Jia Yang’s research while affiliated with Shandong University of Traditional Chinese Medicine and other places

Notch signaling pathway is activated abnormally in solid and hematological tumors, which perform essential functions in cell differentiation, survival, proliferation, and angiogenesis. The activation of Notch signaling and communication among Notch and other oncogenic pathways heighten malignancy aggressiveness. Thus, targeting Notch signaling offers opportunities for improved survival and reduced disease incidence. Already, most attention has been given to its role in the cancer cells. Recent research shows that natural bioactive compounds can change signaling molecules that are linked to or interact with the Notch pathways. This suggests that there may be a link between Notch activation and the growth of tumors. Here, we sum up the natural bioactive compounds that possess inhibitory effects on human cancers by impeding the Notch pathway and preventing Notch crosstalk with other oncogenic pathways, which provoke further study of these natural products to derive rational therapeutic regimens for the treatment of cancer and develop novel anticancer drugs. This review revealed Notch as a highly challenging but promising target in oncology.

Ethnopharmacological relevance: Mahuang Xixin Fuzi Decoction (MXF), as a classical prescription of traditional Chinese medicine (TCM), has been used to treat the immunocompromised individuals infected with influenza A virus (IAV). Aim of the study: The study aims to explore the regulatory of MXF on inflammation and secretory immunoglobulin A (SIgA) antibodies immune response in BALB/c-nude mice infected with IAV. Materials and methods: The BALB/c-nude mice were infected with IAV, then different dosages of MXF were orally administrated to the mice. The weight, rectal temperature, spontaneous activity, spleen index, lung index, pathological changes of lung tissues, and the relative mRNA expression level of H1N1 M gene were measured for the purpose of valuing the antiviral effect of MXF. The expression levels of cytokines in lungs and immunoglobulin A (IgA) in serum of BALB/c-nude mice were determined with Cytometric Bead Array System (CBA). SIgA in bronchoalveolar lavage fluids (BALF) was detected with Enzyme-linked Immunosorbent Assay (ELISA). The mRNA and protein expression levels of B cell activating factor (BAFF), chemokine receptors 10 (CCR10), and polymeric immunoglobulin receptor (pIgR) in the lung tissues, which are related to the secretion of SIgA, were determined by using RT-PCR and Western blot. Results: MXF could alleviate the clinical features and reduce the severity of viral lung lesions, including improving the body weight, rectal temperature and spontaneous activity of nude mice infected with IAV, increasing spleen index, decreasing lung index, alleviating pathological damage, and decreasing the relative expression level of H1N1 M gene. Levels of pro-inflammatory cytokines, including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), interleukin-12p70 (IL-12p70), and interleukin-17A (IL-17A) were also significantly decreased after treatment with MXF. Interferon-γ (IFN-γ), an antiviral cytokine, was significantly up-regulated in high dose MXF (3.12 g/kg) group. Moreover, after MXF treatment, the expressions of SIgA in BALF and IgA in serum were both at relatively low levels. And the mRNA and protein expressions of BAFF, CCR10, and pIgR were significantly decreased after treatment with MXF. Conclusions: MXF has obviously protective effects on BALB/c-nude mice infected with IAV by inhibiting virus replication, calming inflammatory cytokine storm, and regulating SIgA immune response weakly.

Ethnopharmacological relevance Mahuang Xixin Fuzi Decoction (MXF), as a classical prescription of traditional Chinese medicine (TCM), has been used to treat the symptoms of fever, nasal congestion and headache in elderly people for almost a thousand years. Aim of the study The purpose of this study was to evaluate the effects and possible mechanisms of MXF on thermal stimulation-induced mouse cardiac myocytes (MCM) cell apoptosis. Materials and methods The apoptosis of the MCM cell model was induced by a PCR-calculated temperature control system with a gradual heating pattern at 43 °C for one hour. The cytotoxic effects were determined using real-time cell analyzer (RTCA) technology. Annexin V-FITC/7-AAD staining, and JC-1 fluorescence were used to assess apoptosis. Specific substrates, enzyme-linked immunosorbent assays (ELISAs), and Western blotting were used to identify proteins in the mitochondrial-mediated pathway. The identification of chemical components in the mouse heart was performed by ultra-performance liquid chromatography–electrospray ionization tandem mass spectrometry analysis. Results MXF inhibited apoptosis through the mitochondrial-mediated signaling pathway, including ameliorating MMP reduction, blocking mitochondrial Cyt C release, reducing Bax levels and increasing Bcl-2 levels, suppressing caspase-9 and caspase-3 activation in cytoplasmic fractions. Moreover, the components of MXF that act on the heart are mainly ephedra alkaloids and aconitine alkaloids. Conclusions The findings demonstrated that MXF treatment markedly reduced MCM cell apoptosis induced by thermal stimulation, which may be ascribed to the mitochondrial-mediated signaling pathway.

