Blockade of the Dopamine D3 Receptor Attenuates Opioids-Induced Addictive Behaviours Associated with Inhibiting the Mesolimbic Dopamine System / 神经科学通报·英文版

Opioid use disorder (OUD) has become a considerable global public health challenge; however, potential medications for the management of OUD that are effective, safe, and nonaddictive are not available. Accumulating preclinical evidence indicates that antagonists of the dopamine D3 receptor (D3R) have effects on addiction in different animal models. We have previously reported that YQA14, a D3R antagonist, exhibits very high affinity and selectivity for D3Rs over D2Rs, and is able to inhibit cocaine- or methamphetamine-induced reinforcement and reinstatement in self-administration tests. In the present study, our results illustrated that YQA14 dose-dependently reduced infusions under the fixed-ratio 2 procedure and lowered the breakpoint under the progressive-ratio procedure in heroin self-administered rats, also attenuated heroin-induced reinstatement of drug-seeking behavior. On the other hand, YQA14 not only reduced morphine-induced expression of conditioned place preference but also facilitated the extinguishing process in mice. Moreover, we elucidated that YQA14 attenuated opioid-induced reward or reinforcement mainly by inhibiting morphine-induced up-regulation of dopaminergic neuron activity in the ventral tegmental area and decreasing dopamine release in the nucleus accumbens with a fiber photometry recording system. These findings suggest that D3R might play a very important role in opioid addiction, and YQA14 may have pharmacotherapeutic potential in attenuating opioid-induced addictive behaviors dependent on the dopamine system.

Progress in research of prophylactic therapy in contacts of rifampicin-resistant tuberculosis patients / 中华流行病学杂志

Tuberculosis (TB) prophylactic therapy for latent infection, which can reduce the risk for the development of active TB, is an important measure in TB control. China recommends prophylactic therapy for latent tuberculosis infection (LTBI) in some key populations to reduce the risk for TB. Contacts of patients with multi-drug and rifampicin-resistant TB (MDR/RR-TB) are at high risk for the infection with drug-resistant pathogen, however, no unified prophylactic therapy regimen has been recommended for LTBI due to exposure to MDR/RR-TB patients. This paper summarizes the current MDR/RR-TB prophylactic therapy regimen and its protection effect based on the results of the retrieval of literature, guidelines, expert consensus and technical specifications to provide reference for the prevention and control of LTBI.

Effect of Main Component of Realgar Arsenic Disulfide （As2S2） on DNA Methylation of SKM-1 Cells with Myelodysplastic Syndrome / 中国实验方剂学杂志

ObjectiveTo explore the effects of the main component of Realgar arsenic disulfide （As2S2） on DNA methylation of SKM-1 cells with myelodysplastic syndrome. MethodCell Counting Kit-8 （CCK-8） was used to detect the inhibitory effect of As2S2（0， 1， 2， 4， 8， 16 μmol·L-1）on SKM-1 cells. Propidium iodide （PI） staining was applied to detect the effect of As2S2（0， 1， 2， 4 μmol·L-1）on the SKM-1 cell cycle. The effect of As2S2 （0， 4 μmol·L-1） on the methylation of SKM-1 cells on a genome-wide scale was observed by using Human Methylation 850K BeadChip， followed by Kyoto Encyclopedia of Genes and Genomes （KEGG） and gene ontology （GO） analyses. According to the microarray data， the antioncogene TUSC3 was selected， and real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were adopted to investigate the effect of As2S2 （0， 1， 2， 4 μmol·L-1） on the mRNA and protein expression of TUSC3， respectively. ResultCompared with the conditions in the blank group， As2S2 inhibited SKM-1 cells， increased the proportion of cells in the G0/G1 phase， and decreased the proportion of cells in the S phase（P<0.05）. The 850K microarray showed that 4 μmol·L-1 As2S2 could significantly induce DNA methylation in SKM-1 cells， with 12 710 differentially methylated genes involved （50% hypermethylated and 50% hypomethylated genes）. KEGG and GO analyses showed that differentially methylated genes were involved in many important biological functions and signaling pathways， including purine metabolism， natural killer cell-mediated cytotoxicity， endocytosis， chemokine signaling pathway， and nuclear ubiquitin ligase complex. In terms of downstream gene expression， Real-time PCR and Western blot showed that As2S2 increased the expression of TUSC3， as compared with the conditions in the blank group （P<0.05）. ConclusionAs2S2， the main component of Realgar， has a significant regulatory effect on the methylation of SKM-1 cells， which is presumedly achieved by increasing the expression of TUSC3.

