Traditional Chinese medicine monomers: Targeting pulmonary artery smooth muscle cells proliferation to treat pulmonary hypertension.

Pulmonary hypertension (PH) is a complex multifactorial disease characterized by increased pulmonary vascular resistance and pulmonary vascular remodeling (PVR), with high morbidity, disability, and mortality. The abnormal proliferation of pulmonary artery smooth muscle cells (PASMCs) is the main pathological change causing PVR. At present, clinical treatment drugs for PH are limited, which can only improve symptoms and reduce hospitalization but cannot delay disease progression and reduce survival rate. In recent years, numerous studies have shown that traditional Chinese medicine monomers (TCMs) inhibit excessive proliferation of PASMCs resulting in alleviating PVR through multiple channels and multiple targets, which has attracted more and more attention in the treatment of PH. In this paper, the experimental evidence of inhibiting PASMCs proliferation by TCMs was summarized to provide some directions for the future development of these mentioned TCMs as anti-PH drugs in clinical.

Low curcumin concentration enhances the anticancer effect of 5-fluorouracil against colorectal cancer.

BACKGROUND: Colon cancer treatments include surgery, radiotherapy, and chemotherapy. Chemotherapy using 5-fluorouracil (5-FU) has been widely applied to treat colorectal cancer (CRC). However, it is important to explore the use of chemotherapy drugs in combination with other agents to decrease severe adverse effects. PURPOSE: This study aimed to investigate the effects of curcumin in combination with 5-FU on the proliferation, migration, and apoptosis of CRC SW620 cell line both in vitro and in vivo. METHODS: Flow cytometry was used to study the effect of curcumin on chemotherapy-induced apoptosis in CRC cells. The mechanism of curcumin's enhanced antitumor effect in vivo was investigated using gene knockdown, TUNEL, western blot, qRT-PCR and immunohistochemistry. RESULTS: The results showed a synergistic effect of the two compounds on CRC cells. Considerable reduction in the proliferation and migration of SW620 cells was observed in the combination treatment group. Significantly increased apoptosis rate extended the survival of immunodeficient mice in the combination group as compared to that of the 5-FU group (p < 0.05). The results showed that curcumin significantly inhibited pERK signaling and downregulated L1 expression in SW620 cells. CONCLUSIONS: We conclude that curcumin promotes chemosensitivity of CRC cells to 5-FU by downregulating L1 expression. Our findings provide experimental evidence for the synergism between curcumin and 5-FU, which can be utilized in clinical applications for reducing the toxicity and adverse effects of 5-FU.

Towards Holistic Governance of China's E-Waste Recycling: Evolution of Networked Policies.

Electronic products are being updated and replaced much faster and there is therefore an increasing growth in electronic waste (e-waste). In order to promote professional recycling of e-waste, the relevant government departments of China have published a series of policies. This paper aims to unearth the evolution tendency of the networked policies towards holistic governance of China's e-waste recycling. Content analysis, quantitative text analysis and network analysis are applied to analyze relevant policy documents from 2001 to 2016. This paper illustrates evolution of policy themes, evolution of intergovernmental relationships, and evolution of policy relations. This study reveals policy intentions, maps policy progress, and unearths governance philosophy, providing an overall understanding of the policy ways by which the Chinese government has deployed its guiding strategies on professional recycling of e-waste. This paper illustrates how to approach holistic governance from perspective of networked policies, contributing to answering the central question of holistic governance about how to achieve it.

Melatonin receptor activation provides cerebral protection after traumatic brain injury by mitigating oxidative stress and inflammation via the Nrf2 signaling pathway.

Traumatic brain injury (TBI) is a principal cause of death and disability worldwide. Melatonin, a hormone made by the pineal gland, is known to have anti-inflammatory and antioxidant properties. In this study, using a weight-drop model of TBI, we investigated the protective effects of ramelteon, a melatonin MT1/MT2 receptor agonist, and its underlying mechanisms of action. Administration of ramelteon (10 mg/kg) daily at 10:00 a.m. alleviated TBI-induced early brain damage on day 3 and long-term neurobehavioral deficits on day 28 in C57BL/6 mice. Ramelteon also increased the protein levels of interleukin (IL)-10, IL-4, superoxide dismutase (SOD), glutathione, and glutathione peroxidase and reduced the protein levels of IL-1ß, tumor necrosis factor, and malondialdehyde in brain tissue and serum on days 1, 3, and 7 post-TBI. Similarly, ramelteon attenuated microglial and astrocyte activation in the perilesional cortex on day 3. Furthermore, ramelteon decreased Keap 1 expression, promoted nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear accumulation, and increased levels of downstream proteins, including SOD-1, heme oxygenase-1, and NQO1 on day 3 post-TBI. However, in Nrf2 knockout mice with TBI, ramelteon did not decrease the lesion volume, neuronal degeneration, or myelin loss on day 3; nor did it mitigate depression-like behavior or most motor behavior deficits on day 28. Thus, timed ramelteon treatment appears to prevent inflammation and oxidative stress via the Nrf2-antioxidant response element pathway and might represent a potential chronotherapeutic strategy for treating TBI.

