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The MYC gene, one of the most common dysregulated driver genes in human cancers, is composed of three paralogous genes C-MYC, N-MYC and L-MYC. It is abnormally activated in more than half of cancer types. Since MYC plays an important role in the formation, maintenance and progression of cancer, targeting MYC is an effective strategy for cancer treatment. As a potential anti-cancer target, MYC is considered "undruggable" because it lacks a suitable pocket for accommodating small molecule inhibitors. Recently, under the guidance of protein structure information and many computational tools, many indirect strategies to inhibit MYC have emerged and shown favorable anti-cancer effects in tumor models. In this paper, the recent small molecules that indirectly target MYC are divided into inhibitors acting on the protein-protein interaction (PPI) among MYC and other proteins, and targeting inhibitors regulating MYC action. Additionally, the introduction and assessment towards compounds with different mechanisms are summarized to provide reference for the further research of MYC inhibitors.
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In the past 37 years, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has undergone various major transmission routes in China, with the world most complex co-circulating HIV-1 subtypes, even the prevalence is still low. In response to the first epidemic outbreak of HIV in injecting drug users and the second one by illegal commercial blood collection, China issued the Anti-Drug Law and launched the Blood Donation Act and nationwide nucleic acid testing, which has avoided 98,232 to 211,200 estimated infections and almost ended the blood product-related infection. China has been providing free antiretroviral therapy (ART) since 2003, which covered >80% of the identified patients and achieved a viral suppression rate of 91%. To bend the curve of increasing the disease burden of HIV and finally end the epidemic, China should consider constraining HIV spread through sexual transmission, narrowing the gaps in identifying HIV cases, and the long-term effectiveness and safety of ART in the future.
Subject(s)
Humans , Acquired Immunodeficiency Syndrome/prevention & control , China/epidemiology , Disease Outbreaks , HIV Infections/prevention & control , PrevalenceABSTRACT
BACKGROUND@#Human immunodeficiency virus (HIV) prevalence among student men who have sex with men (MSM) in college is more than 5.0% and keeps on increasing in China. This study aims to clarify the proportion of HIV recent infection, its propeller and the source among college student MSM.@*METHODS@#We conducted a multicenter cross-sectional study in seven major Chinese cities during 2012-2013. HIV recent infections (≤ 168 days) and incidence was measured and estimated by BED HIV-1 capture enzyme immunoassay (BED-CEIA) testing strategy. HIV-related behaviors and transmitted drug resistance (TDR) were investigated and compared between the college student MSM, <25-year-old non-student youth MSM (NSYM), and ≥25-year-old non-student non-youth MSM (NSNYM), using structured survey, and analyses of drug resistance.@*RESULTS@#Overall, 4,496 (4496/4526, 99.3%) were eligible for enrollment, comprising 565 college student MSM, 1,094 NSYM, and 2,837 NSNYM. The proportion of HIV recent infection were 70.3% (26/37), 50.8% (65/128) and 35.1% (95/271), the HIV incidence rate were 10.0 (95% CI: 6.2-13.9)/100PY, 12.9 (95% CI: 9.8-16.1)/100PY, 6.8 (95% CI: 5.4-8.2)/100PY, and TDR prevalence were 7.4% (2/27), 2.0%, (2/98) and 4.9% (11/226), among student MSM, NSYM, and NSNYM, respectively. Among HIV positive student MSM with age< 21-year-old, the proportion of HIV recent infection is 90.9% (10/11). Factors independently associated with HIV recent infection in student MSM was usage of recreational drug in the past 6 months (AOR: 2.5; 95% CI: 1.0-5.8).@*CONCLUSIONS@#College student MSM had higher proportion of HIV recent infection and TDR than the youth and older MSM in China during 2012-2013. The HIV infections were more likely to happen during the early year of college life among student MSM.
