Research progress of antineoplastic drugs targeting platelets / 中国药理学通报

Platelets have long been recognized as key players in hemostasis and thrombosis; however, there is growing evidence that they are also involved in cancer. Preclinical and clinical studies have shown that platelets can promote tumorigenesis and metastasis through various crosstalks between platelets and cancer cells. Platelets play an active role in all stages of tumorigenesis, including tumor growth, tumor cell extravasation, and metastasis. In addition, thrombocytosis in cancer patients is associated with poor patient survival. Platelets are also well-placed to coordinate local and distant tumor-host interactions due to the a- bundance of microparticles and exosomes. Therefore, antitumor drugs targeting platelets have great development and application prospects. The following will review the research progress of anti-tumor drugs targeting platelets.

Effect of electroacupuncture at different time points on postoperative urination function in patients with mixed hemorrhoids surgery / 中国针灸

OBJECTIVE@#To observe the effect of preoperative, intraoperative and postoperative electroacupuncture (EA) intervention on postoperative urination function in patients with mixed hemorrhoid surgery.@*METHODS@#A total of 240 patients with mixed hemorrhoid surgery under lumbar anesthesia were randomly divided into an EA preconditioning group (group A, 60 cases, 9 cases dropped off), an intraoperative EA group (group B, 60 cases, 4 cases dropped off), a postoperative EA group (group C, 60 cases, 6 cases dropped off), and a non-acupuncture group (group D, 60 cases, 3 cases dropped off). In the groups A, B and C, EA was exerted at Zhongliao (BL 33) and Huiyang (BL 35) , with disperse-dense wave, 4 Hz/20 Hz in frequency, and lasting 30 min, at 30 min before lumbar anesthesia, immediately after lumbar anesthesia and 6 h after surgery, respectively. No EA intervention was performed in the group D. The postoperative urination smoothness score in each group was observed 24 h after surgery. The first urination time, first urination volume, urine residual volume after first urination were recorded, and incidence of indwelling catheterization, postoperative visual analogue scale (VAS) score, number of remedial analgesia, and the incidence of postoperative nausea and vomiting were observed in each group.@*RESULTS@#In the groups A, B and C, the postoperative urination smoothness scores were superior to the group D (P<0.05), and the time of first urination was earlier than the group D (P<0.05). In the group C, the time of first urination was earlier than the group A and the group B (P<0.05), the first urination volume was higher than the group D (P<0.05), and the urine residual volume after first urination was lower than the group D (P<0.05). There was no significant difference in the incidence of indwelling catheterization and postoperative nausea and vomiting among the 4 groups (P>0.05). The VAS scores of the group A, B and C were lower than that in the group D (P<0.05), and the number of remedial analgesia cases was lower than that in the group D (P<0.05).@*CONCLUSION@#EA intervention could promote the recovery of urination function and relieve postoperative pain in patients with mixed hemorrhoids surgery. Early postoperative EA intervention is more conducive to the recovery of urination function.

Total salvianolic acid combined with anti-PD-Ll inhibits development of breast cancer by regulating infiltration of myeloid macrophages / 中国药理学通报

Aim To explore the effect of total salvianolic acid (TSA) combined with anti-PD-Ll on the development of breast cancer by inhibiting the infiltration of myelogenous macrophages into tumors. Methods E0771 breast cancer subeutaneous tumor model was constructed. Twenty-five mice were randomly divided into control group, model group, total salvianolic acid group (TSA 10 g • kg

The antitumor mechanism of ginsenoside Rg3 activating MAPK/ERK pathway to promote T cell function / 中国药理学通报

Aim To elucidate the mechanism by which Rg3 regulates the function of CD8

Advances in involvement of pericyte in tumour microenvironment in tumour metastasis / 中国药理学通报

Pericytes are essential components of vessel mural cells that function to regulate blood flow, clear or phagocytose debris, and are contractile cells enwrapping capillaries throughout the body. It controls vascular permeability and is involved in the development of blood vessels and is an important regulator and potential drug target of angiogenesis and vascular function. Pericytes are also thought to play a key role in the tumor microenvironment, especially during tumor growth and distal metastasis. Therefore,in this review we discuss the relationship between pericytes involved in tumor angiogenesis and tumor metastasis, as well as the use of targeted pericytes to treat tumors,with a view to providing a basis for subsequent studies.

