Breast Neoplasms ; diagnosis ; genetics ; metabolism ; Carcinoma, Intraductal, Noninfiltrating ; genetics ; metabolism ; Chromosomes, Human, Pair 17 ; genetics ; Female ; Genetic Heterogeneity ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Polyploidy ; Receptor, ErbB-2 ; genetics ; metabolism

We analyzed the anticancer effect and mechanism of the novel indoleamine 2,‍3-dioxygenase 1 (IDO1) inhibitor NLG-919 combined with temozolomide (TMZ) on human glioma cell lines. The anti-tumor activity of NLG-919 and temozolomide after single and combined treatments was detected by MTT assay. Colony formation assay, invasion assay and migration assays were used to detect the effects of NLG-919 and temozolomide alone or in combination on proliferation, invasion and migration of human glioma cells. A flow cytometry assay was used to detect cell apoptosis, cell cycle arrest, reactive oxygen species (ROS) production and mitochondrial membrane potential damage (JC-1). An immunofluorescence assay was used to detect the expression level of IDO1 and HPLC was used to detect the expression level of L-kynurenine (Kyn) to explore the anti-tumor mechanism of NLG-919 and temozolomide. The results show that NLG-919 had a weak in vitro inhibitory effect compared to that of temozolomide. The IC₅₀ of NLG-919 on U251 cells and U87 after 72 h was 26.9 and 30.7 μmol·L^-1, respectively. However, when NLG-919 was used in combination with temozolomide, its anti-glioma activity was significantly increased. Compared with the single treatment, the combination treatment had a potent ability to inhibit proliferation, invasion and migration of glioma cells. Combination treatment improved the capacity of temozolomide to induce cell cycle arrest and inhibit the growth of glioma cells. NLG-919 significantly down-regulated the expression and activity of IDO1 in glioma cells, and the inhibitory effect was improved after combination with temozolomide, and effectively blocked the production of Kyn through the metabolism of L-tryptophan (Trp). In conclusion, the IDO1 inhibitor NLG-919 and temozolomide showed synergistic effects in the anticancer therapy of human glioma cell lines.

In the study, to explore the anti-tumor effects and mechanisms of chlorpromazine (CPZ) and perphenazine (PPZ) combined with temozolomide (TMZ) on human glioma cell lines, we performed MTT assays to determine the growth inhibitory rate of CPZ, PPZ and TMZ in mono and combined treatments. The anti-tumor effects of CPZ and PPZ alone or in combination with TMZ were determined by colony formation, cell apoptosis, cell cycle arrest, reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) detection (JC-1). The expression level of p53 was detected by immunofluorescence assay. Furthermore, autophagy under different administrations was detected by flow cytometry and confocal imaging to explore the anti-tumor mechanism of CPZ and TMZ. Protein phosphatase 2A (PP2A), cancerous inhibitor of protein phosphatase 2A (CIP2A) and proto-oncogene protein (c-Myc) were detected by immunofluorescence assay, tumor stem cell markers (CD44, CD133) and aldehyde dehydrogenase (ALDH) were detected by flow cytometry to explore the anti-tumor mechanism of PPZ and TMZ. The results showed that after 72 h treatments of combinations, the values of half maximal inhibitory concentration (IC₅₀) of TMZ on U87 and U251 cells were reduced, and the ability of TMZ to induce apoptosis and cycle arrest was improved. In addition, the combination of CPZ and TMZ could induce an increased effect of autophagy via activating the relevant pathway of p53 gene in glioma cells. The combination of PPZ and TMZ increased the sensitivity of glioma cells to TMZ, and the underlying mechanism might be related to the inhibition of CIP2A/PP2A/c-Myc signaling pathway. In conclusion, CPZ and PPZ combined with TMZ, showed the significant synergistic effects in cancer treatment, which are the novel and potential therapeutic regimens providing a new treatment strategy for human glioma.

