m6

AIM: To investigate the metabolism and disposition characteristics of HSK7653 in healthy male Chinese participants. METHODS: A single oral dose of 80 μCi (25 mg) [14 C]HSK7653 capsules was administered to six healthy participants, and blood, plasma, urine and faeces were collected. Quantitative and qualitative analysis was conducted to investigate the pharmacokinetics, blood-to-plasma ratio, mass balance and metabolism of HSK7653. RESULTS: The drug was well absorbed and reached a maximum concentration at 1...

BACKGROUND: Our previous research shows that Curcumin (CUR) attenuates myocardial ischemia-reperfusion injury (MIRI) by reducing intracellular total RNA m6 A levels. However, the mechanism remains unknown. METHODS: For ischemia-reperfusion (IR), H9c2 cells were cultured for 6 h in serum-free low-glycemic (1 g/L) medium and a gas environment without oxygen, and then cultured for 6 h in high-glycemic (4.5 g/L) medium supplemented with 10% FBS and a 21% oxygen environment...

N6-methyladenosine (m6 A) is a mRNA modification with important roles in gene expression. In African trypanosomes, this post-transcriptional modification is detected in hundreds of transcripts and it affects the stability of the variant surface glycoprotein (VSG) transcript in the proliferating blood stream form. However, how the m6 A landscape varies across the life cycle remains poorly defined. Using full-length, non-fragmented RNA, we immunoprecipitated and sequenced m6 A-modified transcripts across three life cycle stages of Trypanosoma brucei - slender (proliferative), stumpy (quiescent), and procyclic forms (proliferative)...

Cervical cancer (CC) remains one of the most common malignancies among women worldwide, posing a serious threat to women's health. N6-methyladenosine (m6 A) modification, as the most abundant type of RNA methylation modification, and has been found to play a crucial role in various cancers. Current research suggests a close association between RNA m6 A modification and the occurrence and progression of CC, encompassing disruptions in m6 A levels and its regulatory machinery. This review summarizes the current status of m6 A modification research in CC, explores the mechanisms underlying m6 A levels and regulators (methyltransferases, demethylases, reader proteins) in CC and examines the application of small-molecule inhibitors of m6 A regulators in disease treatment...

Myeloid-derived suppressor cells (MDSCs) are closely related to the occurrence and development of many cancers, but the specific mechanism is not fully understood. It has been found that N6-methyladenosine (m6 A) plays a key role in RNA metabolism, but its function in MDSCs has yet to be revealed. In this study, we found that MDSCs in mice with colorectal cancer (CRC) have significantly elevated levels of m6 A, while ALKBH5 expression is decreased. Overexpression of ALKBH5 can reduce the immunosuppressive function of MDSCs in vivo and in vitro, and attenuates the protumorigenic ability of MDSCs...

STUDY DESIGN: Case report and literature review. OBJECTIVE: To report the relatively rare complication of delayed infection after cervical disc arthroplasty (CDA). BACKGROUND: Delayed infection of the M6 device has been a rarely reported complication, with all cases described outside of the United States. The reliability of positive intraoperative cultures remains an ongoing debate. METHODS: Cases were reviewed, and findings were summarized...

Direct RNA sequencing offers the possibility to simultaneously identify canonical bases and epi-transcriptomic modifications in each single RNA molecule. Thus far, the development of computational methods has been hampered by the lack of biologically realistic training data that carries modification labels at molecular resolution. Here, we report on the synthesis of such samples and the development of a bespoke algorithm, mAFiA (m6 A Finding Algorithm), that accurately detects single m6 A nucleotides in both synthetic RNAs and natural mRNA on single read level...

Esophageal cancer ranks among the most prevalent malignant tumors, and esophageal squamous cell carcinoma (ESCC) constitutes its predominant histological form. Despite its impact, a thorough insight into the molecular intricacies of ESCC's development is still incomplete, which hampers the advancement of targeted molecular diagnostics and treatments. Recently, B-cell lymphoma-2-associated transcription factor 1 (BCLAF1) has come under investigation for its potential involvement in tumor biology, yet its specific role and mechanism in ESCC remain unclear...

The N6 -methyladenosine (m6 A) mRNA modification is crucial for plant development and stress responses. In rice, the male sterility resulting from the deficiency of OsFIP37, a core component of m6 A methyltransferase complex, emphasizes the significant role of m6 A in male fertility. m6 A is reversible and can be removed by m6 A demethylases. However, whether mRNA m6 A demethylase regulates male fertility in rice has remained unknown. Here, we identify the mRNA m6 A demethylase OsALKBH9 and demonstrate its involvement in male fertility regulation...

Long interspersed elements-1(LINE-1) is the only autonomous transposon in human genome，and its retrotransposition results in change of cellular genome structure and function, leading occurrence of various severe diseases. As a central key intermediated component during life cycle of LINE-1 retrotransposition, the host modification of LINE-1 mRNA affects the LINE-1 transposition directly. N6 -adenosine methylation(m6 A), the most abundant epigenetic modification on eukaryotic RNA, is dynamically reversible...