Research progress on the regulation and mechanism of reactive oxygen species on tumor immune checkpoints / 药学学报

Immune checkpoints (ICs) are immunosuppressive molecules expressed on immune cells, which can regulate immune cells' activation. Immune checkpoint inhibitors (ICIs) which can block the interaction of immune checkpoints and their ligands, improve the cytotoxic effect of the immune system on tumor cells. Immunotherapy such as employing ICIs has gradually become a conventional therapeutic strategy for cancer treatment. However, the low response rate and the emergence of drug resistance have seriously affected the clinical efficacy of ICIs. Reactive oxygen species (ROS) are electronic reduction products of active oxygen, as well as natural by-products of cell metabolism, which can be used as regulators of intercellular signals. Tumor microenvironment (TME) is often in the state of oxidative stress (OS), which is the imbalance between oxidative system and antioxidant system. ROS can affect the interaction with its ligands by regulating the expression and activity of immune checkpoints in TME, thus affecting the anti-tumor effect of immune cells. Accumulating studies have shown that ROS could regulate tumor immune checkpoints through several pathways. Due to different types and stages of tumor, it would be clinical beneficial to understand the mechanistic link of ROS on tumor immune checkpoint, and choose appropriate ROS regulators combined with immune checkpoint inhibitors to maximize anti-tumor effects. This article reviews the common metabolic sources and characteristics of ROS, the regulatory effect and mechanism of ROS on tumor immune checkpoints and its therapeutic application.

Anti-pseudo-allergic components in licorice extract inhibit mast cell degranulation and calcium influx / 中国天然药物

Pseudo-allergic reactions (PARs) widely occur upon application of drugs or functional foods. Anti-pseudo-allergic ingredients from natural products have attracted much attention. This study aimed to investigate anti-pseudo-allergic compounds in licorice. The anti-pseudo-allergic effect of licorice extract was evaluated in rat basophilic leukemia 2H3 (RBL-2H3) cells. Anti-pseudo-allergic compounds were screened by using RBL-2H3 cell extraction and the effects of target components were verified further in RBL-2H3 cells, mouse peritoneal mast cells (MPMCs) and mice. Molecular docking and human MRGPRX2-expressing HEK293T cells (MRGPRX2-HEK293T cells) extraction were performed to determine the potential ligands of MAS-related G protein-coupled receptor-X2 (MRGPRX2), a pivotal target for PARs. Glycyrrhizic acid (GA) and licorice chalcone A (LA) were screened and shown to inhibit Compound48/80-induced degranulation and calcium influx in RBL-2H3 cells. GA and LA also inhibited degranulation in MPMCs and increase of histamine and TNF-α in mice. LA could bind to MRGPRX2, as determined by molecular docking and MRGPRX2-HEK293T cell extraction. Our study provides a strong rationale for using GA and LA as novel treatment options for PARs. LA is a potential ligand of MRGPRX2.

Discussion on tumor proliferation and metastasis from perspective of neurogenesis / 中国药理学通报

In the tumor microenvironment, tumor cells and nerv e eells infiltrate each other, ultimately promoting the occurrence and development of tumor.Numerous evidence shows that neuro-genesis plays a key role in the regulation of tumor microenviron¬ment.By reviewing the interaction between neurogenesis and tumor and tumor microenvironment.this paper summarizes the factors including nerve growth factor that affects neurogenesis mediated tumor proliferation and metastasis, and the significance of tumor detection and treatment by regulating nerve signal.'Hie purpose of this study is to assist clinical treatment of tumor pro¬liferation and metastasis from the perspective of neurogenesis.

Research progress on breast cancer's mechanism of lung pre-metastatic niche formation and Traditional Chinese medicine intervention / 中国药理学通报

Breast cancer is currently one of the caneers with the highest incidence.Clinically, most breast eaneer patients often die due to distant metastasis.In the complex easeade of metasta¬sis, the formation of the pre-metastasis niche ( PMN) has been considered to he cnrcial in the process of distant metastasis of tumors in recent years.Tumors at the primary site secrete tumor- derived secretory factors (TDSF) , extracellular vesicles ( EV) and so on to metastasize target organs.thereby changing the mi- croenvironment of the target organs to adapt to the subsequent distant metastasis of the tumor.Breast cancer is a kind of cancer number of studies have revealed the mechanism of the breast cancer pre-metastatic niche, showing that inhibiting the PMN can reduce breast cancer metastasis.The multi-target and multi- component features of traditional Chinese medicine have been re¬ported to effectively interfere with the formation of PMN.This review summarizes the breast cancer's mechanism of lung pre- metastatic niche formation and traditional Chinese medicine in¬tervention.

