Nobiletin inhibits breast cancer cell migration and invasion by suppressing the IL-6-induced ERK-STAT and JNK-c-JUN pathways.

BACKGROUND: Breast cancer is one of the most common cancers in women, affecting more than 2 million women worldwide annually. However, effective treatments for breast cancer are limited. Nobiletin is a flavonoid present in the dried mature pericarp of mandarin orange (Citrus reticulata Blanco), which is used to prepare Citri Renetulatae Pericarpium and can inhibit tumour growth and progression according to modern pharmacological studies. However, whether nobiletin exhibits an antimetastatic role in breast cancer and its potential mechanism need to be further investigated. PURPOSE: This study aims to evaluate the inhibitory effect of nobiletin on breast cancer and to elucidate potential mechanisms against invasion and migration. METHODS: Cell viability was determined by cell counting kit-8 and colony formation assays. Wound healing and Boyden chamber assays detected cancer cell migration and invasion capabilities. Immunoblotting and qPCR were applied to determine the protein and mRNA expression levels of extracellular signal-regulated kinases (ERK) and the c-Jun N-terminal kinase (JNK) signalling pathways. Molecular docking was used to assess the degree of nobiletin binding to phosphatidylinositol 3-kinase (PI3K). Xenografts and liver metastases were constructed in BALB/c nude mice to evaluate the anticancer effect of nobiletin in vivo. H&E staining and immunohistochemistry were used to detect proliferation and the expression of related proteins. RESULTS: Nobiletin induced cell death in a concentration- and time-dependent manner and possessed anti-invasion and anti-migration effects on MCF-7 and T47D cells by suppressing the interleukin-6-induced ERK and JNK signalling pathways. In addition, nobiletin docked with the binding site of PI3K, and the binding score was -8.0 kcal/mol. Furthermore, the inhibition of breast cancer growth and metastasis by nobiletin was demonstrated by constructing xenografts and liver metastases in vivo. CONCLUSION: Nobiletin inhibited liver metastasis of breast cancer by downregulating the ERK-STAT and JNK-c-JUN pathways, and its safety and efficacy were verified, indicating the potential of nobiletin as an anticancer agent.

Amyloid Protein-Biofunctionalized Polydopamine Nanoparticles Demonstrate Minimal Plasma Protein Fouling and Efficient Photothermal Therapy.

Polydopamine (PDA) shows great application potential in photothermal therapy (PTT) of tumors due to its excellent photothermal performance. However, PDA rich in a large number of catechin structures, with strong adhesion, can readily attach to plasma proteins in blood to form protein corona, which greatly hinders the transfer efficiency to tumors and reduces the bioavailability. In this paper, a simple, rapid phase-transitioned albumin biomimetic nanocorona (TBSA) is used for the surface camouflage of PDA nanoparticles for minimal plasma protein fouling and efficient PTT. TBSA coating is formed by the BSA-derived amyloid through the hydrophobic aggregation near the isoelectric point and the rupture of disulfide bonds by tris(2-carboxyethyl) phosphine. The stable PDA@TBSA complexes are formed by camouflaging TBSA onto the surface of PDA through hydrophobic, electrostatic, and covalent binding between TBSA and PDA, which showed excellent anti-plasma protein adsorption properties profited from the surface charge of PDA@TBSA approaching equilibrium and the surface passivation of BSA. The plasma protein thickness of the PDA@TBSA surface is 6 times lower than that of PDA at adsorption saturation. In vitro and in vivo experiments have revealed that PDA@TBSA has an excellent photothermal antitumor effect compared to PDA. Both PDA and PDA@TBSA treatment plus 808 nm laser irradiation result in more than 70% inhibition on tumor cell proliferation. In addition, PDA@TBSA does not cause a significant inflammatory response and tissue damage. Taken together, the TBSA coating endows PDA with low-fouling functions in blood and improves the residence time of PDA in blood and enrichment in the tumor tissue. This work offers a novel and efficient strategy for the design of functional nanosystems exploiting the speciality of the biomolecular corona formation around nanomaterials.

The Role of Chronic Inflammation in Various Diseases and Anti-inflammatory Therapies Containing Natural Products.

