Phase-transition nanodroplets with immunomodulatory capabilities for potentiating mild magnetic hyperthermia to inhibit tumour proliferation and metastasis.

BACKGROUND: Magnetic hyperthermia (MHT)-mediated thermal ablation therapy has promising clinical applications in destroying primary tumours. However, traditional MHT still presents the challenges of damage to normal tissues adjacent to the treatment site and the destruction of tumour-associated antigens due to its high onset temperature (> 50 °C). In addition, local thermal ablation of tumours often exhibits limited therapeutic inhibition of tumour metastasis. RESULTS: To address the above defects, a hybrid nanosystem (SPIOs + RPPs) was constructed in which phase transition nanodroplets with immunomodulatory capabilities were used to potentiate supermagnetic iron oxide nanoparticle (SPIO)-mediated mild MHT (< 44 °C) and further inhibit tumour proliferation and metastasis. Magnetic-thermal sensitive phase-transition nanodroplets (RPPs) were fabricated from the immune adjuvant resiquimod (R848) and the phase transition agent perfluoropentane (PFP) encapsulated in a PLGA shell. Because of the cavitation effect of microbubbles produced by RPPs, the temperature threshold of MHT could be lowered from 50℃ to approximately 44℃ with a comparable effect, enhancing the release and exposure of damage-associated molecular patterns (DAMPs). The exposure of calreticulin (CRT) on the cell membrane increased by 72.39%, and the released high-mobility group B1 (HMGB1) increased by 45.84% in vivo. Moreover, the maturation rate of dendritic cells (DCs) increased from 4.17 to 61.33%, and the infiltration of cytotoxic T lymphocytes (CTLs) increased from 10.44 to 35.68%. Under the dual action of mild MHT and immune stimulation, contralateral and lung metastasis could be significantly inhibited after treatment with the hybrid nanosystem. CONCLUSION: Our work provides a novel strategy for enhanced mild magnetic hyperthermia immunotherapy and ultrasound imaging with great clinical translation potential.

NIR luminogen for low-temperature photothermal therapy by triggering HSP90α down-regulation.

A near-infrared (NIR) luminogen TST was designed and used to efficiently trigger HSP90α protein knockdown through photo-thermal conversion based on a gene interference strategy, by which in vitro and in vivo tumor ablation were significantly acquired at low-temperature.

Tannic Acid-Aminated Sugar Beet Pectin Nanoparticles as a Stabilizer of High-Internal-Phase Pickering Emulsions.

Pickering stabilizers with additional antioxidant, photostabilizing, and metal-chelating properties are suitable for structuring multifunctional Pickering emulsion systems. Tannic acid (TA) is a potential material which when adsorbed onto the interface may impart antioxidant, UV-light-shielding, and chelating properties to Pickering stabilizers. Herein, we report a type of TA polyelectrolyte nanoparticles (NPs) fabricated following a complexation between TA and aminated sugar beet pectin (SBP-NH2). This study is geared toward investigating the performance of TA/SBP-NH2 NPs in stabilizing Pickering emulsions and protecting ß-carotene from degradation. TA/SBP-NH2 NPs formed under optimum conditions had a mean diameter of 82 nm with a sphere-like shape. Because of their favorable surface wettability (91.2°), TA/SBP-NH2 NPs promoted formation of the low-, medium-, and high-internal-phase Pickering emulsions (HIPEs) in an oil volume fraction (φ)-dependent manner; the TA/SBP-NH2 NP-stabilized HIPE demonstrated viscoelastic properties increasing with the increasing concentration (c) of nanoparticles. Due to the excellent storage stability and UV light-absorbing capacity, the photostability of ß-carotene was significantly improved by a TA/SBP-NH2 NP-stabilized HIPE (φ = 0.75; c = 3 mg/mL). Altogether, this study highlights that TA/SBP-NH2 NPs have potential applications in structuring Pickering emulsions with improved protective effects on loaded lipophilic compounds.

Rice bran-modified wheat gluten nanoparticles effectively stabilized pickering emulsion: An interfacial antioxidant inhibiting lipid oxidation.

