NAT10-mediated mRNA N-acetylcytidine reprograms serine metabolism to drive leukaemogenesis and stemness in acute myeloid leukaemia.

RNA modification has emerged as an important epigenetic mechanism that controls abnormal metabolism and growth in acute myeloid leukaemia (AML). However, the roles of RNA N-acetylcytidine (ac4C) modification in AML remain elusive. Here, we report that ac4C and its catalytic enzyme NAT10 drive leukaemogenesis and sustain self-renewal of leukaemic stem cells/leukaemia-initiating cells through reprogramming serine metabolism.

Triglyceride-glucose index and glycemic dynamics in pancreatic ductal adenocarcinoma: implications for disease progression and prognosis.

Background: To elucidate the relationship between the triglyceride-glycemic index (TyG) and clinical characteristics of pancreatic ductal adenocarcinoma (PDAC).

Methods: A total of 1,594 individuals diagnosed with pancreatic and periampullary neoplasms were categorized into four groups: PDAC-early (n = 403), locally advanced PDAC (LAPC, n = 315), PDAC-late with distant metastasis (n = 371), and other tumor types (n = 505). TyG-high was defined as a TyG index greater than 8.

Ac4C Enhances the Translation Efficiency of Vegfa mRNA and Mediates Central Sensitization in Spinal Dorsal Horn in Neuropathic Pain.

N4-Acetylcytidine (ac4C), a highly conserved post-transcriptional machinery with extensive existence for RNA modification, plays versatile roles in various cellular processes and functions. However, the molecular mechanism by which ac4C modification mediates neuropathic pain remains elusive. Here, it is found that the enhanced ac4C modification promotes the recruitment of polysome in Vegfa mRNA and strengthens the translation efficiency following SNI.

Serum Creatinine and Amylase in Drain to Predict Pancreatic Fistula Risk after Pancreatoduodenectomy.

Introduction: The identification of patients with low risk of clinically relevant postoperative pancreatic fistula (CR-POPF) and postoperative hemorrhage (PPH) can guide drain removal after pancreatoduodenectomy (PD). However, drain fluid amylase (DFA) ≤5,000 U/L on postoperative day (POD) 1 does not robustly predict the absence of CR-POPF.

Methods: Consecutive patients undergoing PD at Sun Yat-sen University Cancer Center between July 2018 and October 2021 were analyzed.

ComProliM: A cell growth assay robust to initial cell number in co-culture system.

Cell growth is conventionally quantified using CCK-8 or MTT assays, but these methods display considerable sensitivity to initial cell quantities. Inherent sampling errors during cell counting and seeding make it impossible to achieve an absolute equivalence of initial cell numbers, potentially confounding the results of CCK-8 or MTT assays. In the present study, we introduce a novel cell proliferation assay, ComProliM, predicated on cell competition theory.

The interplay between non-coding RNAs and alternative splicing: from regulatory mechanism to therapeutic implications in cancer.

Alternative splicing (AS) is a common and conserved process in eukaryotic gene regulation. It occurs in approximately 95% of multi-exon genes, greatly enriching the complexity and diversity of mRNAs and proteins. Recent studies have found that in addition to coding RNAs, non-coding RNAs (ncRNAs) are also inextricably linked with AS.

CircFhit Modulates GABAergic Synaptic Transmission via Regulating the Parental Gene Fhit Expression in the Spinal Dorsal Horn in a Rat Model of Neuropathic Pain.

Effective treatments for neuropathic pain are lacking due to our limited understanding of the mechanisms. The circRNAs are mainly enriched in the central nervous system. However, their function in various physiological and pathological conditions have yet to be determined.

The mA reader IGF2BP2 regulates glutamine metabolism and represents a therapeutic target in acute myeloid leukemia.

N-Methyladenosine (mA) modification and its modulators play critical roles and show promise as therapeutic targets in human cancers, including acute myeloid leukemia (AML). IGF2BP2 was recently reported as an mA binding protein that enhances mRNA stability and translation. However, its function in AML remains largely elusive.

