Comprehensive regulation of traditional Chinese medicine on proliferation and differentiation of neural stem cells

Since the diccovery of neural stem cells(NSCs)in the embryonic and adult mammalian central nerous system,it provided novel ideas forneurogenesis as the potential of proliferation and differentiation of NSCs.One of the ways to promote the clinical application of neural stem cells(NSCs)is searching effective methods which regulate the proliferation and differentiation.This is also a problem urgently to be solved in medical field.Plenty of earlier studies have shown that traditional chinese medicine can promote the proliferation and differentiation of NSCs by regulating the related signaling pathway in vivo and in vitro.The reports of Chinese and foreign literatures on regulating the proliferation and differentiation of neural stem cells in recent ten years and their target and signaling pathways is analyzed in this review.The traditional chinese medicine regulate proliferation and differentiation of NSCs by the signaling pathways of Notch,PI3K/Akt,Wnt/β-catenin,and GFs.And,those signaling pathways have cross-talk in the regulation progress.Moreover,some traditional Chinese medicine,such as astragalus,has a variety of active ingredients to regulate proliferation and differentiation of NSCs through different signaling pathways.However,to accelerate the clinical application of neural stem cells,the studies aboutthe proliferation and differentiation of NSCs and Chinese medicine should be further deepened,the mechanism of multiple targets and the comprehensive regulation function of traditional Chinese medicine should be clarified.

Studies on the Degranulation of RBL-2H3 Cells Induced by Traditional Chinese Medicine Injections

Aims: To study RBL-2H3 cell degranulation phenomena induced by some TCMIs through cell morphological and ultra-structural observation, released enzyme activity and establish RBL-2H3 cell degranulation test indicated by β- hexosaminidase activity as a method to evaluate TCMIs at nonclinical stage. Methods: RBL-2H3 cells were used to study the degranulation by co-culture with positive control C48/80 and some TCMIs through morphological and ultra-structure observation, β-hexosaminidase activity detection. RBL-2H3 cell degranulation test was established to detect β-hexosaminidase activity caused by 17 kinds of TCMIs and their ingredients. The cytotoxicity effect of some TCMIs on both RBL 2H3 and BRL cells was measured by CCK-8 assay. Results: Toluidine blue staining and ultra-structure of electronic microscope observation of treated RBL-2H3 cells showed degranulation morphologically. Detection of β-hexosaminidase activity in the supernatant of treated cells showed some TCMIs had elevated enzyme release rates. Further analysis of the ingredients and compound in Tanreqing Injection and Shengmai Injection showed Scutellaria baicalensis Georgi in Tanreqing Injection, Red ginseng and Fructus Schisandrae Chinensis in Shengmai Injection were responsible to the degranulation of RBL-2H3 cells. Osmotic pressures and pH influenced RBL-2H3 degranulation. High Osmotic pressure of Tanreqing Injection and low pH of chlorogenic acid at 2.5 and 5.0 mmol/L congcentration might be responsible to high β-hexosaminidase activity. Most of the TCMIs inducing degranulation had cytotoxicity effect for both RBL-2H3 and BRL cells, but some TCMIs inducing degranulation had no cytotoxicity effect. Conclusion: Some TCMIs can induce degranulation of RBL-2H3 cells;RBL-2H3 cell degranulation test can be used in non-clinical stage to detect the risk causing anaphylactoid reactions. Osmotic pressures and pH influenced RBL-2H3 degranulation, and they should be measured before testing. The mechanism of degranulation caused by some TCMIs is cytotoxic, and some are non-cytotoxic and may be through exicytosis.

