Transcriptome and metabolome analyses reveal anthocyanins pathways associated with fruit color changes in plum (Prunus salicina Lindl.).

Plum (Prunus salicina Lindl.) is one of the most widely cultivated and important fruit trees in temperate and cold regions. Fruit color is a significant trait relating to fruit quality in plum. However, its development mechanism has not been studied from the aspects of transcriptional regulation and metabolomic progress. To reveal the mechanism of fruit color developments in plums, we selected the fruits of two plum cultivars, 'Changli84' (Ch84, red fruit) and 'Dahuangganhe' (D, yellow fruit) as plant materials for transcriptome sequencing and metabolomic analysis were performed. Based on the data of transcriptome and metabolome at three fruit developmental stages, young fruit stage, color-change stage, and maturation stage, we identified 2,492 differentially expressed genes (DEGs) and 54 differential metabolites (DMs). The KEGG analysis indicated that "Flavonoid biosynthesis" was significantly enriched during three fruit development stages. Some DEGs in the "Flavonoid biosynthesis" pathway, had opposite trends between Ch84 and D, including chalcone synthase (CHS), dihydroflavonol 4-reductase (DFR) and flavonol synthase (FLS). Also, the genes encoding MYB-bHLH-WD (MBW) protein complexes, especially MYBs and bHLHs, showed a close relationship with plum fruit color. In the current study, DMs like procyanidin B1, cyanidin 3-glucoside, and cyanidin-3-O-alpha-arabinopyranoside were key pigments (or precursors), while the carotene and carotenoids did not show key relationships with fruit color. In conclusion, the anthocyanins dominate the color change of plum fruit. Carotenes and carotenoids might be related to the color of plum fruit, but do not play a dominate role.

Anti-hyperlipidemia on rats in vivo and new compounds from the seeds of Psoralea corylifolia.

In this study, it was confirmed at first time that the crude extracts of Psoralea corylifolia seeds (PCE34) can reduce serum lipids (AST, ALT, TG, TC, LDL, ALP, ACP and LDH), body weight and serum sugar, increase HDL and serum insulin in hyperlipidemic wistar rat induced by high-fat diet in vivo. Furthermore, eight new chalcones 1-8, one new flavanone 12, one new coumarin 14, three new meroterpenes 15-17 and one new bakuchiol 20 together with seven known compounds (9-11, 13, 18-19 and 21) were isolated from the PCE34. Their structures were elucidated based on analyses of their spectroscopic (UV, CD, NMR and HREIMS) data. All the isolates were evaluated for in vitro inhibitory activity against DGAT1/2, PTP1B and α-Glucosidase. Among them, compounds 1-3, 8-11, 14-17, 19 and 20 were found to exhibit selective inhibitory activity on DGAT1 with IC50 values ranging from 66.7 ± 1.2 to 87.2 ± 1.3 µM; 1, 8-12, 14 and 20 has the best inhibit active on PTP1B with IC50 values ranging from 13.8 ± 1.1 to 19.1 ± 1.6 µM; 1-12 and 14 displayed the significant inhibitory activities on α-Glucosidase with IC50 values ranging from 29.1 ± 1.2 to 79.4 ± 1.2 µM.

A Study of Logistic Regression for Fatigue Classification Based on Data of Tongue and Pulse.

Methods: The Tongue and Face Diagnosis Analysis-1 instrument and Pulse Diagnosis Analysis-1 instrument were used to collect the tongue image and sphygmogram of the subhealth fatigue population (n = 252) and disease fatigue population (n = 1160), and we mainly analyzed the tongue and pulse characteristics and constructed the classification model by using the logistic regression method. Results: The results showed that subhealth fatigue people and disease fatigue people had different characteristics of tongue and pulse, and the logistic regression model based on tongue and pulse data had a good classification effect. The accuracies of models of healthy controls and subhealth fatigue, subhealth fatigue and disease fatigue, and healthy controls and disease fatigue were 68.29%, 81.18%, and 84.73%, and the AUC was 0.698, 0.882, and 0.924, respectively. Conclusion: This study provided a new noninvasive method for the fatigue diagnosis from the perspective of objective tongue and pulse data, and the modern tongue diagnosis and pulse diagnosis have good application prospects.

