The relationship between the network of non-coding RNAs-molecular targets and N6-methyladenosine modification in tumors of urinary system.

N6-methyladenosine (m6A) methylation, a prevalent eukaryotic post-transcriptional modification, is involved in multiple biological functions, including mediating variable splicing, RNA maturation, transcription, and nuclear export, and also is vital for regulating RNA translation, stability, and cytoplasmic degradation. For example, m6A methylation can regulate pre-miRNA expression by affecting both splicing and maturation. Non-coding RNA (ncRNA), which includes microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), does not encode proteins but has powerful impacts on transcription and translation. Conversely, ncRNAs may impact m6A methylation by affecting the expression of m6A regulators, including miRNAs targeting mRNA of m6A regulators, or lncRNAs, and circRNAs, acting as scaffolds to regulate transcription of m6A regulatory factors. Dysregulation of m6A methylation is common in urinary tumors, and the regulatory role of ncRNAs is also important for these malignancies. This article provides a systematic review of the role and mechanisms of action of m6A methylation and ncRNAs in urinary tumors.

Knowledge mapping and current trends of m6A methylation in the field of cancer.

Background: Cancer is a serious threat to people's lives and health, killing millions of people every year. Here, we performed a bibliometric analysis of tumor N6-methyladenosine methylation data between 2001 and 2022 to understand research trends and potential future directions. Methods: A total of 890 papers published in the Web of Science core collection database between January 1, 2001 and December 31, 2022 were analyzed. Bibliometric analysis was performed using VOSviewer software to explore citations, co-authorship, co-citations, and co-occurrence. Results: Although few papers were published before 2018, there was a rapid increase in publications after 2018. The People's Republic of China published 810 papers with 16,957 citations, both ranking first in the word. Sun Yat Sen University had the highest number of citations and published articles (67 published papers and 2702 citations), indicative of its active collaborative research status. Wang Xiao was the most co-cited author with 546 co-citations. Huang Yufei and Meng Jia ranked first with a link strength of 22, making them the most active collaborative authors. Frontiers in Oncology and Nature were the most active and co-cited journals, with 57 papers and 1953 co-citations, respectively. Studies of tumor N6-methyladenosine methylation can be divided into three categories: "tumor metabolism", "tumor bioinformatics and immunity", and "tumor progression". Conclusions: This study systematically summarized the research on tumor N6-methyladenosine methylation during the past 20 years and suggested potential ways to explore its biomarkers and immunotherapy in the future.

Emerging strategy for the treatment of urothelial carcinoma: Advances in antibody-drug conjugates combination therapy.

Urothelial carcinoma (UC) is a prevalent malignant tumor involving the urinary system. Although there are various treatment modalities, including surgery, chemotherapy, and immune checkpoint inhibitor (ICI) therapy, some patients experience disease recurrence and metastasis with poor prognosis and dismal long-term survival. Antibody-drug conjugates (ADCs), which combine the targeting ability of antibody drugs with the cytotoxicity of chemotherapeutic drugs, have recently emerged as a prominent research focus in the development of individualized precision cancer therapy. Although ADCs have improved the overall response rate in patients with UC, their effectiveness remains limited. Currently, ADC-based combination therapies, particularly ADC combined with ICIs, have demonstrated promising efficacy. This combination approach has advanced the treatment of UC, exhibiting the potential to become the standard first-line therapy for advanced UC in the future. This article reviewed clinical trials involving ADC-based combination therapy for UC and discussed the possible challenges and future perspectives to provide guidance for the clinical treatment of UC.

Serotonin syndrome caused by a CYP2C19-mediated interaction between low-dose escitalopram and clopidogrel: a case report.

Background: Serotonin syndrome has been recognized as a serious adverse reaction to antidepressants and is characterized by sudden or severe autonomic nerve dysfunction and neuromuscular symptoms. Without an accurate diagnosis and prompt treatment, serotonin syndrome progresses rapidly and can be life-threatening. It is usually related to the dose of 5-hydroxytryptamine drugs, and the dose is the basis for diagnosis. Therefore, serotonin syndrome induced by low-dose antidepressants rarely occurs, and clinicians are more likely to misdiagnose patients who take low-dose antidepressants with similar symptoms. Here, we present a case study of serotonin syndrome caused by a relatively low dose of escitalopram, which is not common in past references. Case summary: The patient was a 74-year-old Asian woman with a 42-year history of schizophrenia. After 6 weeks of antidepressant treatment, our patient presented with characteristic myoclonus in the lower limbs and closed eyes with fluttering. Initially, she was misdiagnosed with neuroleptic malignant syndrome (NMS) due to antipsychotic medication and was treated accordingly, even with discontinuation of clozapine. However, her symptoms persisted, and then therapeutic drug monitoring was initiated with the involvement of a clinical pharmacist. Eventually, she was diagnosed with serotonin syndrome due to escitalopram levels reaching the warning level. Subsequently, the patient's treatment was modified, and her clinical outcome was satisfactory without any other serious adverse reactions. Gene detection was also performed, and a cytochrome P450 enzyme (CYP) 2C19-mediated interaction between low-dose escitalopram and clopidogrel seems to be a possible mechanism. Conclusion: Data on this is extremely scarce, and to the best of our knowledge, serotonin syndrome caused by low-dose antidepressants has not yet been discussed to any great extent in the literature. Our case provides more clinical experience in the treatment of serotonin syndrome.