Chronic inflammation represents a long-term reaction of the body's immune system to noxious stimuli. Such a sustained inflammatory response sometimes results in lasting damage to healthy tissues and organs. In fact, chronic inflammation is implicated in the development and progression of various diseases, including cardiovascular diseases, respiratory diseases, metabolic diseases, neurodegenerative diseases, and even cancers. Targeting nonresolving inflammation thus provides new opportunities for treating relevant diseases. In this review, we will go over several chronic inflammation-associated diseases first with emphasis on the role of inflammation in their pathogenesis. Then, we will summarize a number of natural products that exhibit therapeutic effects against those diseases by acting on different markers in the inflammatory response. We envision that natural products will remain a rich resource for the discovery of new drugs treating diseases associated with chronic inflammation.

FLOT Neoadjuvant Chemotherapy Followed by Laparoscopic D2 Gastrectomy in the Treatment of Locally Resectable Advanced Gastric Cancer.

Background: The prognosis of patients with advanced gastric cancer remains unsatisfactory, highlighting the need for improved therapeutic strategies. We analyzed 23 resectable advanced gastric cancer patients who received FLOT followed by laparoscopic gastrectomy with D2 lymphadenectomy to evaluate the efficacy and safety. Methods: Patients aged 18-75 years with gastric adenocarcinoma (stage cT3-4 and/or N + M0) underwent neoadjuvant FLOT therapy (four preoperative and four postoperative 2-week cycles) at Shanghai East Hospital. Laparoscopic gastrectomy was scheduled 3-4 weeks after completion of the last cycle of preoperative chemotherapy. The type of surgical procedure was determined by the location and extent of the primary tumor. Results: 23 patients were reviewed in the study. 20 patients (81.2%) received four courses of FOLT therapy, while 3 patients (18.8%) received three courses of treatment. There were 3 (13.0%) complete responses, 13 (56.5%) partial responses, 4 (26.1%) of stable disease, and 1 (4.3%) of progressive disease. The clinical efficacy response rate was 69.6%. The R0 resection rate was 91.3%. Only one patient exhibited grade III postoperative complications. The pathologic complete remission was 13%. The common grade 3/4 adverse events from chemotherapy were leucopenia (17.4%), neutropenia (30.4%), anemia (13%), anorexia (13%), and nausea (17.4%). Postoperative complications occurred in 5 patients (26.1%). There was no treatment-related mortality or reoperation. The most reason for not completing chemotherapy was the patient's request. Conclusions: These findings suggest that FLOT neoadjuvant chemotherapy, followed by laparoscopic D2 gastrectomy, is effective and safe in advanced, resectable advanced gastric cancer.

Internet videos and colorectal cancer in mainland China: a content analysis.

BACKGROUND: Colorectal cancer incidence and mortality have been increasing in China and as one of the most important health problems facing the nation. Adequate dissemination of correct information about colorectal cancer could help in reducing cancer-related morbidity and mortality. This study aims to assess the completeness and reliability of colorectal cancer-related information available on the video website of Youku in mainland China. METHODS: Youku ( https://www.youku.com /) was searched on September 15, 2016 for the search terms colorectal cancer. Only Chinese videos were included. Two reviewers independently evaluate the videos for characteristics, information source and usefulness. Content was analysed under six categories (aetiology, anatomy, symptoms, preventions, treatments and prognosis). Completeness was evaluated with a checklist developed by the researchers. Any discrepancies were resolved by consensuses. SPSS software was used to analyze data. RESULTS: There were 242 videos with relevant information about colorectal cancer. The type of source were as follows: independent users, 118 (49%); health information web sites, 60 (25%); medical doctors, 31 (13%); news network, 22 (9%); and hospital/university, 11 (4%). In all, 57% of videos had useful information about colorectal cancer, 21% were misleading. Videos posted by medical doctors (P = 0.021) and health information web sites (p = 0.039) were less incomplete than videos by independent users. Of the Traditional Chinese medicine (TCM) videos, 97 (76%) had information about treatments of colorectal cancer. 30% TCM videos contain misleading information, whose misleading rate was higher than total's (21%). CONCLUSIONS: The colorectal cancer videos in mainland China represented by Youku varied base on ownership and content and information incompleteness were fairly high. It is necessary that professionals adapt to the advanced technology and think useful methods to solve the variable quality of information of internet video websites in mainland China.

Flammulina velutipes polysaccharides improve scopolamine-induced learning and memory impairment in mice by modulating gut microbiota composition.