A parallel-group study of near-infrared spectroscopy-neurofeedback in children with attention deficit hyperactivity disorder.

The present study aimed to assess the efficacy of Near-infrared spectroscopy (NIRS) real-time neurofeedback (NF) vs. atomoxetine (AT) in children with attention deficit hyperactivity disorder (ADHD). A parallel-group study was conducted to enroll children with ADHD between 8 and 12 years of age. Participants were assigned into the NIRS group and AT group as their wish. Subjects in the NIRS group received 12 sessions of NF training within 6 weeks, and subjects in the AT group were given oral medication. Changes in Swanson, Nolan, and Pelham-V rating scales (SNAP-IV), and performance of Go/No-Go and N-back working memory tasks at week 3, 6 and 8 were evaluated. Forty-nine patients completed the study, including 18 ADHD in the NIRS group and 31 in the AT group. Total scores of SNAP-IV significantly decreased from baseline to week 3, week 6, and week 8 in both groups. Patients in the NIRS group showed significant lower scores on the inattention subscale of SNAP-IV at week 3 and week 6, compared to the AT group. NIRS group had a shorter reaction time during the Go/No-Go task at week 6 and fewer errors during 2-back than the AT group at week 3. The findings revealed that NIRS real-time NF is more efficacious relative to AT in improving behavioral performance, highlighting its potential role and advantages in treating patients with ADHD.

Chinese herbal medicine (Bu-Shen-Tian-Jing Formula) for outcomes of IVF in Chinese patients with polycystic ovary syndrome: a retrospective cohort study.

BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most common causes of anovulatory infertility. Chinese herbal medicine (CHM) has many advantages in treating PCOS. We conducted a retrospective cohort study to investigate the effects of CHM (Bu-Shen-Tian-Jing Formula, BSTJF) on the outcomes of IVF in Chinese patients with PCOS and the potential underlying mechanism. METHODS: A total of 111 patients with PCOS who undergone IVF between November 2009 and July 2018 were included. Fifty-four patients received a three-month BSTJF therapy before controlled ovarian hyperstimulation, while the other 57 patients didn't. The data of the PCOS patients was collected. Anti-Müllerian hormone (AMH), growth differentiation factor-8 (GDF-8) levels in the follicular fluid were evaluated. RESULTS: BSTJF helped patients with PCOS to get more retrieved oocytes (P<0.05) and fertilized oocytes (P<0.05). The clinical cumulative pregnancy rate, live birth rate, and term delivery rate were significantly higher in the same stimulated cycle of the PCOS patients with BSTJF treatment (P<0.05). No significant differences existed between the two groups in the rate of fertilization, hospitalization rate of ovarian hyper stimulation syndrome and obstetrical or neonatal complications. BSTJF significantly decreased the AMH levels in the follicular fluids (P<0.05). CONCLUSION: BSTJF significantly may improve the outcomes of IVF in Chinese patients with PCOS through decreasing AMH levels in follicular fluids. However, the evidence is limited due to the small sample size and the several potential bias.

Diacylglycerol acyltransferase inhibitory new meroterpenes from the seeds of Psoralea corylifolia, and their structure-activity relationship study.

Five new meroterpenes, 12α-Psoracorylifol F (1), 7ß,8α-hydroxy-12ß-Psoracorylifol F (2), 8-ketone-Cyclobakuchiol C (3), 7α,8ß-hydroxy-12ß-Cyclobakuchiol C (4) and 8α-hydroxy-Cyclobakuchiol C (5) together with six known compounds (6-11) were isolated from seeds of Psoralea corylifolia, and their structures were elucidated on the basis of spectroscopic and physicochemical analyses. All the isolates were evaluated for in vitro inhibitory activity against DGAT1/2. Among them, compounds 1-6 were found to exhibit selective inhibitory activity on DGAT1 with IC50 values ranging from 61.5 ± 1.1 to 89.1 ± 1.2 µM.

Two new sesquiterpenes from the stems of Tripterygium wilfordii.