Nature products of traditional Chinese medicine provide new ideas in γδT cells for tumor immunotherapy

Due to the unique features of innate immune cells, the role of γδT cells in tumor immunity has gradually attracted more and more attention. Previous studies have found that γδT cells play a dual role in tumor immunology: tumor-promoting and tumor-controlling.The anti-tumor therapy of γδT cells has made remarkable success in clinical application. Especially in recent years, researchers have provided some novel effective ways such as γδT cells exosomes and adoptive chimeric antigen receptor-γδT cells immunotherapy. However, some problems remain to be solved, such as low expansion rate, poor targeting, and tumor microenvironment limiting the effectiveness of γδT immunotherapy. Traditional Chinese medicine is expected to play a positive role in the body immune-enhancing function, promoting the proliferation and activation of γδT cells, and inducing the differentiation ofγδT cells. In this review, we summarize the recent research progress and urgent problems of γδT cells in anti-tumor immunotherapy. Moreover, some new strategies of γδT cells for tumor immunotherapy were proposed.

Progress in diagnosis and treatment of small cell lung cancer with integrated traditional Chinese and Western medicine

Lung cancer is one of the most common major diseases that seriously threaten human health,lung cancer includes small cell lung cancer(SCLC)and non-small cell lung cancer(NSCLC).Although patients with SCLC account for about 20%of the total number of patients with lung cancer,the mortality rate is much higher than that of patients with NSCLC.Integrated traditional Chinese and Western medicine has obvious advantages in the treatment of patients with SCLC.According to the relevant literature reports on the treatment of SCLC in recent years,this article will summarize the research progress of integrated traditional Chinese and western medicine in the treatmentof SCLC from the aspects of traditional Chinese medicine(TCM)combined with surgery,chemotherapy,radiotherapy,and molecular targeted therapy.

Research progress of protective effect of traditional Chinese medicine on brain cells

Objective:To review the protective effect of traditional Chinese medicine(TCM)on brain cells.Methods:The domestic journals and literature are searched and reviewed,classifies them according to the mechanisms of TCM,summaries their protective effect on brain cells.Results:Some single medicine and prescriptions possess a variety of biological activity,and has a protective effect on brain cells.Conclusion:Some TCM possess a variety of biological activity and have a protective effect on brain cells,so there are broad prospects to develop and apply these TCM.

Experimental Study of the Anti-human Papilloma Virus Mechanisms by a Traditional Chinese Medicine “Keyouling”

To investigate the anti-human papilloma virus (HPV) effect of the external liniment of traditional Chinese medicine “Keyouling”, the efficacy of this drug acting upon the proliferation and growth of the normal epidermis cells of rabbits′ penis prepuce in different concentrations was observed. An experimental model of pathology of histocytes infected with HPV in vitro was established by using the human HPV infected prepuce epidermis cells as virus carrier to infect the sub-cultured epidermis cells of rabbits′ penis prepuce. The direct killing effect and the blocking effect of infections of epidermis cells in rabbits′ penis prepuce induced by HPV with different concentrations of “Keyouling” were determined by 3 kinds of culture methods: (1) the infected epidermis cells of rabbits′ penis prepuce were challenged by co-culture with HPV suspension and with culture medium containing drug; (2) the co-culture with epidermis cells of rabbits′ penis prepuce and HPV suspension was challenged with drug; (3) co-culture with culture medium containing drug and epidermis cells of rabbits′ penis prepuce was challenged with HPV suspension. It was found that “Keyouling” had little effect on the proliferation and growth of the normal epidermis cells of rabbits′ penis prepuce, but it had direct killing effect on HPV, and blocked effectively the infection of the epidermis cells of rabbits′ penis prepuce by HPV. It concludes that “Keyouling” has significant killing effect to HPV, but not normal histocytes in vitro , indicating that it is safe for clinical use. Its blocking effect on the HPV infection of rabbits′ penis prepuce epidermis cells suggested “Keyouling” may be clinically used to prevent the development of tumors or to inhibit the further progression or metastasis of tumors.

