Tanshinone IIA potentiates the chemotherapeutic effect of doxorubicin against breast cancer cells and attenuates the cardiotoxicity of doxorubicin by regulating ERK1/2 pathway.

Doxorubicin (Dox) is frequently employed as a chemotherapy agent for breast cancer. As the chemotherapy moves forward, breast cancer cells tend to develop resistance to Dox, besides that, Dox are also easy to cause cardiotoxicity related to cumulative dose. Therefore, how to potentiate the chemosensitivity of breast cancer cells to Dox while attenuating its cardiotoxicity has become a research hotspot. Tanshinone IIA (Tan IIA) is known for its anticancer activity as well as for its cardioprotective effects. In view of the aforementioned facts, we assessed whether Tan IIA possesses synergism and attenuation effect on Dox for breast cancer chemotherapy. Our studies in vitro indicated that, Tan IIA could potentiate the effect of Dox on breast cancer cells proliferation inhibition and apoptosis promotion by inhibiting ERK1/2 pathway, but interestingly, Tan IIA attenuated the cytotoxicity of Dox to myocardial cells by activating ERK1/2 pathway. Additionally, our studies in vivo also suggested that Tan IIA potentiated the chemotherapeutic effect of Dox against breast cancer while attenuating Dox-induced myocardial injury. Given that Tan IIA had a synergism and attenuation effect on Dox, we believed that Tan IIA can be used as an ideal drug in combination with Dox for breast cancer therapy.

Quercetin inhibits chronic stress-mediated progression of triple-negative breast cancer by blocking ß2-AR/ERK1/2 pathway.

Chronic stress-mediated sustained release of neurotransmitters, which ultimately leads to the activation of ß2-adrenergic receptor (ß2-AR) signaling, is one of the most important reasons for triple-negative breast cancer (TBNC) progression. Quercetin (Que) has been proven to have the advantage of ameliorating stress psychological disorder. Our present study aimed to investigate the effect of Que on tumor growth and metastasis in TNBC xenograft mice undergoing stress, and to explore its underlying mechanisms. We first evaluated the effect of Que on the progression of TNBC in nude mice in vivo. The results showed that, Que could inhibit chronic stress-induced TNBC growth and occurrence of lung metastasis. We subsequently employed epinephrine (E) as a representative of stress hormone to investigate its possible mechanism in vitro. The results showed that, Que could inhibit E-mediated proliferation and migration of TNBC cells by blocking ß2-AR/ERK1/2 pathway. In conclusion, our data demonstrated that Que could inhibit chronic stress-induced ERK1/2 activity in TNBC cells, and thereby weakening the potential for TNBC growth and metastasis.

Assessing residual motor function in patients with disorders of consciousness by brain network properties of task-state EEG.

Recent achievements in evaluating the residual consciousness of patients with disorders of consciousness (DOCs) have demonstrated that spontaneous or evoked electroencephalography (EEG) could be used to improve consciousness state diagnostic classification. Recent studies showed that the EEG signal of the task-state could better characterize the conscious state and cognitive ability of the brain, but it has rarely been used in consciousness assessment. A cue-guide motor task experiment was designed, and task-state EEG were collected from 18 patients with unresponsive wakefulness syndrome (UWS), 29 patients in a minimally conscious state (MCS), and 19 healthy controls. To obtain the markers of residual motor function in patients with DOC, the event-related potential (ERP), scalp topography, and time-frequency maps were analyzed. Then the coherence (COH) and debiased weighted phase lag index (dwPLI) networks in the delta, theta, alpha, beta, and gamma bands were constructed, and the correlations of network properties and JFK Coma Recovery Scale-Revised (CRS-R) motor function scores were calculated. The results showed that there was an obvious readiness potential (RP) at the Cz position during the motor preparation process in the MCS group, but no RP was observed in the UWS group. Moreover, the node degree properties of the COH network in the theta and alpha bands and the global efficiency properties of the dwPLI network in the theta band were significantly greater in the MCS group compared to the UWS group. The above network properties and CRS-R motor function scores showed a strong linear correlation. These findings demonstrated that the brain network properties of task-state EEG could be markers of residual motor function of DOC patients. Supplementary Information: The online version contains supplementary material available at 10.1007/s11571-021-09741-7.