Subject(s)
Adolescent , Adult , Aged , Humans , Male , Young Adult , China/epidemiology , Cities , Cross-Sectional Studies , Drug Resistance , HIV Infections/epidemiology , Homosexuality, Male , Incidence , Prevalence , Risk Factors , Sexual Behavior , Sexual and Gender Minorities , StudentsABSTRACT
Evodiamine is the natural component extracted from Euodiae Fructus.Recently,growing evidence has proved that evodiamine has great effects on suppressing cell viability and proliferation,arresting cell cycle,inducing apoptosis,promoting autophagy,inhibiting the formation of microvascular angiogenesis as well as affecting epigenetic modification in cancer.Recent studies have continuously revealed related signal pathways involved in evodiamine such as PI3K-Akt and JAK-STAT pathways,as well as the impact of evodiamine on survivin,vascular endothelial growth factor and miRNAs.With the development and synthesis of evodiamine derivatives and related herbal formulations,the understanding of antitumor activity of evodiamine is gradually deepening.The important clinical significance and market value of evodiamine can be prospected.
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AIM:To investigate the effect of reactive oxygen species(ROS)on the apoptosis of HepG2 cells induced by artesunate.METHODS:The effect of artesunate on the viability of HepG 2 cells was measured by MTT assay. The morphological changes of the apoptotic cells were observed by the method of Hoechst 33258 fluorescence staining.The apoptosis of HepG2 cells was analyzed by flow cytometry.DCFH-DA was used to detect the changes of ROS generation dur-ing the process of apoptosis.The protein levels of Bax ,Bcl-2,cleaved caspase-3 and cytochrome C(Cyt C)were deter-mined by Western blot.HepG2 cells were pretreated with apocynin and then Western blot was used to detect the expression of p47phox and p22phox,and ROS changes were analyzed by flow cytometry.RESULTS:Compare with control group,the cell viability was obviously inhibited after treatment with artesunate for 24 h(P<0.05).The nuclei were densely stained ,and the proportion of apoptotic cells was increased(P<0.05).ROS was increased significantly(P<0.05).The results of Western blot demonstrated that the expression level of Bax was increased ,Bcl-2 was decreased ,the ratio of Bax/Bcl-2 was increased ,and the protein levels of cleaved caspase-3 and Cyt C were increased.Pretreatment with apocynin reduced the expression of p47phox and p22phox and the generation of ROS in the artesunate treatment group.CONCLUSION:Artesu-nate induces the apoptosis of HepG 2 cells.The possible mechanism may be related to the increase in the generation of ROS.
ABSTRACT
Evodiamine is the natural component extracted from Euodiae Fructus. Recently, growing evidence has proved that evodiamine has great effects on suppressing cell viability and proliferation, arresting cell cycle, inducing apoptosis, promoting autophagy, inhibiting the formation of microvascular angiogenesis as well as affecting epigenetic modification in cancer. Recent studies have continuously revealed related signal pathways involved in evodiamine such as PI3K-Akt and JAK-STAT pathways, as well as the impact of evodiamine on survivin, vascular endothelial growth factor and miRNAs. With the development and synthesis of evodiamine derivatives and related herbal formulations, the understanding of antitumor activity of evodiamine is gradually deepening. The important clinical significance and market value of evodiamine can be prospected.