Two new ß-dihydroagarofuran-type sesquiterpenes 1ß,2α,6α,8ß,15- pentaacetoxy- 9α-benzoyloxy- ß-dihydroagarofuran (1) and 1ß,2ß,6α,15-tetraacetoxy-9ß-benzoyloxy- ß-dihydroagarofuran (2), together with five known abietane diterpenoids (3-7) were isolated from ethyl acetate extract of stems of Tripterygium wilfordii. Their structures were elucidated on the basis of detailed spectroscopic and physico-chemical analyses. All the isolates were evaluated for in vitro inhibitory activity against A549, HOS and MCF-7. Among them, compounds 4 and 5 exhibited manifest inhibition on A549, HOS and MCF-7 cancer cell lines.

Discovery of hCES2A inhibitors from Glycyrrhiza inflata via combination of docking-based virtual screening and fluorescence-based inhibition assays.

Human carboxylesterase 2 (hCES2A) is a key target to ameliorate the intestinal toxicity triggered by irinotecan that causes severe diarrhea in 50%-80% of patients receiving this anticancer agent. Herbal medicines are frequently used for the prevention and treatment of the intestinal toxicity of irinotecan, but it is very hard to find strong hCES2A inhibitors from herbal medicines in an efficient way. Herein, an integrated strategy via combination of chemical profiling, docking-based virtual screening and fluorescence-based high-throughput inhibitor screening assays was utilized. Following the screening of a total of 73 herbal products, licorice (the dried root of Glycyrrhiza species) was found with the most potent hCES2A inhibition activity. Further investigation revealed that the chalcones and several flavonols in licorice displayed strong hCES2A inhibition activities, while isoliquiritigenin, echinatin, naringenin, gancaonin I and glycycoumarin exhibited moderate inhibition of hCES2A. Inhibition kinetic analysis demonstrated that licochalcone A, licochalcone C, licochalcone D and isolicoflavonol potently inhibited hCES2A-mediated fluorescein diacetate hydrolysis in a reversible and mixed inhibition manner, with Ki values less than 1.0 µM. Further investigations demonstrated that licochalcone C, the most potent hCES2A inhibitor identified from licorice, dose-dependently inhibited intracellular hCES2A in living HepG2 cells. In summary, this study proposed an integrated strategy to find hCES2A inhibitors from herbal medicines, and our findings suggested that the chalcones and isolicoflavonol in licorice were the key ingredients responsible for hCES2A inhibition, which would be very helpful to develop new herbal remedies or drugs for ameliorating hCES2A-associated drug toxicity.

A double-blind, randomized, sham-controlled study of cranial electrotherapy stimulation as an add-on treatment for tic disorders in children and adolescents.

AIM: The aim of this study was to determine the efficacy and safety of cranial electrotherapy stimulation (CES) as an add-on treatment for TD. METHODS: A randomized, double-blind, sham-controlled trial was conducted at an outpatient, single-center academic setting. A total of 62 patients aged 6-17 years with TD and lack of clinical response to 4 weeks' pharmacotherapy were enrolled. Patients were divided randomly into 2 groups and given 4 weeks' treatment, including 30 min sessions of active CES (500 µA-2 mA) or sham CES (lower than 100 µA) per day for 40 d on weekdays. Change in Yale Global Tic Severity Scale (YGTSS), Clinical Global Impression-severity of illness-severity (CGI-S) and Hamilton Anxiety Scale-14 items (HAMA-14) were performed at baseline, week 2, week 4. Adverse events (AEs) were also evaluated. RESULTS: 53 patients (34 males and 9 females) completed the trial, including 29 in the active CES group and 24 in the sham CES group. Both groups showed clinical improvement in tic severities compared to baseline respectively at week 4. Participants receiving active CES showed a reduction of 31.66 % in YGTSS score, compared with 23.96 % in participants in sham CES group, resulting in no significant difference between the two groups (t = 1.54, p = 0.13). CONCLUSION: Four-week's treatment of CES for children and adolescents with TD is effective and safe, but the improvement for tic severity may be related to placebo effect.

Neoadjuvant Modified FOLFOX6 With or Without Radiation Versus Fluorouracil Plus Radiation for Locally Advanced Rectal Cancer: Final Results of the Chinese FOWARC Trial.

