of mitochondrial DNA (mtDNA), a new and incompletely described phenomenon that regulates the structure and function of mitochondria, is associated with ageing. However, the relationship between mtDNA methylation and POD has not been established.

Astrocyte-neuron lactate transport in the ACC contributes to the occurrence of long-lasting inflammatory pain in male mice.

Lactate transport is an important means of communication between astrocytes and neurons and is implicated in a variety of neurobiological processes. However, the connection between astrocyte-neuron lactate transport and nociceptive modulation has not been well established. Here, we found that Complete Freund's adjuvant (CFA)-induced inflammation pain leads to a significant increase in extracellular lactate levels in the anterior cingulate cortex (ACC).

NONO-TFE3 Fusion Promotes Aerobic Glycolysis and Angiogenesis by Targeting HIF1A in NONO-TFE3 Translocation Renal Cell Carcinoma.

Background: NONO-TFE3 translocation renal cell carcinoma (tRCC), one of the RCCs that are associated with Xp11.2 translocation/TFE3 gene fusion (Xp11.2 tRCCs), involves an X chromosome inversion between NONO and TFE3 with the characteristics of endonuclear aggregation of NONO-TFE3 fusion protein.

Low expression of TRAF3IP2-AS1 promotes progression of NONO-TFE3 translocation renal cell carcinoma by stimulating N-methyladenosine of PARP1 mRNA and downregulating PTEN.

Background: NONO-TFE3 translocation renal cell carcinoma (NONO-TFE3 tRCC) is one subtype of RCCs associated with Xp11.2 translocation/TFE3 gene fusions RCC (Xp11.2 tRCCs).

Dorsal root ganglia NR2B-mediated Epac1-Piezo2 signaling pathway contributes to mechanical allodynia of bone cancer pain.

Mechanical allodynia is a painful perception of mechanical stimuli and one of the typical symptoms in bone cancer pain (BCP). Previous studies have revealed that mice and humans lacking mechanically activated Piezo2 channels do not sense mechanical stimuli. However, the underlying mechanism of Piezo2 in BCP has not been well established.

The positive regulation loop between NRF1 and NONO-TFE3 fusion promotes phase separation and aggregation of NONO-TFE3 in NONO-TFE3 tRCC.

TFE3 gene fusions often place TFE3 under the control of a more active promoter and cause overexpression of the TFE3 proteins in renal cell carcinoma associated with Xp11.2 translocations (Xp11.2 tRCC).

PRCC-TFE3 fusion-mediated PRKN/parkin-dependent mitophagy promotes cell survival and proliferation in PRCC-TFE3 translocation renal cell carcinoma.

TFE3 (transcription factor binding to IGHM enhancer 3) nuclear translocation and transcriptional activity has been implicated in PINK1-PRKN/parkin-dependent mitophagy. However, the transcriptional control governing the mitophagy in TFE3/Xp11.2 translocation renal cell carcinoma ( tRCC) is largely unknown.

B7-H3 is spliced by SRSF3 in colorectal cancer.

B7-H3, an important co-inhibitor, is abnormally highly expressed in a variety of malignancies. The antibodies targeting B7-H3 have exhibited beneficial therapeutic effects in clinical trials. Therefore, discovery of the regulatory factors in B7-H3 expression may provide new strategies for tumor therapy.

Metformin Inhibits Propofol-Induced Apoptosis of Mouse Hippocampal Neurons HT-22 Through Downregulating Cav-1.

Objective: To elucidate the neuroprotective function of metformin in suppressing propofol-induced apoptosis of HT-22 cells.

Methods: HT-22 cells were treated with 0, 10 or 100 μmol/L propofol, followed by determination of their proliferative ability. Subsequently, changes in proliferation and apoptosis of propofol-treated HT-22 cells induced with metformin were assessed.

KIF15 promotes the evolution of gastric cancer cells through inhibition of reactive oxygen species-mediated apoptosis.

Kinesin family member 15 (KIF15) is a member of the kinesin superfamily of proteins, which promotes cell mitosis, participates in the transport of intracellular materials, and helps structural assembly and cell signaling pathways transduction. However, its biological role and molecular mechanisms of action in the development of gastric cancer (GC) remain unclear. In the present study, an integrated analysis of The Cancer Genome Atlas (TCGA), Gene Expression Omnibus database, and Kaplan-Meier plotter database was performed to predict the expression and prognostic value of KIF15 in GC patients.

PRCC-TFE3 regulates migration and invasion of translocation renal cell carcinomas via activation of Drp1-dependent mitochondrial fission.

PRCC-TFE3 translocation renal cell carcinomas (tRCC) is a common subtype of TFE3 tRCCs in which TFE3 fusions are indicated as oncogenes to promote tumor development. PRCC-TFE3 fusions are often accumulated in the nucleus and related to poorer outcomes and higher stages (III/IV). In this study, we found that PRCC-TFE3 could positively regulate expression of both dynamin-related protein 1 (Drp1) and fission protein 1, and alter distribution of mitochondria, which could promote cell migration and invasion independent of matrix metalloproteinase-2 (MMP-2) and MMP-9.