Search

Zhi-Zi Hou-Po Decoction (ZHD) has been widely used in the treatment of depression for centuries. This study aimed to investigate the antidepressant effects of the water extract of ZHD (ZHD-WE) and ethanol extract of ZHD (ZHD-EE) using behavioral despair tests in mice, and to further explore the neuroprotective effects in a PC12 cell injury model induced by corticosterone (CORT). Mice were divided into a control group (normal saline), ZHD-WE groups (4, 8, and 16 g kg−1), ZHD-EE groups (4, 8, and 16 g kg−1) and the fluoxetine group (20 mg kg−1). The forced swimming test (FST) and tail suspension test (TST) were used to screen the antidepressant effects of ZHD-WE and ZHD-EE after oral administration for seven consecutive days. The level of brain-derived neurotrophic factor (BDNF) in the hippocampus was determined by ELISA. The MTT, lactate dehydrogenase (LDH) and flow cytometry analysis were performed to elucidate the neuroprotective effect of ZHD-EE on a PC12 cell injury model. Additionally, the mRNA and proteins expression of apoptotic molecules Bax, Bcl-2 and BDNF were detected by RT-PCR and western blot assay. It showed that ZHD-EE at concentrations of 8 and 16 g kg−1 significantly decreased the immobility time in the TST and FST, and increased the BDNF levels in the hippocampus. While ZHD-WE at concentrations of 4, 8, and 16 g kg−1 had no significant effect on the immobility time in the TST, and only the 16 g kg−1 of extract group significantly decreased the immobility time in the FST. In vitro, the obtained results showed that PC12 cells pre-incubated with ZHD-EE at concentrations of 100 and 400 μg ml−1 improved cell viability, decreased LDH release, and reduced apoptosis rate of PC12 cells. Moreover, ZHD-EE significantly increased the mRNA and proteins expression of Bcl-2 and BDNF, while decreased the mRNA and protein expression of Bax. ZHD-EE significantly improved despair-like behavior in mice, and its mechanism may be related to BDNF upregulation in the hippocampus. This study also showed that ZHD-EE had a protective effect on CORT-induced injury in PC12 cells by upregulating the expression of BDNF and restoring Bcl-2/Bax balance.

Neurofeedback cognitive training is a promising tool used to promote cognitive functions effectively and efficiently. In this study, we investigated a novel functional near-infrared spectroscopy (fNIRS)-based frontoparietal functional connectivity (FC) neurofeedback training paradigm related to working memory, involving healthy adults. Compared with conventional cognitive training studies, we chose the frontoparietal network, a key brain region for cognitive function modulation, as neurofeedback, yielding a strong targeting effect. In the experiment, 10 participants (test group) received three cognitive training sessions of 15 min using fNIRS-based frontoparietal FC as neurofeedback, and another 10 participants served as the control group. Frontoparietal FC was significantly increased in the test group ( $p =0.03$ ), and the cognitive functions (memory and attention) were significantly promoted compared with the control group (accuracy of 3-back test: $p =0.0005$ , reaction time of 3-back test: $p =0.0009$ ). After additional validations on long-term training effect and on different patient populations, the proposed method exhibited considerable potential to be developed as a fast, effective, and widespread training approach for cognitive function enhancement.

Hepatocellular carcinoma (HCC) remains one of the most lethal malignancies. The current chemotherapy with typically low tumor uptake and high toxicity reveals a poor anti-HCC efficacy. Here, we report transferrin-guided polycarbonate-based polymersomal doxorubicin (Tf-Ps-Dox) as a low-toxic and potent nanotherapeutic agent for effective treatment of liver tumor using a transferrin receptor (TfR)-positive human liver tumor SMMC-7721 model. Tf-Ps-Dox was facilely fabricated with small size of ca. 75 nm and varying Tf densities from 2.2% to 7.0%, by postmodification of maleimide-functionalized Ps-Dox (Dox loading content of 10.6 wt%) with thiolated transferrin. MTT assays showed that Tf-Ps-Dox had an optimal Tf surface density of 3.9%. The cellular uptake, intracellular Dox level, and anticancer efficacy of Tf-Ps-Dox to SMMC-7721 cells were inhibited by supplementing free transferrin, which supports that Tf-Ps-Dox is endocytosed through TfR. Interestingly, Tf-Ps-Dox exhibited a high accumulation of 8.5%ID/g (percent injected dose per gram of tissue) in subcutaneous SMMC-7721 tumors, which was 2- and 3-fold higher than that of nontargeted Ps-Dox and clinically used liposomal Dox formulation (Lipo-Dox), respectively. The median survival times of mice bearing orthotopic SMMC-7721 tumors increased from 82, 88 to 96 days when treated with Tf-Ps-Dox at Dox doses from 8, 12 to 16 mg/kg, which was significantly longer than that of Ps-Dox at 8 mg/kg (58 days) and Lipo-Dox at 4 mg/kg (48 days) or PBS (36 days). Notably, unlike Lipo-Dox, no body weight loss and damage to major organs could be discerned for all Tf-Ps-Dox groups, indicating that Tf-Ps-Dox caused low systemic toxicity. This transferrin-dressed polymersomal doxorubicin provides a potent and low-toxic treatment modality for human hepatocellular carcinoma. STATEMENT OF SIGNIFICANCE: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. Vast work has focused on developing HCC-targeted nanotherapeutics. However, none of the nanotherapeutics has advanced to clinics, partly because the ligands used have not been validated in patients. Transferrin (Tf) is a natural ligand for transferrin receptor (TfR) that is overexpressed on cancerous cells, and it is currently under clinical trials (MBP-426 and CALAA-01) for the treatment of solid tumors. We designed Tf-functionalized polymersomal doxorubicin (Tf-Ps-Dox) for targeted therapy of orthotopic SMMC-7721 tumor in nude mice. Tf-Ps-Dox showed potent anti-HCC efficacy and significantly improved survival time with low toxicity as compared with nontargeted Ps-Dox and clinical liposomal Dox (Lipo-Dox). Hence, Tf-Ps-Dox is very appealing for targeted treatment of HCC.

