Scutellarin, a flavonoid compound from Scutellaria barbata, suppresses growth of breast cancer stem cells in vitro and in tumor-bearing mice.

BACKGROUND: Scutellaria barbata D. Don (SB), commonly known as Ban Zhi Lian and firstly documented by Shigong Chen, is a dried whole plant that has been studied for its therapeutic effects on breast cancer, colon cancer, and prostate cancer. Among its various compounds, scutellarin (SCU) has been demonstrated with anti-tumor effects. PURPOSE: This study aimed to evaluate the effects of SB water extract (SBW) and scutellarin on breast cancer stem cells (BCSCs), and to investigate their potential therapeutic effects on breast tumors in mice. METHODS: BCSCs were enriched from human breast cancer cells (MDA-MB-231 and MDA-MB-361) and their characteristics were analyzed. The effects of varying concentrations of SBW and scutellarin on cell viability, proliferation, self-renewal, and migration abilities were studied, along with the underlying mechanisms. The in vivo anti-tumor effects of scutellarin were further evaluated in SCID/NOD mice. Firstly, mice were inoculated with naïve BCSCs and subjected to treatment with scutellarin or vehicle. Secondly, BCSCs were pre-treated with scutellarin or vehicle prior to inoculation into mice. RESULTS: The derived BCSCs expressed CD44, CD133 and ALDH1, but not CD24, indicating that BCSCs have been successfully induced from both MDA-MB-231 and MDA-MB-361 cells. Both SBW and scutellarin reduced the viability, proliferation, sphere and colony formation, and migration of BCSCs. In mice with tumors derived from naïve BCSCs, scutellarin significantly reduced tumor growth, expression of proliferative (Ki67) and stem cell markers (CD44), and lung metastasis. In addition, pre-treatment with scutellarin also slowed tumor growth. Western blot results suggested the involvement of Wnt/ß-catenin, NF-κB, and PTEN/Akt/mTOR signaling pathways underlying the inhibitory effects of scutellarin. CONCLUSION: Our study demonstrated for the first time that both SB water extract and scutellarin could reduce the proliferation and migration of BCSCs in vitro. Scutellarin was shown to possess novel inhibitory activities in BCSCs progression. These findings suggest that Scutellaria barbata water extract, in particular, scutellarin, may have potential to be further developed as an adjuvant therapy for reducing breast cancer recurrence.

Mechanistic insights into the anti-tumor and anti-metastatic effects of Patrinia villosa aqueous extract in colon cancer via modulation of TGF-ß R1-smad2/3-E-cadherin and FAK-RhoA-cofilin pathways.

BACKGROUND: Patrinia villosa, a traditional medicinal herb commonly used for treating intestinal-related diseases, has been commonly prescribed by Chinese medicine practitioners as a key component herb to treat colon cancer, although its anti-tumor effect and mechanisms of action have not been fully elucidated. HYPOTHESIS/PURPOSE: This study aimed to investigate the anti-tumor and anti-metastatic effects of Patrinia villosa aqueous extract (PVW), and its underlying mechanisms. METHOD: The chemical profile of PVW was analysed by high-performance liquid chromatography with photodiode-array detection (HPLC-DAD) method. Cell-based functional assays MTT, BrdU, scratch, and transwell were conducted to evaluate the effects of PVW on human colon cancer HCT116 and murine colon26-luc cells, assessing cytotoxicity, cell proliferation, motility, and migration, respectively. Western blotting was performed to assess the effect of PVW on the expression of key intracellular signaling proteins. In vivo studies were conducted using zebrafish embryos and tumor-bearing mice to evaluate the anti-tumor, anti-angiogenesis, and anti-metastatic effects of PVW in colon cancer. RESULTS: Five chemical markers were identified and quantified in PVW. PVW exhibited significant cytotoxicity and anti-proliferative activity, as well as inhibitory effects on cell motility and migration in both HCT116 and colon 26-luc cancer cells via modulating protein expressions of TGF-ß R1, smad2/3, snail, E-cadherin, FAK, RhoA, and cofilin. PVW (0.01-0.1 mg/ml) could significantly decrease the length of subintestinal vessels of zebrafish embryos through decreasing mRNA expressions of FLT1, FLT4, KDRL, VEGFaa, VEGFc, and Tie1. PVW (> 0.05 mg/ml) also significantly suppressed colon cancer cells migration in the zebrafish embryos. Furthermore, oral administration of PVW (1.6 g/kg) significantly inhibited tumor growth by decreasing the expressions of tumor activation marker Ki-67 and CD 31 in tumor tissues of HCT116 tumor-bearing mice. PVW could also significantly inhibit lung metastasis in colon 26-luc tumor-bearing mice by modulating their tumor microenvironment, including immune cells populations (T cells and MDSCs), levels of cytokines (IL-2, IL-12, and IFN-γ), as well as increasing the relative abundance of gut microbiota. CONCLUSION: This study revealed for the first time the anti-tumor and anti-metastatic effects of PVW through regulation of TGF-ß-smad2/3-E-cadherin, and FAK-cofilin pathways in colon cancer. These findings provide scientific evidence to support the clinical use of P. villosa in patients with colon cancer.