Mechanism of tanshinone IIA to prevent spontaneous breast cancer in mice / 药学学报

To explore the effect of tanshinone IIA (TanIIA) on the occurrence and development of breast cancer, we employed the mouse mammary tumor virus-polyomavirus middle T antigen (MMTV-PyMT) transgenic mice as a spontaneous breast cancer mouse model. Animal welfare and experimental procedures were in accordance with the regulations of the Animal Ethics Committee of Nanjing University of Chinese Medicine. The animals were divided into control group, low-dose TanIIA treatment group (30 mg·kg-1·day-1), and high-dose TanIIA treatment group (60 mg·kg-1·day-1). The treatment was administered orally and daily for 5 weeks. The mice were sacrificed after final treatment. Mammary gland and lung were collected for histopathology studies. We evaluated the chemoprophylaxis effect of TanIIA on breast cancer in mice according to the pathological characteristics of breast cancer at different stages of development. Immunofluorescence staining were employed for blood vessel analysis. The expression levels of E-cadherin, proliferating nuclear antigen (PCNA), and oncogene c-Myc were detected by immunohistochemistry. Flow cytometry was used to analyze cell cycle and Cytoscape was used to construct drug-disease protein-protein interaction (PPI) network. Our results showed that TanIIA inhibits breast tumor progression by delaying malignancy from adenoma to early carcinoma, and inhibits blood vessel formation during tumor development. TanIIA (60 mg·kg-1·day-1) inhibits the expression levels of PCNA and c-Myc, upregulates the expression of E-cadherin. In addition, cell cycle experiments showed that the cell cycle of PyMT primary mammary cells in the high-dose TanIIA group was arrested in the G0/G1 phase. Our study demonstrated that TanIIA can significantly inhibit breast tumor progression in MMTV-PyMT mouse model, which may be related to the inhibition of angiogenic switch and cell cycle arrest.

Challenges and strategies in progress of drug delivery system for traditional Chinese medicine Salviae Miltiorrhizae Radix et Rhizoma (Danshen) / 中草药·英文版

Traditional Chinese medicines (TCMs), with a history of thousands of years, are widely used clinically with effective treatment. However, the drug delivery systems (DDSs) for TCMs remains major challenges due to the characteristics of multi-components including alkaloids, flavones, anthraquinones, glycosides, proteins, volatile oils and other types. Therefore, the novel preparations and technology of modern pharmaceutics is introduced to improve TCM therapeutic effects due to instability and low bioavailability of active ingredients. Salviae Miltiorrhizae Radix et Rhizoma, the radix and rhizomes of Salvia miltiorrhiza Bunge (Danshen in Chinese), is a well known Chinese herbal medicine for protecting the cardiovascular system, with active ingredients mainly including lipophilic tanshinones and hydrophilic salvianolic acids. In this review, this drug is taken as an example to present challenges and strategies in progress of DDSs for TCMs. This review would also summary the characteristics of active ingredients in it including physicochemical properties and pharmacological effects. The purpose of this review is to provide inspirations and ideas for the DDSs designed from TCMs by summarizing the advances on DDSs for both single- and multi-component from Danshen.

Research progress of breast cancer driver genes and precision therapy / 中国药理学通报

A large number of genetic mutations occur in the development of tumors, but only driver mutations determine the evolutionary direction of tumors. A variety of algorithmic tools and stationary analysis processes are available to search for driver genes with driver mutations. AS driver genes are different in different times and spaces, they are not the same in different stages of the development of breast cancer, leading to the different sensitivity of breast cancer patients to targeted therapy, which has become a major challenge for targeted therapy of breast cancer. This article reviews the progress and challenges of precision therapy for breast cancer from the perspective of driver genes.

Study on molecular mechanism of circulating tumor cell clusters promoting hematogenous metastasis / 中国药理学通报

Tumor metastasis is an important cause of death in tumor patients. Once metastasis occurs, cancer will become more difficult to treat. Many studies have observed circulating tumor cells (CTCs) in the circulatory system of patients with metastasis. CTCs may occasionally appear in the form of clusters during the process of hematogenous metastasis. These aggregated tumor cell clusters have higher efficacy than the single CTC. The development of circulating tumor cell cluster capture technology provides new insights into tumor metastasis. The molecular mechanism of CTC clusters formation and their role in tumor hematogenous metastasis are discussed here, and their use as biomarkers and target in therapy is evaluated.