Quercetin attenuates the cardiotoxicity of doxorubicin-cyclophosphamide regimen and potentiates its chemotherapeutic effect against triple-negative breast cancer.

Doxorubicin combined with cyclophosphamide (AC) is the most commonly used regimen for triple-negative breast cancer (TNBC) chemotherapy; however, its clinical application is severely limited by its serious adverse effect on cardiomyocytes. The cardiotoxicity of AC is mainly the result of oxidative stress caused by the imbalance between reactive oxygen species (ROS) and antioxidants, and it also involves multiple signaling pathways. Quercetin (Que) has been proven to possess strong antioxidant activity, and therefore we investigated whether it had potential protective effect against AC-induced cardiotoxicity. Meanwhile, we also evaluated its effect on the antitumor activity of AC. Our in vitro studies showed that Que could attenuate AC-induced cardiotoxicity by inhibiting ROS accumulation and activating ERK1/2 pathway in cardiomyocytes, but interestingly, Que could enhance the antitumor activity of AC by inhibiting ROS accumulation and ERK1/2 pathway in TNBC cells. In addition, our in vivo studies further confirmed that Que could enhance the chemotherapeutic effect of AC against TNBC while it reduced the injury of cardiotoxicity induced by AC. Therefore, Que could be used as a novel agent for the treatment of cardiotoxicity induced by AC regimen in TNBC chemotherapy.

Tanshinone II A improves the chemosensitivity of breast cancer cells to doxorubicin by inhibiting ß-catenin nuclear translocation.

Numerous evidence link aberrant nuclear ß-catenin accumulation to the development of breast cancer resistance, therefore, targeted inhibition of ß-catenin nuclear translocation may effectively improve the chemosensitivity of breast cancer. Doxorubicin (Dox) is the most commonly used chemotherapeutic drug for breast cancer. Here, we determined that tanshinone II A (Tan II A) could improve the sensitivity of Dox-resistant breast cancer MCF-7/dox cells to Dox, and evaluated whether the sensitization effect of Tan II A on Dox was targeted to inhibit ß-catenin nuclear translocation. The results showed that Tan II A not only significantly inhibited the nuclear translocation of ß-catenin in MCF-7/dox cells treated by Dox but also inhibited the nuclear translocation of ß-catenin in MCF-7 cells treated by Dox to a certain degree. Furthermore, when the above two cells treated by Dox combined with Tan II A were intervened with ß-catenin agonist WAY-262611, with the re-nuclear translocation of ß-catenin in the cells, the sensitization effect of Tan II A on Dox was greatly reduced. These results indicated that Tan II A could improve the chemosensitivity of breast cancer cells to Dox by inhibiting ß-catenin nuclear translocation. Therefore, Tan II A could be used as a potential chemosensitizer in combination with Dox for breast cancer chemotherapy.

Tanshinone IIA promotes cardiac differentiation and improves cell motility by modulating the Wnt/ß­catenin signaling pathway.

Although the cardiovascular pharmacological actions of Tanshinone IIA (TanIIA) have been extensively studied, research on its roles in cardiac regeneration is still insufficient. The present study employed the cardiac myoblast cell line H9c2 to evaluate the possible roles of TanIIA in cardiac regeneration. It was found that certain concentration of TanIIA inhibited cell proliferation by suppressing the expression of proteins related to the cell cycle [cyclin dependent kinase (CDK)4, CDK6 and cyclin D1] and proliferation [c­Myc, octamer­binding transcription factor 4 (Oct4) and proliferating cell nuclear antigen (PCNA)] without inducing apoptosis. In this process, the expression of cardiac troponin in the treated cells was significantly increased and the migration of the treated cells toward the wound area was significantly enhanced. Meanwhile, TanIIA inhibited the canonical signaling pathway through increasing the expression of glycogen synthase kinase 3ß (GSK­3ß) and adenomatous polyposis coli (APC) and increased the expression of Wnt11 and Wnt5a in the noncanonical Wnt signaling pathway. Following ß­catenin agonist WAY­262611 intervention, the effect of TanIIA on the promotion of cardiac differentiation and improved cell migration was significantly reduced. In conclusion, it was hypothesized that TanIIA could promote cardiac differentiation and improve cell motility by modulating the Wnt/ß­catenin signaling pathway. These results suggest that TanIIA may play beneficial roles in myocardial regeneration following stem cell transplantation.