[Effect of transcutaneous acupoint electrical stimulation at Neiguan (PC 6) on general anesthesia under preserving spontaneous breathing in thoracoscopic lobectomy].

OBJECTIVE: To evaluate the effect of transcutaneous acupoint electrical stimulation (TEAS) at Neiguan (PC 6) on general anesthesia under preserving spontaneous breathing in thoracoscopic lobectomy. METHODS: A total of 66 patients of primary lung cancer undergoing thoracoscopic lobectomy were divided to an observation group (33 cases, 1 case discontinued) and a control group (33 cases). In the observation group, TEAS at Neiguan (PC 6) was used 30 min before anesthesia induction till the end of surgery. The surgery time, maximum value of partial pressure of end-tidal carbon dioxide (PETCO2) and minimum value of oxygen saturation (SpO2) of the two groups were recorded. The dosage of propofol, sufentanil, remifentanil and dexmedetomidine were analyzed. Separately, before induction (T0), at the start of surgery (T1), thoracic exploration (T2) and lobectomy (T3), as well as 30 min (T4) and 60 min (T5) after lobectomy, the mean arterial pressure (MAP), heart rate (HR), respiratory rate (RR), serum cortisol (Cor) and norepinephrine (NE) were measured. The time of post anesthesia care unit (PACU) stay, ambulation, flatus, chest drainage and the incidence of nausea and vomiting were compared between the two groups. RESULTS: The maximum value of PETCO2, the dosage of propofol and remifentanil in the observation group were lower than those in the control group (P < 0.05, P < 0.01), the minimum value of SpO2 in the observation group was higher than that of the control group (P < 0.01). At T1-T5, the MAP, HR, serum Cor and NE levels in the observation group were all lower than those in the control group (P < 0.05). The ambulation time, the time for the flatus, chest drainage time, and the incidence of nausea and vomiting in the observation group were all lower than those in the control group (P<0.001, P < 0.01). CONCLUSION: For the general anesthesia under preserving spontaneous breathing in thoracoscopic surgery, TEAS at Neiguan (PC 6) relieves stress response, reduces opioids dosage and promotes postoperative recovery.

Comparison of Ophiopogon japonicus and Liriope spicata var. prolifera from Different Origins Based on Multi-Component Quantification and Anticancer Activity.

The tuberous root of Ophiopogon japonicus (Thunb.) Ker-Gawl. is a well-known Chinese medicine also called Maidong (MD) in Chinese. It could be divided into "Chuanmaidong" (CMD) and "Zhemaidong" (ZMD), according to the geographic origins. Meanwhile, the root of Liriope spicata (Thunb.) Lour. var. prolifera Y. T. Ma (SMD) is occasionally used as a substitute for MD in the market. In this study, a reliable pressurized liquid extraction and HPLC-DAD-ELSD method was developed for the simultaneous determination of nine chemical components, including four steroidal saponins (ophiopojaponin C, ophiopogonin D, liriopesides B and ophiopogonin D'), four homoisoflavonoids (methylophiopogonone A, methylophiopogonone B, methylophiopogonanone A and methylophiopogonanone B) and one sapogenin (ruscogenin) in CMD, ZMD and SMD. The method was validated in terms of linearity, sensitivity, precision, repeatability and accuracy, and then applied to the real samples from different origins. The results indicated that there were significant differences in the contents of the investigated compounds in CMD, ZMD and SMD. Ruscogenin was not detected in all the samples, and liriopesides B was only found in SMD samples. CMD contained higher ophiopogonin D and ophiopogonin D', while the other compounds were more abundant in ZMD. Moreover, the anticancer effects of the herbal extracts and selected components against A2780 human ovarian cancer cells were also compared. CMD and ZMD showed similar cytotoxic effects, which were stronger than those of SMD. The effects of MD may be due to the significant anticancer potential of ophiopognin D' and homoisoflavonoids. These results suggested that there were great differences in the chemical composition and pharmacological activity among CMD, ZMD and SMD; thus, their origins should be carefully considered in clinical application.

Cortical connectomic mediations on gamma band synchronization in schizophrenia.