This study investigated the fabrication of Pickering emulsion stabilized by rice bran-modified wheat gluten nanoparticle (RGNP) and evaluated the effect of rice bran-modification on lipid oxidation of emulsified soybean oil, with native wheat gluten nanoparticle (CGNP) as the control. Compared with CGNP, RGNP exhibited stronger antioxidant activities due to high content of polyphenols. RGNP were roughly spherical (mean size of about 250 nm) with balanced wettability (104.6 ± 2.3°) and had excellent colloidal thermal stability. When used at a concentration of 1.5 wt%, both CGNP and RGNP could stabilize Pickering emulsions at varying oil volume fractions (0.20-0.85). For high internal phase emulsions, nanoparticles adsorbed at an oil-water interface forming an interconnected network structure, depressing the oxidation of soybean oil. RGNP as an interfacial antioxidant further improved the Pickering emulsion' oxidative stability. This work may expand the application of wheat gluten as an antioxidant solid particle in Pickering emulsion.

Photo-Enhanced Chemotherapy Performance in Bladder Cancer Treatment via Albumin Coated AIE Aggregates.

The implementation of cisplatin-based neoadjuvant chemotherapy (NAC) plays a key role in conjunction with surgical resection in preventing bladder cancer progression and recurrence. However, the significant dose-dependent toxic side effects of NAC are still a major challenge. To solve this problem, we developed a photoenhanced cancer chemotherapy (PECC) strategy based on AIEgen ((E)-3-(2-(2-(5-(4-(diphenylamino)phenyl)thiophen-2-yl)vinyl)-1,1-dimethyl-1H-3λ4-benzo[e]indol-3-yl)propane-1-sulfonate), which is abbreviated as BITT. Multifunctional BITT@BSA-DSP nanoparticles (NPs) were employed with an albumin-based nanocarrier decorated with the cisplatin(IV) prodrug and loaded to produce strong near-infrared fluorescence imaging (NIR FLI), and they exhibited good photoenhancement performance via photodynamic therapy (PDT) and photothermal therapy (PTT). In vitro results demonstrated that BITT@BSA-DSP NPs could be efficiently taken up by bladder cancer cells and reduced to release Pt (II) under reductase, ensuring the chemotherapy effect. Furthermore, both in vitro and in vivo evaluation verified that the integration of NIR FL imaging-guided PECC efficiently promoted the sensitivity of bladder cancer to cisplatin chemotherapy with negligible side effects. This work provides a promising strategy to enhance the sensitivity of multiple cancers to chemotherapy drugs and even achieve effective treatments for drug-resistant cancers.

Enhanced treatment of low-temperature and low carbon/nitrogen ratio wastewater by corncob-based fixed bed bioreactor coupled sequencing batch reactor.

In this study, a combined corncob-based fixed bed bioreactor and sequencing batch reactor system (CCF-SBR) was developed to treat low-temperature (3-12 °C) and low carbon/nitrogen ratio (C/N = 2) wastewater with a single SBR as the control. Results showed similarly low COD concentration of CCF-SBR (20.4 ± 3.7 mg·L-1) and control SBR (24.9 ± 6.7 mg·L-1) effluent. However, the total nitrogen (TN) removal rate of CCF-SBR was significantly higher than that of control SBR (29.6 ± 2.7% vs 8.6 ± 2.3%). According to the nitrification and denitrification activities and the analysis of microbial community, CCF mainly played the role of denitrification based on fermentation genera and denitrifying genera, and SBR mainly implemented nitrification with Nitrospira and Acinetobacter. This study explores a promising way for agricultural waste resource utilization and wastewater treatment under low-temperature and low C/N ratio.

Assessment of heavy metals should be performed before the development of the selenium-rich soil: A case study in China.