Glypican-3 (GPC3) is an oncofetal protein anchored on the plasma membrane and highly expressed in hepatocellular carcinoma (HCC).GPC3 could he used as a biomarker for the diagnosis of HCC and the serum levels of GPC3 in liver cancer patients has a significant role for their prognosis.Moreover, GPC3 in HCC cells is immunoreactive, rendering it a suitable target for the treatment of HCC.Nowadays, several clinical trials targeting GPC3 for HCC therapy have already been conducted: new anti- GPC3 antibodies are generated; the clinical trials about its combination administration with other targeted medicines are being in progress; (tP(3-targeted TRAB, GPC3 vaccines and GPC3-based chimeric antigen receptor T-cells (CAR-T) therapy are under investigation.In this review, we briefly discuss the structure of GPC3, its role in HCC pathogenesis and summarize the recent development in the clinical application of GPC3.We firmly believe that GPC3 would be a promising target for HCC therapy.And further studies focusing on GPC3 should provide us more solid evidence.

Objective To discuss the important role of undergraduate students' social practice in medical education.Methods Questionnaires on social practice activity were answered by medical students,and the characteristics and shortages of social practice were analyzed.The development policy was proposed after expert inquiry and comparison with other universities. Results Undergraduate students' social practice in School of Medicine,Shanghai Jiaotong University presentd the four characteristics: positive participation,obvious characteristic,abundance items,and wide range of services.But there were insufficiencies in form of action,multiplication of selected topic,socialized operation method,and time arrangement. Conclusion The results suggest that further improvement is necessary in the service quality,advance in the activities' pertinence,development in innovation ability,and enhancement in base construction and support system.

Based on the octahedral modifiable structures and kinetic inertness, platinum (IV) complexes have become antitumor prodrug candidates to mitigate platinum (II) drug resistance and side effects. The nitrobenzoxadiazole derivative (NBDHEX) can inhibit the activity of glutathione S-transferases (GSTs) and be introduced to conjugate with platinum(II) complexes DN603 and DN604 to yield two platinum (IV) complexes DN603/DN604-NBD. In vitro assays demonstrated that DN603/DN604-NBD could significantly inhibit the proliferation of cisplatin-sensitive A549 and resistant A549/cDDP cancer cells. The uptake of DN603/DN604-NBD in A549/cDDP cells was much higher than that of cisplatin, causing a higher rate of cell apoptosis and a greater ratio of Bax/Bcl-2, the activation of caspase-3 and cleavage of DNA repair enzyme (PARP), inducing the mitochondria-dependent cell apoptosis pathway. DN603/DN604-NBD could induce higher reactive oxygen species (ROS) levels, significantly enhance phosphorylation of histone H2AX on Ser-139 (γ-H2AX) fluorescence intensity and cause a greater degree of DNA double-stranded damage. Studies have shown that GSTs kinase GSTP1 was highly expressed in cisplatin-resistant cancer cells. Moreover, DN603/DN604-NBD targeted GSTP1 to suppress its expression level. By using the ROS scavenger NAC and the c-Jun N-terminal kinase (JNK) inhibitor SP600125 in advance, it was found that DN603/DN604-NBD could significantly increase the number of living cells and decrease the phosphorylation levels of JNK and c-Jun. The results indicated that DN603/DN604-NBD could produce higher levels of ROS to activate JNK-mediated signaling pathway, induce apoptosis in tumor cells to overcome cisplatin resistance. All the animal experiments were approved by Animal Ethics Committee of Southeast University (grant No. 20210303025). In vivo assays confirmed that DN603/DN604-NBD could inhibit the growth of A549 xenograft tumors with nearly no toxicity and fewer side effects. Taken together, DN603/DN604-NBD are investigated as two potential novel platinum (IV) prodrug candidates for anticancer therapy.

OBJECTIVETo establish an efficient and stable method for protein extraction of Streptococcus mutans.

METHODSThe collected bacteria were treated by freeze-thaw and ultrasonic (method 1), ultrasonic (method 2), boiling (method 3), boiling and ultrasonic (method 4), respectively. The index such as state of bacteria broken, concentration of extracted protein and SDS-PAGE of protein were employed to evaluate the effects of above four methods.