Aberrant gamma frequency neural oscillations in schizophrenia have been well demonstrated using auditory steady-state responses (ASSR). However, the neural circuits underlying 40 Hz ASSR deficits in schizophrenia remain poorly understood. Sixty-six patients with schizophrenia spectrum disorders and 85 age- and gender-matched healthy controls completed one electroencephalography session measuring 40 Hz ASSR and one imaging session for resting-state functional connectivity (rsFC) assessments. The associations between the normalized power of 40 Hz ASSR and rsFC were assessed via linear regression and mediation models. We found that rsFC among auditory, precentral, postcentral, and prefrontal cortices were positively associated with 40 Hz ASSR in patients and controls separately and in the combined sample. The mediation analysis further confirmed that the deficit of gamma band ASSR in schizophrenia was nearly fully mediated by three of the rsFC circuits between right superior temporal gyrus-left medial prefrontal cortex (MPFC), left MPFC-left postcentral gyrus (PoG), and left precentral gyrus-right PoG. Gamma-band ASSR deficits in schizophrenia may be associated with deficient circuitry level connectivity to support gamma frequency synchronization. Correcting gamma band deficits in schizophrenia may require corrective interventions to normalize these aberrant networks.

Time Course Changes of Synthetic Relaxation Time During Neoadjuvant Chemotherapy in Breast Cancer: The Optimal Parameter for Treatment Response Evaluation.

BACKGROUND: Synthetic MRI (syMRI) has enabled quantification of multiple relaxation parameters (T1/T2 relaxation time [T1/T2], proton density [PD]), and their longitudinal change during neoadjuvant chemotherapy (NAC) promises to be valuable parameters for treatment response evaluation in breast cancer. PURPOSE: To investigate the time course changes of syMRI parameters during NAC and evaluate their value as predictors for pathological complete response (pCR) in breast cancer. STUDY TYPE: Retrospective, longitudinal. POPULATION: A total of 129 women (median age, 50 years; range, 28-69 years) with locally advanced breast cancer who underwent NAC; all performed multiple conventional breast MRI examinations with added syMRI during NAC. FIELD STRENGTH/SEQUENCE: A 3.0 T, T1-weighted dynamic contrast enhanced and syMRI acquired by a multiple-dynamic, multiple-echo sequence. ASSESSMENT: Breast MRI was set at four time-points: baseline, after one cycle, after three or four cycles of NAC and preoperation. SyMRI parameters and tumor diameters were measured and their changes from baseline were calculated. All parameters were compared between pCR and non-pCR. Interaction between syMRI parameters and clinicopathological features was analyzed. STATISTICAL TESTS: Mann-Whitney U tests, random effects model of repeated measurement, receiver operating characteristic (ROC) analysis, interaction analysis. RESULTS: Median synthetic T1/T2/PD and tumor diameter generally decreased throughout NAC. Absolute T1 at early-NAC, T1, and PD at mid-NAC were significantly lower in the pCR group. After early-NAC, the T1 change was significantly higher in the pCR (median ± IQR, 18.17 ± 11.33) than the non-pCR group (median ± IQR, 10.90 ± 10.03), with the highest area under the ROC curves (AUC) of 0.769 (95% CI, 0.684-0.838). Interaction analysis showed that histological grade III patients had higher odds ratio (OR) (OR = 1.206) compared to grade II patients (OR = 1.067). DATA CONCLUSION: Synthetic T1 changes after one cycle of NAC maybe useful for early evaluating NAC response in breast cancer during whole treatment cycles. However, its discriminative ability is significantly affected by histological grade. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Approaching the quantum limit in two-dimensional semiconductor contacts.

The development of next-generation electronics requires scaling of channel material thickness down to the two-dimensional limit while maintaining ultralow contact resistance1,2. Transition-metal dichalcogenides can sustain transistor scaling to the end of roadmap, but despite a myriad of efforts, the device performance remains contact-limited3-12. In particular, the contact resistance has not surpassed that of covalently bonded metal-semiconductor junctions owing to the intrinsic van der Waals gap, and the best contact technologies are facing stability issues3,7. Here we push the electrical contact of monolayer molybdenum disulfide close to the quantum limit by hybridization of energy bands with semi-metallic antimony ([Formula: see text]) through strong van der Waals interactions. The contacts exhibit a low contact resistance of 42 ohm micrometres and excellent stability at 125 degrees Celsius. Owing to improved contacts, short-channel molybdenum disulfide transistors show current saturation under one-volt drain bias with an on-state current of 1.23 milliamperes per micrometre, an on/off ratio over 108 and an intrinsic delay of 74 femtoseconds. These performances outperformed equivalent silicon complementary metal-oxide-semiconductor technologies and satisfied the 2028 roadmap target. We further fabricate large-area device arrays and demonstrate low variability in contact resistance, threshold voltage, subthreshold swing, on/off ratio, on-state current and transconductance13. The excellent electrical performance, stability and variability make antimony ([Formula: see text]) a promising contact technology for transition-metal-dichalcogenide-based electronics beyond silicon.

