Design of small molecules targeting molecular chaperone system: review and perspective / 药学学报

Molecular chaperone system, which mainly consist of heat shock proteins family and their cochaperones, is crucial for maintaining proteostasis in life. It assists in folding, maturation and ubiquitin-proteasome-mediated degradation of proteins, thus to play a key role in cell proliferation and apoptosis. Functional disorder of molecular chaperone system is highly relevant to occurrence and development of multiple diseases including cancers, autoimmune disease/inflammatory, infective diseases, neurodegenerative disease, etc. Therefore, molecular chaperone system has long been regarded as potential drug targets. In this review, we outline the progress in the design of small molecules targeting molecular chaperone system and analyze the features of small molecules with different mechanisms. Finally, we put forward expects about potential development directions for future drug design in this field.

The public health human resource of CDCs in Zhejiang Provincefrom 2016 to 2020 / 预防医学

Objective@#To investigate the development of public health human resource of the Centers for Disease Control and Prevention (CDCs) in Zhejiang Province from 2016 to 2020, so as to put forward the strategies for the talent team construction of CDCs.@*Methods@#The general information of personnel of CDCs in Zhejiang Province from 2016 to 2020 was collected through China Information System for Disease Control and Prevention. A questionnaire survey and a qualitative interview were conducted to collect the data of staffing, talent training, salary and employee turnover, and to analyze the development of the talent team of CDCs. @*Results@#By 2020, there were 105 CDCs, including 1 provincial, 11 prefectural and 93 county-level CDCs, and 5 277 staff on-the-job. From 2016 to 2020, the number of staff per 10 000 permanent residents in the province, prefecture and county levels were 0.062-0.070, 0.170-0.188 and 0.585-0.604, respectively, which did not meet the standard for the personnel establishment in Zhejiang CDCs; the proportion of the staff with bachelor degree or above increased from 90.05% to 94.25%; the proportion of the health professionals decreased from 82.91% to 80.01%; the proportion of the staff with senior professional titles increased from 35.20% to 45.25%. The results of the qualitative interview indicated a lack of health professionals and high-end talents, a gap between the approved staffing and post requirements, as well as demands for a stable team and higher pay. @*Conclusion@#From 2016 to 2020, the structure of educational background, major and professional title among the on-the-job staff of CDCs in Zhejiang Province has been improving; however, the total allocation of human resource is insufficient, and the stability and treatment of staff need to be further improved.

miR-1297 promotes malignant biological behaviors of breast cancer MCF-7 cells by down-regulating TET3 / 中国肿瘤生物治疗杂志

@# Objective: To investigate the regulatory effect of miR-1297 on the malignant biological behaviors of breast cancer cells and its underlying mechanism. Methods: Twenty pairs of breast cancer tissues and para-cancer tissues resected at the Department of Thyroid and Breast Surgery of Leshan People′ s Hospital from May 2016 to May 2018, as well as breast cancer cell lines MCF-7, SW626, HCC1937 and human breast epithelial MCF-10A cells were collected for this study. qPCR was performed to evaluate the expression of miR-1297 in breast cancer tissues and cell lines. The experimental cells were divided into control group, miR-1297 inhibitor group; TET3 over-expression group and simultaneous over-expression of TET3 and miR-1297 group. CCK-8 assay was used to detect the cell proliferation of MCF-7 cells; Transwell assay was carried out to detect the migration and invasion of MCF-7 cells; and WB was used to measure the expressions of TET3 and EMT related proteins (E-cadherin, N-cadherin and vimentin). Dual luciferase reporter gene assay was used to verify the relationship between miR-1297 and TET3. Results: miR-1297 was up-regulated in both breast cancer tissues and cell lines (P<0.01 or P<0.05). Knockdown of miR-1297 dramatically repressed the proliferation, migration, invasion and EMT of MCF-7 cells (P<0.01 or P<0.05). Over-expression of TET3 significantly up-regulated the expression of TET3 in MCF-7 cells (P<0.05). Simultaneous over-expression of TET3 and miR-1297 could reverse the expression level of TET3 in MCF-7 cells and the inhibitory effect of TET3 on the proliferation, migration, invasion and EMT of MCF-7 cells. Dual luciferase reporter gene assay results showed that miR-1297 targetedly bound to the 3' UTR of TET3. Further experiment results demonstrated that miR-1297 targetedly down-regulated TET3 and promoted the malignant biological behaviors of MCF-7 cells. Conclusion: miR-1297 is up-regulated in breast cancer tissues and cells; it promotes the malignant biological behaviors such as proliferation, migration, invasion and EMT through targetedly down-regulating the expression of TET3.

