1.Ultrasensitive quantification of trace amines based on N-phosphorylation labeling chip 2D LC-QQQ/MS
Xiqing BIAN ; Yida ZHANG ; Na LI ; Menglin SHI ; Xiaolin CHEN ; Hui-Lu ZHANG ; Jie LIU ; Jian-Lin WU
Journal of Pharmaceutical Analysis 2023;13(3):315-322
Trace amines(TAs)are metabolically related to catecholamine and associated with cancer and neuro-logical disorders.Comprehensive measurement of TAs is essential for understanding pathological pro-cesses and providing proper drug intervention.However,the trace amounts and chemical instability of TAs challenge quantification.Here,diisopropyl phosphite coupled with chip two-dimensional(2D)liquid chromatography tandem triple-quadrupole mass spectrometry(LC-QQQ/MS)was developed to simul-taneously determine TAs and associated metabolites.The results showed that the sensitivities of TAs increased up to 5520 times compared with those using nonderivatized LC-QQQ/MS.This sensitive method was utilized to investigate their alterations in hepatoma cells after treatment with sorafenib.The significantly altered TAs and associated metabolites suggested that phenylalanine and tyrosine metabolic pathways were related to sorafenib treatment in Hep3B cells.This sensitive method has great potential to elucidate the mechanism and diagnose diseases considering that an increasing number of physiological functions of TAs have been discovered in recent decades.
2.High-risk factors of stroke in people over 40 years old in Anqing area and intervention for high-risk population
Li CAO ; Liangjin YUAN ; Xueying SHI ; Xiangyang TANG ; Fei TAO ; Lei WANG ; Menglin WANG
Journal of Public Health and Preventive Medicine 2020;31(6):114-116
Objective To investigate the high-risk factors of stroke in Anqing area, and to analyze the value of standard treatment for the intervention of high-risk population for stroke. Methods A total of 3 062 permanent residents over 40 years of age in Anqing were surveyed by a questionnaire for the high-risk population of stroke. Physical examination was carried out for people at a high risk of stroke. The physical examination included general physical examination, laboratory tests, and carotid artery color Doppler ultrasound examination. People at a high risk of stroke were investigated on whether or not they received standardized symptomatic treatment and prevention interventions. Results Hypertension or taking antihypertensive drugs accounted for the highest risk factors of stroke in Anqing area, followed by smoking and seldom physical exercise. The abnormal rates of body mass index, blood pressure, contents of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL) , homocysteine (HYC), and blood glucose (GLU), as well as intimal thickening, plaque and carotid artery stenosis in people at high risk of stroke receiving standardized treatment were significantly lower than those in people receiving no standardized treatment, and the difference was statistically significant (P<0.05). The standard treatment was an independent factor influencing the body mass index, blood pressure, TC, TG, LDL, HDL, HYC, GLU, intimal thickening, plaque and carotid artery stenosis (P<0.05). Conclusion Hypertension accounted for the highest proportion of high-risk factors for stroke in Anqing area. Standardized symptomatic treatment can effectively control the physical indicators, laboratory test indicators and carotid artery state of stroke high-risk populations, which can play a positive role in the prevention of stroke.
3.Roles of m6A modification in neurological diseases.
Yuan ZHANG ; Si ZHANG ; Mengmeng SHI ; Menglin LI ; Jiayu ZENG ; Jie HE
Journal of Central South University(Medical Sciences) 2022;47(1):109-115
N6-methyladenosine (m6A) methylation modification is one of the most common epigenetic modifications for eukaryotic mRNA. Under the catalytic regulation of relevant enzymes, m6A participates in the body's pathophysiological processes via mediating RNA transcription, splicing, translation, and decay. In the past, we mainly focused on the regulation of m6A in tumors such as hematological tumors, cervical cancer, breast cancer. In recent years, it has been found that m6A is enriched in mRNAs of neurogenesis, cell cycle, and neuron differentiation. Its regulation in the nervous system is gradually being recognized. When the level of m6A modification and the expression levels of relevant enzyme proteins are changed, it will cause neurological dysfunction and participate in the occurrence and conversion of neurological diseases. Recent studies have found that the m6A modification and its associated enzymes were involved in major depressive disorder, Parkinson's disease, Alzheimer's disease, Fragile X syndrome, amyotrophic lateral sclerosis, and traumatic brain injury, and they also play a key role in the development of neurological diseases and many other neurological diseases. This paper mainly reviewed the recent progress of m6A modification-related enzymes, focusing on the impact of m6A modification and related enzyme-mediated regulation of gene expression on the central nervous system diseases, so as to provide potential targets for the prevention of neurological diseases.
Adenosine/metabolism*
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Depressive Disorder, Major
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Epigenesis, Genetic
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Humans
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Methylation
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RNA, Messenger/metabolism*
4.Glutamine synthetase-negative hepatocellular carcinoma has better prognosis and response to sorafenib treatment after hepatectomy.
Mingyang SHAO ; Qing TAO ; Yahong XU ; Qing XU ; Yuke SHU ; Yuwei CHEN ; Junyi SHEN ; Yongjie ZHOU ; Zhenru WU ; Menglin CHEN ; Jiayin YANG ; Yujun SHI ; Tianfu WEN ; Hong BU
Chinese Medical Journal 2023;136(17):2066-2076
BACKGROUND:
Glutamine synthetase (GS) and arginase 1 (Arg1) are widely used pathological markers that discriminate hepatocellular carcinoma (HCC) from intrahepatic cholangiocarcinoma; however, their clinical significance in HCC remains unclear.
METHODS:
We retrospectively analyzed 431 HCC patients: 251 received hepatectomy alone, and the other 180 received sorafenib as adjuvant treatment after hepatectomy. Expression of GS and Arg1 in tumor specimens was evaluated using immunostaining. mRNA sequencing and immunostaining to detect progenitor markers (cytokeratin 19 [CK19] and epithelial cell adhesion molecule [EpCAM]) and mutant TP53 were also conducted.
RESULTS:
Up to 72.4% (312/431) of HCC tumors were GS positive (GS+). Of the patients receiving hepatectomy alone, GS negative (GS-) patients had significantly better overall survival (OS) and recurrence-free survival (RFS) than GS+ patients; negative expression of Arg1, which is exclusively expressed in GS- hepatocytes in the healthy liver, had a negative effect on prognosis. Of the patients with a high risk of recurrence who received additional sorafenib treatment, GS- patients tended to have better RFS than GS+ patients, regardless of the expression status of Arg1. GS+ HCC tumors exhibit many features of the established proliferation molecular stratification subtype, including poor differentiation, high alpha-fetoprotein levels, increased progenitor tumor cells, TP53 mutation, and upregulation of multiple tumor-related signaling pathways.
CONCLUSIONS
GS- HCC patients have a better prognosis and are more likely to benefit from sorafenib treatment after hepatectomy. Immunostaining of GS may provide a simple and applicable approach for HCC molecular stratification to predict prognosis and guide targeted therapy.
Humans
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Carcinoma, Hepatocellular/metabolism*
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Sorafenib/therapeutic use*
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Liver Neoplasms/metabolism*
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Glutamate-Ammonia Ligase/metabolism*
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Hepatectomy
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Retrospective Studies
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Prognosis
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Neoplasm Recurrence, Local/surgery*