Amygdalin Ameliorates Liver Fibrosis through Inhibiting Activation of TGF-ß/Smad Signaling.

OBJECTIVE: To observe the effect of amygdalin on liver fibrosis in a liver fibrosis mouse model, and the underlying mechanisms were partly dissected in vivo and in vitro. METHODS: Thirty-two male mice were randomly divided into 4 groups, including control, model, low- and high-dose amygdalin-treated groups, 8 mice in each group. Except the control group, mice in the other groups were injected intraperitoneally with 10% carbon tetrachloride (CCl4)-olive oil solution 3 times a week for 6 weeks to induce liver fibrosis. At the first 3 weeks, amygdalin (1.35 and 2.7 mg/kg body weight) were administered by gavage once a day. Mice in the control group received equal quantities of subcutaneous olive oil and intragastric water from the fourth week. At the end of 6 weeks, liver tissue samples were harvested to detect the content of hydroxyproline (Hyp). Hematoxylin and eosin and Sirius red staining were used to observe the inflammation and fibrosis of liver tissue. The expressions of collagen I (Col-I), alpha-smooth muscle actin (α-SMA), CD31 and transforming growth factor ß (TGF-ß)/Smad signaling pathway were observed by immunohistochemistry, quantitative real-time polymerase chain reaction and Western blot, respectively. The activation models of hepatic stellate cells, JS-1 and LX-2 cells induced by TGF-ß1 were used in vitro with or without different concentrations of amygdalin (0.1, 1, 10 µmol/L). LSECs. The effect of different concentrations of amygdalin on the expressions of liver sinusoidal endothelial cells (LSECs) dedifferentiation markers CD31 and CD44 were observed. RESULTS: High-dose of amygdalin significantly reduced the Hyp content and percentage of collagen positive area, and decreased the mRNA and protein expressions of Col-I, α-SMA, CD31 and p-Smad2/3 in liver tissues of mice compared to the model group (P<0.01). Amygdalin down-regulated the expressions of Col-I and α-SMA in JS-1 and LX-2 cells, and TGFß R1, TGFß R2 and p-Smad2/3 in LX-2 cells compared to the model group (P<0.05 or P<0.01). Moreover, 1 and 10 µmol/L amygdalin inhibited the mRNA and protein expressions of CD31 in LSECs and increased CD44 expression compared to the model group (P<0.05 or P<0.01). CONCLUSIONS: Amygdalin can dramatically alleviate liver fibrosis induced by CCl4 in mice and inhibit TGF-ß/Smad signaling pathway, consequently suppressing HSCs activation and LSECs dedifferentiation to improve angiogenesis.

Discovery of dearomatized isoprenylated acylphloroglucinols with colon tumor suppressive activities in mice via inhibiting NFκB-FAT1-PDCD4 signaling activation.

Dearomatized isoprenylated acylphloroglucinols (DIAPs) are specific natural products mainly distributed in the plants of genus Hypericum. In this study, guided by HPLC-UV screening, 46 DIAPs (approximately 70% of all DIAPs) including 20 new ones and an unprecedented architecture, were discovered from the roots of Hypericum henryi, which were elucidated by comprehensive spectroscopic, X-ray crystallography, and ECD methods. Compounds 1-7, 39, and 41-42 exhibited remarkable cytotoxicities (IC50 = 0.84-5.63 µM) in human colon cancer HCT116 cells, in which 2 and 6 possessed selective cytotoxicities towards colon cancer cells. The preliminary structure-activity relationships of these tested compounds were discussed. In addition, mechanistic investigations demonstrated that 2 and 6 could significantly suppress the expressions of NFκB, FAT1, and promoted novel tumor suppressor gene PDCD4 in HCT116 cells. Furthermore, in HCT116 colon xenograft-bearing mouse model, treatments with 2 and 6 reduced the growth of xenograft tumors in dose-dependent manner. Expressions of FAT1 in tumors were also decreased in mice treated with 2 and 6, suggesting their anti-tumor effects were via FAT1 signaling pathway. In conclusion, this is the first report on the mechanistic and in vivo studies of DIAP, indicating that these metabolites can be considered as a new type of anti-colon cancer lead agents for further drug development.