Diagnostic value of single and combined measurement of serum hs-CRP,Cys-C, andβ2-MG in diabetic nephropathy of early stage / 国际检验医学杂志

Objective To evaluate the diagostic value of hypersensitive C-reactive protein(hs-CRP),β2-microglobulin(β2-MG) and cystatin C(Cys-C)tests in diabetic nephropathy(DN)of early stage.Methods The turbidimetric immunoassay was adopted to determine serum hs-CRP,β2-MG and Cys-C concentrations in type 2 diabetic patients,including 100 cases with DN of early stage (DN group),50 cases without DN(NDN group)and 100 cases healthy controls(control group).Results Serum hs-CRP,β2-MG and Cys-C concentrations in DN group were significantly higher than that in control group and NDN group(P <0.05).Conclusion Hs-CRP,β2-MG and Cys C are sensitive indicators in the diagosis of DN.The combined determination of the three indicators im-proves the sensitivity of early DN diagnosis and is useful for monitoring the development of DN in early stage.

Oxidative damage to lung tissue and peripheral blood in endotracheal PM2.5-treated rats / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the oxidative damage to lung tissue and peripherial blood in PM2.5-treated rats.</p><p><b>METHODS</b>PM2.5 samples were collected using an auto-sampling instrument in summer and winter. Treated samples were endotracheally instilled into rats. Activity of reduced glutathione peroxidase (GSH-Px) and concentration of malondialdehyde (MDA) were used as oxidative damage biomarkers of lung tissue and peripheral blood detected with the biochemical method. DNA migration length (microm) and rate of tail were used as DNA damage biomarkers of lung tissue and peripheral blood detected with the biochemical method.</p><p><b>RESULTS</b>The activity of GSH-Px and the concentration of MDA in lung tissue significantly decreased after exposure to PM2.5 for 7-14 days. In peripheral blood, the concentration of MDA decreased, but the activity of GSH-Px increased 7 and 14 days after experiments. The two indicators had a dose-effect relation and similar changing tendency in lung tissue and peripheral blood. The DNA migration length (microm) and rate of tail in lung tissue and peripheral blood significantly increased 7 and 14 days after exposure to PM2.5. The two indicators had a dose-effect relation and similar changing tendency in lung tissue and peripheral blood.</p><p><b>CONCLUSION</b>PM2.5 has a definite oxidative effect on lung tissue and peripheral blood. The activity of GSH-Px and the concentration of MDA are valuable biomarkers of oxidative lung tissue damage induced by PM2.5. The DNA migration length (microm) and rate of tail are simple and valuable biomarkers of PM2.5-induced DNA damage in lung tissues and peripheral blood. The degree of DNA damage in peripheral blood can predict the degree of DNA damage in lung tissue.</p>

Effect of antimicrobial agents on the toll-like receptors and inflammatory cytokines in liver tissue of the alcohol-induced liver disease in rats with Vibrio vulnificus sepsis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Septicemia and inflammation-mediated septic shock caused by Vibrio vulnificus (VV) is strongly associated with chronic liver disease. This study examined the effects of antimicrobial therapy on expression of hepatic toll-like receptors and inflammatory cytokines in rats with alcohol-induced liver disease complicated by VV sepsis.</p><p><b>METHODS</b>Male Sprague-Dawley rats were assigned to the following treatment groups: normal control (N), alcoholic liver disease control (A), antimicrobial-treated alcoholic liver disease control (AA), alcoholic liver disease with VV sepsis (AV), and antimicrobial-treated alcoholic liver disease with VV sepsis (AVA). Alcohol-induced liver disease was observed in all groups except N. Expression of mRNAs encoding hepatic toll-like receptors 2 and 4, myeloid differentiation protein-2, tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6 and IL-10 was determined by RT-PCR.</p><p><b>RESULTS</b>mRNAs encoding toll-like receptors 2 and 4 and myeloid differentiation protein-2 were significantly up-regulated in group AV as compared to control groups at 2 - 24 hours of sepsis; peak expression occurred at 12 hours. These mRNAs were also up-regulated in group AVA but to lesser degrees than in group AV at comparable time post-infection. mRNAs encoding TNF-alpha, IL-1beta and IL-6 were significantly elevated in group AV as a function of infection. In group AVA as compared to AV, expression of TNF-alpha and IL-1beta mRNAs was lower at 12 - 24 hours post-infection and expression of IL-6 mRNA was lower at 24 hours post-infection. Compared with control groups, IL-10 mRNA expression in group AV was markedly higher at 12 - 24 hours of sepsis. Expression of IL-10 mRNA was lower in group AVA as compared to AV at 24 hours of sepsis.</p><p><b>CONCLUSIONS</b>Antimicrobial therapy reduces expression of toll-like receptors and cytokines in rats with alcohol-induced liver disease complicated by VV sepsis. Monitoring hepatic toll-like receptor and cytokine expression during antibiotic therapy may be valuable for determining the course of VV sepsis in subjects with liver disease.</p>

