1. Research progress of the mTOR signaling pathway underlying the antidepressant actions of ketamine
Chinese Pharmaceutical Journal 2015;50(8):653-657
Depression is a common, serious psychiatric disease. Despite a wide range of antidepressants available, only one third of the patients show significant mood improvement in response lo an initial antidepressant treatment. Moreover, there is a time-lag of weeks to months with currently available medications; the suffering of patients could not be relieved quickly. Ketamine was found to produce rapid antidepressant responses in treatment resistant major depressive disorder patients. Molecular and cellular studies in rodent models demonstrated that ketamine stimulates mammalian target of rapamycin (mTOR) signaling and increases the initial translation of mTOR and downstream molecules, these effects of ketamine are accompanied by increasing levels of maturity and quantity of spine synapses in the prefrontal cortex. Ketamine was found to produce rapid antidepressant responses in treatment of depression. These studies identify the characterization of the mTOR signaling pathway in depression and its action in response to antidepressants shows great potential for the identification of new therapeutic targets for the development of antidepressant drugs.
2.miR-144-3p Inhibits the Invasion and Metastasis of Lung Adenocarcinoma Cells by Targeting IRS1.
Jun BAI ; Yaqiong HU ; Xinlu CHEN ; Lin CHEN ; Liping ZHANG ; Chonggao YIN ; Hongli LI
Chinese Journal of Lung Cancer 2021;24(5):323-330
BACKGROUND:
MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression, influence cellular processes, and promote disease development. Variations in miRNA expression have been observed in many diseases, including hepatitis, cardiovascular disease, and cancer. The aim of this study is to investigate the effect of miR-144-3p on the invasion and metastasis of lung adenocarcinoma by targeting recombinant insulin receptor substrate 1 (IRS1).
METHODS:
The expression of miR-144-3p in patients with lung adenocarcinoma was queried through bioinformatics database. MirTarPathway was used to analyze the KEGG enrichment pathway of miRNA. The expression and plasmid transfection efficiency of miR-144-3p in lung adenocarcinoma cell lines were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Transwell assay was used to detect the changes of cell invasion and migration ability in different groups. Bioinformatics determined the key genes (Hub genes) of miR-144-3p; Double luciferase target assay was used to detect the mutual binding of miR-144 and IRS1. Western blot assay was used to detect the expression of IRS1 in different cell lines and the expression of after overexpression of miR-144.
RESULTS:
The expression of miR-144-3p in lung adenocarcinoma tissues was decreased, qRT-PCR results indicated that the expression of miR-144-3p in lung adenocarcinoma cell A549 was significantly decreased (P<0.05), and the overexpressed plasmid was successfully transfected (P<0.05). Overexpression of miR-144 decreased the ability of cell migration and invasion (P<0.05). The expression of IRS1 was up-regulated in lung adenocarcinoma tissues. Survival analysis showed that patients with lung adenocarcinoma with high IRS1 expression had a poor prognosis (P<0.05). Double luciferase assay results showed that miR-144 could specifically identify 3'-UTR of IRS1 and inhibit reporter enzyme expression (P<0.05). Western blot indicated that the expression of IRS1 was increased in A549 cells (P<0.05). After overexpression of miR-144, the expression level of IRS1 protein was decreased (P<0.05). Transwell experiment proved that miR-144-3p could inhibit invasion and metastasis of lung adenocarcinoma cells by targeting IRS1 (P<0.05).
CONCLUSIONS
MiR-144-3p inhibits the invasion and migration of A549 cells through targeted regulation of IRS1, thus playing an anticancer role in tumors.
3.miR-30b-3p Inhibits the Proliferation and Invasion of Lung Adenocarcinoma by Targeting COX6B1.
Lin CHEN ; Xinlu CHEN ; Lu LIU ; Yanqiao ZHAO ; Wei ZUO ; Chonggao YIN ; Hongli LI
Chinese Journal of Lung Cancer 2022;25(8):567-574
BACKGROUND:
Lung adenocarcinoma (LUAD) is the most common clinical histological subtype of lung cancer and microRNAs (miRNAs) are a type of small non-coding RNAs which play a central role in cells. miR-30b-3p plays a key effect in many types of carcinoma, but there is still very little research on how it works in lung adenocarcinoma. The role and mechanism of miR-30b-3p in the proliferation and invasion of LUAD were explored in this study, to provide new targets for inhibiting the proliferation and invasion of LUAD.
METHODS:
NCBI database was used to screen out miRNA with obvious differential expression, and the differential expression and survival curve were searched by StarBase database. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the relative expression of miR-30b-3p in each lung adenocarcinoma cell line. 5-ethynyl-2'-deoxyuridine (EdU) cell proliferation assay and Transwell invasion assay were used to detect the proliferation and invasion of A549 cells in each group. The target genes of miR-30b-3p were determined by the target gene prediction websites. Western blot assay was used to detect the expression of COX6B1 in each group of A549 cells. Double luciferase assay was used to verify the targeted binding relationship between miR-30b-3p and COX6B1.