Keratinase improves the growth performance, meat quality and redox status of broiler chickens fed a diet containing feather meal.

The objective of this study was to assess the effects of dietary supplementation of keratinase on the production of broilers fed a diet containing feather meal. A total of 162 1-d-old Cobb 500 male broiler (n = 9 cages/diet with 6 chicks/cage) were randomly allocated to 3 dietary treatments. The broilers were fed a corn-soybean-feather meal based diet (BD), or BD supplemented with keratinase at 100,000 or 200,000 U/kg for 6 weeks. Compared to the control, dietary supplementation with 200,000 U/kg keratinase increased (P < 0.05) body weight gain (3.6-4.3%) and reduced feed conversion ratio (2.4-5.6%) during the various experimental periods, and also improved (P < 0.05) apparent total tract digestibility of ash and calcium by 45.0% and 8.8%, respectively. Meanwhile, dietary supplementation of keratinase at 100,000 U/kg reduced (P < 0.05) the drip loss (29.2%), while 200,000 U/kg keratinase supplementation increased (P < 0.05) the pH value (1.6%) at 45 min and decreased (P < 0.05) the lightness (L* value; 13.6%) and drip loss (22.1%) of pectoral muscle. Moreover, dietary supplementation of keratinase at both levels of 100,000 and 200,000 U/kg increased (P < 0.05) Glutathione peroxidase activity (82.5-87.5%) and decreased the Malondialdehyde concentration (14.5-18.3%) in the pectoral muscle. In conclusion, dietary supplementation of keratinase at 200,000 U/kg can improve the performance, meat quality, apparent total tract digestibility of nutrients, and redox status of broiler chickens fed a diet containing feather meal.

Potential effects and mechanisms of Chinese herbal medicine in the treatment of psoriasis.

ETHNOPHARMACOLOGICAL RELEVANCE: Psoriasis is a chronic inflammatory dermatosis related to high morbidity and mortality. The incidence of psoriasis is increasing in recent decades. Some patients with psoriasis are anxious about the underlying side effects of synthetic drugs they are on. Therefore, they are eager to seek alternative and efficient therapy, such as Chinese herbal medicine (CHM). Researchers have found some CHM provides best source for the development of anti-psoriatic drugs because of their structural diversity and fewer adverse reactions. Some of CHM formulas or active constituents extracted from CHM have been rapidly developed into clinical drugs with good efficacy. At present, along with the CHM formulas, single CHM and its active components have been extensively accepted and utilized in the treatment of psoriasis, whose therapeutic mechanisms hitherto have not been thoroughly illustrated. AIM OF THE STUDY: This review aimed to comprehensively summarize about the existing therapeutic mechanisms of CHM in the treatment of psoriasis and to provide a reference to develop future related studies in this field. MATERIALS AND METHODS: Relevant literatures about how CHM treated psoriasis were acquired from published scientific studies (including PubMed, CNKI, Web of Science, Baidu Scholar, The Plant List, Elsevier and SciFinder). All plants appearing in the review have been included in The Plant List or Medicinal Plant Names Services (MPNS). RESULTS: In this review, we collect numerous literatures about how CHM treats psoriasis via immune cells, signaling pathways and disease-related mediators and systematically elucidates potential mechanisms from the point of the suppression of oxidative stress, the inhibition of abnormal abnormal proliferation and differentiation, the inhibition of immune responses, and the suppression of angiogenesis. CONCLUSIONS: Psoriasis is considered as a complicated disease caused by interaction among various mechanisms. The CHM formulas, single CHM and its active components have considerable positive reports about the treatment of psoriasis, which brings hope for a promising future of CHM in the clinical therapy of psoriasis. In the paper, we have concluded that the existing therapeutic mechanisms of CHM in the treatment of psoriasis.

[Effect of electroacupuncture at Neiguan (PC 6) on pulmonary function during one-lung ventilation in patients with lobectomy].