Deguelin inhibits proliferation and regulates the expression of MCM3-CDC45 in MCF-7 and H1299 cells in vitro / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the effects of deguelin on the proliferation of breast cancer MCF-7 cells and lung cancer H1299 cells in vitro and the expression of minichromosome maintenance protein 3 (MCM3) and CDC45 in the cells.</p><p><b>METHODS</b>MTT assay was used to evaluate the proliferation of MCF-7 and H1299 cells exposed to different concentrations of deguelin for 48, 72 or 96 h. The growth of the cells was observed microscopically and the changes of MCM3 and CDC45 expressions in MCF-7 and H1299 cells following deguelin treatment were detected with fluorescence quantitative PCR.</p><p><b>RESULTS</b>The proliferation of MCF-7 cells was significantly inhibited by exposure to 0.25, 0.5, 1, 5, 10, 30, and 50 µmol/L deguelin for 48, 72, and 96 h in a concentration- and time-dependent manner. In MCF-7 cells, the ICof deguelin at 48, 72, and 96 h was 9, 3, and 2 µmol/L, respectively. Deguelin treatments of H1299 cells at 0.5, 1, 5, 10, 30, 50, and 100 µmol/L also resulted in a concentration- and time-dependent inhibition of the cell growth with an ICat 96 h of 2 µmol/L. Optical microscopy of the cells revealed a decreased number of viable cells with obvious cell shrinkage following deguelin treatments. The expression of MCM3 and CDC45 were significantly reduced in the cells after deguelin treatments.</p><p><b>CONCLUSION</b>Deguelin can inhibit the proliferation of MCF-7 and H1299 cells in vitro and down-regulate the expression of MCM3 and CDC45 in the cells.</p>

Differences in Liver Injury and Trophoblastic Mitochondrial Damage in Different Preeclampsia-like Mouse Models / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Preeclampsia is a multifactorial disease during pregnancy. Dysregulated lipid metabolism may be related to some preeclampsia. We investigated the relationship between triglycerides (TGs) and liver injury in different preeclampsia-like mouse models and their potential common pathways.</p><p><b>METHODS</b>Preeclampsia-like models (Nw-nitro-L-arginine-methyl ester [L-NAME], lipopolysaccharide [LPS], apolipoprotein C-III [Apo] transgnic mice + L-NAME, β2 glycoprotein I [βGPI]) were used in four experimental groups: L-NAME (LN), LPS, Apo-LN and βGPI, respectively, and controls received saline (LN-C, LPS-C, Apo-C, βGPI-C). The first three models were established in preimplantation (PI), early-, mid- and late-gestation (EG, MG and LG). βGPI and controls were injected before implantation. Mean arterial pressure (MAP), 24-hour urine protein, placental and fetal weight, serum TGs, total cholesterol (TC) and pathologic liver and trophocyte changes were assessed.</p><p><b>RESULTS</b>MAP and proteinuria were significantly increased in the experimental groups. Placenta and fetal weight in PI, EP and MP subgroups were significantly lower than LP. Serum TGs significantly increased in most groups but controls. TC was not different between experimental and control groups. Spotty hepatic cell necrosis was observed in PI, EG, MG in LN, Apo-LN and βGPI, but no morphologic changes were observed in the LPS group. Similar trophoblastic mitochondrial damage was observed in every experimental group.</p><p><b>CONCLUSIONS</b>Earlier preeclampsia onset causes a higher MAP and urine protein level, and more severe placental and fetal damage. Preeclampsia-like models generated by varied means lead to different changes in lipid metabolism and associated with liver injury. Trophoblastic mitochondrial damage may be the common terminal pathway in different preeclampsia-like models.</p>