Allium macrostemon Saponin Inhibits Activation of Platelet via the CD40 Signaling Pathway.

Allium macrostemon saponin is a traditional Chinese medicine that exhibits anti-atherosclerosis effects. However, the mechanism of its action has not been fully clarified. Platelet activation induced by CD40L plays an important role in the process of atherosis. In the present study, we demonstrate for the first time that A. macrostemon saponin inhibits platelet activation induced by CD40L. Moreover, the effects of saponin on platelet activation were achieved by activation of the classical CD40L-associated pathway, including the PI3K/Akt, MAPK and NF-κB proteins. In addition, the present study further demonstrated that saponin exhibited an effect on the TRAF2-mediated ubiquitination degradation, which contributed to the inhibition of the CD40 pathway and its downstream members. The findings determine that A. macrostemon saponin inhibits activation of platelets via activation of downstream proteins of the CD40 pathway. This in turn affected TRAF2-associated ubiquitination degradation and caused an anti-thrombotic effect.

Combination of tanshinone IIA and doxorubicin possesses synergism and attenuation effects on doxorubicin in the treatment of breast cancer.

Doxorubicin (Dox) is a first-line drug for breast cancer chemotherapy. However, with the prolongation of chemotherapy cycle, breast cancer cells are increasingly tempt to resist Dox, and meanwhile, high cumulative dose of Dox brings enhancing toxic side effects, and these effects may lead to chemotherapy failure. Hence, it is necessary to search an agent in combination medication with Dox, which can not only enhance the chemosensitivity of Dox but also reduce the toxic side effects. Tanshinone IIA (Tan IIA) is reported to have antitumor activity in addition to its cardiovascular protective effects. We employed human breast cancer MCF-7 and MCF-7/dox cells in order to assess whether Tan IIA might perform such function. Our in vitro studies showed that Tan IIA could enhance the sensitivity of breast cancer cells to Dox through inhibiting the PTEN/AKT pathway and downregulating the expression of efflux ABC transporters including P-gp, BCRP, and MRP1. In addition, our in vivo studies showed Tan IIA enhanced the chemotherapeutic effect of Dox against breast cancer while reducing its toxic side effects including weight loss, myelosuppression, cardiotoxicity, and nephrotoxicity. Therefore, Tan IIA could be used as a novel agent combined with Dox in breast cancer therapy.

Quercetin reversed MDR in breast cancer cells through down-regulating P-gp expression and eliminating cancer stem cells mediated by YB-1 nuclear translocation.

Overexpression of P-glycoprotein (P-gp) plays an important role in mediating multidrug resistance (MDR), resulting in chemotherapy failure of tumor patients and enhancement of cancer stem cell characteristics. By preparing doxorubicin (Dox) resistant human breast cancer MCF-7 cells, here, we wanted to evaluate the effects of quercetin (Que) on MDR reversal activity and investigate its possible mechanism. MCF-7 and MCF-7/dox cells were respectively treated by Dox, paclitaxel (Pac), or vincristine (Vcr) with or without Que intervention for 24 hr. Cell viability, cell apoptosis, cell cycle, intracellular drug accumulation, the expression of P-gp and Y-box binding protein 1 (YB-1), and breast cancer stem cells (BCSCs) were then assessed. The results showed that Que significantly enhanced the antitumor activities of Dox, Pac, and Vcr in breast cancer cells. In addition, combined treatment of Dox, Pac, or Vcr with Que significantly downregulated P-gp expression and eliminated BCSCs. Furthermore, combined treatment of Dox, Pac, or Vcr with Que significantly inhibited nuclear translocation of YB-1. Thus, we speculated that Que reversed MDR in breast cancer cells through downregulating P-gp expression and eliminating cancer stem cells mediated by YB-1 nuclear translocation.

Quercetin enhances chemotherapeutic effect of doxorubicin against human breast cancer cells while reducing toxic side effects of it.