Progress in research of single-flavor Chinese medicine extracts in treatment of non-small cell lung cancer

Lung cancer is one of the diseases with high morbidity and mortality,and non-small cell lung cancer accounts for a large proportion of it.Traditional Chinese medicine has a long history in treating tumors.More and more researchers have paid more attention to it.At present,many studies have proved that traditional Chinese medicine extracts such as astragalus,turmeric,ginseng,coix seed,and gallbladder can inhibit tumor cell proliferation,and have synergistic effects when used in combination with radiotherapy and chemotherapy Its mechanism of action is mostly related to regulating the cell cycle,inhibiting the expression of cancer-related genes,and inducing apoptosis.It is believed that with the development of purification technology,Chinese medicine extracts will play a greater role.

Therapeutic potential of natural compounds from Chinese medicine in acute and subacute phases of ischemic stroke

Stroke is one of the leading causes of death and disability in adults worldwide,resulting in huge social and financial burdens.Extracts from herbs,especially those used in Chinese medicine,have emerged as new pharmaceuticals for stroke treatment.Here we review the evidence from preclinical studies investigating neuroprotective properties of Chinese medicinal compounds through their application in acute and subacute phases of ischemic stroke,and highlight potential mechanisms underlying their therapeutic effects.It is noteworthy that many herbal compounds have been shown to target multiple mechanisms and in combinations may exert synergistic effects on signaling pathways,thereby attenuating multiple aspects of ischemic pathology.We conclude the paper with a general discussion of the prospects for novel natural compound-based regimens against stroke.

How do Chinese medicines that tonify the kidney inhibit dopaminergic neuron apoptosis?

Wistar rats were intragastrical y perfused with Chinese medicines used for tonifying the kidney. These included 0.180 g/mL of Herba Epimedi （Epimedium）, Semen Cuscutae （Dodder Seed）, or Herba Cistanches （Desertliving Cistanche）, 0.04 mg/mL monoamine oxidase-B inhibitor selegiline, or distil ed water for 14 consecutive days to prepare drug-containing serum or blank serum. MES23.5 cells in the logarithmic phase were cultured in media supplemented with 15%drug-containing serum for 24 hours, fol owed by incubation in culture solution containing 100μmol/L H2O2 for 3 hours. 3-（4,5-Dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide （MTT） and flow tometry results showed that al drug-containing serums improved the survival rate of H 2 O 2-injured MES23.5 cells, inhibited pro-apoptotic FasL and caspase-3 expression, promoted anti-apoptotic Bcl-2 expression. However, drug-containing serums had little influence on Fas expression in H 2 O 2-injured MES23.5 cells. Enzyme-linked immunosorbent assay results showed that serum containing Herba Cistanches or Herba Epimedi increased the expression of nerve growth factor, brain-derived neurotrophic factor, and glial cellline-derived neurotrophic factor in injured MES23.5 cells;serum containing Semen Cuscutae only increased brain-derived neurotrophic factor expres-sion; while expression of the above neurotrophic factors remained the same in cells treated with serum containing selegiline. These findings indicate that Chinese medicines used to tonify the kid-ney can protect nerve cells by regulating the expression of apoptosis-related factors and neuro-trophic factors in MES23.5 cells.

Traditional Chinese medicines for non-small cell lung cancer: Therapies and mechanisms

The most common subtype of lung cancer is non-small cell lung cancer(NSCLC), which has a poor prognosis and seriously threatens the health of human beings. The multidisciplinary comprehensive treatment model has gradually become the mainstream of NSCLC treatment. Traditional Chinese medicine(TCM) can be used effectively either as an adjunctive therapy or alone throughout the NSCLC therapy,which has a significant impact on survival, quality of life, and reduction of toxicity. Therefore, this paper reviewed the theoretical basis, the latest clinical application, and combined treatment mechanisms in order to explore the advantage stage of TCM treatment and the synergistic therapeutic mechanisms.

