OBJECTIVEThe purpose of this review is to discuss some critical issues of isoflavones protective against the development of prostate cancer (PCa).

DATA SOURCESData cited in this review were obtained primarily from PubMed and Embase from 1975 to 2015.

STUDY SELECTIONArticles were selected with the search terms "isoflavone", "Phytoestrogen", "soy", "genistin", and "PCa ".

RESULTSIsoflavones do not play an important role on prostate-specific antigen levels reduction in PCa patients or healthy men. The effect of isoflavones on sex hormone levels and PCa risk may be determined by equol converting bacteria in the intestine, specific polymorphic variation and concentrations of isoflavones. The intake of various types of phytoestrogens with lower concentrations in the daily diet may produce synergistic effects against PCa. Moreover, prostate tissue may concentrate isoflavones to potentially anti-carcinogenic levels. In addition, it is noteworthy that isoflavones may act as an agonist in PCa.

CONCLUSIONSIsoflavones play a protective role against the development of PCa. However, careful consideration should be given when isoflavones are used in the prevention and treatment of PCa.

Humans ; Isoflavones ; therapeutic use ; Male ; Phytoestrogens ; therapeutic use ; Prostatic Neoplasms ; prevention & control

OBJECTIVE: To explore the mechanism underlying the hepatoprotective effect of dihydromyricetin (DMY) against lipid accumulation in light of the lipophagy pathway and the inhibitory effect of DMY on HepG2 cell proliferation. METHODS: LO2 cells were cultured in the presence of 10% FBS for 24 h and treated with 100 μg/mL DMY, or exposed to 50% FBS for 24 h followed by treatment with 50, 100, or 200 μg/mL DMY; the cells in recovery group were cultured in 50% FBS for 24 h and then in 10% FBS for another 24 h. Oil red O staining was used to observe the accumulation of lipid droplets in the cells, and the levels of TC, TG, and LDL and activities of AST, ALT and LDH were measured. The expression of LC3 protein was detected using Western blotting. AO staining and transmission electron microscopy were used to determine the numbers of autophagolysosomes and autophagosomes, respectively. The formation of autophagosomes was observed with MDC staining, and the mRNA expression levels of LC3, ATG7, AMPK, mTOR, p62 and Beclin1 were determined with q-PCR. Flow cytometry was performed to analyze the effect of 50, 100, and 200 μg/mL DMY on cell cycle and apoptosis of HepG2 cells; DNA integrity in the treated cells was examined with cell DNA fragmentation test. RESULTS: DMY treatment and pretreatment obviously inhibited lipid accumulation and reduced the levels of TC, TG, LDL and enzyme activities of AST, ALT and LDH in LO2 cells (P < 0.05). In routinely cultured LO2 cells, DMY significantly promoted the formation of autophagosomes and autophagolysosomes and upregulated the expression of LC3 protein. DMY obviously attenuated high FBS-induced inhibition of autophagosome formation in LO2 cells, up- regulated the mRNA levels of LC3, ATG7, Beclin1 and AMPK, and downregulated p62 and mTOR mRNA levels (P < 0.05 or 0.01). In HepG2 cells, DMY caused obvious cell cycle arrest, inhibited cell proliferation, and induced late apoptosis and DNA fragmentation. CONCLUSION DMY reduces lipid accumulation in LO2 cells by regulating the AMPK/ mTOR-mediated lipophagy pathway and inhibits the proliferation of HepG2 by causing cell cycle arrest and promoting apoptosis.
AMP-Activated Protein Kinases/metabolism* ; Autophagy ; Beclin-1 ; Cell Proliferation ; Flavonols ; Hep G2 Cells ; Humans ; Lipids ; RNA, Messenger ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism*

