1.Double-stranded RNA inhibits the growth and migration of malignant gliomas through the activation of the PKR/eIF2α pathway
Qun YAN ; Sha-Sha BIAN ; Min-Feng SHU
Fudan University Journal of Medical Sciences 2024;51(3):295-305
Objective To investigate the impact of radiotherapy simulant Zeocin induced double-stranded RNA(dsRNA)on double-stranded RNA-dependent protein kinase(PKR)activation and explore its molecular mechanism in inhibiting the growth and migration of malignant gliomas.Methods We employed scratch assays,colony formation assays,and CCK8 assays to assess the impact of Zeocin on glioma growth and migration inhibition.Western blot and RT-qPCR were employed to measure the expression levels of methyl-modifying enzymes in glioma cells.The J2 antibody was used to detect endogenous dsRNA in malignant glioma cells treated with Zeocin.Western blot was used to assess the phosphorylation levels of PKR and eukaryotic initiating factor 2α(eIF2α).Results Zeocin significantly inhibited growth and migration of glioma cells;Zeocin treatment induced the production of endogenous dsRNA in malignant glioma cells;as the concentration of Zeocin increased,phosphorylated PKR and eIF2αprotein level also significantly increased;Zeocin downregulated the total m6A level of glioma cells in a dose-dependent manner;Zeocin selectively downregulated the protein level of methylase METTL14;Zeocin had no effect on mRNA levels of m6A modifying enzymes.Conclusion Zeocin probably triggered more dsRNA by downregulating the m6A level of RNA in malignant glioma cells,which in turn activated the PKR/eIF2α pathway,ultimately leading to tumor growth inhibition.
2.Effects of lepirudine on acute pulmonary embolism in rats
Cong-Long HU ; Chen WU ; Sha-Sha XIAO ; Yi-Qun LIU
The Chinese Journal of Clinical Pharmacology 2024;40(18):2719-2723
Objective To explore the mechanism of lepirudine in inhibiting thrombin activation by regulating the Notch signaling pathway for the treatment of acute pulmonary embolism.Methods SD rats were randomly divided into sham group,model group and experimental group,with 10 rats in each group.Acute pulmonary embolism model was established by autologous thrombosis in model group and experimental group.Experimental group was intraperitoneally injected with lepiludine(2.0 mg·kg-1)at 24 h,0.5 h before and 24 h after modeling,respectively,while sham group and model group were intraperitoneally injected with 0.9%NaCl at the same time point.The contents of platelet P-selectin 62(CD62P),platelet granule membrane protein-140(GMP-140),N-terminal pro-brain natriuretic peptide(NT-proBNP)and cardiac troponin T(cTnT)in rat plasma were detected by enzyme-linked immunosorbent assay(ELISA).The contents of thromboxane B2(TXA2)and prostacyclin(PGI2)in rat plasma were detected by RIA.The protein expression levels of Notch receptor protein 1(Notch1)and Notch ligand protein 1(JAGGED1)in lung tissue of rats were detected by Western blot.Results The plasma CD62P content in sham group,model group and experimental group were(9.31±1.31),(25.03±2.66)and(11.42±2.21)ng·mL-1;the contents of GMP-140 were(43.23±5.61),(114.33±14.02)and(73.44±6.97)ng·mL-1;the contents of NT-proBNP were(14.71±1.93),(20.57±3.46)and(11.07±3.06)ng·mL-1;cTnT content were(81.07±9.77),(233.24±27.61)and(134.76±15.00)pg·mL-1;TXA2 content were(231.06±17.33),(378.69±29.10)and(268.61±24.15)pg·mL-1;PGI2 content were(147.25±16.44),(104.37±11.62)and(136.09±13.40)pg·mL-1;the relative expression levels of Notch1 protein in lung tissue were 1.24±0.21,0.51±0.06 and 0.87±0.09;the relative expression levels of JAGGED1 protein were 1.02±0.15,0.17±0.02 and 0.28±0.06.Compared with sham group and experimental group,there were statistically significant differences in the above indexes in model group(P<0.01,P<0.001).Conclusion Lepirudine can inhibit thrombin activation in the treatment of acute pulmonary embolism by activating the Notch signaling pathway.
3.Evaluation of spike quality of Schizonepeta tenuifolia based on fingerprint and chemometrics
Qun ZHANG ; Sha LUO ; Jie LI ; Bei LI ; Wen-yi NIU ; Rui TAN
Acta Pharmaceutica Sinica 2022;57(7):2146-2152
The quality control and evaluation methods of
4.Two Cases of Intrauterine Adhesions with Rare Hysteroscopic Findings.