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<p><b>OBJECTIVE</b>To explore the protection of high intensity microwave radiation on hypothalamo-pituitary-adrenal axis (HPAA) activity and hippocampal CA1 structure in rats and the protectiveeffect of Qindan Granule (QG) on radiation injured rats.</p><p><b>METHODS</b>Totally 48 Wistar rats were randomlydivided into 8 groups, i.e., the normal control group, post-radiation day 1, 7, and 10 groups, 7 and 10days prevention groups, day 7 and 10 treatment groups, 6 in each group. Rats in prevention groups wererespectively administered with QG liquid (1 mL/100 g, 4. 75 g crude drugs) for 7 days and 10 days bygastrogavage and then microwave radiation. Then preventive effect for radiation injury was statisticallycalculated with the normal control group and the post-radiation day 1 group. Rats in treatment groupswere firstly irradiated, and then administered with QG liquid (1 mL/100 g, 4.75 g crude drugs). Finally preventive effect for radiation injury was statistically calculated with the normal control group, post-radiation day 7 and 10 groups. Contents of corticotrophin releasing hormone (CRH), beta endorphin (beta-EP), adrenocorticotropic hormone (ACTH), and heat shock protein 70 (HSP70) were detected. Morphological changes and structure of hippocampal CA1 region were observed under light microscope.</p><p><b>RESULTS</b>Compared with the normal control group, contents of CRH and beta-EP significantly decreased in each radiation group. Serum contents of ACTH and beta-EP significantly increased in post-radiation day 1 and 7 groups (P < 0.05). Compared with radiation groups, beta-EP content in serum and pituitary significantly increased, and serum ACTH content significantly decreased in prevention groups (P < 0.05). Pituitary contents of CRH and beta-EP significantly increased in prevention groups. Serum contents of ACTH, beta-EP, and HSP70 were significantly lower in day 7 treatment group than post-radiation day 7 group (P < 0.05). Morphological results showed that pyramidal neurons in the hippocampal CA1 region arranged in disorder, with swollen cells, shrunken and condensed nucleus, dark dyeing cytoplasm, unclear structure. Vessels in partial regions were dilated with static blood; tissues were swollen and sparse. In prevention and treatment groups pathological damage of hippocampal CA1 region was obviously attenuated; neurons were arranged more regularly; swollen, pycnotic, or deleted neuron number were decreased; vascular dilatation and congestion was lessened.</p><p><b>CONCLUSION</b>QG could affect HPAA function and activity of high intensity microwave radiated rats, showing certain preventive and therapeutic effects of microwave radiated rats by adjusting synthesis and release of partial bioactive peptides and hormones in HPAA, improving pathological injury in hippocampal CA1 region.</p>
Subject(s)
Animals , Rats , Adrenocorticotropic Hormone , Blood , CA1 Region, Hippocampal , Pathology , Radiation Effects , Corticotropin-Releasing Hormone , Metabolism , Drugs, Chinese Herbal , Pharmacology , HSP70 Heat-Shock Proteins , Blood , Hypothalamo-Hypophyseal System , Radiation Effects , Microwaves , Pituitary-Adrenal System , Radiation Effects , Random Allocation , Rats, Wistar , beta-Endorphin , Blood , MetabolismABSTRACT
<p><b>OBJECTIVE</b>The aim of this study was to understand the rates of infection and spontaneous clearance on hepatitis C virus (HCV) among HIV-infected men who have sex with men (MSM) in China.</p><p><b>METHODS</b>HIV-infected MSM from Shenyang, Beijing, Changsha and Kunming were selected to take the HCV antibody and HVC-RNA tests, and then classified into 'under recovery (RNA-/Ab+) ' or being chronic (RNA+/Ab+). Information on demography, CD4(+) T cell, HIV viral load and liver biochemical indicators were also collected.