UV RESISTANCE LOCUS 8 From Chrysanthemum morifolium Ramat (CmUVR8) Plays Important Roles in UV-B Signal Transduction and UV-B-Induced Accumulation of Flavonoids.

UV Resistance Locus 8 (UVR8), an ultraviolet-B (UV-B; 280-315 nm) photoreceptor, participates in the regulation of various plant growth and developmental processes. UV-B radiation is an important factor enhancing the production of active components in medicinal plants. To-date, however, studies on UV-B photoreceptors have largely focused on Arabidopsis, and the functions of UVR8 in medicinal plants are still largely unknown. In the present study, a homolog of Arabidopsis UVR8, CmUVR8, was isolated from Chrysanthemum morifolium Ramat, and its structure and function were analyzed in detail. Protein sequence analysis showed that CmUVR8 contained nine conserved regulators of chromosome condensation 1 repeats, seven conserved bladed propellers, one C27 region, three "GWRHT" motifs and several crucial amino acid residues (such as 14 Trps and 2 Args), similar to AtUVR8. 3-D structural analysis of CmUVR8 indicated that its structure was similar to AtUVR8. Heterologous expression of CmUVR8 could rescued the deficient phenotype of uvr8-6, a mutant of UVR8 in Arabidopsis, indicating the role of CmUVR8 in the regulation of hypocotyl elongation and HY5 gene expression under UV-B irradiation. Moreover, CmUVR8 regulates UV-B-induced expression of four flavonoids biosynthesis-related genes and the UV-B-induced accumulation of flavonoids. Furthermore, the interaction between CmUVR8 and CmCOP1 were confirmed using a yeast two-hybrid assay. These results indicated that CmUVR8 plays important roles in UV-B signal transduction and the UV-B-induced accumulation of flavonoids, as a counterpart of AtUVR8.

Broccoli Sprout Extract Alleviates Alcohol-Induced Oxidative Stress and Endoplasmic Reticulum Stress in C57BL/6 Mice.

The potential efficacy of sulforaphane in protecting alcohol-induced hepatic injury in vivo and its underlying mechanism were investigated. Male C57BL/6 mice were orally administrated with broccoli sprout extract (BSE) containing sulforaphane [7.6, 25.2, and 50.4 mg/kg of body weight (bw)] once a day for 14 days. At the 13th day, mice were challenged with alcohol (5 g/kg of bw) every 12 h for 3 times, which increased malondialdehyde (MDA) levels (4.44 ± 1.24 nmol/mg of protein, p < 0.01) in the liver. Our results showed that low-, medium-, and high-dose BSE markedly reversed the decrease of antioxidant capacity through enhancing glutathione (GSH) (2.07 ± 0.31 mg/g of protein, p < 0.05; 2.31 ± 0.32 mg/g of protein, p < 0.01; and 2.46 ± 0.21 mg/g of protein, p < 0.01), superoxide dismutase (SOD) (483.20 ± 62.76 units/mg of protein; 500.81 ± 49.82 units/mg of protein, p < 0.05; and 605.00 ± < 64.32 units/mg of protein, p < 0.01), glutathione peroxidase (GSH-Px) (318 ± 60.74 units/mg of protein; 400.67 ± 72.47 units/mg of protein, p < 0.01; and 394.72 ± 62.97 units/mg of protein, p < 0.01), and glutathione S-transferase (GST) (31.84 ± 6.34 units/mg of protein, p < 0.05; 30.34 ± 6.40 units/mg of protein, p < 0.05; and 38.08 ± 7.05 units/mg of protein, p < 0.01) in the liver. The protective actions are also associated activation of phase 2 enzymes via nuclear erythoriod-2-related factor 2 (Nrf2). The endoplasmic reticulum (ER)-stress-specific proteins, such as glucose-regulated protein 78 (GRP78), activating transcription factor 6, and protein kinase RNA (PKR)-like ER kinase (PERK), were also significantly attenuated by BSE. These results indicate that BSE protects the liver against alcohol challenge via upregulating antioxidant capacity and downregulating ER stress.

PSY-1, a Taxus chinensis var. mairei extract, inhibits cancer cell metastasis by interfering with MMPs.