Multiplex reverse transcription-polymerase chain reaction for simultaneous screening of 29 chromosomal translocation in hematologic malignancies / 华中科技大学学报（医学）（英德文版）

Multiplex reverse transcription-polymerase chain reaction (M-RT-PCR) has been proved to possess great clinical potential for simultaneous screening of 29 chromosomal translocations in acute leukemia. To evaluate the clinical value of M-RT-PCR in hematologic malignancies, bone marrow samples from 90 patients with various hematologic malignancies, including 25 acute myelogenous leukemia (AML), 22 acute lymphoblastic leukemia (ALL), 27 chronic myelogenous leukemia (CML), 4 myeloproliferative diseases (MPD), 3 chronic lymphoblastic leukemia (CLL), 3 non-Hodgkin's lymphoma (NHL), 3 myelodysplastic syndrome (MDS), 2 multiple myeloma (MM) and 1 malignant histocytosis (MH) were subjected to both M-RT-PCR and chromosome karyotypic analysis. Some of cases were subjected to follow-up examination of M-RT-PCR during the period of clinical complete remission (CR) for detection of minimal residual leukemia. In our hand, 12 of 29 chromosomal translocation transcripts including TEL/PDGFR, DEK/CAN, MLL/AF6, AML1/ETO, MLL/AF9, BCR/ABL, MLL/MLL, PML/RARu, TLS/ERG, E2A/HLF, EVI1 and HOXI1 were detected in 57 cases (63.3 %) of the 90 samples, which were in consistence with the results of karyotypic analysis. Furthermore, M-RT-PCR had also shown good clinical relevance when used as an approach to detect minimal residual leukemia. We concluded that M-RT-PCR could be used as an efficient and fast diagnostic tool not only in the initial diagnosis of hematologic malignancies but also in subsequent monitor of minimal residual leukemia.

Changes in histamine level in striatum in rats with neuropathic pain and the effects of intracerebralventricular histamine on neuropathic pain / 中华麻醉学杂志

Objective To investigate the changes in histamine level in striatum in rats with neuropathic pain and to find out if histamine has any analgesic effect on neuropathic pain.Methods The experiment was performed in 4 parts.In partⅠ24 healthy male SD rats weighing 180-250g were randomly divided into 2 groups(n =12 each):control group received sham operation and neuropathic pain group in which left sciatic nerve was partially ligated.Two weeks after operation microdialysis catheter was inserted into right striatum and fixed.The microdialysate was collected for determination of histamine concentration.In partⅡanother 24 healthy male SD rats were randomly divided into control group and neuropathic pain group as in partⅠ.Metoprine 5 mg?kg~(-1)(a L- histidine decarbonase inhibitor)was injected intraperitoneally(IP)in both groups.Then microdialysate was collected from striatum once an hour for 5 h for determination of histamine concentration and the withdrawal threshold to von Frey hair stimulation of the plantar surface of the left hindpaw was measured at 5 h after IP metoprine.In partⅢandⅣthe effects of intracerebral-ventricular histamine 30?g or 300?g and IP L-histidine 500 mg?kg~(-1) on mechanical pain threshold were measured in rats with neuropathic pain.Results In partⅠthere was no significant difference in the extracellular concentration of histamine in the striatum between the two groups. In partⅡthe extracellular concentration of histamine in the striatum was increased after IP metoprine in both groups but the increase was significantly larger in neuropathic pain group than in control group.The pain threshold was also significantly increased in neuropathic pain group after IP metoprine.In partⅢandⅣintracerebral- ventricular histamine 30?g or IP L-histidine 500 mg?kg~(-1) induced hyperalgesia while intracerebral-ventricular histamine 300?g produced analgesia in rats with neuropathic pain.Conclusion The histamine metabolism is more active in the striatum in rats with neuropathic pain.The neuropathic pain is ameliorated by large dose of histamine administered in cerebral-ventricle and metoprine can induce accumulation of histamine in the striatum.