Doxorubicin (Dox) is an efficient drug for breast cancer chemotherapy, however, its toxic side effects on non-tumor tissues, especially on myocardial cells, sometimes limit its clinical application. Therefore, it is necessary to develop a new drug, which can be combined with Dox to potentiate the anti-tumor effect of Dox at a lower concentration and attenuate the toxic side effects of it. Quercetin (Que) has anti-tumor activity in addition to its protective effects on various cells. By preparing human non-tumoral MCF-10A mammary cells, human breast cancer MCF-7 and MDA-MB-231 cells and human myocardial AC16 cells, here, we wanted to evaluate whether Que might represent such an agent and investigate its possible mechanisms of potentiating the anti-tumor effect of Dox at a lower concentration. The results showed that Que could increase intracellular accumulation of Dox in breast cancer cells through down-regulating the expression of efflux ABC transporters including P-gp, BCRP and MRP1, which can effectively eliminate cancerous cells including breast cancer stem cells (BCSCs), thereby potentiating the anti-tumor effect of Dox. Furthermore, Que attenuated the cytotoxicity of Dox to non-tumoral MCF-10A mammary cells and myocardial AC16 cells. Therefore, Que could be used as a novel agent combined with Dox in breast cancer therapy, which could potentiate the anti-tumor effect of Dox at a lower concentration and attenuate the toxic side effects of it.

Effective component of Salvia miltiorrhiza in promoting cardiomyogenic differentiation of human placenta­derived mesenchymal stem cells.

Our previous study indicated that Salvia miltiorrhiza (SM) induced human placenta­derived mesenchymal stem cells (hPDMSCs) to differentiate into cardiomyocytes, however, the effective component of SM in promoting cardiomyogenic differentiation remained to be elucidated. In the present study, the most commonly examined components of SM, including danshensu, salvianolic acid B, protocatechuic aldehyde, tanshinone I (TS I), TS IIA and cryptotanshinone, were used to determine the effective components of SM in promoting cardiomyogenic differentiation. The above components of SM slowed cell growth rate and altered cell morphology with a spindle or irregular shape to different degrees. The cells treated with the above components of SM showed increasing of cardiac protein expression to differing degrees, including GATA­binding protein 4, atrial natriuretic factor, α­sarcomeric actin and cardiac troponin­I. Among the components of SM, TS IIA induced the most marked effects. In addition, the above components of SM increased the expression of phosphorylated glycogen synthase kinase­3ß, but decreased the expression of ß­catenin to different degrees, with TS IIA also having the most marked effects. In conclusion, the results of the present study suggested that TS IIA was the most effective active component of SM in inducing hPDMSCs to differentiate into cardiomyocytes, and that Wnt/ß­catenin signaling was important in the process of TS IIA promoting cardiomyogenic differentiation.

A large outbreak of acute gastroenteritis caused by the human norovirus GII.17 strain at a university in Henan Province, China.

BACKGROUND: Human noroviruses are a major cause of viral gastroenteritis and are the main etiological agents of acute gastroenteritis outbreaks. An increasing number of outbreaks and sporadic cases of norovirus have been reported in China in recent years. There was a large acute gastroenteritis outbreak at a university in Henan Province, China in the past five years. We want to identify the source, transmission routes of the outbreak by epidemiological investigation and laboratory testing in order to provide the effective control measures. METHODS: The clinical cases were investigated, and analysed by descriptive epidemiological methods according to factors such as time, department, grade and so on. Samples were collected from clinical cases, healthy persons, the environment, water, and food at the university. These samples were tested for potential bacteria and viruses. The samples that tested positive for norovirus were selected for whole genome sequencing and the sequences were then analysed. RESULTS: From 4 March to 3 April 2015, a total of 753 acute diarrhoea cases were reported at the university; the attack rate was 3.29%. The epidemic curve showed two peaks, with the main peak occurring between 10 and 20 March, accounting for 85.26% of reported cases. The rates of norovirus detection in samples from confirmed cases, people without symptoms, and environmental samples were 32.72%, 17.39%, and 9.17%, respectively. The phylogenetic analysis showed that the norovirus belonged to the genotype GII.17. CONCLUSIONS: This is the largest and most severe outbreak caused by genotype GII.17 norovirus in recent years in China. The GII.17 viruses displayed high epidemic activity and have become a dominant strain in China since the winter of 2014, having replaced the previously dominant GII.4 Sydney 2012 strain.

[Investigation of Aerosol Mixed State and CCN Activity in Nanjing].