Cancer is the most common disease worldwide, with death often occurring as a result of metastasis. Thus, interfering with metastasis has been regarded as a promising strategy to improve the current cancer treatments. However, exploration and development of novel anti-metastatic agents remains a major challenge. Recent evidence indicated that a polysaccharide isolated from Taxus yunnanensis suppressed tumor cells proliferation. With the objective of seeking bioactive extracts, we had previously isolated, purified and characterized a complex, water-soluble polysaccharides, PSY-1, from the leaves of Taxus chinensis var. mairei, and identified its anti-neoplastic effects. In this study, we focused on the effects of PSY-1 on cancer metastasis and its mechanism(s). The results illustrated that PSY-1 effectively suppressed the migration and invasion ability of the melanoma cancer cell line B16-F10, caused down-regulation of MMP-2 and MMP-9, and that the NF-kappaB pathway was involved in the anti-metastatic effects imposed by PSY-1.

Sceptridium ternatum extract exerts antiasthmatic effects by regulating Th1/Th2 balance and the expression levels of leukotriene receptors in a mouse asthma model.

AIM OF THE STUDY: Sceptridium ternatum Lyon (ST), a common Chinese herb, has been used in treatment of allergic asthma and whooping cough. In the present study, we investigated the Th1/Th2 ratio of peripheral blood and mRNA levels of leukotriene receptors after the treatment of ST in allergic asthma mouse model. MATERIALS AND METHODS: Mouse asthma model was developed by ovalbumin (OVA) sensitization followed by the inhalation of aerosol allergen. Montelukast (10mg/kg), as a positive control drug, and ST were administrated six days before the OVA sensitization for ten days. Airway responsiveness was evaluated by the Medlab 12.0 biological signal processing system. The ratio of Th1/Th2 cells was determined by flow cytometry. The expression level of Cyslt1 was measured by PCR. Pathological changes of lung tissues were examined by H&E staining. RESULTS: ST significantly reduced the airway responsiveness, elevated the ratio of Th1/Th2, and decreased Cyslt1 mRNA level in a dose-dependent manner. High-dose ST distinctly prevented the pathological changes of lung tissues. CONCLUSION: High-dose ST had the same efficacy as Montelukast in a mouse asthma model, and ST could be a potential anti-asthmatic agent.

[Mechanism of MBL inhibiting the LPS-induced DC maturation].

The study was aimed to investigate the mechanism of mannan-binding lectin (MBL) on bacterial lipopolysaccharide (LPS)-induced human peripheral blood monocyte-derived dendritic cell (DC) maturation. The monocytes were prepared from the peripheral blood of healthy adult volunteers. The immature dendritic cells (imDC) were induced by 5-day-culture in medium supplemented with rhGM-CSF and rhIL-4. FACS was used to investigate the interaction of MBL with imDC and the impact of MBL on LPS binding to imDC. ELISA and Western blot was used to analyze the interaction of MBL with soluble TLR4 ectodomain protein (sTLR4); Western blot was used to detect LPS-induced NF-κB translocation in imDC. The results showed that MBL could directly bind to imDC in the presence of calcium. sTLR4 protein or LPS could competitively inhibit the binding of MBL to imDC. ELISA and Western blot showed that MBL could evidently bind to sTLR4 protein in a concentration-dependent manner. FACS showed that MBL could competitively inhibit the binding of LPS to imDC by binding to imDC directly. Western blot showed that MBL decreased LPS-induced NF-κB translocation in imDC. It is concluded that MBL may competitively inhibit the binding of LPS to imDC by binding to TLR4 expressed on imDC, resulted in inhibition of LPS-induced DC maturation, suggesting that MBL can regulate DC maturation through ligand-binding. This study provides the good foundation to clarify the mechanism of MBL inhibiting the LPS-induced DC maturation.

[Therapeutic effect of pelvic methotrexate injection via the posterior fornix for treatment of tubal pregnancy].

OBJECTIVE: To evaluate the therapeutic effect and safety of pelvic methotrexate (MTX) injection via the posterior fornix for treatment of tubal pregnancy. METHODS: Ninety-six patients with tubal pregnancy (mean age 21-40 years) were randomized into 3 groups for treatment with pelvic MTX injection via the posterior fornix+mifepristone+traditional Chinese medicine (experiment group), intramuscular MTX injection+mifepristone+traditional Chinese medicine (control group I), or mifepristone+traditional Chinese medicine (control group II). On days 4 and 7 of the treatment, blood ß-HCG of the patients in different groups was detected, and in cases with continuous reduction of blood ß-HCG or a reduction by over 15%, ß-HCG was checked every week. One week after the treatment, the size of the mass was measured by B-mode ultrasound. The clearance time of ß-HCG and the hospital stay of the patients were recorded. RESULTS: Twenty-nine patients in the experimental group were treated successfully, with a cure rate of 90.6%, which was significantly higher than those in the two control groups (P<0.05). The clearance time of ß-HCG and hospital stay were also much shorter in the experimental group (P<0.05). CONCLUSION: Pelvic MTX injection via the posterior fornix is a convenient procedure associated with minimal complications and serves as a good alternative for treatment of tubal pregnancy.