OBJECTIVE: To observe the protective effect of electroacupuncture (EA) at Neiguan (PC 6) on pulmonary function during one-lung ventilation (OLV) in patients with lobectomy, and explore its action mechanism. METHODS: Sixty patients with lobectomy were randomly divided into an observation group and a control group, 30 cases in each one. The patients in the control group were treated with general anesthesia, and OLV was given when surgery began; when the surgery finished, air was removed from the thoracic cavity and two-lung ventilation was performed. On the basis of the treatment in the control group, the patients in the observation group were treated with EA (disperse-dense wave, 2 Hz/100 Hz of frequency) at Neiguan (PC 6) 30 min before anesthesia induction until the end of the surgery. The pulmonary function indexes [arterial partial pressure of oxygen (PaO2), oxygenation index (OI), compliance of lung (CL), respiratory index (RI)] and serum levels of superoxide dismutase (SOD), malondialdehyde (MDA), interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) were observed before surgery (T0), 30 min into OLV (T1), 60 min into OLV (T2) and after operation (T3). The total incidence of complications, pressing times of postoperative patient-controlled analgesia pump in 48 h after surgery and hospital stay were compared between the two groups. RESULTS: Compared with T0, the PaO2, OI, CL and serum SOD at T1, T2 and T3 in the two groups were decreased (P<0.05), and those in the observation group were higher than those in the control group (P<0.05). The RI and serum levels of MDA, IL-6, TNF-α at T1, T2 and T3 in the two groups were increased, and those in the observation group were lower than those in the control group (P<0.05). The total incidence of complications in the observation group was lower than that in the control group [3.3% (1/30) vs 23.3% (7/30), P<0.05]. The pressing times of postoperative patient-controlled analgesia pump in 48 h after surgery and hospital stay in the observation group were less than those in the control group (P<0.05). CONCLUSION: EA at Neiguan (PC 6) has protective effects on lung injury induced by OLV after lobectomy, and its mechanism may be related to the improvement of oxidative stress and inflammatory response.

Effectiveness of Scutellaria barbata water extract on inhibiting colon tumor growth and metastasis in tumor-bearing mice.

The plant Scutellaria barbata (SB) is commonly used as herbal medicines for treating cancer. The present pre-clinical study aimed to validate the Chinese Pharmacopoeia (CP) recommended dosages of SB water extract (SBW) in treating colon tumors. The content of chemical marker scutellarin in SBW was quantified using UPLC. Mice bearing human HCT116 xenografts or murine colon26 tumors received oral administration of SBW or scutellarin for 4 weeks. Results showed that SBW (615 and 1,230 mg/kg) and scutellarin (7 mg/kg) treatments significantly reduced human xenograft weights by 28.7, 36.9 and 28.8%, respectively. Lung metastasis area could be ameliorated after SBW (615 mg/kg) and scutellarin (7 mg/kg) treatments by 23.4 and 29.5%, respectively. Expressions of colon cancer metastasis-related proteins E-cadherin, Tspan 8 and CXCR4, as well as Src kinase in tumors were first shown to be regulated by SBW. Furthermore, in murine colon26 tumor-bearing mice, SBW (615 mg/kg) and scutellarin (7 mg/kg) treatments reduced the orthotopic tumor burden by 94.7% and lung metastatic tumor burden by 94.1%, respectively. Our findings provided evidences that SBW (at the mouse equivalent dosages to clinical dosages recommended by CP) could exert anti-tumor and anti-metastatic effects in colon cancer animal models.

Electrophysiological Evidence of Early Cortical Sensitivity to Human Conspecific Mimic Voice as a Distinct Category of Natural Sound.

Purpose From an anthropological perspective of hominin communication, the human auditory system likely evolved to enable special sensitivity to sounds produced by the vocal tracts of human conspecifics whether attended or passively heard. While numerous electrophysiological studies have used stereotypical human-produced verbal (speech voice and singing voice) and nonverbal vocalizations to identify human voice-sensitive responses, controversy remains as to when (and where) processing of acoustic signal attributes characteristic of "human voiceness" per se initiate in the brain. Method To explore this, we used animal vocalizations and human-mimicked versions of those calls ("mimic voice") to examine late auditory evoked potential responses in humans. Results Here, we revealed an N1b component (96-120 ms poststimulus) during a nonattending listening condition showing significantly greater magnitude in response to mimics, beginning as early as primary auditory cortices, preceding the time window reported in previous studies that revealed species-specific vocalization processing initiating in the range of 147-219 ms. During a sound discrimination task, a P600 (500-700 ms poststimulus) component showed specificity for accurate discrimination of human mimic voice. Distinct acoustic signal attributes and features of the stimuli were used in a classifier model, which could distinguish most human from animal voice comparably to behavioral data-though none of these single features could adequately distinguish human voiceness. Conclusions These results provide novel ideas for algorithms used in neuromimetic hearing aids, as well as direct electrophysiological support for a neurocognitive model of natural sound processing that informs both neurodevelopmental and anthropological models regarding the establishment of auditory communication systems in humans. Supplemental Material https://doi.org/10.23641/asha.12903839.

Effect of a Multi-Carbohydrase and Phytase Complex on the Ileal and Total Tract Digestibility of Nutrients in Cannulated Growing Pigs.