The Effectiveness of Trigeminal Nerve Stimulation on Traumatic Brain Injury.

Objectives: Trigeminal nerve stimulation (TNS) is a promising strategy in treating diseases of the nervous system. In this study, the effects of TNS on traumatic brain injury (TBI) were investigated in a mouse model.

Materials And Methods: TBI was induced using a weight-drop device, and TNS treatment was delivered in the first hour after the TBI.

Trigeminal nerve electrical stimulation: An effective arousal treatment for loss of consciousness.

Background: To determine if trigeminal nerve electrical stimulation (TNS) would be an effective arousal treatment for loss of consciousness (LOC), we applied neuroscientific methods to investigate the role of potential brain circuit and neuropeptide pathway in regulating level of consciousness.

Methods: Consciousness behavioral analysis, Electroencephalogram (EEG) recording, Chemogenetics, Microarray analysis, Milliplex MAP rat peptide assay, Chromatin immune-precipitation (ChIP), Dual-luciferase reporter experiment, Western blot, PCR and Fluorescence in situ hybridization (FISH).

Results: TNS can markedly activate the neuronal activities of the lateral hypothalamus (LH) and the spinal trigeminal nucleus (Sp5), as well as improve rat consciousness level and EEG activities.

NFATc2-dependent epigenetic upregulation of CXCL14 is involved in the development of neuropathic pain induced by paclitaxel.

Background: The major dose-limiting toxicity of paclitaxel, one of the most commonly used drugs to treat solid tumor, is painful neuropathy. However, the molecular mechanisms underlying paclitaxel-induced painful neuropathy are largely unclarified.

Methods: Paw withdrawal threshold was measured in the rats following intraperitoneal injection of paclitaxel.

Distinct roles of srGAP3-Rac1 in the initiation and maintenance phases of neuropathic pain induced by paclitaxel.

Key Points: Spinal cord dorsal horn srGAP3 (slit-robo GTPase activating protein 3) increases in the initiation phase of neuropathic pain and decreases in the maintenance phase. However, Rac1 activity, which can be reduced by srGAP3, decreases in the initiation phase and increases in the maintenance phase. The increased srGAP3 in the initiation phase promotes new immature dendritic spines instigating neuropathic pain.

Upregulation of TRPC6 Mediated by PAX6 Hypomethylation Is Involved in the Mechanical Allodynia Induced by Chemotherapeutics in Dorsal Root Ganglion.

Background: Although the action mechanism of antineoplastic agents is different, oxaliplatin, paclitaxel, or bortezomib as first-line antineoplastic drugs can induce painful neuropathy. In rodents, mechanical allodynia is a common phenotype of painful neuropathy for 3 chemotherapeutics. However, whether there is a common molecular involved in the different chemotherapeutics-induced painful peripheral neuropathy remains unclear.

CircAnks1a in the spinal cord regulates hypersensitivity in a rodent model of neuropathic pain.

Circular RNAs are non-coding RNAs, and are enriched in the CNS. Dorsal horn neurons of the spinal cord contribute to pain-like hypersensitivity after nerve injury in rodents. Here we show that spinal nerve ligation is associated with an increase in expression of circAnks1a in dorsal horn neurons, in both the cytoplasm and the nucleus.

GATA3-dependent epigenetic upregulation of CCL21 is involved in the development of neuropathic pain induced by bortezomib.

The incidence of bortezomib-induced neuropathic pain hampers the progress of therapy for neoplasia and also negatively affects the quality of life of patients. However, the molecular mechanism underlying bortezomib-induced neuropathic pain remains unknown. In this study, we found that the application of bortezomib significantly increased the expression of GATA-binding protein 3 (GATA3) in the spinal dorsal horn, and intrathecal administration of GATA3 siRNA attenuated mechanical allodynia.