Flammulina velutipes polysaccharides (FVP) have been proved to be effective in improving learning and memory impairment in mice. However, their underlying mechanism remains unclear. The aim of this study was to investigate the relationship between memory improvement and gut microbiota regulation of FVP. The results showed a significant decrease in the relative abundances of Clostridia and Bacilli but a significant increase in Bacteroidia, Erysipelotrichia and Actinobacteria in the FVP-treated group versus the control group. Fecal microbiota transplantation of mice with 'FVP microbiota' derived from FVP-fed mice resulted in improved learning and memory function compared to colonization with 'common microbiota' derived from control individuals. FVP and 'FVP microbiota' significantly increased the numbers of platform crossings and the swimming distance of mice in the probe test and decreased the escape latency and total swimming distance of mice in the hidden platform test. Moreover, FVP and 'FVP microbiota' regulated cytokines, such as IL-1ß, TNF-α, IL-6 and IL-10, suggesting a mechanism involving the suppression of neuroinflammation. This study indicated that the regulation of the gut microbiome may have a causal role in improving scopolamine-induced impairment of learning and memory.

Polyphenols-rich extract from Pleurotus eryngii with growth inhibitory of HCT116 colon cancer cells and anti-inflammatory function in RAW264.7 cells.

Edible mushrooms are rich sources of bioactive components. In this study, a polyphenol-rich extract, designated as PPEP, was isolated from an edible mushroom, Pleurotus eryngii. Using ultra high performance liquid chromatograph combined with triple time-of-flight mass spectrometry (UPLC-TOF/MS/MS), gallic acid monohydrate, 3-(3,4-dihydroxyphenyl)-propionic acid, methyl gallate, syringic acid, ellagic acid and catechin were identified in PPEP. This phenolic-rich extract PPEP exhibited anti-inflammatory effect in lipopolysaccharide-stimulated RAW264.7 macrophages by inhibiting the overproduction of pro-inflammatory mediators including nitric oxide (NO) and reactive oxygen species (ROS). It was demonstrated that the anti-inflammatory effects of PPEP were associated with the inhibition of iNOS expression, suppression of p-IκB protein expression and inhibition of NF-κB and IκB mRNA expression. Next, the inhibitory effect of PPEP against human colon cancer cells was also determined. PPEP suppressed cell proliferation of human colon cancer HCT116 cells in a dose- and time-dependent fashion, while it showed no inhibitory effect on normal human colonic myofibroblasts CCD-18Co cells at the same tested concentrations (0-200 µg mL-1). Moreover, PPEP induced cell cycle arrest and led to extensive cellular apoptosis in human colon cancer cells, which was associated with the downregulation of cell cycle-related signaling protein, e.g. cyclin B and cyclin E, and the upregulation of apoptosis-related signaling protein caspase-3 and cleaved caspase-3. Overall, our results provided a basis for using PPEP as a promising preventive agent against inflammatory disease and colon cancer.

Enrichment of Bread with Nutraceutical-Rich Mushrooms: Impact of Auricularia auricula (Mushroom) Flour Upon Quality Attributes of Wheat Dough and Bread.

Edible mushrooms contain a variety of bioactive molecules that may enhance human health and wellbeing. Consequently, there is increasing interest in fortifying functional foods with these nutraceutical-rich substances. However, incorporation of mushroom-based ingredients into foods should not adversely affect the quality attributes of the final product. In this study, the impact of incorporating powdered Auricularia auricula, a widely consumed edible mushroom, into bread products was examined. The rheological and structural properties of wheat dough and bread supplemented with 0% to 10% (w/w) A. auricula flour were measured. Supplementation of wheat doughs with A. auricula flour increased the peak viscosity and enhanced their water holding capacity. Rapid viscosity analysis showed that peak and final viscosities of the blended flour (wheat flour with A. auricula flour) were higher than wheat flour alone. However, dough stability and elastic modulus were reduced by blending wheat flour with A. auricula flour. SEM observation showed that doughs with up to 5% (w/w) A. auricula flour had acceptable gluten network microstructure. Characterization of the quality attributes of bread indicated that incorporation of A. auricula flour at levels >5% negatively impacted bread volume, height, texture, and appearance.

