Apatinib inhibits tumour progression and promotes antitumour efficacy of cytotoxic drugs in oesophageal squamous cell carcinoma.

Apatinib, a highly selective inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2), inhibits the angiogenesis of tumours. The function and mechanism of apatinib in oesophageal squamous cell carcinoma (ESCC) remain unknown. In present study, we found that the development of ESCC in patients was controlled by treatment of combination of apatinib and a chemotherapeutic drug. Moreover, apatinib efficiently promotes cell apoptosis, inhibits cell proliferation, invasion, epithelial-mesenchymal transition (EMT) and activity of the Akt/mTOR pathway in ESCC cells. Western blot analysis showed that apatinib significantly increased vimentin protein levels, decreased Bcl2, matrix metalloproteinase 9 (MMP9), E-cadherin, p-Akt and p-mTOR protein levels in ESCC cells. Furthermore, apatinib enhanced chemosensitivity of cytotoxic drugs paclitaxel (TAX), 5-fluorouracil (5-FU) and cisplatin (DDP) by upregulating expression of vimentin protein, and downregulating expression of Bcl2, MMP9 and E-cadherin protein in vitro. Compared with single-agent groups, the combination of apatinib with each chemotherapeutic drug significantly repressed tumour growth and angiogenesis through blocking the expression of Ki67 and VEGFR-2 in vivo. Taken together, apatinib efficiently inhibits cell growth through blocking Bcl2 and Akt/mTOR pathway, and suppresses metastasis via inhibiting MMP9 and EMT in ESCC cells. Apatinib promoted antitumour effect of chemotherapeutic agents through promoting cell apoptosis and inhibiting EMT and angiogenesis in ESCC.

Ursolic Acid Alleviates Cancer Cachexia and Prevents Muscle Wasting via Activating SIRT1.

Skeletal muscle wasting is the most remarkable phenotypic feature of cancer cachexia that increases the risk of morbidity and mortality. However, there are currently no effective drugs against cancer cachexia. Ursolic acid (UA) is a lipophilic pentacyclic triterpene that has been reported to alleviate muscle atrophy and reduce muscle decomposition in some disease models. This study aimed to explore the role and mechanisms of UA treatment in cancer cachexia. We found that UA attenuated Lewis lung carcinoma (LLC)-conditioned medium-induced C2C12 myotube atrophy and muscle wasting of LLC tumor-bearing mice. Moreover, UA dose-dependently activated SIRT1 and downregulated MuRF1 and Atrogin-1. Molecular docking results revealed a good binding effect on UA and SIRT1 protein. UA rescued vital features wasting without impacting tumor growth, suppressed the elevated spleen weight, and downregulated serum concentrations of inflammatory cytokines in vivo. The above phenomena can be attenuated by Ex-527, an inhibitor of SIRT1. Furthermore, UA remained protective against cancer cachexia in the advanced stage of tumor growth. The results revealed that UA exerts an anti-cachexia effect via activating SIRT1, thereby downregulating the phosphorylation levels of NF-κB and STAT3. UA might be a potential drug against cancer cachexia.

UPLC-ESI-QTOF-MS/MS Analysis of the Phytochemical Compositions From Chaenomeles speciosa (Sweet) Nakai Fruits.

Chaenomeles speciosa (Sweet) Nakai (C. speciosa Nakai) is a popular fruit widely used in China for its health-promoting properties. The presences of phytochemical compositions in the plants play an important role in the health benefits. Nevertheless, the detailed information of these ingredients is still unknown. Therefore, in this work, an untargeted analytical method based on ultra-high-performance liquid chromatography-quadrupole-time of flight coupled to mass spectrometry in two different ionization modes was used to qualitative the phytochemicals in C. speciosa Nakai, meanwhile, the anti-inflammatory activity of these phytochemicals was researched through detecting the inhibition of nitric oxide (NO) that was induced by lipopolysaccharide in RAW 264.7 murine macrophage cells. The results showed that there were totally 175 primary and secondary metabolites were identified in the fruit of C. speciosa Nakai, including phenols, terpenoids, flavonoids and other phyto-constituents. Actually, most compounds were described in C. speciosa Nakai fruits for the first time. Besides, the anti-inflammatory activity was measured by the result of NO inhibition rate, the consequence showed that the value of half-inhibitory concentration (IC50) was 365.208 µg/mL. These results indicate that C. speciosa Nakai is an efficient medicinal fruit, which owns various bioactivities and has the potential to treat various diseases.

Pharmacological Inhibition of HMGB1 Prevents Muscle Wasting.

Background: Cachexia is a multifactorial disorder characterized by weight loss and muscle wasting, making up for about 20% of cancer-related death. However, there are no effective drugs to combat cachexia at present. Methods: In this study, the effect of CT26 exosomes on C2C12 myotubes was observed. We compared serum HMGB1 level in cachexia and non-cachexia colon cancer patients. We further explored HMGB1 expression level in CT26 exosome. We added recombinant HMGB1 to C2C12 myotubes to observe the effects of HMGB1 on C2C12 myotubes and detected the expression level of the muscle atrophy-related proteins. Then, we used the HMGB1 inhibitor glycyrrhizin to reverse the effects of HMGB1 on C2C12 myotubes. Finally, HMGB1 inhibitor glycyrrhizin was utilized to relieve cachexia in CT26 cachexia mouse model. Results: Exosomes containing HMGB1 led to muscle atrophy with significantly decreased myotube diameter and increased expression of muscle atrophy-related proteins Atrogin1 and MuRF1. Further, we detected that HMGB1 induced the muscle atrophy mainly via TLR4/NF-κB pathway. Administration of the HMGB1 inhibitor glycyrrhizin could relieve muscle wasting in vitro and attenuate the progression of cachexia in vivo. Conclusion: These findings demonstrate the cachectic role of HMGB1, whether it is soluble form of HMGB1 or secreted from tumor cells as part of exosomes. HMGB1 inhibitor glycyrrhizin might be a promising drug in colon cancer cachexia.