Traditional Chinese medicine targets on hepatic stellate cells for the treatment of hepatic fibrosis: A mechanistic review

Liver cirrhosis is a leading cause of death from liver‐related diseases accompanied by a variety of complications;however,hepatic fibrosis,an inevitable stage of cirrhosis,is possible to be reversed and cured.Hepatic stellate cells(HSCs)are the primary cells that secrete extracellular matrix in the liver and play a dominant role in the pathogenesis of hepatic fibrosis.Effective therapeutic approaches for reversing hepatic fibrosis aim at inhibiting the activation of HSCs and inducing their inactivation or death.This review highlights the mechanism by which traditional Chinese medicine(TCM)regulates the activity of HSCs and exerts antifibrotic effects,providing insights and prospects for the treatment of hepatic fibrosis with TCM.

Lung Cancer Treatment in Traditional Chinese Medicine: History, Current Status, and Development

Objective:This article discusses the following aspects,including the history of traditional Chinese medicine(TCM)in the treatment of lung cancer,the breakthrough in the theory of TCM in treatment of lung cancer,clinical study of TCM in treating lung cancer,microscientific interpretation of TCM treatment for lung cancer and the prospect of TCM in treating lung cancer.Materials and Methods:In this paper,through a systematic search,combing traditional Chinese medicine prevention and treatment of lung cancer ancient books and modern literature.Results:A series of large sample and multi-centered clinical studies have proved that TCM comprehensive treatment significantly improves the clinical efficacy for lung cancer.“TCM treatment system for non-small cell lung cancer”based on staged and standardized integration of TCM and Western medicine has been well developed and popularized in practice.Furthermore,in virtue of the international cooperation platform established by the National Cancer Institute of the United States,the scientific connotation of TCM in the prevention and treatment of lung cancer is systematically and deeply studied,thereby promoting the research and development of new Chinese drugs for lung cancer.Conclusions:Nowadays,TCM has realized a landmark breakthrough in treating lung cancer,bringing benefits to all lung cancer patients.

Comparison of intestinal absorption characteristics between rhubarb traditional Chinese medicine preparation and activity ingredients using in situ and in vitro model

Objective: The intestinal absorption characteristics of active ingredients are very important for oral administration of traditional Chinese medicine(TCM) to achieve the desired therapeutic effect.However, a deeper understanding about active ingredients absorption characteristics is still lack. The aim of this study was to investigate the absorption properties and mechanism of rhubarb active ingredients in TCM preparation and pure form.Methods: The intestinal absorption behavior of active ingredients in Shenkang extract(SKE) and rhubarb anthraquinone ingredients(RAI) were investigated by in situ single-pass intestinal perfusion model. And the bidirectional transport characteristics of these active ingredients were assessed by in vitro Caco-2 cell monolayer model.Results: In situ experiment on Sprague-Dawley rats, the effective permeability coefficient values of aloeemodin, emodin and chrysophanol in RAI were higher than those in SKE, and the value of rhein in RAI was lower than that in SKE. But the easily absorbed segments of intestine were consistent for all ingredients,whether in SKE or in RAI. In vitro experiment, the apparent permeability coefficient values of rhein, emodin and chrysophanol in RAI were higher than those in SKE, and this value of aloe-emodin in RAI was lower than that in SKE. But their efflux ratio(ER) values in SKE and RAI were all similar.Conclusion: Four rhubarb anthraquinone ingredients in SKE and RAI have similar absorption mechanism and different absorption behavior, and the microenvironment of the study models influenced their absorption behavior. The results may provide an aid for understanding of the absorption characteristics of the TCM active ingredients in complex environments and the complementarities of different research models.