A review of current evidence about lncRNA MEG3: A tumor suppressor in multiple cancers.

Long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3) is a lncRNA located at the DLK1-MEG3 site of human chromosome 14q32.3. The expression of MEG3 in various tumors is substantially lower than that in normal adjacent tissues, and deletion of MEG3 expression is involved in the occurrence of many tumors. The high expression of MEG3 could inhibit the occurrence and development of tumors through several mechanisms, which has become a research hotspot in recent years. As a member of tumor suppressor lncRNAs, MEG3 is expected to be a new target for tumor diagnosis and treatment. This review discusses the molecular mechanisms of MEG3 in different tumors and future challenges for the diagnosis and treatment of cancers through MEG3.

lncRNA PVT1: a novel oncogene in multiple cancers.

Long noncoding RNAs are involved in epigenetic gene modification, including binding to the chromatin rearrangement complex in pre-transcriptional regulation and to gene promoters in gene expression regulation, as well as acting as microRNA sponges to control messenger RNA levels in post-transcriptional regulation. An increasing number of studies have found that long noncoding RNA plasmacytoma variant translocation 1 (PVT1) plays an important role in cancer development. In this review of a large number of studies on PVT1, we found that PVT1 is closely related to tumor onset, proliferation, invasion, epithelial-mesenchymal transformation, and apoptosis, as well as poor prognosis and radiotherapy and chemotherapy resistance in some cancers. This review comprehensively describes PVT1 expression in various cancers and presents novel approaches to the diagnosis and treatment of cancer.

Functions and underlying mechanisms of lncRNA HOTAIR in cancer chemotherapy resistance.

Chemotherapy has been one of the most important treatments for advanced cancer in recent decades. Although the sensitivity rate of initial chemotherapy is high, patients with chemotherapy resistant tumors, experience tumor recurrence. In recent years, many studies have shown that homeobox transcript antisense intergenic RNA (HOTAIR) is involved in many pathological processes including carcinogenesis. The abnormal regulation of a variety of cell functions by HOTAIR, such as apoptosis, the cell cycle, epithelial-mesenchymal transition, autophagy, self-renewal, and metabolism, is associated with chemotherapy resistance. Therefore, there is an urgent need to understand the biology and mechanism underlying the role of HOTAIR in tumor behavior and its potential as a biomarker for predicting the effect of chemotherapy. In this manuscript, we review the mechanisms underlying HOTAIR-related drug resistance and discuss the limitations of current knowledge and propose potential future directions.

The global status of research in prostate cancer bone metastasis: A bibliometric and visualized analysis.

Background: Prostate cancer (PCa) is a serious threat to the health of elderly aged groups. It is very important to understand the occurrence and development of PCa for early diagnosis, treatment and metastasis control. This study aims to elucidate the international frontier research direction and literature distribution through bibliometric and visual analyses of PCa bone metastasis. Methods: Data were obtained from the Web of Science core collection database, which collected 2,246 papers related to PCa bone metastasis from 1 January 2012 to 31 December 2021. The collected data were analyzed using the VOSviewer software for citation, co-authorship, co-citation, bibliometric coupling, and co-occurrence. Results: Over the past decade, published papers have increased annually. The United States of America has published 890 papers with 29,161 citations, far more than any other country, and it has the most extensive collaboration with other countries. For example, 33 articles by Saad Fred were cited 2,721 times, and 91 articles from the University of Texas MD Anderson CANC CTR were cited 3,037 times, the most cited author and organization. Peng Xinsheng and Duke UNIV comprise the most active collaborative author and organization, respectively. The most co-cited journal was CANCER RES, with 3,195 citations. Studies of PCa bone metastasis can be divided into four categories: "basic research," "auxiliary diagnosis and treatment," "clinical trial," and "prognosis." Conclusion: Our results provide a comprehensive overview of the research priorities and future directions of PCa bone metastasis, which can further accurately guide researchers in diagnosis, treatment, and personalized prevention.

Predicting the risk of cardiac myxoma in Carney complex.