Discovering bioactive compounds from medicinal herbs is crucial for drug discovery. Ultrafiltration is often used in the screening of bioactive compounds from natural herbs because of its simple and rapid operations. However, the ultrafiltration results are often disturbed by the undissolved compounds and the non-target compounds, which reduces the accuracy of the results. Herein, an affinity interaction guided two-dimensional (2D) separation system was developed. Discovery of the potential neuraminidase (NA) inhibitors from the dried roots of Reynoutria japonica Houtt. (RRJ) was used as an example. Only the small molecules showing affinity interaction with NA could be screened by the affinity interaction guided 2D separation system. Firstly, the NA and crude extract were incubated to form a sample solution (containing NA-inhibitor complexes, NA, and three types of small molecules with different polarities) by affinity interaction. Then the sample solution was separated and detected by the 2D separation system. This aimed to reduce the interference of the undissolved compounds and non-target compounds, and pick out the NA-inhibitor complexes (NA-Is). The collected NA-Is were denatured to release small molecular inhibitors (Is) for LC-MS/MS analysis. Compared with the ultrafiltration, more obvious peak area differences were observed in the results, and four potential NA inhibitors were successfully identified. In all, we provided a simple strategy with better performance in the screening of natural bioactive compounds.

Malignant tumor remains a huge threat to human health and chemotherapy still occupies an important place in clinical tumor treatment. As a kind of potent antimitotic agent, taxanes act as the first-line broad-spectrum cancer drug in clinical use. However, disadvantages such as prominent hydrophobicity, severe off-target toxicity or multidrug resistance lead to unsatisfactory therapeutic effects, which restricts its wider usage. The efficient delivery of taxanes is still quite a challenge despite the rapid developments in biomaterials and nanotechnology. Great progress has been made in prodrug-based nanomedicines (PNS) for cancer therapy due to their outstanding advantages such as high drug loading efficiency, low carrier induced immunogenicity, tumor stimuli-responsive drug release, combinational therapy and so on. Based on the numerous developments in this filed, this review summarized latest updates of taxanes prodrugs-based nanomedicines (TPNS), focusing on polymer-drug conjugate-based nanoformulations, small molecular prodrug-based self-assembled nanoparticles and prodrug-encapsulated nanosystems. In addition, the new trends of tumor stimuli-responsive TPNS were also discussed. Moreover, the future challenges of TPNS for clinical translation were highlighted. We here expect this review will inspire researchers to explore more practical taxanes prodrug-based nano-delivery systems for clinical use.

Background: Thermal stimulation is a potent inducer of apoptosis in many cell lines. At present, water bath heating is often used to thermal stimulation-induced apoptosis, but this method has poor reproducibility and low efficiency. The aim of this study was to build a simple and reproducible apoptosis model caused by thermal stimulation. Methods and Results: The apoptosis and necrosis rate were detected under different thermal stimulation conditions by flow cytometer. We also analyzed the difference of growth curves between the thermal stimulation model group and the normal group. According to the cell growth curve, the cell re-culture time after thermal stimulation was preliminarily detected, and the reasonability of the time was verified by flow cytometer. The conditions for establishing the model are: PCR calculated temperature control system with a gradual heating pattern, 37°C, 2 min; 38°C, 2 min; 39°C, 2 min; 40°C, 2 min; 41°C, 2 min; 42°C, 2 min; 43°C, 60 min; 42°C, 2 min; 41°C, 2 min; 40°C, 2 min; 39°C, 2 min; 38°C, 2 min; 37°C, 2 min. In this way, the proportion of cell apoptosis is higher than that of cell necrosis with satisfied reproducibility. Conclusions: The present work provide a new method to induce cell apoptosis by thermal stimulation.

In this paper, Asarum polysaccharides(AP) were extracted, and its composition was analyzed to study the activity against H1 N1 influenza virus in vitro and its intervention effect on mice with kidney Yang deficiency syndrome. AP was prepared by the strategy of water extraction and alcohol precipitation, the content was determined, and its monosaccharide composition was analyzed. The cell Real-time monitoring system and Reed-Muench model were adopted to evaluate the antiviral activity of AP in vitro. And the mouse model of kidney Yang deficiency syndrome was established in vivo to compare the efficacy of Mahuang Xixin Fuzi Decoction(MXF) and AP. MXF group and AP group were treated with clinical equivalent doses of 1.8 g·kg~(-1)·d~(-1) and 0.077 g·kg~(-1)·d~(-1) respectively, once a day for 6 consecutive days. Real-time PCR was used to detect the relative expression of M gene of H1 N1 influenza virus and cytokines in lung tissue. The content of AP in Asarum was 25.22%, and the protein content was 0.8%. And the monosaccharide composition was identified as L-rhamnose, D-arabinose, D-xylose, D-glucose, D-galactose and D-mannose. TI values of Tamiflu, MXF and AP were 30.00, 8.06 and 10.33, respectively. Three different doses of AP could significantly reduce the concentration of virus in supernatant. Compared with the model mice, lung indexes of MXF group and AP group decreased significantly(P<0.05), and the relative expression of M gene decreased significantly(P<0.05). The relative expressions of IL-10 and IFN-γ were up-regulated to varying degrees, while the relative gene expressions of IL-1β, IL-6 and MCP-1 were down-regulated to different degrees. In addition, AP could significantly enhance the expression of TNF-α(P<0.01). AP had a good anti-influenza virus activity in vitro, and could protect mice with kidney Yang deficiency syndrome by reducing the viral load in lung tissue, decreasing inflammation damage in lung tissue, and regulating the expression of inflammatory cytokines. Compared with the prescription of MXF, AP had a better antiviral activity.