The current study evaluated the influence of a multi-carbohydrase and phytase complex (MCPC) on the ileal and total tract digestibility of nutrients in growing pigs. A total of eight barrows (initial BW = 30.7 ± 1.1 kg) were surgically fitted with a T-cannula at the distal ileum and randomly allotted to four groups. The experiment was conducted according to a 4 × 4 Latin square design, each period lasting 10 days. Pigs were fed four experimental diets, which consisted of two basal diets (BD1, low phytate; BD2, high phytate) with or without MCPC containing at least 1800 U xylanase, 6600 U α-arabinofuranosidase, 1244 U ß-glucanase, and 1000 U phytase per/kg corn-soybean meal with 15% corn distillers based diet. The high phytate diet reduced (p < 0.05) the apparent ileal digestibility (AID) of crude protein by 1.4% and the apparent total tract digestibility (ATTD) of organic matter, crude protein, and gross energy by 1.7, 2.3, and 1.9%, respectively, and tended to decrease (p = 0.10) the ATTD of Ca by 17.3%, relative to the low phytate diet. The dietary supplementation of the MCPC increased (p < 0.05) the AID of phosphorus (P) and calcium (Ca) by 34.2% and 31.1% for BD1 and 26.7% and 41.3% for BD2, respectively, and increased (p < 0.05) ATTD of crude fat, P, and Ca by 1.4%, 45.6%, and 9.6% for BD1 and 3.1%, 66.0%, and 52.7% for BD2, respectively. The MCPC supplementation did not significantly increase the AID and (or) ATTD of crude protein, organic matter, and starch. In conclusion, the dietary supplementation of the MCPC could improve the AID of P and Ca and the ATTD of crude fat, P, and Ca.

Immunomodulatory and antitumour bioactive labdane diterpenoids from Leonurus japonicus.

OBJECTIVES: Two labdane diterpenoids, leojapone B and heteronone B, were isolated from Leonurus japonicus Houtt., and their biological activity were evaluated in this study. METHODS: Human and mouse cancer cells, human peripheral blood mononuclear cells (PBMCs) and mouse macrophages (RAW264.7 cells) were used to evaluate the activity of leojapone B and heteronone B, while the in vivo effects of leojapone B were further examined in Lewis Lung Cancer tumour-bearing mice. KEY FINDINGS: In vitro studies showed that leojapone B selectively inhibited the proliferation of lung cancer cells, and both leojapone B and heteronone B inhibited the production of pro-inflammatory cytokines in activated PBMCs. In tumour-bearing mice model, lung tumours were reduced in size in mice treated with intraperitoneal injections of leojapone B at 20 and 30 mg/kg for 14 days. The population ratio of CD4+ /CD8+ T cells in mouse spleens was found to be increased, while regulatory T cells were decreased after leojapone B treatment. CONCLUSIONS: The inhibitory effects of leojapone B in mouse lung tumours were demonstrated for the first time in this study. The immunomodulatory activity of heteronone B were also demonstrated. Our findings indicated that both leojapone B and heteronone B may act as active components in L. japonicus.

A review on the immunomodulatory activity of Acanthopanax senticosus and its active components.

Acanthopanacis Senticosi Radix et Rhizoma seu Caulis, the dried root and rhizome or stem of Acanthopanax senticosus, is commonly known as Siberian ginseng or Ciwujia in Chinese. It is used all over the world as an adaptogen to enhance physical and mental performance for the sake of normal physiological functioning of human bodies under stress. In the theory of traditional Chinese medicine, Ciwujia can strengthen the spleen that is an essential organ for immunological response. Its traditional applications include inflammation, fatigue and cancer in which the immune-regulating function is always involved. In this article, the immunomodulatory activities of Ciwujia extracts, fractions and pure compounds were extensively reviewed first. Then, the possibility of upgrading the chemical markers to bioactive markers was explored. Finally, the potency of aqueous extract and ethanol extract in regulating cytokines production from human peripheral blood mononuclear cells was compared. We conclude that although various phytochemicals such as isofraxidin, syringin and eleutheroside E from Ciwujia have been shown to modulate immunological functions, the aqueous extract of Ciwujia as a whole possesses the most potent efficacy. Therefore, aqueous (rather than ethanol) extract of Ciwujia should be used in order to benefit from its immunomodulatory properties.

Is Danggui Safe to be Taken by Breast Cancer Patients?-A Skepticism Finally Answered by Comprehensive Preclinical Evidence.