PURPOSE: Carney complex (CNC), is an autosomal dominant multiple neoplasia and lentiginosis syndrome. We aimed to identify risk factors associated with the occurrence and recurrence of cardiac myxomas, the predominant cause of death in CNC patients. METHODS: Patients with CNC were monitored prospectively between 1995 and 2020 for the development of cardiac myxomas. RESULTS: Of the 319 patients studied, 136 (42.6%) developed myxomas. The mean age at diagnosis was 28.7 ± 16.6 years in females and 25.0 ± 16.4 years in males. By age 30, 35% of females and 45% of males had at least one myxoma. The CNC-related lesions, lentigines, cutaneous, mucosal, or breast myxomas, thyroid nodules, pituitary adenoma, and schwannoma were significantly more frequent (all p < 0.05) among patients with myxomas. Forty-four percent of patients had recurrences; nearly all within the first 8 and 16 years for males and females, respectively. Recurrences were more common in females. CONCLUSION: This is the largest study to date and provides the first-time risk estimates by age and gender for cardiac myxomas in CNC patients. Cardiac myxomas are common by age 30 and often recur, especially in women, but the risk drops in 10 to 20 years. These findings may guide patient counseling, screening intervals, and surgical approaches. CLINICAL TRIAL REGISTRATION: Clinical Trial Registration: Defining the Genetic Basis for the Development of Primary Pigmented Nodular Adrenocortical Disease and the Carney complex, Registration number: NCT00001452 URL: https://clinicaltrials.gov/ct2/show/NCT00001452.

Altered expression of the CSMD1 gene in the peripheral blood of schizophrenia patients.

BACKGROUND: Schizophrenia (SCZ) is a heritable, refractory, and devastating psychiatric disorder. Previous studies have shown that the variants of CUB and sushi multiple domains 1 (CSMD1) demonstrate significant genome-wide association with SCZ. However, few studies have been conducted on the effect of antipsychotics on the expression levels of CSMD1. This study explored whether a change occurs in the expression of the CSMD1 gene before and after antipsychotic treatment in SCZ patients. METHODS: The study population comprised Han Chinese patients from eastern China, including 32 SCZ patients and 48 healthy controls. The expression of CSMD1 before and after treatment in the SCZ group and between the two groups was analyzed using real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: The expression levels of the CSMD1 gene in the peripheral blood mononuclear cells (PBMCs) of SCZ patients were lower than those in the healthy controls. The expression levels of the CSMD1 gene in the PBMCs of the SCZ patients after antipsychotic treatment were higher than those in the baseline SCZ patients (all P <  0.05). CONCLUSIONS: Our results showed that the expression levels of CSMD1 are correlated with the development and treatment of SCZ, providing further evidence for the involvement of CSMD1 in SCZ.

Mot1 regulates the DNA binding activity of free TATA-binding protein in an ATP-dependent manner.

Mot1 is an essential Snf2/Swi2-related Saccharomyces cerevisiae protein that binds the TATA-binding protein (TBP) and removes TBP from DNA using ATP hydrolysis. Mot1 functions in vivo both as a repressor and as an activator of transcription. Mot1 catalysis of TBP.DNA disruption is consistent with its function as a repressor, but the Mot1 mechanism of activation is unknown. To better understand the physiologic role of Mot1 and its enzymatic mechanism, MOT1 mutants were generated and tested for activity in vitro and in vivo. The results demonstrate a close correlation between the TBP.DNA disruption activity of Mot1 and its essential in vivo function. Previous results demonstrated a large overlap in the gene sets controlled by Mot1 and NC2. Mot1 and NC2 can co-occupy TBP.DNA in vitro, and NC2 binding does not impair Mot1-catalyzed disruption of the complex. Residues on the DNA-binding surface of TBP are important for Mot1 binding and the Mot1.TBP binary complex binds very poorly to DNA and does not dissociate in the presence of ATP. However, the binary complex binds DNA well in the presence of the transition state analog ADP-AlF(4). A model for Mot1 action is proposed in which ATP hydrolysis causes the Mot1 N terminus to displace the TATA box, leading to ejection of Mot1 and TBP from DNA.

Tabtoxin-resistant protein: overexpression, purification, and characterization.

One of the self-protection mechanisms in Pseudomonas syringae pv. tabaci, a pathogen of tobacco wildfire, is thought to be due to its tabtoxin-resistance gene (ttr). In this study, the ttr gene was inserted into an expression vector, pQE30, and successfully expressed in Escherichia coli M15 at high levels. The purified recombinant tabtoxin-resistant protein (TTR) had an apparent molecular mass of about 21 kDa on SDS-PAGE as well as by mass spectroscopy and had a pI of 6.6 on isoelectric focusing-PAGE. Spectral analysis showed that TTR possesses a maximum fluorescence wavelength (lambda(max)) of 325 nm upon excitation at 282 nm and a positive band with a maximum at 195 nm and a broad negative band with a minimum at 215 nm in the far-UV CD spectrum. The spectrophotometric assay demonstrated the strong detoxification activity of TTR. These results are the first report of the characterization of the purified tabtoxin-resistant protein. Its capacity to detoxify tabtoxinine-beta-lactam shows that it must be one of the self-protection mechanisms in pv. tabaci.