A resurging interest in targeted covalent inhibitors (TCIs) focus on compounds capable of irreversibly reacting with nucleophilic amino acids in a druggable target. p97 is an emerging protein target for cancer therapy, viral infections and neurodegenerative diseases. Extensive efforts were devoted to the development of p97 inhibitors. The most promising inhibitor of p97 was in phase 1 clinical trials, but failed due to the off-target-induced toxicity, suggesting the selective inhibitors of p97 are highly needed. We report herein a new type of TCIs (i.e., FL-18) that showed proteome-wide selectivity towards p97. Equipped with a Michael acceptor and a basic imidazole, FL-18 showed potent inhibition towards U87MG tumor cells, and in proteome-wide profiling, selectively modified endogenous p97 as confirmed by in situ fluorescence scanning, label-free quantitative proteomics and functional validations. FL-18 selectively modified cysteine residues located within the D2 ATP site of p97. This covalent labeling of cysteine residue in p97 was verified by LC‒MS/MS-based site-mapping and site-directed mutagenesis. Further structure-activity relationship (SAR) studies with FL-18 analogs were established. Collectively, FL-18 is the first known small-molecule TCI capable of covalent engagement of p97 with proteome-wide selectivity, thus providing a promising scaffold for cancer therapy.

BACKGROUNDRepetitive transcranial magnetic stimulation (rTMS) and event-related potentials (ERPs) are a noninvasive technique that widely used in neurophysiological field. Although rTMS has shown clinical utility for a number of neurological conditions, Recently,there was little understanding of the the efficacy of rTMS on Schizophrenia(SZ) and the change of ERP between before and after rTMS treatment. The objective of this study was to investigate the characteristics of N400, mismatch negativity (MMN), and P300 before and after treatment with rTMS in SZ.

METHODSOne hundred and twenty-seven SZ patients hospitalized in Shanghai Mental Health Center from March 2015 to July 2017, divided into two groups (85 patients were recruited as rTMS group and 42 were recruited as sham rTMS [ShrTMS] group) and 76 normal controls (NCs) who were the staff and refresher staff in our hospital were recruited at the same time. A Chinese-made rTMS and a Runjie WJ-1 ERPs instrument were used in the present experiment. N400 was elicited by congruent and noncongruent Chinese idioms. After rTMS treatment, N400, P300, and MMN characteristics were compared with those before treatment and NC group.

RESULTSCompared with NC, the SZ patients exhibited delays in N400, P300, and MMN latency and decreased N400, P300, and MMN amplitudes in their frontal area (P < 0.05). After 25 rTMS treatments, N400 amplitudes in the frontal area (elicited by idioms with same phonic and different shape and meaning and with different phonic, shape, and meaning) were increased in the SZ patients (P < 0.05). However, there was no significant change in N400 before and after treatment with ShrTMS in SZ patients (P > 0.05). Amplitudes for MMN and target P300 also increased in SZ patients after rTMS treatment (P < 0.05).

CONCLUSIONSBased on our preliminary findings, we believe that the combined usage of N400, MMN, and P300 could be a valuable index and an electrophysiological reference in evaluating the effects of rTMS treatment in SZ patients.

OBJECTIVETo explore the mRNA expression of Aurora-A,B,C(AUR-A,B,C) in acute leukemia(AL) and their correlations with the clinical indications.

METHODSThe mRNA expression levels of AUR-A,B,C in 73 cases of newly diagnosed AL (untreated group), 20 cases of AL with remission (remission group) and 14 healthy volunteers as control (healthy group) were detected by QRT-PCR, and the difference of expression levels in difference groups, their correlations with clinical indicators and the correlation between the AUR-A,B,C mRNA expression levels themselves were analyzed.