PURPOSE: In the multicenter, open-label, phase III FOWARC trial, modified infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) plus radiotherapy resulted in a higher pathologic complete response rate than fluorouracil plus radiotherapy in Chinese patients with locally advanced rectal cancer. Here, we report the final results. METHODS: Adults ages 18 to 75 years with stage II/III rectal cancer were randomly assigned (1:1:1) to five cycles of infusional fluorouracil (leucovorin 400 mg/m2, fluorouracil 400 mg/m2, and fluorouracil 2.4 g/m2 over 48 hours) plus radiotherapy (46.0 to 50.4 Gy delivered in 23 to 25 fractions during cycles 2 to 4) followed by surgery and seven cycles of infusional fluorouracil, the same treatment plus intravenous oxaliplatin 85 mg/m2 on day 1 of each cycle (mFOLFOX6), or four to six cycles of mFOLFOX6 followed by surgery and six to eight cycles of mFOLFOX6. The primary end point was 3-year disease-free survival (DFS). RESULTS: In total, 495 patients were randomly assigned to treatment. After a median follow-up of 45.2 months, DFS events were reported in 46, 39, and 46 patients in the fluorouracil plus radiotherapy, mFOLFOX6 plus radiotherapy, and mFOLFOX6 arms. In each arm, the probability of 3-year DFS was 72.9%, 77.2%, and 73.5% (P = .709 by the log-rank test), the 3-year probability of local recurrence after R0/1 resection was 8.0%, 7.0%, and 8.3% (P = .873 by the log-rank test), and the 3-year overall survival rate was 91.3%, 89.1%, and 90.7% (P = .971 by log-rank test), respectively. CONCLUSION: mFOLFOX6, with or without radiation, did not significantly improve 3-year DFS versus fluorouracil with radiation in patients with locally advanced rectal cancer. No significant difference in outcomes was found between mFOLFOX6 without radiotherapy and fluorouracil with radiotherapy, which requires additional investigation of the role of radiotherapy in these regimens.

Inhibitory effects of scoparone from chestnut inner shell on platelet-derived growth factor-BB-induced vascular smooth muscle cell migration and vascular neointima hyperplasia.

BACKGROUND: Compounds of the inner shell of chestnut (Castanea crenata) have diverse biological activities, including anti-cancer and anti-oxidant activities. Here we explored the effects of an extract of chestnut inner shells and of its bioactive component scoparone on vascular smooth muscle cell migration and vessel damage. RESULTS: The ethanol extract of chestnut inner shells, containing 11 major compounds, inhibited platelet-derived growth factor (PDGF)-BB-induced migration of rat aortic smooth muscle cells (RASMCs). Among these compounds, scoparone (6,7-dimethoxycoumarin) suppressed RASMC migration and wound healing in response to PDGF-BB but did not affect RASMC proliferation. In RASMCs, scoparone inhibited the PDGF-BB-induced rat aortic sprout outgrowth and attenuated the PDGF-BB-mediated increase in phosphorylation of mitogen-activated protein kinases (MAPKs), p38 MAPK and extracellular signal-regulated kinase 1/2. The in vivo administration of scoparone resulted in the attenuation of neointima formation in balloon-injured carotid arteries of rats. CONCLUSION: These findings demonstrate that scoparone, found in chestnut inner shells, may inhibit cell migration through suppression of the phosphorylation of MAPKs in PDGF-BB-treated RASMCs, probably contributing to the reduction of neointimal hyperplasia induced after vascular injury. Therefore, scoparone and chestnut inner shell may be a potential agent or functional food, respectively, for the prevention of vascular disorders such as vascular restenosis or atherosclerosis. © 2019 Society of Chemical Industry.

Motor Cortex Mapping in Patients With Hepatic Myelopathy After Transjugular Intrahepatic Portosystemic Shunt.