During 11-18 September 2014, the size-resolved aerosol Cloud Condensation Nuclei (CCN) activity and mixing state were measured using Cloud Condensation Nuclei Counter (CCNC), Aerosol Particle Mass (APM) and Scanning Mobility Particle Sizer (SMPS). The results showed that aerosols mainly existed as an internal mixture. For 76, 111, 138 and 181 nm particles, black carbon (BC) accounted for 5.4%, 10%, l0.7% and 6.7% of the particle mass, but as high as 51%, 57%, 70% and 59% of the particle number concentrations, respectively, suggesting that BC was a type of important condensation nuclei in the atmosphere and made significant contributions to particle numbers. The occasionally observed external mixtures were mainly present in 111 and 138 nm particles. The critical supersaturation was 0.25%, 0.13%, 0.06% and 0.015% for 76, 111, 138 and 181 nm particles, respectively. Precipitation and haze had significant effects on the particle CCN activity. The hygroscopicity parameter K was 0.37, 0.29 and 0.39 in rainy, clear and hazy days, respectively. Particle density and CCN activity were impacted by chemical compositions. Compared with clear days, higher contents of inorganic salts and lower contents of organics were found on hazy days, accompanied by lower particle density and higher CCN activity.

An intensive study on aerosol optical properties and affecting factors in Nanjing, China.

The optical properties of aerosol as well as their impacting factors were investigated at a suburb site in Nanjing during autumn from 14 to 28 November 2012. More severe pollution was found together with lower visibility. The average scattering and absorption coefficients (Bsca and Babs) were 375.7 ± 209.5 and 41.6 ± 18.7 Mm(-1), respectively. Higher Ångström absorption and scattering exponents were attributed to the presence of more aged aerosol with smaller particles. Relative humidity (RH) was a key factor affecting aerosol extinction. High RH resulted in the impairment of visibility, with hygroscopic growth being independent of the dry extinction coefficient. The hygroscopic growth factor was 1.8 ± 1.2 with RH from 19% to 85%. Light absorption was enhanced by organic carbon (OC), elemental carbon (EC) and EC coatings, with contributions of 26%, 44% and 75% (532 nm), respectively. The Bsca and Babs increased with increasing N100 (number concentration of PM2.5 with diameter above 100 nm), PM1 surface concentration and PM2.5 mass concentration with good correlation.

Quercetin Increase the Chemosensitivity of Breast Cancer Cells to Doxorubicin Via PTEN/Akt Pathway.

Our previous study indicated that nontoxic doses of quercetin (Que) could increase the chemosensitivity of breast cancer cells to doxorubicin (Dox) although the mechanism still remains elusive. Therefore, in this study, we aimed to investigate the underlying mechanisms. MCF-7 cells and MCF-7/dox cells were exposed to PTEN inhibitor bpV (HOpic), Dox, or combination of Dox and Que with or without bpV (HOpic) intervention for 24 hours. Cell proliferation, cell apoptosis, cell invasion and expression of PTEN and phospho-Akt (p-Akt) were then assessed. bpV (HOpic) had little effect on cell proliferation at concentrations less than 1 µM. Compared to treatment with Dox alone, combined treatment with Dox and Que significantly inhibited cell proliferation and invasion, increased cell apoptosis, up-regulated the expression of PTEN and down-regulated the expression of p-Akt. However, co-treatment with PTEN inhibitor bpV (HOpic) could revert the effects of Que on Dox. These data indicate that Que can increase the sensitivity of breast cancer cells to Dox through down regulation of p-Akt expression arising from increased expression of PTEN.

[Effect of ASO Blood Stasis Syndrome Serum on Vascular Endothelial Cell Injury and Regulation of Taohong Siwu Decoction on it].

OBJECTIVE: To explore the effect of arteriosclerosis obliterans (ASO) blood stasis syndrome (BSS) serum on vascular endothelial cell injury and to study the regulation of Taohong Siwu Decoction (TSD) on it. METHODS: Umbilical vein endothelial cell culture system was established. The serum endothelial cell injury model with ASO BSS was prepared. Low, medium, and high concentrations TSD containing serums were respectively added. The endothelial cell proliferation activity was observed by MTT method. Ultrastructures of endothelial cells were observed under transmission electron microscope. Changes of intracellular calcium ion concentration and the cytoskeleton were observed under laser confocal microscope. Contents of ET, NO, and transforming growth factor beta1 (TGF-beta1) in endothelial cell culture supernatant were detected by ELISA. RESULTS: In ASO BSS serum group endothelial cell proliferation activities decreased, the cell structure was obviously destroyed, calcium ion concentration increased, contents of ET, NO and TGF-beta1 increased significantly (P < 0.01), and ET/NO ratio was imbalanced. After incubating with TSD drug containing serum, endothelial cell proliferation activities and injured cell structures were obviously improved; ET, NO and TGF-beta1 levels decreased (P < 0.05, P < 0.01), ET/NO ratios approximated to the normal level. CONCLUSION: The main mechanism of TSD for treating ASO ASS lied in improving injured vascular endothelial cells and endocrine disorder.