Background Prostate cancer (PCa) incidence was increased substantially in the last two decades in China. We evaluated the performance of prostate health index (PHI) in predicting the presence of PCa in Chinese people. Methods A total of 108 consecutive patients were recruited to develop a PHI-based nomogram to predict PCa. Serum total prostate specific antigen (tPSA), free PSA (fPSA), and p2PSA were measured by Beckman Coulter’s DxI 800 Immunoassay System. PHI was calculated by [p2PSA/fPSA]×. Performance of individual PSA and PHI measurements in discriminating clinical outcomes was measured using the detection rate of PCa, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). Results Among all patients, PHI was a better predictor of PCa compared with tPSA. PHI achieved the highest AUC of 76.6% in discriminating PCa from non-PCa compare to tPSA measurement, the difference of AUC area between PHI and PSA was about 6% in the entire cohort. The PHI-based nomogram reduced the number of biopsies. With the cutoff value (tPSA >4 ng/mL, PHI >40), there were 37 patients need to do biopsies in tPSA >4 ng/mL group, while with PHI >40, only 30 patients need to do. Seven patients could avoid unnecessary biopsies. When combined with the two values (tPSA >4 ng/mL, PHI >40) only 24 patients remained. Conclusions Our finding has implication PHI and provides added value over tPSA for PCa detecting in Chinese people.

Ping Zhong,1,2 Xiaolei Gu,1,2 Ru Cheng,1,2 Chao Deng,1,2 Fenghua Meng,1,2 Zhiyuan Zhong1,2 1Biomedical Polymers Laboratory, 2Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, China Abstract: Antibody-mertansine (DM1) conjugates (AMCs) are among the very few active targeting therapeutics that are approved or clinically investigated for treating various cancers including metastatic breast cancer. However, none of the AMCs are effective for the treatment of triple-negative breast cancers (TNBCs). Here, we show that cRGD-decorated, redox-activatable micellar mertansine prodrug (cRGD-MMP) can effectively target and deliver DM1 to αvβ3 integrin overexpressing MDA-MB-231 TNBC xenografts in nude mice, resulting in potent tumor growth inhibition. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays showed that cRGD-MMP had obvious targetability to MDA-MB-231 cells with a low half-maximal inhibitory concentration (IC50) of 0.18µM, which was close to that of free DM1 and 2.2-fold lower than that of micellar mertansine prodrug (MMP; nontargeting control). The confocal microscopy studies demonstrated that cRGD-MMP mediated a clearly more efficient cellular uptake and intracellular release of doxorubicin (used as a fluorescent anticancer drug model) in MDA-MB-231 cells. Notably, cRGD-MMP loaded with 1,1'-dioctadecyltetramethyl indotricarbocyanine iodide (DiR; a hydrophobic near-infrared dye) was shown to quickly accumulate in the MDA-MB-231 tumor with strong DiR fluorescence from 2 to 24h post injection. MMP loaded with DiR could also accumulate in the tumor, although significantly less than cRGD-MMP. The biodistribution studies revealed a high DM1 accumulation of 8.1%ID/g in the tumor for cRGD-MMP at 12h post injection. The therapeutic results demonstrated that cRGD-MMP effectively suppressed MDA-MB-231 tumor growth at 1.6mg DM1 equiv./kg without causing noticeable side effects, as shown by little body weight loss and histological analysis. This MMP has appeared as a promising platform for potent treatment of TNBCs. Keywords: breast cancer, reduction-sensitive, drug conjugates, micelles, cRGD

Herein voltammetric behaviors of semicarbazide (SEM) are investigated by employing a graphene modified working electrode, which displays attractive electroanalytical properties. In the acetate buffer solution of pH 4.00, there is a well-defined oxidative peak of SEM, attributing to the irreversible and adsorption-controlled electrode reaction with 2 electrons participation. The values of apparent heterogeneous electron transfer rate constant k′s with the redox are 0.0061 s−1 and 0.0009 s−1, respectively, for two scan rate section. After the experimental parameters, which influence the voltammetric responses of SEM, including supporting electrolyte, pH, accumulation time and accumulation potential, etc., are optimized, it is found that the anodic peak current of SEM is proportional to its concentration in the range of 4 - 40 μmol/L with a detection limit of 1 μmol/L (S/N = 3). Then, an electrochemical method for detecting SEM quantitatively is developed successfully. The concentrations of SEM in fortified tap water samples are tested with satisfactory recovery, indicating that the novel method is strongly promising in the environmental monitoring application.