The Effectiveness of Ultrasound-Guided Steroid Injection Combined with Miniscalpel-Needle Release in the Treatment of Carpal Tunnel Syndrome vs. Steroid Injection Alone: A Randomized Controlled Study.

Objectives: Carpal tunnel syndrome (CTS) is one of the most common nerve entrapment syndromes, which has a serious impact on patients' work and life. The most effective conservative treatment is steroid injection but its long-term efficacy is still not satisfactory. The aim of this study was to evaluate the effectiveness of steroid injection combined with miniscalpel-needle (MSN) release for treatment of CTS under ultrasound guidance versus steroid injection alone.

TNF-α/STAT3 pathway epigenetically upregulates Nav1.6 expression in DRG and contributes to neuropathic pain induced by L5-VRT.

Background: Studies showed that upregulation of Nav1.6 increased the neuronal excitability and participated in neuropathic pain in the dorsal root ganglion (DRG). However, the molecular mechanisms underlying Nav1.

Palmitoylation of δ-catenin promotes kinesin-mediated membrane trafficking of Na1.6 in sensory neurons to promote neuropathic pain.

Palmitoylation of δ-catenin is critical to synapse plasticity and memory formation. We found that δ-catenin palmitoylation is also instrumental in the development of neuropathic pain. The abundances of palmitoylated δ-catenin and the palmitoyl acyltransferase DHHC3 were increased in dorsal root ganglion (DRG) sensory neurons in rat models of neuropathic pain.

Upregulation of NLRP3 via STAT3-dependent histone acetylation contributes to painful neuropathy induced by bortezomib.

Painful neuropathy, as a severe side effect of chemotherapeutic bortezomib, is the most common reason for treatment discontinuation. However, the mechanism by which administration of bortezomib leads to painful neuropathy remains unclear. In the present study, we found that application of bortezomib significantly increased the expression of NOD-like receptor family pyrin domain containing 3 (NLRP3) and phosphorylated signal transducer and activator of transcription-3 (STAT3) in dorsal root ganglion (DRG).

AKAP150 involved in paclitaxel-induced neuropathic pain via inhibiting CN/NFAT2 pathway and downregulating IL-4.

Antitubulin chemotherapeutics agents, such as paclitaxel, are effective chemotherapy drugs for cancer treatment. However, painful neuropathy is a major adverse effect limiting the wider application of chemotherapeutics. In this study, we found that A-kinase anchor protein 150 (AKAP150) was significantly upregulated after paclitaxel injection.

Synergistic Interaction Between Dexmedetomidine and Ulinastatin Against Vincristine-Induced Neuropathic Pain in Rats.

Unlabelled: Antimicrotubulin chemotherapeutic agents such as vincristine (VCR), often induce peripheral neuropathic pain. It is usually permanent and seriously harmful to cancer patients' quality of life and can result in the hampering of clinical treatments. Currently, there is no definitive therapy, and many of the drugs approved for the treatment of other neuropathic pain have shown little or no analgesic effect.

Accumulation of methylglyoxal increases the advanced glycation end-product levels in DRG and contributes to lumbar disk herniation-induced persistent pain.

Lumbar disk herniation (LDH) with discogenic low back pain and sciatica is a common and complicated musculoskeletal disorder. The underlying mechanisms are poorly understood, and there are no effective therapies for LDH-induced pain. In the present study, we found that the patients who suffered from LDH-induced pain had elevated plasma methylglyoxal (MG) levels.

The possible involvement of JNK activation in the spinal dorsal horn in bortezomib-induced allodynia: the role of TNF-α and IL-1β.

Purpose: Bortezomib (BTZ), a widely used chemotherapeutic drug, is closely associated with the development of painful peripheral neuropathy, but the mechanism underlying the induction of this disorder by BTZ remains largely unclear. To examine this association, we have evaluated the activation of mitogen-activated protein kinase (MAPK) family members in the spinal dorsal horn and the role of tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) in BTZ-induced allodynia in rats.

Methods: Male Sprague-Dawley rats were used as the model animals.