Feng-Xian FU ; Hua DUAN ; Sha WANG ; Yi-Qun TANG ; Lu GAN ; Qian XU
Chinese Medical Journal 2018;131(20):2474-2476
5.Effects of mild moxibustion on the uterine microcirculation in patients of primary dysmenorrhea.
Qun LIU ; Xuemei LI ; Kuiyu REN ; Sha YANG
Chinese Acupuncture & Moxibustion 2018;38(7):717-720
OBJECTIVETo observe the effects of mild moxibustion on the uterine microcirculation in patients of primary dysmenorrhea (PD) and explore the potential mechanism of mild moxibustion in the treatment of PD.
METHODSA total of 30 patients were randomized into a treatment group and a waiting list group, 15 cases in each one. Additionally, 15 healthy people were collected in the healthy group. In the treatment group, the mild moxibustion was used at Guanyuan (CV 4) and Sanyinjiao (SP 6). The treatment was given once a day since 5 to 7 days before menstruation until menses, 20 min each time. The treatment lasted for 3 menstrual cycles. No any intervention was provided in the waiting list group and the healthy group. The three-dimensional Doppler ultrasound test was adopted to observe the changes of the relevant indexes of uterine arterial blood, such as the systolic velocity (Vs), the diastolic velocity (Vd), the mean velocity (Vm), peak systolic velocity/end diastolic velocity (S/D), pulsatility index (PI) and the resistance index (RI) before treatment and at the end of 3-menstrual-cycle treatment.
RESULTSBefore treatment, as compared with the healthy group, Vs, Vd and Vm reduced in the treatment group and the waiting list group, S/D, PI and RI increased in the treatment group (all <0.05). The differences were not significant in S/D, PI and RI between the waiting list group and the healthy group (all >0.05). After treatment for 3 menstrual cycles, Vs, Vd and Vm increased in the treatment group (all <0.05), S/D, PI and RI reduced (all <0.05). The difference was not significant in every index before and after trial in the waiting list group and the healthy group (all >0.05). After treatment, Vs, Vd and Vm in the treatment group were higher than those in the waiting list group (all <0.05) and the difference was not significant as compared with those in the healthy group (all >0.05). S/D, PI and RI in the treatment group were lower than those in the waiting list group and the healthy group (all <0.05).
CONCLUSIONThe mild moxibustion remarkably improves the uterine microcirculation in PD patients, which is achieved possibly by increasing blood velocity and reducing vascular resistance.
6.Preliminary study on RC membrane permeability and mechanism of seven traditional Chinese medicine alkaloids such as berberine.
Li XU ; Yi-Qun LI ; Wei-Wei YAO ; Hua-Xu ZHU ; Zhi-Shu TANG ; Wei-Hong XING ; Sha-Sha HUANG ; Jing PENG ; Bo LI ; Hong-Bo LIU ; Li-Wei GUO
China Journal of Chinese Materia Medica 2018;43(19):3876-3883
In order to analyze the law of membrane permeation of different alkaloids, seven traditional Chinese medicine alkaloids with different parent nucleus and substituent structures, including berberine, palmatine, sinomenine, matrine, oxymatrine, sophoridine, and tetrandrine, were prepared into the simulated solution with same molar concentration, and the membrane penetrating experiments with membrane RC1K and membrane RC5K were carried out. The dynamic transmittance, the total transmittance and the total adsorption rate of each substance were measured, and the scanning electron microscopy (SEM) images of the membrane surface before and after the membrane experiment were considered to predict and analyze the reason of differences in dynamic transmittance of different alkaloids. The results showed that there were significant differences in the dynamic transmittance of the chemical constituents of different alkaloids during penetrating the two membranes. The contamination degree on the surface of the membrane material was also different. The transmittance of the same compound through the RC5K membrane was larger than that through RC1K membrane. Within a certain range, the smaller the pore size of the membrane, the better the selective screening effect on the chemical constituents of traditional Chinese medicine. All the membrane surfaces were less polluted. The difference in transmittance between different substances on the same membrane showed a positive correlation with the difference in structural complexity, providing an experimental basis for the surface modification design in contamination control of membrane materials. In the design of membrane modified material, the surface properties of the membrane can be improved by grafting different polar groups, thereby changing the adsorption characteristics of the membrane surface. The pore size was designed accordingly to achieve the high transmittance and low pollution of the corresponding compounds.
Berberine Alkaloids
;
chemistry
;
Drugs, Chinese Herbal
;
chemistry
;
Medicine, Chinese Traditional
;
Permeability
7.The infection status of Leptospira in rodents on the Heixiazi island of Heilongjiang province, China,in 2011.