RATIONALE AND OBJECTIVES: As a special movement disorder, hepatic myelopathy (HM) is characterized by spastic paraperesis and may be secondary to transjugular intrahepatic portosystemic shunt (TIPS). The prediction and diagnosis of HM is difficult due to largely unknown neuropathological underpinnings and a lack of specific biomarkers. We aimed to delve into the alterations in motor system of HM patients' brain and their potential clinical implication. MATERIAL AND METHODS: Twenty-three patients with HM and 23 without HM after TIPS and 24 demographically matched healthy controls were enrolled. High-spatial-resolution structural imaging and functional data at rest were acquired. Motor areas were included as seed regions for functional connectivity analysis. Then, we performed brain volume analysis. RESULTS: We found decreased right supplementary motor area (SMA)-seeded functional connectivity with bilateral insula, thalamus and midbrain, left cerebellum and middle temporal gyrus, and right middle cingulate gyrus in HM compared to non-HM patients (p < 0.001). The right insula revealed decreased volume (p < 0.001), and white matter volume reduced in the right corona radiata beneath the right SMA (p < 0.001) in HM relative to non-HM patients. Furthermore, the strength of right SMA-seeded connectivity with insula was positively correlated with folic acid level in HM patients (r = 0.60, p = 0.03), showing an accuracy of 0.87 to distinguish HM from non-HM. CONCLUSION: Our study demonstrates the HM-specific dysconnectivity with an anatomical basis, and its correlation with laboratory findings and diagnostic value. Detecting these abnormalities might help to predict and diagnose post-TIPS HM.

Fabrication of Gradient Nanopattern by Thermal Nanoimprinting Technique and Screening of the Response of Human Endothelial Colony-forming Cells.

Nanotopography can be found in various extracellular matrices (ECMs) around the body and is known to have important regulatory actions upon cellular reactions. However, it is difficult to determine the relation between the size of a nanostructure and the responses of cells owing to the lack of proper screening tools. Here, we show the development of reproducible and cost-effective gradient nanopattern plates for the manipulation of cellular responses. Using anodic aluminum oxide (AAO) as a master mold, gradient nanopattern plates with nanopillars of increasing diameter ranges [120-200 nm (GP 120/200), 200-280 nm (GP 200/280), and 280-360 nm (GP 280/360)] were fabricated by a thermal imprinting technique. These gradient nanopattern plates were designed to mimic the various sizes of nanotopography in the ECM and were used to screen the responses of human endothelial colony-forming cells (hECFCs). In this protocol, we describe the step-by-step procedure of fabricating gradient nanopattern plates for cell engineering, techniques of cultivating hECFCs from human peripheral blood, and culturing hECFCs on nanopattern plates.

Four new compounds isolated from Psoralea corylifolia and their diacylglycerol acyltransferase (DGAT) inhibitory activity.

A new bakuchiol compound Δ11-12-hydroxy-12-dimethyl bakuchiol (1), a new flavanone compound 2(S)-6-methoxy-7- hydroxymethylene-4'-hydroxyl-flavanone (8), and two new isoflavanone compounds 4',7-dihydroxy-3'-(6"ß-hydroxy-3″,7″-dimethyl-,2″,7″-dibutenyl)-geranylisoflavone (9) and 4',7-dihydroxy-3'-(7″-hydroxy-7″-methyl-2″,5″-dibutenyl)-geranylisoflavone (10) together with eight known compounds (2-7, 11, 12) were isolated from the P. corylifolia. Their structures were elucidated on the basis of spectroscopic and physico-chemical analyses. All the isolates were evaluated for in vitro inhibitory activity against DGAT1/2. Among them, compounds 3, 9 and 10 were found to exhibit selective inhibitory activity on DGAT1 with IC50 values ranging from 93.7 ±â€¯1.3 to 96.2 ±â€¯1.1 µM. Compound 1 showed inhibition activity on DGAT1 with IC50 values 73.4 ±â€¯1.3 µM and inhibition of DGAT2 with IC50 value 121.1 ±â€¯1.3 µM.

Low-power laser irradiation inhibits PDGF-BB-induced migration and proliferation via apoptotic cell death in vascular smooth muscle cells.