As the most abundant mRNA modification, m6 A controls and influences many aspects of mRNA metabolism including the mRNA stability and degradation. However, the role of specific m6 A sites in regulating gene expression still remains unclear. In additional, the multicollinearity problem caused by the correlation of methylation level of multiple m6 A sites in each gene could influence the prediction performance. To address the above challenges, we propose an elastic-net regularized negative binomial regression model (called m6 Aexpress-enet) to predict which m6 A site could potentially regulate its gene expression...

Meat production performance is the most important economic trait in broilers, and skeletal muscle, as the largest organ in animals, is directly related to meat production during embryonic and postnatal growth and development. N6-Methyladenosine (m6 A) is a chemical modification occurs on RNA adenosine that has been reported to participate in a variety of biological processes in all species. However, there are still few reports on the regulatory role of muscle growth and development in poultry after birth. This study aims to reveal the distribution of m6 A modification sites in chicken pectoralis major muscle after birth and find out the regulatory relationship between m6 A and muscle development...

BACKGROUND: Doxorubicin (DOX) is a chemotherapeutic drug, while its clinical use is greatly limited by the life-threatening cardiotoxicity. N6 -methyladenosine (m6 A) RNA modification participates in varieties of cellular processes. Nonetheless, it remains elusive whether m6 A modification and its methyltransferase METTL3 are involved in the progression of DOX-induced cardiotoxicity (DIC). METHODS: Mice were administrated with DOX (accumulative dosage of 20 mg/kg) repeatedly to establish a chronic DIC model...

Piperlonguminine (PLG) is a major alkaloid found in Piper longum fruits. It has been shown to possess a variety of biological activities, including anti-tumor, anti-hyperlipidemic, anti-renal fibrosis and anti-inflammatory properties. Previous studies have reported that PLG inhibits various CYP450 enzymes. The main objective of this study was to identify reactive metabolites of PLG in vitro and assess its ability to inhibit CYP450. In rat and human liver microsomal incubation systems exposed to PLG, two oxidized metabolites (M1 and M2) were detected...

BACKGROUND: Liver ischemia/reperfusion (I/R) injury is usually caused by hepatic inflow occlusion during liver surgery, and is frequently observed during war wounds and trauma. Hepatocyte ferroptosis plays a critical role in liver I/R injury, however, it remains unclear whether this process is controlled or regulated by members of the DEAD/DExH-box helicase (DDX/DHX) family. METHODS: The expression of DDX/DHX family members during liver I/R injury was screened using transcriptome analysis...

BACKGROUND: Sepsis-induced acute lung injury (ALI) is one of the serious life-threatening complications of sepsis and is pathologically associated with mitochondrial dysfunction. Ginsenoside Rg1 has good therapeutic effects on ALI. Herein, the pharmacological effects of Rg1 in sepsis-induced ALI were investigated. METHODS: Sepsis-induced ALI models were established by CLP operation and LPS treatment. HE staining was adopted to analyze lung pathological changes. The expression and secretion of cytokines were measured by RT-qPCR and ELISA...

BACKGROUND: Increasing evidence has demonstrated that N6-methyladenosine (m6 A) RNA modification plays an essential role in a wide range of pathological conditions. Impaired autophagy is a critical hallmark of acute pancreatitis (AP). AIM: To explore the role of the m6 A modification of ZKSCAN3 in the regulation of autophagy in AP. METHODS: The AP mouse cell model was established by cerulein-treated mouse pancreatic acinar cells (MPC-83), and the results were confirmed by the levels of amylase and inflammatory factors...

High-grade serous ovarian cancer (HGSOC) remains the most lethal female cancer by far. Herein, clinical HGSOC samples had higher N6 -methyladenosine (m6 A) modification than normal ovarian tissue, and its dysregulation had been reported to drive aberrant transcription and translation programs. However, Kringle containing transmembrane protein 2 (KREMEN2) and its m6 A modification have not been fully elucidated in HGSOC. In this study, the data from the high-throughput mRNA sequencing (RNA-seq) of clinical samples were processed using the weighted correlation network analysis (WGCNA) and functional enrichment analysis...

In this study, dip coating method was investigated to prepare superhydrophilic MIL-101 (Cr)-coated copper mesh for highly efficient oil/water emulsion separation. To increase the surface area of synthesized MIL-101 (Cr), a purification procedure was developed to remove unreacted H2 BDC crystals present in the channel of the initial MIL-101 (Cr) sample synthesized. After that, a dispersing solution of MIL-101 (Cr) was needed to coat on the copper mesh. Thermoplastic polyurethane (TPU) was used as a binder in this procedure...

N6 -methyladenosine (m6 A) is essential for RNA metabolism in cells. The YTH domain, conserved in the kingdom of Eukaryotes, acts as an m6 A reader that binds m6 A-containing RNA. In plants, the YTH domain is involved in plant hormone signaling, stress response regulation, RNA stability, translation, and differentiation. However, little is known about the YTH genes in tea-oil tree, which can produce edible oil with high nutritional value. This study aims to identify and characterize the YTH domains within the tea-oil tree ( Camellia chekiangoleosa Hu) genome to predict their potential role in development and stress regulation...