The Analyses of Chemical Components From Oldenlandia hedyotidea (DC.) Hand.-Mazz and Anticancer Effects in vitro.

Oldenlandia hedyotidea (DC.) Hand.-Mazz (OH), also known as sweet tea, is a valuable functional food with medicinal properties and is used for the treatment of cold, cough, gastroenteritis, heatstroke, herpes zoster, and rheumatoid arthritis. The phytochemicals in plant-based foods are responsible for the occurrence of these diseases to some extent. However, there is a scarcity of information on the chemical components of OH. We, therefore, aimed to investigate the phytochemical components of OH using ultra high-performance liquid chromatography-mass spectrometry (UHPLC-MS) and UHPLC triple time-of-flight mass spectrometry (UHPLC-Triple-TOF-MS). The main component of the OH extract, asperulosidic acid, was additionally quantified using UHPLC with ultraviolet detection (UHPLC-UV). The anticancer activity of the OH extract was assessed by a cell proliferation assay and a scratch assay using an esophageal cancer cell line. Ten compounds were tentatively identified in the aqueous extract of OH, including five iridoids, two anthraquinones, and one phenolic acid. The content of asperulosidic acid in the aqueous extract of OH was approximately 42 µg ml-1, and the extract exerted definite in vitro anticancer effects. The results can be used for quality control and assessment of the OH extract, which can serve as a promising source of functional ingredients for potential use in the food and drug industries.

Anti-hypertensive and cardioprotective activities of traditional Chinese medicine-derived polysaccharides: A review.

Cardiovascular diseases (CVDs), a leading cause of death in modern society, have become a major public health issue globally. Although numerous approaches have been proposed to reduce morbidity and mortality, the pursuit of pharmaceuticals with more preventive and/or therapeutic value remains a focus of attention. Being a vast treasure trove of natural drug molecules, Traditional Chinese Medicine (TCM) has a long history of clinical use in the prophylaxis and remedy of CVDs. Increasing lines of preclinical evidence have demonstrated the effectiveness of TCM-derived polysaccharides on hindering the progression of CVDs, e.g. hypertension, myocardial infarction. However, to the best of our knowledge, there are few reviews on the application of TCM-derived polysaccharides in combating CVDs. Hence, we provide an overview of primary literature on the anti-hypertensive and cardioprotective activities of herbal polysaccharides. Additionally, we also discuss the current limitations and propose a new hypothesis about how polysaccharides exert cardiovascular effects based on the metabolism of polysaccharides.

An effective method for extracting anthocyanins from blueberry based on freeze-ultrasonic thawing technology.

The aim of this study was to develop an effective method for extracting anthocyanins from blueberry Vaccinium spp. (ABVS) using freeze-ultrasonic thawing technology (FUTE). Various parameters including freezing time, ultrasonic time, ultrasonic temperature and liquid-solid ratio were optimized by a single-factor design and multiple response surface methodology. The amounts of extracted anthocyanin and cyanidin-3-O-glucoside were measured by UV and HPLC respectively. The maximum yield of anthocyanins was achieved by freezing the samples for 5.43 min in liquid nitrogen at the liquid-solid ratio of 24.07:1 mL/g, followed by ultrasonic thawing at 41.64 °C for 23.56 min. The yield and antioxidant effects of ABVS extracted using FUTE, ultrasound-assisted extraction (UAE) and freeze-thawing extraction (FTE) were compared in order to determine the overall efficacy of FUTE. In addition to the higher content, FUTE extracted ABVS showed greater ability to scavenge DPPH·, ABTS+ and superoxide anions, and inhibit lipid peroxidation compared to the ABVS extracted by UAE or FTE. The reducing power of the FUTE-derived ABVS was intermediate between that of the UAE and FTE samples. Taken together, FUTE can rapidly and effectively extract ABVS and retain its antioxidant capacity.

Clinical analysis of 547 patients with neuroendocrine tumors in a Chinese population: A single-center study.

BACKGROUND: Neuroendocrine tumors (NETs) are rare, which has resulted in a lack of published data on their epidemiology and clinical features. We therefore aimed to investigate the epidemiology, clinical features, treatments, and prognosis of patients with NETs. METHODS: The clinicopathologic characteristics of 547 patients who were pathologically diagnosed with NETs were retrospectively analyzed, including age, sex, primary and metastatic sites, symptoms, pathology, treatment, and prognosis. RESULTS: The 547 patients had a wide age range (9-87 years), with a male to female ratio of 1:1.1. The primary tumor sites included 413 in the digestive system, 74 in the lung, 15 in the mediastinum, 8 in unknown sites, and 37 in other sites. Of the 413 patients with digestive system NETs, the pancreas, rectum, and stomach were the most common primary sites. Blood metastases were found in 84 patients at initial diagnosis, and the liver, bone, and lung were the most frequent sites of metastasis. Lymph node metastases were found in 82 patients at initial diagnosis. Surgery and chemotherapy were the most widely applied treatments. Statistical analysis showed that age <50 years, female sex, lower-grade tumor, no distant metastasis, intestinal NET and surgery indicated a favorable prognosis. CONCLUSIONS: A difference between China and other countries is that small intestinal NETs are quite common in other countries but are rare in China. In China, the most common primary sites are the pancreas, rectum, and stomach. Furthermore, no unified treatments exist, though prognoses could be improved by using methods such as surgery, targeted therapies, and somatostatin analogs. CLINICAL TRIAL REGISTRATION: This study was not a clinical trial.