Vascular restenosis after injury of blood vessel has been implicated in various responses including apoptosis, migration, and proliferation in vascular smooth muscle cells (VSMCs) stimulated by diverse growth factors underlying platelet-derived growth factor (PDGF). Previous studies evaluated the effects of low-power laser (LPL) irradiation over various wavelength ranges on VSMC events in normal and pathologic states. However, whether VSMC responses are affected by LPL irradiation remains unclear. The purpose of this study is to explore the effects of LPL (green diode laser 532-nm pulsed wave of 300 mW at a spot diameter of 1 mm) irradiation on the responses, apoptosis, migration, and proliferation of VSMCs. The effect of LPL irradiation was tested on VSMCs through cytotoxicity, proliferation, migration, and apoptotic assays. Aortic ring assay was used to assess the effect of LPL irradiation on aortic sprout outgrowth. Protein expression levels were determined by western blotting. LPL irradiation did not affect VSMC viability but slightly attenuated PDGF-BB-induced proliferation in VSMCs. In addition, LPL irradiation inhibited PDGF-BB-evoked migration of VSMCs. Aortic sprout outgrowth in response to PDGF-BB was diminished in cells treated with LPL. In contrast, LPL irradiation evoked apoptosis in VSMCs in the presence of PDGF-BB. Similarly, activation of caspase-3 and Bax, as well as p38 mitogen-activated protein kinase (MAPK), in VSMCs treated with PDGF-BB was enhanced by exposure to LPL. These findings indicate that LPL irradiation induces vascular apoptosis via p38 MAPK activation and simultaneously inhibits VSMC proliferation and migration in response to PDGF-BB.

Transcutaneous Electrical Acupoint Stimulation Improves the Outcomes of In Vitro Fertilization: A Prospective, Randomized and Controlled Study.

OBJECTIVES: To explore whether transcutaneous electrical acupoint stimulation (TEAS) can improve the outcomes of in vitro fertilization (IVF). DESIGN: A prospective, randomized, and controlled study. SETTING: IVF center in a university hospital. PARTICIPANTS: Four hundred and eighty-one infertile patients with bilateral tubal blockage who were referred for IVF. Patients were randomized into four groups. INTERVENTION: TEAS was administered for 30min, respectively, at 24h before TVOR and two hours before ET. The acupoints included SP10 (Xuehai, bilateral), SP8 (Diji, bilateral), LR3 (Taichong, bilateral), ST36 (Zusanli, bilateral), EX-CA1 (Zigong, bilateral), RN4 (Guanyuan), PC6 (Neiguan, bilateral), and RN12 (Zhongwan). Based on different frequencies of TEAS, patients were grouped into a TEAS-2Hz group, a TEAS-100Hz group and a TEAS-2/100Hz group. Patients in the control group only received routine IVF treatment and no TEAS was applied on them. PRIMARY AND SECONDARY OUTCOME MEASURES: The number of mature oocytes, normally fertilized oocytes and good-quality embryos were used to evaluate oocyte developmental competence of the patients. Data of clinical pregnancy rate (CPR), implantation rate (IR), and live birth rate (LBR) were also obtained. The levels of neuropeptide Y (NPY), transforming growth factor alpha and granulocyte colony-stimulating factor in the follicular fluids were measured with enzyme-linked immunosorbent assay (ELISA). RESULTS: No significant differences were found between the control, TEAS-2Hz, TEAS-100Hz and TEAS-2/100Hz groups on the numbers of metaphase II oocytes, normally fertilized zygotes, early cleavage embryos or good quality embryos (P > .05). However, the CPR, IR and LBR of the TEAS-2/100Hz group were significantly higher than those of the other groups, respectively (P < .05). The NPY levels in the follicular fluids of TEAS-2/100Hz group were significantly higher than those of the other groups (P < .05). CONCLUSION: TEAS using a frequency of 2/100Hz could help to improve the IVF outcomes partly by increasing NPY levels in the follicular fluids.

Desalted Salicornia europaea extract attenuated vascular neointima formation by inhibiting the MAPK pathway-mediated migration and proliferation in vascular smooth muscle cells.

Salicornia europaea L. (SE) has been used as folk medicine for the treatment of various diseases such as obesity, diabetes, and cancer. However, its effects on atherosclerotic events in vascular smooth muscle cells (VSMCs) remain unknown. The present study explored the effects of the ethyl acetate fraction of desalted SE hot water extract (SEWEAF) on atherosclerotic responses (especially migration and proliferation) in VSMCs and vascular neointima formation. Treatment with the SEWEAF significantly suppressed the platelet-derived growth factor (PDGF)-BB-induced VSMC migration and proliferation as well the phosphorylation of mitogen-activated protein kinases (MAPKs) such as the p38 MAPK and extracellular signal-regulated kinase (ERK) 1/2. Moreover, oral administration of the SEWEAF resulted in the attenuation of neointima formation in balloon-injured rat carotid arteries. Additionally, HPLC analysis showed that the major components in the two subfractions of the SEWEAF were five phenolic acids and four flavonols. In the SEWEAF components, for which atherosclerosis-linked responses in VSMCs have not been known, p-coumaric acid, quercetin-3-ß-d-glucoside, and isorhamnetin-3-ß-d-glucoside inhibited both PDGF-BB-induced migration and proliferation and isorhamnetin attenuated only PDGF-BB-stimulated VSMC proliferation. These results suggest that the SEWEAF may suppress PDGF-BB-induced VSMC migration by downregulating the phosphorylation of p38 MAPK and ERK1/2, thus leading to the reduction of neointimal hyperplasia during vascular remodeling. Therefore, the desalted SE extract, SEWEAF may be a potential ingredient for dietary supplements or nutraceuticals to ameliorate and/or prevent vascular remodeling-related disorders.