Traditional Chinese medicinal herbs combined with epidermal growth factor receptor tyrosine kinase inhibitor for advanced non-small cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) targeted treatment has been a standard therapy for advanced non-small cell lung cancer (NSCLC), but it is not tolerated well by all patients. In China, some studies have reported that traditional Chinese medicinal herbs (TCMHs) may increase efficacy and reduce toxicity when combined with EGFR-TKI, but outside of China few studies of this kind have been attempted. OBJECTIVE: This study is intended to systematically review the existing clinical evidence on TCMHs combined with EGFR-TKI for treatment of advanced NSCLC. SEARCH STRATEGY: PubMed, the Cochrane Library, the Excerpta Medica Database (EMBASE), the China BioMedical Literature (CBM), and the China National Knowledge Infrastructure (CNKI) and web site of the American Society of Clinical Oncology (ASCO), the European Society for Medical Oncology (ESMO), the World Conference of Lung Cancer (WCLC) were searched; the search included all documents published in English or Chinese before October 2013. INCLUSION CRITERIA: We selected randomized controlled trials based on specific criteria, the most important of which was that a TCMH plus EGFR-TKI treatment group was compared with an EGFR-TKI control group in patients with advanced NSCLC. DATA EXTRACTION AND ANALYSIS: The modified Jadad scale was used to assess the quality of studies. For each included study, patient characteristics, treatment details, therapeutic approach and clinical outcomes were collected on a standardized form. When disagreements on study inclusion or data extracted from a study emerged, the consensus of all coauthors provided the resolution. The clinical outcome metrics consisted of objective response rate (ORR; complete response + partial response divided by the total number of patients), disease control rate (DCR; complete response + partial response + no change divided by the total number of patients), survival rate, improved or stabilized Karnofsky performance status (KPS), and severe toxicity. RevMan 5.0 software was used for data syntheses and analyses. Risk ratio (RR) and 95% confidence interval (CI) were calculated; if the hypothesis of homogeneity was not rejected (P>0.1, I(2)<50%), the fixed-effect model was used to calculate the summary RR and the 95% CI. Otherwise, a random-effect model was used. RESULTS: In this review, 19 studies were included based on the selection criteria. Of them, 13 studies were of high quality and 6 studies were of low quality, according to the modified Jadad scale. When the TCMH plus EGFR-TKI treatment groups were compared with the EGFR-TKI control groups the meta-analysis demonstrated a statistically significant higher ORR (RR 1.34; 95% CI 1.15 to 1.57; P=0.000 2), DCR (RR 1.18; 95% CI 1.09 to 1.27; P<0.000 1), one-year survival rate (RR 1.21; 95% CI 1.01 to 1.44; P=0.04), 2-year survival rate (RR 1.91; 95% CI 1.26 to 2.89; P=0.002) and improved or stable KPS (RR 1.38; 95% CI 1.26 to 1.51; P<0.000 01). Severe toxicity for rash was decreased (RR 0.55; 95% CI 0.32 to 0.94; P=0.03), as were nausea and vomiting (RR 0.17; 95% CI 0.04 to 0.72; P=0.02) and diarrhea (RR 0.46; 95% CI 0.24 to 0.89; P=0.02). Sensitivity analysis indicated that findings of the meta-analysis were robust to study quality. In the funnel plot analysis, asymmetry was observed, and publication bias was indicated by Egger's test (P=0.03). CONCLUSION: TCMH intervention can increase efficacy and reduce toxicity when combined with EGFR-TKI for advanced NSCLC, although this result requires further verification by more well designed studies.

Traditional Chinese medicinal herbs combined with epidermal growth factor receptor tyrosine kinase inhibitor for advanced non-small cell lung cancer: a systematic review and meta-analysis / 中西医结合学报