Zhen-dong WANG ; Sha-sha WANG ; Li-juan LIU ; Yu YANG ; Ming LI ; Tian-yu GUO ; Ying-qun FU ; Yong HOU ; Xiao-hong SUN ; Bao-liang XU ; Jing WANG
Chinese Journal of Preventive Medicine 2013;47(6):510-513
OBJECTIVETo study the infection status of Leptospira in rodents on Heixiazi island Heilongjiang province in 2011.
METHODSA total of 356 rodents were captured by night trap on the Heixiazi island from April to October 2011. The kidney tissue samples were collected by asepsis operation and the genomic DNA were extracted from them. Leptospira strains were confirmed by polymerase chain reaction(PCR) amplification of the 482 bp 23 S rDNA gene. Fifteen PCR products selected by the month were purified and sequenced by the methods of Sanger dideoxy, the sequences then compared with other Leptospira strains in Genebank, and phylogenetic analyses were drafted by software Mega 4.0.
RESULTSAmong 356 rodents, the dominant species were Clethrionomys rutilus (39.3%, 140/356) and Apodemus agrarius (36.0%, 128/356). The infection rate of Leptospira was 11.0%, with 39 rodent samples detected positive. All the rodent species were infected except for Rattus norvegicus. The infection rate was 9.4% (12/128) in Apodemus agrarius, 12.9%(18/140) in Clethrionomys rutilus, 10.8%(7/65) in Microtus fortis Buchner. No significant difference was found between the infection rate and the species of rodents by chi square test(χ(2) = 1.92, P > 0.05). Among months, the infection rate was 5.6% (4/72) in May, 8.8% (5/57) in June, 12.8% (5/39) in July, 9.8% (5/51) in August, 33.3% (11/33) in September, 22.5% (9/40) in October,but no infection in April. There was significant difference in infection in different months (χ(2) = 32.92, P < 0.05). All the Leptospira in rodents on the Heixiazi island were in the same phylogenetic branch with a high similarity of 97.1%-99.6%, close with the Australia strain U90865 by the similarity above 96.3%.
CONCLUSIONLeptospira is probably prevalent in rodents on the Heixiazi island, and the phylogene of the strains were similar. The infection rate in rodents was significantly different in months but not in hosts.
Animals ; China ; Leptospira ; isolation & purification ; Leptospirosis ; prevention & control ; Murinae ; microbiology ; Phylogeny ; Rats
8.CD16 expression is an independent prognostic factor for extranodal NK/T cell lymphoma of nasal type.
Zhuo ZUO ; Qun-pei YANG ; Yuan TANG ; Sha ZHAO ; Jian-bo YU ; Yan-mei LIU ; Li-min GAO ; Wei-ping LIU
Chinese Journal of Pathology 2013;42(4):227-233
OBJECTIVETo analyze the clinicopathologic features of extranodal NK/T cell lymphoma, nasal type (ENKTCL-N), to explore the expression of NK cell-associated receptors in ENKTCL-N and the relationship with prognosis, and to establish a prognostic model.
METHODSOne hundred and twenty-six cases of ENKTCL-N were selected from the files of the Department of Pathology, West China Hospital of Sichuan University. The relevant clinical and follow-up data were collected, and the histopathology was reviewed. All specimens were stained immunohistochemically for CD16, ICAM-1 and LFA-1. RT-PCR was used to detect the expression of CD94, NKG2 and KIR. The relationship between the prognosis of ENKTCL-N, clinical features, histopathological characteristics and expression of these markers were also analyzed.
RESULTSENKTCL-N mainly occurred in middle-age and young patients (median age, 41 years). The male to female ratio was 3.2:1. Sites more commonly involved were the nose and upper aerodigestive tract whereas those for the non-nasal type were the skin and gut. Only six cases involved two or more extranodal sites. Most (86.5%, 109/126) of the patients were in clinical stages I/II. The tumors showed predominately medium-sized tumor cells and large-sized tumor cells accounted for only 9.5% (12/126). Coagulative necrosis was present in all cases. The expression rates of CD56, CD16, CD94, LFA-1 and ICAM-1 were 82.6% (95/115), 15.1% (19/126), 55.4% (41/74), 40.5% (51/126) and 0, respectively. The expression rate of NKG2 receptor was 90.5% (67/74) overall. NKG2 receptor expression was independent of CD94. The overall expression rate of KIR receptor was 33.8% (25/74) and KIR receptor restriction was not detected in 20.8% (5/24) of the cases. Follow-up data was available in all patients, with median and average survival time being 15 months and 20.2 months, respectively. Survival analysis showed that prognostic factors included the gender, age, disease type, extranodal involvement, stage, the expression of CD16, LFA-1 and CD94. Cox's proportional hazard regression analysis revealed four factors, age, involved site, stage and CD16 expression, were independent prognostic factors.