Celastrol activates caspase-3/GSDME-dependent pyroptosis in tumor cells by inducing endoplasmic reticulum stress Author links open overlay panel

Objective:To investigate the pyroptosis-inducing effects of celastrol on tumor cells and to explore the potential mechanisms involved,specifically focusing on the role of the caspase-3/gasdermin E(GSDME)signaling pathway and the impact of endoplasmic reticulum(ER)stress and autophagy.Methods: Necrostatin-1(Nec-1),lactate dehydrogenase release(LDH)assay,and Hoechst/propidium iodide(PI)double staining were employed to validate the mode of cell death.Western blot was used to detect the cleavage of GSDME and the expression of light chain 3(LC3)and BIP.Results: Celastrol induced cell swelling with large bubbles,which is consistent with the pyroptotic phenotype.Moreover,treatment with celastrol induced GSDME cleavage,indicating the activation of GSDME-mediated pyroptosis.GSDME knockout via CRISPR/Cas9 blocked the pyroptotic morphology of celastrol in HeLa cells.In addition,cleavage of GSDME was attenuated by a specific caspase-3 inhibitor in celastrol-treated cells,suggesting that GSDME activation was induced by caspase-3.Mechanistically,celastrol induced endoplasmic reticulum(ER)stress and autophagy in HeLa cells,and other ER stress inducers produced effects consistent with those of celastrol.Conclusion: These findings suggest that celastrol triggers caspase-3/GSDME-dependent pyroptosis via activation of ER stress,which may shed light on the potential antitumor clinical applications of celastrol.

Advances in mesenchymal stem cells combined with traditional Chinese medicine therapy for liver fibrosis

Liver fibrosis is a primary cause of liver cirrhosis, and even hepatocarcinoma. Recently, the usage of mesenchyrnal stem cells （MSCs） has been investigated to improve liver fibrosis. It has been reported that the differentiation, proliferation and migration of MSCs can be regulated by traditional Chinese medicine treatment; however, the mechanisms are still unclear. In this article, the authors review the characteristics of MSCs such as multidirectional differentiation and homing, and its application in animal experiments and clinical trials. The authors also list areas that need further investigation, and look at the future prospects of clinical application of MSCs.

Traditional Chinese medicine targeting cancer stem cells as an alternative treatment for hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is a prevalent and highly malignant cancer throughout the world.Effective treatment of this disease is impeded by the high rate of metastasis, recurrence, and chemoresistance. Recent studies have revealed the close relationship between the malignant phenotype of HCC and cancer stem cells(CSCs). Therefore, CSC-targeted therapy is considered a promising strategy to eradicate HCC. Traditional Chinese medicine(TCM) can be effective in preventing recurrence and metastasis of some advanced HCC. A growing amount of literature has discovered that extracts or compounds derived from TCM exert an anti-CSC effect. This review introduces some formulas and chemical compounds derived from TCMs that have been reported to inhibit CSCs of HCC;these TCM-related drugs may help to provide an alternative approach to help manage cancers, especially for HCC which has a great potential of metastasis, recurrence, and chemoresistance.

Dendritic Cells as a Pharmacological Target of Traditional Chinese Medicine

Dendritic cells （DCs） represent a heterogeneous population of professional antigen-presenting cells （APCs） that play a central role in the initiation and regulation of immune responses. There is considerable evidence that DCs can be used as therapeutic targets for pharmacological modulation of immune responses. Traditional Chinese medicine （TCM） has a long-standing history of using herbal medicine in the treatment of variety of human diseases. Many of the clinical effects of TCM have reportedly been attributed to the up- or down-regulation of immune responses. Accumulating evidence indicates that TCM and its components can interfere with immune responses at the earliest stage by targeting key functions of DCs. Here, we review those published studies of TCM with respect to their effects on immunobiological functions of DCs. Investigations based on both chemical entities derived from TCM as well as TCM herbal mixtures are presented. These studies suggest that various TCM herbal medicines have the capacity to inhibit or promote major functions of DCs, such as differentiation, maturation, cytokine production, survival, antigen uptake and presentation as well as trafficking. These studies have revealed novel biological effects of TCM and documented the utility of this approach to discover novel biological modifier of DC functions derived from natural sources.