RESULTSBeside the method 3, the other three methods could break the bacteria effectively, of which ultrasonic was the key factor. The pattern of SDS-PAGE which treated by method 1, method 2 and method 4 was almost same, but method 1 resulted in the best abundance. There was significantly difference among the four protein concentration extracted by four methods (P < 0.05). All methods exhibited good stability and reproducibility.

CONCLUSIONMethod of freeze-thaw and ultrasonic resulted in an efficient proteins extraction of Streptococcus mutans which demonstrated good stability and reproducibility and easy to handle.

Bacterial Proteins ; Reproducibility of Results ; Streptococcus mutans

OBJECTIVETo investigate the antibacterial activity of decoction of Radix glycyrrhizae against Streptococcus mutans (S. mutans) in vitro.

METHODSThe decoction of Radix glycyrrhizae was prepared by boiling particles of Radix glycyrrhizae, the diameter was 0.2-3.2 mm. In distilled water and filtered, the filtrate was collected for study. The minimal inhibitory concentration (MIC) and the minimal bactericidal concentration (MBC) of the decoction against S. mutans were detected using double dilution. The effect of decoction on growth and acidogenic profile of S. mutans were investigated by detecting the Abs of bacteria suspension and the pH value of medium at definite time intervals(0, 3, 7, 12, 23, 40 h) during cultured.

RESULTSThe MIC determined for decoction was 50 mg x mL(-1) and there was no bactericidal effect when concentration of decoction lower than 100 mg x mL(-1). The decoction inhibitted multiplication of bacteria significantly and the effects became stronger with concentration increasing. The decoction also inhibitted S. mutans producing acid and the effect became stronger with concentration increasing. The most efficient inhibition were observed when incubated 12 hours.

CONCLUSIONThe decoction of Radix glycyrrhizae can inhibite the growth and acid-production of S. mutans in vitro.

Anti-Bacterial Agents ; Bacteria ; In Vitro Techniques ; Microbial Sensitivity Tests ; Plant Extracts ; Streptococcus mutans

The expressions of vimentin and NF-?B were detected in thyroid tissue by immuno- histoehemistry in 26 cases with Hashimoto′s thyroiditis and 9 normal subjects.The results showed that there was a significantly increased expression of vimentin in Hashimoto′s thyroiditis as compared with the normal controls.It indicated that epithelial-mesenchymal transformation existed in follicular epithelial ceils of Hashimoto′s thyroiditis. Furthermore,the expression of vimentin was closely related with NF-?B.

OBJECTSTo investigate the distribution of vitamin D receptor (VDR) genotypes among the Hans of a lead contaminated mine in Shanxi and explore the relationship between blood lead levels and the genetic polymorphism of VDR gene.

METHODSVDR genotypes were determined by polymerase-chain-reaction and restrictive fragment length polymorphism (PCR-RFLP) and the blood lead level was measured by using the graphite furnace atomic absorption spectrometry in a population of 120 pre-school children aged 5 - 6 years who were from the mine kindergarten and were unrelated Hans. An environmental questionnaire in relation to blood lead level was filled for each subject.

RESULTS(1) The gene distribution of the VDR phenotypes in these children was VDRBB, 1.7%; VDRBb, 9.2%; VDRbb, 89.2%. (2) The mean blood lead level of the children who had VDR B allele [(0.910 8 +/- 0.265 0) micromol/L] was significantly higher than that whose VDR genotype was bb [(0.740 1 +/- 0.270 1) micromol/L (mean +/- standard deviation)] (t = 2.155, P < 0.05). (3) Many factors were found to affect the blood lead levels, such as the VDR genotype, the type of fuel, educational level of mothers and so on. After controlling the possible confounding variables by multiple regression, the contribution of the VDR phenotype to the blood lead levels was still statistically significant.

CONCLUSIONThese results indicated that the frequency distribution of the VDR genotype in these children was apparently different from that in Caucasians who had high frequencies of VDR B. The results also indicated that the individuals carrying the VDR B allele were more susceptible to lead poisoning.

Child ; Child, Preschool ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Lead ; blood ; Lead Poisoning ; genetics ; Multivariate Analysis ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length ; Receptors, Calcitriol ; genetics ; Regression Analysis ; Surveys and Questionnaires