<p><b>BACKGROUND</b>Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) targeted treatment has been a standard therapy for advanced non-small cell lung cancer (NSCLC), but it is not tolerated well by all patients. In China, some studies have reported that traditional Chinese medicinal herbs (TCMHs) may increase efficacy and reduce toxicity when combined with EGFR-TKI, but outside of China few studies of this kind have been attempted.</p><p><b>OBJECTIVE</b>This study is intended to systematically review the existing clinical evidence on TCMHs combined with EGFR-TKI for treatment of advanced NSCLC.</p><p><b>SEARCH STRATEGY</b>PubMed, the Cochrane Library, the Excerpta Medica Database (EMBASE), the China BioMedical Literature (CBM), and the China National Knowledge Infrastructure (CNKI) and web site of the American Society of Clinical Oncology (ASCO), the European Society for Medical Oncology (ESMO), the World Conference of Lung Cancer (WCLC) were searched; the search included all documents published in English or Chinese before October 2013.</p><p><b>INCLUSION CRITERIA</b>We selected randomized controlled trials based on specific criteria, the most important of which was that a TCMH plus EGFR-TKI treatment group was compared with an EGFR-TKI control group in patients with advanced NSCLC.</p><p><b>DATA EXTRACTION AND ANALYSIS</b>The modified Jadad scale was used to assess the quality of studies. For each included study, patient characteristics, treatment details, therapeutic approach and clinical outcomes were collected on a standardized form. When disagreements on study inclusion or data extracted from a study emerged, the consensus of all coauthors provided the resolution. The clinical outcome metrics consisted of objective response rate (ORR; complete response + partial response divided by the total number of patients), disease control rate (DCR; complete response + partial response + no change divided by the total number of patients), survival rate, improved or stabilized Karnofsky performance status (KPS), and severe toxicity. RevMan 5.0 software was used for data syntheses and analyses. Risk ratio (RR) and 95% confidence interval (CI) were calculated; if the hypothesis of homogeneity was not rejected (P>0.1, I(2)<50%), the fixed-effect model was used to calculate the summary RR and the 95% CI. Otherwise, a random-effect model was used.</p><p><b>RESULTS</b>In this review, 19 studies were included based on the selection criteria. Of them, 13 studies were of high quality and 6 studies were of low quality, according to the modified Jadad scale. When the TCMH plus EGFR-TKI treatment groups were compared with the EGFR-TKI control groups the meta-analysis demonstrated a statistically significant higher ORR (RR 1.34; 95% CI 1.15 to 1.57; P=0.000 2), DCR (RR 1.18; 95% CI 1.09 to 1.27; P<0.000 1), one-year survival rate (RR 1.21; 95% CI 1.01 to 1.44; P=0.04), 2-year survival rate (RR 1.91; 95% CI 1.26 to 2.89; P=0.002) and improved or stable KPS (RR 1.38; 95% CI 1.26 to 1.51; P<0.000 01). Severe toxicity for rash was decreased (RR 0.55; 95% CI 0.32 to 0.94; P=0.03), as were nausea and vomiting (RR 0.17; 95% CI 0.04 to 0.72; P=0.02) and diarrhea (RR 0.46; 95% CI 0.24 to 0.89; P=0.02). Sensitivity analysis indicated that findings of the meta-analysis were robust to study quality. In the funnel plot analysis, asymmetry was observed, and publication bias was indicated by Egger's test (P=0.03).</p><p><b>CONCLUSION</b>TCMH intervention can increase efficacy and reduce toxicity when combined with EGFR-TKI for advanced NSCLC, although this result requires further verification by more well designed studies.</p>

[Clinical research of intraperitoneal chemotherapy plus Shenmai Injection in treating advanced colorectal cancer].

OBJECTIVE: To study the effects of intraperitoneal chemotherapy (IPC) plus Shenmai Injection (SMI) in treating advanced colorectal cancer following radical resections. METHODS: Fifty-eight cases of colorectal cancer in stage B2 and C following radical resections were divided into two groups: SMI+IPC group (36 cases) and IPC group (22 cases). In the SMI+IPC group, IPC (5-fluorouracil combined with cisplatin) plus SMI was administered, while in the IPC group, only IPC was administered. Clinical symptoms, quality of life (Karnofsky score), white blood cell counts, natural killer cells and CD4/CD8 were observed, and disease-free survival (DFS) rate was also evaluated. RESULTS: The total short-term response rate was 83.33% in the SMI+IPC group, significantly higher than 63.64% in the IPC group (P<0.05). The data of clinical symptoms, quality of life, white blood cell counts, natural killer cells and CD4/CD8 in the SMI+IPC group were also significantly improved as compared with those in the IPC group (P<0.05 or P<0.01). In the SMI+IPC group, 1-, 3- and 5-year DFS rates were 91.7% (33/36), 77.8% (28/36) and 72.2% (26/36) respectively, and those in the IPC group were 90.9% (20/22), 72.7% (16/22) and 45.5% (10/22) respectively. The 5-year DFS rate was significantly improved in the SMI+IPC group as compared with that in the IPC group (P<0.05), while the 1-year and 3-year DFS rates had no significant difference between these two groups. CONCLUSION: IPC plus SMI is effective in treating post-operative patients with advanced colorectal cancer.