</p><p><b>RESULTS</b>In 513 HIV-infected MSM, the positive rate of HCV antibody was 1.94% (10/513) and the positive rate of HVC-RNA was 0.77% (4/513). Five patients showed clearance of HVC-RNA, spontaneously. These 5 patients had low levels of both alanine transaminase (ALT) and aspartate aminotransferase (AST), and with high level of CD4(+) T cells, when compared to those who were not able to clear the HVC-RNA.</p><p><b>CONCLUSION</b>Currently, the HCV infection rate was still at quite low level among the HIV-infected MSM in China. Dynamic of HIV/HCV co-infection should be monitored so as to develop suitable strategy on prevention and treatment among this population, in China.</p>
Subject(s)
Adult , Humans , Male , Young Adult , China , Epidemiology , Coinfection , Epidemiology , Virology , HIV Seropositivity , HIV-1 , Hepacivirus , Hepatitis C , Epidemiology , Virology , Homosexuality, Male , RNA, Viral , Blood , Remission, Spontaneous , Viral LoadABSTRACT
AIM:To explore the potentially beneficial clinical effects of traditional Chinese medicine(TCM) combined with photocoagulation for diabetic retinopathy(DR).METHODS:Chinese patients with DR were divided into two groups. A joint treatment group received both the TCM ziyinliangxuesanyutang and photocoagulation, while a control group received only photocoagulation laser treatment. Visual acuity tests, visual field retinal sensitivity tests, and fundus fluorescein angiography (to measure neovascular regression) were performed. Vision was compared between the two groups 1 month, 6, and 12 months after treatment.RESULTS:Twelve months after treatment, the recovery of visual acuity (62.3% vs 43.1%, P=0.037) and retinal sensitivity \[17.0±3.7 decibels (dB) vs 14.9±3.7dB, P=0.002\] as well as neovascular regression (67.2% vs 48.3%, P=0.036) in the joint treatment group were all significantly greater than that of the control group.CONCLUSION:Compared with laser treatment alone, the joint application of TCM and photocoagulation is shown to be more effective than DR treatment method.
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<p><b>OBJECTIVES</b>To investigate the prevalence of celiac disease in children with chronic diarrhea in China.</p><p><b>METHODS</b>Inpatients of the pediatric hospitals in Shanghai, Jinan, Wuhan and Chengdu who were diagnosed as chronic diarrhea were recruited from Jan. 2005 to Dec. 2008. Their clinical history, physical examination and laboratory data were collected. The SPSS version 11.5 statistical package for Microsoft Windows was used for statistical analysis.</p><p><b>RESULTS</b>Data of 199 patients and finally enrolled 118 hospitalized chronic diarrhea inpatients during the observation period were collected and 14 (12%) of the chronic diarrhea patients were suspected as having celiac disease and in one the diagnosis of celiac disease was confirmed. Gluten-free diet (GFD) treatment was effective. M/F: 12/2, the age ranged from 6 months to 12 years; 43% (6/14) had malnutrition, 29% (4/14) had anemia, villous atrophy was found in 4 patients by endoscopy. Duodenal biopsies revealed stage I in 1, stage II in 2, stage IIIa in 7, stage IIIb in 3 and stage IIIc in 1 patient according to the modified Marsh classification.</p><p><b>CONCLUSION</b>This study was the first time to report the research of celiac disease in children with chronic diarrhea in China. The percentage of suspicious celiac disease patients was 12% (14/118) in children and one was confirmed. CD exists in China. Chinese pediatricians should pay attention to the disease.</p>
Subject(s)
Adolescent , Child , Female , Humans , Infant , Male , Celiac Disease , Epidemiology , Pathology , China , Epidemiology , Diarrhea , Epidemiology , Pathology , Duodenum , Pathology , Endoscopy, Digestive System , Intestinal Mucosa , Pathology , PrevalenceABSTRACT