RESULTS:
The expression of miR-30b-3p in lung adenocarcinoma tissues and lung adenocarcinoma cells was downregulated (P<0.05). Low expression levels of miR-30b-3p were associated with poor prognosis in patients with lung adenocarcinoma (P=0.005,8). Overexpression of miR-30b-3p could inhibit the proliferation and the invasion of lung adenocarcinoma cells (P<0.05). Double luciferase assay proved that miR-30b-3p could target and bind to COX6B1 (P<0.05). Western blot analysis showed that the overexpression of miR-30b-3p could downregulate the expression of COX6B1 in A549 cells (P<0.05). EdU cell proliferation assay and Transwell invasion assay showed that the overexpression of miR-30b-3p could reverse the promoting effect of upregulation of COX6B1 on proliferation and invasion in lung adenocarcinoma cells (P<0.05).
CONCLUSIONS
miR-30b-3p acts as a tumor suppressor gene in lung adenocarcinoma, and it can inhibit the proliferation and invasion of lung adenocarcinoma by targeting the expression of COX6B1.
Adenocarcinoma of Lung/pathology*
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Cell Line, Tumor
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Cell Movement/genetics*
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Cell Proliferation/genetics*
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Gene Expression Regulation, Neoplastic
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Humans
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Lung Neoplasms/pathology*
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MicroRNAs/metabolism*
5.The recent advance of direct anti-HBV drug candidates in clinical trials
Mei WANG ; Lin-yue LIU ; Chuan-ju LI ; Jun LIU ; Hai-yong JIA
Acta Pharmaceutica Sinica 2022;57(10):2972-2984
Hepatitis B virus (HBV) infection is a serious global public health problem. Chronic hepatitis B virus infection can cause health problems such as cirrhosis, liver metabolism disorders and hepatocellular carcinoma. Nucloes(t)ide analogues and interferon drugs used to treat chronic HBV infection do not completely eradicate covalently closed circular DNA (cccDNA) and integrated genome of HBV DNA, so that they cannot achieve the functional cure of chronic HBV infection. Currently, a series of drugs targeting the phases of HBV lifecycle and immunomodulators have entered clinical trials. Here, we review the current status of the therapeutic drugs as well as the recent advance of direct antiviral agents.
6.Research progress of allergen immunotherapy mechanism and efficacy of allergic conjunctivitis
Xuequan SUN ; Jijiao LIN ; Yating ZHAO ; Yaqin JIANG ; Fei XIA
International Eye Science 2024;24(10):1595-1599
Allergic conjunctivitis is the most common type of allergic eye disease, and the incidence in children and adolescents is increasing year by year. Drug therapy can only relieve some symptoms and only in a short period, while allergen immunotherapy is currently a therapy that can significantly improve the symptoms of chronic allergy and the course of the disease. This method has been used abroad for many years but has yet to be reported in China. The author reviews the effective mechanism and clinical efficiency of allergen immunotherapy and provides a reference for the further clinical application in China.
7.Seeking Truth and Tracing to the Source:"Stomach Disharmony Leading to Restlessness"
Journal of Traditional Chinese Medicine 2024;65(11):1165-1169
By sorting out the different understandings by ancient and modern doctors on "stomach disharmony leading to restlessness", this paper found that the difference is whether "restlessness" means being unable to lie down or to sleep peacefully, and pointed out the limitations of the two views. The passage of Basic Questions on Diseases Caused by Qi Counterflow and Irregularities (《素问·逆调论篇》) comprehensively explains the etiology, location, and condition of qi counterflow syndrome by taking qi counterflow as the principle, "breathing" disturbance caused by the unfavorable qi movement of the lungs, stomach, and kidneys as the main manifestation, and whether one can lie down and take activities as the standards. It is pointed out that "stomach disharmony leading to restlessness" is not the original text of the Inner Canon of Yellow Emperor (《黄帝内经》), and it may be a derivative of the mistakenly posted comments.
8.Identification and bactericidal activity of a novel Cathelicidin family member from skin of Bufu bufo gargarizans.
Bo ZHAN ; Yuan-Yuan GAO ; Wei-Ping LIN ; Guang-Tao JIA ; Tong-Yi SUN ; Wen-Hui LEE
China Journal of Chinese Materia Medica 2016;41(4):630-635
The skin transcriptome of Bufu bufo gargarizans was determined by conventional methods. A novel full length cDNA coding for a Cathelicidin precursor was identified by transcriptomic data assembling, annotation and blast search of corresponding data banks. According to the known processing methods of Cathelicidin family members, present reported novel Cathelicidin precursor of B. bufo gargarizans might be cleaved at 2 possible sites of the same precursor and generate both BG-CATH25 and BG-CATH29 as mature molecules. The deduced BG-CATH25 and BG-CATH29 were synthesized with purity>95% to evaluate the properties and bactericidal activities. The secondary structural characteristics of both BG-CATH25 and BG-CATH29 in different solutions were determined by Circular Dichroism (CD) Analysis. CD results indicated that random coil conformation were the main structural elements for both BG-CATH25 and BG-CATH29 in different buffer systems. Antimicrobial activities against tested bacterial strains were carried out by plating method. Both BG-CATH25 and BG-CATH29 showed strong antibacterial activities against Aeromonas hydrophila, with MIC values of 1.25, 10 mg•L⁻¹, respectively. However, both of them showed weak bactericidal activities against human pathogenic bacteria, like Escherichia coli (ATCC25922),Staphylococcus aureus (ATCC25923)and Pseudomonas aeruginosa (ATCC 27853).
9.Reverse variant of follicular lymphoma: report of a case.
Yi LIN ; Xiao Jie WANG ; Xiao Li LIU ; Jin BAO ; Xiao Ai CHENG ; Haixia YUAN
Chinese Journal of Pathology 2022;51(11):1177-1179