Role of β-adrenergic receptors in development of breast cancer / 中国药理学通报

; β-adrenergic receptors (β-ARs) are widely found in organs of the human body and play an important role in regulating heart function, blood vessel dilation, energy metabolism, etc. Studies have shown that β-ARs are abnormally high in breast cancer cells, which can promote the occurrence and development of breast cancer by affecting the growth and metabolism of breast cancer, invasive metastasis, and angiogenesis. Clinical studies have shown that blocking β-ARs signaling improves the prognosis of breast cancer patients, so β-ARs may be a potential treatment target for breast cancer. This paper summarizes the role of β-ARs in the development of breast cancer, with a view to providing some reference for follow-up research and clinical treatment.

Study on anti-inflammatory effect of Salvia miltiorrhiza-Kushen herbpairs extract based on network pharmacology / 中国药理学通报

Aim To predict the potential targets of Salvia miltiorrhiza- Kushen herb pairs extracts (SK) and explore its anti-inflammatory effect on modelsbased on network pharmacology, so as to provide the research foundation of both new drugs and anti-inflammatory mechanism. Methods Network pharmacology was used to predict the potential anti-inflammatory targets of SK. Ear edema model was used to study the anti-in- flammatoiy effects of SK. Luminex liquid-phase chip analysis technology was used to observethe changes in secretion of pro-inflammatory cytokines in peripheral serumafter transdermal administration in mice by SK. Intraperitoneal injection of Evans blue experiment was used to simulate the exudation of inflammatory factors, and the effect of SK on capillary permeability in mice- was explored. Results Network pharmacology was used to predict that the anti-inflammatory effect of SK- was mainly related to immune-related processes and VEGF signaling pathways, unravelingthe relationship between the anti-inflammatory mechanismand the decrease of pro-inflammatory factors and vascular permea- bility. Conclusions The experiments verify that the results are the same as the prediction by network pharmacology. The anti-inflammatory effect involves decline the IL-6 levels, granulocyte colony-stimulating factor( G-CSF) levels and vascular permeability in the STAT3 pathway. Asthemain components of SK, tanshi- none, matrine and oxymatrine are linked to anti-in- flammatory effects.

Advance of synergism of immune checkpoint blockade and anti-angiogenesis in cancer treatment / 中国药理学通报

Immune checkpoint inhibitor ( ICI) activates the host' s anti-tumor immune response by blocking negative regulatory immune signals. A series of clinical trials showed that ICI could effectively induce tumor regression in a subset of advanced cancer patients. Anti-angiogenesis drugs commonly used to block tumor angiogenesis can inhibit the growth of tumors, but they cannot improve the survival of patients with limitations in application such as drug resistance. Tumor immune response is closely related to angiogenesis. In turn, tumor angiogenesis highly depends on immunosuppressive microenvironment. Recent studies have indicated that ICI resistance could be alleviated by combination therapy with anti-angiogenesis treatment, and the efficacy of combination therapy was superior to that of monotherapy. The reciprocal regulation between tumor vascular normalization and immune reprogramming forms a reinforcing loop that reconditions the tumor immune microenvironment to induce durable antitumor immunity. This review clarifies the latest understanding of ICI combined anti-angiogenesis therapy and provides ideas for subsequent research.

Study on influence of TRPA1 in gastric cancer based on cellular metabolomics and mechanism / 中国药理学通报

Aim To explore the effect of THPA1 in the metasta- sis of gastric cancer and the underlying mechanism. Methods The correlation between TRPA1 and the survival time of gastric cancer patients was analyzed using Kaplan-Meier plotter data base. The expressions of TRPA1 in different cells were detected by Western blot. Docking was used to explore the binding poten tial between cardamonin and TRPA1. Long-term dynamic cell imaging, CCK-8 and Transwell were used to evaluate the effects of HC-030031 and cardamonin on the proliferation and migration of MKN-45 cells. The differential metabolites between normal gastric epithelial cells and gastric cancer cells were studied by GC-MS. Results The expression of TRPA1 in gastric cancer patients was significantly negatively correlated with their surviv al. TRPA1 was overexpressed in gastric cancer cells. And the migration of gastric cancer cells was positively correlated with the expression and activation of TRPA1. Cardamonin had similar pharmacological effects with HC-030031, both of which could reduce the migration of gastric cancer cells. The metabolic path ways of asparagine and myo-inositol were found to be different between gastric cancer cells and normal gastric epithelial cells by cell metabolomics analysis. Conclusions TRPAI may be an indicator for detecting gastric cancer metastasis. Cardamonin in hibits metastasis by binding to TRPAI, meanwhile restrains the activation of TRPAI. Cardamonin may inhibit the function of TRPAI by binding to TRPAI, playing a role in inhibiting gastric cancer metastasis.