Angelica sinensis (AS, Danggui) has long been regarded to stimulate breast cancer growth; hence, the use of AS in breast cancer patients remains a major concern for both patients and practitioners. Since safety studies of herbs would be unethical to carry out in patients, the present study aimed to investigate the potential unsafe effects of AS in a systematic pre-clinical approach. Human breast cancer cells, breast orthotopic tumor-bearing mouse models, as well as primary breast cancer cells from patients' tumors were used to evaluate the effect of AS hot water extract on the progression of breast tumors and/or growth of breast cancer cells. We showed that AS is not that stimulatory in breast cancer both in vitro and in vivo, though AS should still be used with caution in estrogen receptor-positive breast cancer patients. This novel approach of applying breast cancer cell lines, xenograft, and syngeneic tumors models, as well as primary breast cancer cells from patients' tumors in Chinese medicines safety evaluation was proven feasible. Our finding is important information for patients, Chinese medicine practitioners, and clinicians on the safety use of AS in breast cancer, which will affect future clinical practice.

Evaluation of the safety profiles of estrogenic Chinese herbal medicines in breast cancer.

BACKGROUND: An increasing number of breast cancer patients in Asian countries has been found to consume dietary supplements including phytoestrogen-rich Chinese herbal medicines with an expectation to alleviate the side effects of conventional cancer therapies. PURPOSE: The question of whether estrogenic Chinese herbal medicines are beneficial or detrimental to the health of breast cancer patients remains uncertain. STUDY DESIGN: The present study aimed at establishing a systematic approach to look at the safety profiles of estrogenic Chinese herbal medicines (CHM). METHODS: The effects of estrogenic CHM on the growth of human breast cancer cells as well as the progression of breast tumors in mice have been investigated. RESULTS: Our results demonstrated that among 10 selected estrogenic CHM, the aqueous extracts of Cistanche deserticola (CD) and Dioscorea opposita (DO) at 0.4 to 1.6 mg/ml significantly stimulated cell viability in both estrogen receptor (ER)-positive (MDA-MB-361 and MCF-7) and ER-negative (SKBR3 and MDA-MB-231) breast cancer cells. However, results from animal studies showed that no significant difference was found on the size of mouse 4T1 breast tumors in CD- and DO-treated mice when compared with the control group, while the number of proliferative cells were found to be increased in DO-treated group. Besides, CD and DO treatments induced significant immunomodulatory effects on 4T1 tumor-bearing mice by increasing the production of cytokines IL-2 and IFN-γ and modulation of regulatory T-cells. Furthermore, CD and DO treatments did not stimulate, but in fact suppressed human triple-negative MDA-MB-231 breast xenografts growth in immunodeficiency mice. CONCLUSION: The considerable concerns on the use of CD and DO in breast cancer patients could be relieved to some extents upon the findings of this pre-clinical study. The potential harmful effects of estrogenic Chinese herbal medicines on breast cancer growth should be verified in both cell-based and tumor-bearing mice models.

Berberine Induces Cell Apoptosis through Cytochrome C/Apoptotic Protease-Activating Factor 1/Caspase-3 and Apoptosis Inducing Factor Pathway in Mouse Insulinoma Cells.

OBJECTIVE: To investigate apoptotic effects of berberine, a significant alkaloids component existing in Rhizoma coptidis, and its possible acting mechanism in insulinoma cells. METHODS: Different concentrations of berberine were used to treat mouse insulinoma (MIN6) cells for various period of time. The viability and apoptosis of the cells were analyzed using methylthiazolyldiphenvl-tetrazolium bromide assay, flow cytometry and enzyme-linked immuno sorbent assay. Changes in the relating pro- and anti-apoptosis proteins were detected by western-blotting. RESULTS: The half-maximal inhibitory concentration (IC50) of berberine was 5.7 µmol/L on MIN6 cells viability for 16 h. Berberine caused a 20% reduction (P<0.05) in cell number after only 4-h incubation; which reached 50% after 24 h (P<0.01). Berberine treatment for 16 h significantly increased the level of DNA fragmentation. The flow cytometry showed the apoptotic rate increased 2.9- and 4.6-fold after treating with berberine (5 µmol/L) for 8 and 16 h, while 3- and 8.7-fold after 10 µmol/L treatment for 8 and 16 h (P<0.01). Berberine treatment dramatically elevated the expression ratio of Bax to Bcl-2. Meanwhile, berberine notably increased the apoptosis-inducing factors and cytochrome C transforming from the mitochondria to the cytoplasm. Apoptotic protease-activating factor 1 (Apaf-1) was subsequently activated after cytochrome C release. Furthermore, caspase-3 and poly adenosine diphosphate-ribose polymerase were also activated to trigger apoptosis cascade. CONCLUSION: High concentration (5 and 10 µmol/L) of berberine could induce the apoptosis of MIN6 cells through cytochrome C/Apaf-1/caspase-3 and apoptosis inducing factor (AIF) pathway.