<p><b>OBJECTIVE</b>To estimate human immunodeficiency virus (HIV)/sexually transmitted diseases (STDs) related knowledge, the prevalence and risk factors for HIV/STDs among tin miners in Gejiu, Yunnan Province.</p><p><b>METHODS</b>A cross-sectional study was conducted in tin miners working at 5 mining regions from March to June 2006 in Gejiu City, Yunnan Province. A total of 1796 miners were enrolled in the study, and a standardized questionnaire was administered probing socio-demographic factors, knowledge of HIV/STDs and sexual behavior. 7 ml-volume venous blood and 15 ml urine specimens were collected for HIV/STDs testing.</p><p><b>RESULTS</b>Twelve participants [0.7%] (12/1760) were identified HIV positive. While, the positive proportions for syphilis, herpes simplex virus type-2 (HSV-2), Neisseria gonorrhea and Chlamydia trachoma were 1.8% (31/1760), 9.6% (169/1760), 0.8% (14/1773), 4.8% (85/1773), respectively. The total prevalence of STDs was 14.9% (264/1776). Factors associated with HIV infection were illegal drug use (adjusted OR = 17.8; 95% CI: 4.0 - 78.8), frequencies of visiting female sex workers in the past twelve months (adjusted OR = 8.7; 95% CI: 1.9 - 39.0), tattoos (adjusted OR = 6.6; 95% CI: 1.8 - 24.0), surgical operation experiences (adjusted OR = 6.0; 95% CI: 1.6 - 22.5) and toothbrush sharing (adjusted OR = 5.6; 95% CI: 1.0 - 31.3). Factors associated with STDs infection were race (adjusted OR = 2.0; 95% CI: 1.5 - 2.7), age (adjusted OR = 1.7; 95% CI: 1.0 - 2.9), illegal drug use (adjusted OR = 2.3; 95% CI: 1.0 - 5.2), living with spouses (adjusted OR = 1.4; 95% CI: 1.1 - 1.9) and visiting female sex workers (adjusted OR = 1.9; 95% CI: 1.4 - 2.6). Only 4.1% (49/1201) of respondents aware the correct transmission routes of HIV. 21.6% (339/1569) of the miners who had previous sexual experience self-reported visiting female sex workers.</p><p><b>CONCLUSION</b>HIV and other STDs are highly prevalent amongst miners in this region. In addition, the awareness of HIV/STDs is low and multiple routes of HIV transmission, such as heterosexual intercourse and IDU, were also observed in these study subject. HIV/STDs interventions should therefore be reinforced among the miners in this region.</p>
Subject(s)
Adolescent , Adult , Humans , Male , Middle Aged , Acquired Immunodeficiency Syndrome , Epidemiology , China , Epidemiology , Cross-Sectional Studies , Health Knowledge, Attitudes, Practice , Mining , Risk Factors , Sexual Behavior , Sexually Transmitted Diseases , Epidemiology , TinABSTRACT
<p><b>OBJECTIVE</b>To explore the epidemic characteristics of vaginal douching, human immunodeficiency virus (HIV) and other sexually transmitted diseases(STD) among female sex workers (FSWs) in Yunnan province.</p><p><b>METHODS</b>FSWs were recruited to be investigated on their demographic data, drug abuse and sexual behavior, HIV/AIDS knowledge and procreation health status. Venous blood were collected to test for HIV, herpes simplex virus 2 (HSV-2) and syphilis while urine specimen was for morphine, cervical secretion for Gonorrhoea and Chlamydia trachomatis, and vaginal secretion for Trichomonas.</p><p><b>RESULTS</b>A total number of 833 blood specimen were collected, in which 84 specimen were confirmed to be HIV positive with a prevalence rate of 10.1%. The prevalence rates of syphilis and HSV-2 were 8.2% and 68.4% respectively. 832 vaginal and cervical secretion specimen were collected with the prevalence rates of Gonorrhoea, Chlamydia trachomatis and Trichomonas were 11.5%, 28.2% and 11.9% respectively. In multivariate logistic analysis, the factors associated with vaginal douching were: being Han nationality, locations of sex work at middle/high level, ever heard of HIV/AIDS, emerged hypogastric pain last year, the number of sex work location > or =4.</p><p><b>CONCLUSION</b>Vaginal douching was shown a risk factor for HIV and some STD.</p>
Subject(s)
Adolescent , Adult , Female , Humans , Middle Aged , Young Adult , China , Epidemiology , Chlamydia Infections , Epidemiology , Gonorrhea , Epidemiology , HIV Infections , Epidemiology , Herpes Genitalis , Epidemiology , Sex Work , Sexually Transmitted Diseases , Epidemiology , Syphilis , Epidemiology , Vaginal DouchingABSTRACT