RESULTSThe mRNA expression levels of AUR-A,B,C in untreated group were all higher than those in healthy group and remission group(P<0.01), but there was not significant difference between healthy group and remission group(P>0.05); the mRNA expressions of AUR-A,B,C in acute lymphoblastic leukemia(ALL) group were all significantly higher than that in AML group(P<0.01). The mRNA expression of AUR-A,B,C in high risk group was higher than that in low risk group(P<0.05), but there was no difference in mRNA expression of AUR-A,B,C between high risk group and middle risk group as well as between middle risk group and low risk group(P>0.05). The mRNA expression of AUR-A, B, C in CD34, CD71 and CD56 negative group was not statistically different from that in CD34,CD71 and CD56 positive group(P>0.05). In 73 cases of newly diagnosed AL, the mRNA expression levels of AUR-A, B significantly were positively correlated with lactate dehydrogenase(LDH) level and risk stratification (r=0.279, P=0.017; r=0.314, P=0.007 and r=0.277, P=0.018; r=0.349, P=0.002), while the mRNA expression levels of AUR-A, B were not significantly correlated with age, WBC count, blast ratio in bone marrow at initial diagnosis and remission or no-remission after 1 cours of chemotherapy; the mRNA expression level of AUR-C was significantly positively correlated with WBC count (r=0.263, P=0.025), and LDH level (r=0.348, P=0.003) at initial diagnosis and risk stratificantion(r=0.376, P=0.001), and negatively correlated with age (r=-0.241, P=0.040), and was not significantly correlated with blast ratio in bone marrow at initial diagnosis and remission or noremission after 1 course of chemotherapy. There were significant positive correlations in the mRNA expression between AUR-A and B (r=0.444, P=0.000), AUR-B and C (r=0.763, P=0.000) as well as AUR-A and C (r=0.616, P=0.000).

CONCLUSIONAur-A, B, C mRNA were highly expressed in patients with newly diagnosed AL, moreover the mRNA expression levels of Aur-A,B,C were positively correlated with each other, the high expression of Aur-A, B, C are associated with leukemia types, risk stratification, WBC count and LDH level at initial diagnosis, so they all maybe used as the prognostic markers and potential therapeutic targets.

BackgroundRisperidone and paliperidone have been the mainstay treatment for schizophrenia and their potential role in neuroprotection could be associated with brain-derived neurotrophic factor (BDNF) and N400 (an event-related brain potential component). So far, different effects on both BDNF and N400 were reported in relation to various antipsychotic treatments. However, few studies have been conducted on the mechanism of risperidone and paliperidone on BDNF and N400. This study aimed to compare the effects of risperidone and paliperidone on BDNF and the N400 component of the event-related brain potential in patients with first-episode schizophrenia.

MethodsNinety-eight patients with first-episode schizophrenia were randomly divided into the risperidone and paliperidone groups and treated with risperidone and paliperidone, respectively, for 12 weeks. Serum BDNF level, the latency, and amplitude of the N400 event-related potential before and after the treatment and Positive and Negative Syndrome Scale (PANSS) scores were compared between the two groups.

ResultsA total of 94 patients were included in the final analysis (47 patients in each group). After the treatment, the serum BDNF levels in both groups increased (all P < 0.01), while no significant difference in serum BDNF level was found between the groups before and after the treatment (all P > 0.05). After the treatment, N400 amplitudes were increased (from 4.73 ± 2.86 μv and 4.51 ± 4.63 μv to 5.35 ± 4.18 μv and 5.52 ± 3.08 μv, respectively) under congruent condition in both risperidone and paliperidone groups (all P < 0.01). Under incongruent conditions, the N400 latencies were shortened in the paliperidone group (from 424.13 ± 110.42 ms to 4.7.41 ± 154.59 ms, P < 0.05), and the N400 amplitudes were increased in the risperidone group (from 5.80 ± 3.50 μv to 7.17 ± 5.51 μv, P < 0.01). After treatment, the total PANSS score in both groups decreased significantly (all P < 0.01), but the difference between the groups was not significant (P > 0.05). A negative correlation between the reduction rate of the PANSS score and the increase in serum BDNF level after the treatment was found in the paliperidone group but not in the risperidone group.

ConclusionsBoth risperidone and paliperidone could increase the serum BDNF levels in patients with first-episode schizophrenia and improve their cognitive function (N400 latency and amplitude), but their antipsychotic mechanisms might differ.

Antipsychotic Agents ; pharmacology ; Brain-Derived Neurotrophic Factor ; drug effects ; China ; Electroencephalography ; Evoked Potentials ; drug effects ; Female ; Humans ; Male ; Paliperidone Palmitate ; pharmacology ; Risperidone ; pharmacology ; Schizophrenia ; drug therapy