CONCLUSIONSThe age, disease type, stage and CD16 expression are independent prognostic factors. Establishment of a prognostic model based on the above four factors can be more accurate in the prognostication of ENKTCL-N. The differences in the clinical features, prognosis, and expression of NK cell-associated receptors are obvious between nasal NK-cell lymphoma and non-nasal NK-cell lymphoma.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; CD56 Antigen ; metabolism ; Child ; Female ; Follow-Up Studies ; Humans ; Intercellular Adhesion Molecule-1 ; metabolism ; Lymphocyte Function-Associated Antigen-1 ; metabolism ; Lymphoma, Extranodal NK-T-Cell ; metabolism ; pathology ; Male ; Middle Aged ; NK Cell Lectin-Like Receptor Subfamily D ; metabolism ; Neoplasm Staging ; Nose Neoplasms ; metabolism ; pathology ; Prognosis ; Proportional Hazards Models ; Receptors, IgG ; metabolism ; Receptors, KIR ; metabolism ; Receptors, NK Cell Lectin-Like ; metabolism ; Survival Rate ; Young Adult
10.Langerhans cell histiocytosis: a clinicopathologic and immunohistochemical analysis of 258 cases.
Xia XU ; Wei-ping LIU ; Qun-pei YANG ; Wei-ya WANG ; Dian-ying LIAO ; Sha ZHAO ; Cheng-feng BI ; Li LIN ; Min MIN
Chinese Journal of Pathology 2012;41(2):91-96
OBJECTIVESTo observe the clinicopathologic features of Langerhans cell histiocytosis (LCH), and to evaluate the values of langerin, CD1a and S-100 protein expression in diagnosis of the tumor.
METHODSTotal 258 cases of Langerhans cell histiocytosis in the past 18 years (from 1992 to 2008) were collected, morphologic review and immunohistochemical staining were performed.
RESULTSIn all 258 cases, the ages of patients older than 16 years or younger than 2 years were 126 (48.8%) and 37 (14.3%), respectively, in the remaining 95 (36.8%) of the cases, the age of the patients ranged from 2 to 16 years. For all of 258 cases, there were 364 diseased sites. Bony lesions accounted for 77.2% (281 cases), especially the skull (112 cases, 39.9%), followed by lymph node (25 cases, 6.9%) and skin (14 cases, 3.8%). Clinically, unisystem or unifocal disease was predominant (201 cases, 77.9%), followed by unisystem and multifocal disease (21 cases, 8.1%), multi-system disease (26 cases, 10.1%), isolated pulmonary LCH (2 cases, 0.8%), and unclassified (8 cases, 3.1%). Histologically, variable number of Langerhans cells was present in 265 samples of 258 cases. Multinucleated giant cells were found in 166 (62.6%) of the samples. Eosinophils were the major infiltrating non-neoplastic cells, and eosinophilic abscess was seen in 57 cases (21.5%). Coagulative necrosis and dead bone were detected in 29 (10.9%) and 124 (46.8%) of the cases, respectively. Immunohistochemically, the expression of S-100 protein, CD1a and langerin was 99.1% (209/211), 100% (206/206) and 98.5% (193/196), respectively, and the sensitivity of them had no statistical difference.
CONCLUSIONSIn this group of LCH cases, the ratio of adult patients is high, but the proportion of multi-organ lesion is low. No significant difference of the sensitivity is found among langerin, CD1a and S-100 expression in diagnosis of LCH.
Adolescent ; Adult ; Antigens, CD ; metabolism ; Antigens, CD1 ; metabolism ; Child ; Child, Preschool ; Diagnosis, Differential ; Eosinophils ; pathology ; Female ; Follow-Up Studies ; Histiocytosis, Langerhans-Cell ; metabolism ; pathology ; surgery ; Humans ; Immunohistochemistry ; Infant ; Langerhans Cells ; pathology ; Lectins, C-Type ; metabolism ; Lymph Nodes ; pathology ; Male ; Mannose-Binding Lectins ; metabolism ; Middle Aged ; S100 Proteins ; metabolism ; Skin ; pathology ; Survival Rate ; Young Adult

Result Analysis
Print
Save
E-mail