The role of glutamate decarboxylase 65 in gastric cancer development, progression, and prognosis.

AIMS: Recent studies have revealed that glutamate decarboxylase 65 (GAD65) plays important roles in cancer progression. The role of GAD65 in gastric cancer development, progression and prognosis is currently unknown, and we aimed to investigate this. METHODS AND RESULTS: Immunohistochemistry revealed that GAD65 expression in 313 gastric cancer tissues was significantly higher than in 60 adjacent non-tumour tissues. Moreover, the expression level of GAD65 significantly correlated with the depth of tumour invasion and TNM stage. GAD65 expression level was a significant prognostic factor in univariate survival analysis, but did not remain an independent prognostic factor following Cox multivariate analysis. For tumours with an intermediate type growth pattern, when those showing low expression of GAD65 were reclassified with expanding type tumours, and those showing high expression with infiltrative type tumours, there was a significant difference in prognosis between these two novel subgroups, and this remained a significant prognostic factor in multivariate analysis. CONCLUSIONS: Our findings indicate that GAD65 is involved in the development and progression of gastric cancer as a tumour oncoprotein. Further elucidation of the molecular mechanisms underlying the role of GAD65 is warranted.

The effect of quercetin on doxorubicin cytotoxicity in human breast cancer cells.

Multidrug resistance has became the major obstacle to cancer chemotherapy. Recent studies suggest that quercetin could enhance the response of tumors to chemotherapy although the mechanism by which quercetin enhances the sensitivity of tumor cells to chemical drugs remains elusive. Therefore, in this study, we examined the effects of quercetin on doxorubicin cytotoxicity in human breast cancer cells and investigated the underlying mechanisms. MCF-7 and MCF-7/ dox cells were exposed to doxorubicin, quercetin, or combination of both agents for 36 hours. Cell proliferation, cell invasion, intracellular doxorubicin concentration and expression of hypoxia-inducible factor-1 alpha (HIF-1α) and P-glycoprotein (P-gp) were then assessed. Quercetin had little effect on cell proliferation at concentrations less than 0.7 µM. Compared to treatment with doxorubicin alone, combined treatment with doxorubicin and quercetin (0.7 µM) significantly inhibited cell proliferation and invasion and suppressed the expression of HIF-1α and P-gp. Quercetin (0.7 µM) increased the intracellular doxorubicin concentration and enhanced doxorubicin cytotoxicity as 1.49-fold in MCF-7 cells and 1.98-fold in MCF-7/dox cells. These data suggest that quercetin can increase the chemosensitivity of breast cancer cells to doxorubicin.

The effects of dan-shen root on cardiomyogenic differentiation of human placenta-derived mesenchymal stem cells.

The aim of this study was to search for a good inducer agent using for cardiomyogenic differentiation of stem cells. Human placenta-derived mesenchymal stem cells (hPDMSCs) were isolated and incubated in enriched medium. Fourth passaged cells were treated with 10mg/L dan-shen root for 20 days. Morphologic characteristics were analyzed by confocal and electron microscopy. Expression of α-sarcomeric actin was analyzed by immunohistochemistry. Expression of cardiac troponin-I (TnI) was analyzed by immunohistofluorescence. Atrial natriuretic factor (ANF) and beta-myocin heavy chain (ß-MHC) were detected by reverse transcriptase polymerase chain reaction (RT-PCR). hPDMSCs treated with dan-shen root gradually formed a stick-like morphology and connected with adjoining cells. On the 20th day, most of the induced cells stained positive with α-sarcomeric actin and TnI antibody. ANF and ß-MHC were also detected in the induced cells. Approximately 80% of the cells were successfully transdifferentiated into cardiomyocytes. In conclusion, dan-shen root is a good inducer agent used for cardiomyogenic differentiation of hPDMSCs.