ATR-Fc is a fusion protein consisting of extracellular domain of human anthrax toxin receptor (ATR) and a fragment (hinge, CH2, and CH3 domains) of the Fc of human IgG1. The aim of ATR-Fc expression is to get an antibody-like molecule binding to protective antigen (PA), a component of anthrax toxins, this fusion protein may compete with cell surface receptor for PA binding, and block the transport of lethal factor (LF) and edema factor (EF) into cells, thereby act as an antitoxin to prevent and treat anthrax infection. A DNA fragment encoding N-terminal amino acids 1-227 of ATR and human IgG1 Fc was inserted into the Hind III and Not I sites of pcDNA3.1 to generate the eukaryotic vector pcDNA3.1/ATR-Fc for expression of ATR-Fc fusion protein. Using lipofectine-mediated gene transfer technique, pcDNA3.1/ATR-Fc was transfected into CHO-K1 cells. After selected with G418, a recombinant CHO cell line, ATR-Fc-1D5, whose expression level was about 10 - 15 microg/(10(6) cells x d), was established. The recombinant protein expressed by the ATR-Fc-1D5 cells was purified with protein A chromatography. The experimental results demonstrated a direct and specific interaction between ATR-Fc and PA assessed by ELISA.
Subject(s)
Animals , Cricetinae , Humans , CHO Cells , Cricetulus , Gene Transfer Techniques , Genetic Vectors , Immunoglobulin Fc Fragments , Genetics , Immunoglobulin G , Genetics , Neoplasm Proteins , Genetics , Receptors, Cell Surface , Genetics , Recombinant Fusion Proteins , Genetics , Allergy and ImmunologyABSTRACT
An expression plasmid carrying anthrax protective antigen (PA) gene was constructed, which has an OmpA signal sequence attached to the 5' end of PA gene. The plasmid was transformed into E. coli and induced to express recombinant PA (rPA) . The recombinant protein, about 10% of the total bacterial protein in volume, was secreted to the periplasmic space of the cell. After a purification procedure including ion-exchange, hydrophobic interaction chromatography, and gel filtration, about 15 mg of 95 % pure rPA was obtained from 1-liter culture. The bioactivity of rPA was proved by in vitro cytotoxicity assay. The polyclonal antiserum from rabbits immunized with rPA could inhibit the action of anthrax lethal toxin in vitro, which suggests that antibodies against rPA can provide high passive protection against anthrax. The results reported here may be helpful to develop a safe and efficacious recombinant PA vaccine against anthrax.
Subject(s)
Animals , Mice , Rabbits , Amino Acid Sequence , Anthrax Vaccines , Allergy and Immunology , Antigens, Bacterial , Chemistry , Genetics , Allergy and Immunology , Toxicity , Bacterial Toxins , Chemistry , Genetics , Allergy and Immunology , Toxicity , Base Sequence , Molecular Sequence Data , Plasmids , Recombinant Proteins , Allergy and Immunology , Vaccines, Synthetic , Allergy and ImmunologyABSTRACT
Bacillus anthracis collagen-like protein(BclA) is a structural component of the exosporium filaments,as well as the immunodominant antigen on the spore surface.The genes encoding BclA proteins were cloned and sequenced from three Bacillus anthracis strains separated from China.It was founded that the BclA proteins of strain A16R and 40048,containing 388 and 322 amino acids,72 and 50 copies of GXX repeat,5 and 3 copies of 21-amino-acid sequence(GPT)_(5)GDTGTT(BclA repeat) respectively,are different from those reported by foreign scholars;while the BclA protein of strain 40022,containing 370 amino acids,66 copies of GXX repeat,and 5 copies of BclA repeat,is identical with that of strain 53169 reported by others.The results are helpful for the molecular typing of B.anthracis strains,and provide a basis for the elucidation of the pathogenesis and immunogenicity of B.anthracis spore.