Research progress on the role of immune cells in tumor hematogenous metastasis / 中国药理学通报

Tumor blood and lymphatic vessel growth are necessary conditions for tumor growth, progression and metastasis, which are closely related with infiltrating nnate as well as adaptive immune cells. On one hand, immune cells rely on adhesion molecules on vascular endothelial cells to penetrate into tumor tissues and show anti-tumor characteristics. On the other hand, they can regulate tumor angiogenesis and lymphangiogenesis by secreting chemokines and cytokines, playing an important role in the process of tumor blood metastasis. In addition, the role of immune cells in promoting tumor blood metastasis highlights the shortcomings of t anti-angiogenic therapy. Therefore, targeting immune cells and tumor angiogenesis improve the effect of therapeutic. Based on these, this article summarizes the effects of immune cells on blood and lymphatic vessels n tumor metastasis, as well as related anti-vascular and immune therapies, in order o provide deas for subsequent research.

Novel technologies and models for studying pharmacological activities of traditional Chinese medicine for promoting blood circulation and removing blood stasis / 中国药理学与毒理学杂志

OBJECTIVE Our previous studies demonstrated that various ingredients from the traditional Chinese medicine (TCM) for promoting blood circulation and removing blood stasis, as exemplified by cryptotanshinone and salvi?anolic acid B, exerted striking effects on modulating angiogenesis and vascular permeability, which suggests that they may be effective in treating vascular leak-driven diseases (e.g. tumor, cerebral cavernous malformation and diabetic reti?nopathy). However, the lack of reliable and advanced technologies and models sets up difficult hurdles for better under?standing the role of TCM for promoting blood circulation and removing blood stasis. To this end, this study is to outline numerous cutting-edge platforms that can be utilized for exploring the function of TCM for promoting blood circulation and removing blood stasis in vascular leak-driven diseases. METHODS Two-photon laser scanning fluorescence micros?copy was used to observe the interactions between neutrophils and blood vessels in a real-time manner. Dynamic flow system was employed to mimic the in vivo behaviors of neutrophils. RIP1-Tag5 spontaneous pancreatic cancer model was used to study the function of tumor blood vessels. CCM2ECKO (deletion of CCM2 in endothelial cells) mice were employed to establish the cerebral cavernous malformation (CCM) animal model. Micro-computed tomography (micro-CT) was utilized to assess the CCM lesion. Müller cell-knockout mouse model was used to study the progression of dia?betic retinopathy. Vascular permeability in this model was assessed by fluorescein angiography. RESULTS The interac?tions between neutrophils and endothelial cells involve a series of complicated processes, including rolling, adhesion, intraluminal crawling and transmigration, which were all monitored in vivo by two-photon laser scanning fluorescence microscopy in a real-time manner. Dynamic flow system was capable of recapitulating the biological behaviors of neutro?phils in vitro. Tumor vascular function in particular vascular perfusion could be assessed in the RIP1-Tag5 spontaneous pancreatic cancer model. In terms of CCM studies, specific deletion of CCM2 in endothelial cells resulted in the initiation of CCM lesion. The size and number of CCM lesions could be visualized and quantified by micro-CT. Furthermore, the Müller cell-knockout mouse model was able to precisely reflect the clinical symptoms of diabetic retinopathy. Vascular leak could be monitored at different time points using fluorescein angiography. CONCLUSION An array of high technol?ogies and animal models can be used in investigating the occurrence and progression of multiple vascular leak-driven diseases. The pre-clinical and clinical studies of TCM for promoting blood circulation and removing blood stasis provide fundamental support for the application of the above-mentioned platforms, with the purpose of uncovering the scientific basis of TCM for promoting blood circulation and removing blood stasis.

Advances in effectively screening anti-tumor peptides / 药学学报

Malignant tumor is a disease that severely threaten human health. Common chemotherapeutical drugs currently used in clinical practice have some problems in severe side effects and chemoresistance. In contrast, natural venom peptides and artificially designed targeting peptides have excellent biological activities and potential druggability due to their small molecular weights and high affinity to tumor tissues. Thus, the methods for the discovery of anti-tumor peptides have attracted much attention. In this paper, we summarized the types of anti-tumor peptides from recent literatures. Then, we systematically reviewed screening theories, methods and applications based on traditional chromatographic separation, peptidomics, phage display, phenotypic screening, and artificial intelligence. These strategies and technologies will provide a methodological reference for accelerating anti-tumor peptides research.