Four new neolignans isolated from Eleutherococcus senticosus and their protein tyrosine phosphatase 1B inhibitory activity (PTP1B).

Four new compounds, erythro-7'E-4-hydroxy-3,3'-dimethoxy-8,5'-oxyneoligna-7'-ene-7,9-diol-9'-al (1), (7S,8S)-4-hydroxy-3,1',3'-trimethoxy-4',7-epoxy-8,5'-neolign-9-ol (5), (7S,8S,7'E)-5-hydroxy-3,3'-dimethoxy-4',7-epoxy-8,5'-neolign-7'-ene-9,9'-diol (6) and (7S,8S,7'E)-5-hydroxy-3,3',9'-trimethoxy-4'-7-epoxy-8,5'-neolign-7'-ene-9-ol (7). Along with four known compounds (2-4, 8) were isolated from the EtOAc-soluble extract of Eleutherococcus senticosus. Their structures were elucidated on the basis of spectroscopic and physicochemical analyses. All the compounds were evaluated for in vitro inhibitory activity against PTP1B, VHR and PP1. Among them, compounds 1-4 and 6-8 were found to exhibit selective inhibitory activity on PTP1B with IC50 values ranging from 17.2±1.6 to 32.7±1.2µM.

Abnormal Effective Connectivity in the Brain is Involved in Auditory Verbal Hallucinations in Schizophrenia.

Information flow among auditory and language processing-related regions implicated in the pathophysiology of auditory verbal hallucinations (AVHs) in schizophrenia (SZ) remains unclear. In this study, we used stochastic dynamic causal modeling (sDCM) to quantify connections among the left dorsolateral prefrontal cortex (inner speech monitoring), auditory cortex (auditory processing), hippocampus (memory retrieval), thalamus (information filtering), and Broca's area (language production) in 17 first-episode drug-naïve SZ patients with AVHs, 15 without AVHs, and 19 healthy controls using resting-state functional magnetic resonance imaging. Finally, we performed receiver operating characteristic (ROC) analysis and correlation analysis between image measures and symptoms. sDCM revealed an increased sensitivity of auditory cortex to its thalamic afferents and a decrease in hippocampal sensitivity to auditory inputs in SZ patients with AVHs. The area under the ROC curve showed the diagnostic value of these two connections to distinguish SZ patients with AVHs from those without AVHs. Furthermore, we found a positive correlation between the strength of the connectivity from Broca's area to the auditory cortex and the severity of AVHs. These findings demonstrate, for the first time, augmented AVH-specific excitatory afferents from the thalamus to the auditory cortex in SZ patients, resulting in auditory perception without external auditory stimuli. Our results provide insights into the neural mechanisms underlying AVHs in SZ. This thalamic-auditory cortical-hippocampal dysconnectivity may also serve as a diagnostic biomarker of AVHs in SZ and a therapeutic target based on direct in vivo evidence.

New neo-lignan from Acanthopanax senticosus with protein tyrosine phosphatase 1B inhibitory activity.

New neo-lignan, (7S, 8R)-3-hydroxyl-4-methoxyl-balanophonin (1), together with seven known compounds (2-8) were isolated from the EtOAc-soluble extract of Acanthopanax senticosus. The structure of the new neo-lignan was elucidated with spectroscopic and physico-chemical analyses. All the isolates were evaluated for in vitro inhibitory activity against PTP1B, VHR and PP1. Among them, the new compound (1) was found to exhibit selective inhibitory activity on PTP1B with IC50 value 15.2 ± 1.4 µM.