Accurate construction of cell membrane biomimetic graphene nanodecoys via purposeful surface engineering to improve screening efficiency of active components of traditional Chinese medicine

Biomimetic nanoengineering presents great potential in biomedical research by integrating cell membrane(CM) with functional nanoparticles. However, preparation of CM biomimetic nanomaterials for custom applications that can avoid the aggregation of nanocarriers while maintaining the biological activity of CM remains a challenge. Herein, a high-performance CM biomimetic graphene nanodecoy was fabricated via purposeful surface engineering, where polyethylene glycol(PEG) was used to modifying magnetic graphene oxide(MGO) to improve its stability in physiological solution, so as to improve the screening efficiency to active components of traditional Chinese medicine(TCM). With this strategy, the constructed PEGylated MGO(PMGO) could keep stable at least 10 days, thus improving the CM coating efficiency. Meanwhile, by taking advantage of the inherent ability of He La cell membrane(HM) to interact with specific ligands, HM-camouflaged PMGO showed satisfied adsorption capacity(116.2 mg/g) and selectivity. Finally, three potential active components, byakangelicol, imperatorin,and isoimperatorin, were screened from Angelica dahurica, whose potential antiproliferative activity were further validated by pharmacological studies. These results demonstrated that the purposeful surfaceengineering is a promising strategy for the design of efficient CM biomimetic nanomaterials, which will promote the development of active components screening in TCM.

Chemotherapy in conjunction with traditional Chinese medicine for survival of elderly patients with advanced non-small-cell lung cancer:protocol for a randomized double-blind controlled trial

BACKGROUND： Traditional Chinese medicine （TCM） is considered an important complementary therapy with beneficial effects for cancer patients. Elderly patients with non-small-cell lung cancer （NSCLC） are a complex patient group with increasing co-morbidity and shrinking physiological reserve, and may derive substantial benefit from the supportive aspects of TCM Researchers from Shanghai Longhua Hospital found that qi and yin deficiency is a common syndrome in patients with stage III or IV lung cancer. This project was designed to study the combination of single-agent chemotherapy with TCM methods of benefiting qi and yin in elderly patients with advanced NSCLC. METHODS AND DESIGN： This is a double-blind controlled, multi-center, and prospective study with randomly selected participants from elderly NSCLC patients in China. Seventy-six patients who meet the inclusion criteria will be allocated into two groups, which will receive treatments of 3-week single-agent chemotherapy with TCM or placebo for four cycles Progression-free survival （PFS） is the primary end point, and the secondary end points are overall survival, objective response rate, time-to-progression, and quality of life （EORTC QLQ-LC43, and TCM syndrome score） Meanwhile, other end points such as toxicity, side effects and safety of the treatments will be assessed. DISCUSSION： Results from this study may provide evidence on the effectiveness, and parameters for the usage of single-agent chemotherapy combined with or without TCM on PFS of elderly patients with NSCLC.

Determination of gallic acid in the traditional Chinese medicine by high-performance capillary electrophoresis

Rhizoma Polygoni Bistortae has been widely used as an important medicinal herb in the Far East for a few thousand years, and it has gained more recognition in the last few decades. In the present study, we used a high-performance capillary electrophoresis （HPCE） method for determination of the gallic acid （GA） in Quanshen （QS） pieces. The analysis of GA in QS pieces was successfully achieved in less than 6 min by capillary electrophoresis with UV detection at a wavelength of 290 nm. The background electrolyte was 20 mmol/L sodium borate solution （pH 9.00）. The separation was performed in an uncoated fused-silica capillary （52 cm^50 lam） with an effective length of 40 cm, and the applied voltage was 20 kV. Sample solutions were injected for l0 s at an atmospheric pressure of 5 KPa. The result showed good resolution and precision （the intra-day RSD was 0.37%）. The calibration curves of the standard solutions were linear in the range of 0.22-2.25 mg/mL, with correlation coefficients greater than 0.9990. The recovery of the method ranged from 100.6% to 107.9%, and the average recovery of GA was 105.9% with an RSD of 3.63%. HPCE is a powerful technology, and it is the first time to successfully apply such a method for the determination of GA in the traditional Chinese medicine.