The use of selenium (Se)-rich soils in China is an effective method for rural revitalization, but assessment of heavy metals is essential prior to the development of Se-rich soils. This study was focused on the Jiangjin district, a typical Se-rich area located in Sichuan Basin of China, to investigate contamination, influencing factors, and sources of As, Cr, Cu, Cd, Ni, Pb, Sb, and Zn based on 156 topsoil samples. This study analyzed and compared the enrichment factor (EF), Nemerow index (PN), geographical information system (GIS), and positive matrix factorization (PMF). Results demonstrate that the average values of As, Cu, Cd, Sb, and Zn in topsoil were higher than the soil background values of western Chongqing by approximately 1.75, 1.11, 1.27, 1.71, and 2.58 times, respectively, indicating that some heavy metals have been enriched in the soils. The polluted areas of As, Cu, Cd, and Zn in topsoil were mainly distributed in the northern and central Jiangjin district, whereas high-Sb soils were located in the southeast. The Cr, Cu, Cd, Pb, and Sb were concentrated in Se-rich soils, indicating that heavy metals pollution should be carefully considered for the utilization of Se-rich soils. Four potential sources of heavy metals were found in this study area: 1) the parent materials (Cr, Ni, Cu); 2) industrial activities with high coal consumption (As); 3) mechanical and chemical industrial activities (Zn, Sb); and 4) transportation and agricultural activities (Pb, Cd). These observations provide a scientific basis for the development, utilization, and protection of Se-rich soil resources.

Grape seed proanthocyanidin-loaded gel-like W/O/W emulsion stabilized by genipin-crosslinked alkaline soluble polysaccharides-whey protein isolate conjugates: Fabrication, stability, and in vitro digestion.

The present work aims to fabricate the genipin-crosslinked alkaline soluble polysaccharides-whey protein isolate conjugates (G-AWC) to stabilize W/O/W emulsions for encapsulation and delivery of grape seed proanthocyanidins (GSP). After crosslinking reaction, the molecular weight was increased and surface hydrophobicity was decreased. Then, the G-AWC and polyglycerol polyricinoleate (PGPR, a lipophilic emulsifier) were employed to prepare a GSP-loaded W/O/W emulsion with the addition of gelatin and sucrose in W1 phase via a two-step procedure. Creamed emulsion could be fabricated at W1/O volume fraction (Φ) of 10%-70% and further increased Φ to 75% or even up to 90% could obtain gel-like emulsion with notably elastic behaviors. In the W1/O/W2 emulsion with Φ of 80%, the encapsulation efficiency (EE) of GSP reached up to 95.86%, and decreased by ca. 10% after a week of storage. Moreover, the encapsulated GSP in the emulsion showed a remarkably higher bioaccessibility (40.72%) compared to free GSP (13.11%) in the simulated gastrointestinal digestion. These results indicated that G-AWC-stabilized W/O/W emulsions could be an effective carrier to encapsulate water-soluble bioactive compounds with enhanced stability and bioaccessibility.

Robust W/O/W Emulsion Stabilized by Genipin-Cross-Linked Sugar Beet Pectin-Bovine Serum Albumin Nanoparticles: Co-encapsulation of Betanin and Curcumin.

Betanin and curcumin hold promise as natural colorants and antioxidants for food purposes due to their anti-hypertensive, anti-inflammation, and anti-tumor effects. However, the thermal stability and bioavailability of betanin and curcumin still need improvement. Here, we fabricated sugar beet pectin-bovine serum albumin nanoparticles (SBNPs) with a mean particle size of 180 ± 5.2 nm through a genipin cross-linking strategy to stabilize a type of Pickering water-in-oil-in-water (W/O/W) emulsion and co-encapsulated betanin and curcumin. First, the W1/O emulsion was homogenized with gelatin (the gelling agent) in the water phase and polyglycerol polyricinoleate (a lipophilic surfactant) in the oil phase. Later, W1/O was homogenized with another water phase containing SBNPs. The microstructure of the emulsion was regulated by the particle concentration (c) and W1/O volume fraction (Φ), especially the gel-like high internal phase emulsions were formed at the Φ up to 70%. In this case, betanin was encapsulated in the internal water phase (encapsulation efficiency = 65.3%), whereas curcumin was in the medium-chain triglyceride (encapsulation efficiency = 84.1%). Meanwhile, the shelf stability of betanin and curcumin was improved. Furthermore, the stability of bioactive compounds was potentiated by an emulsion gel in simulated gastrointestinal digestion, resulting in higher bioaccessibility. The aforementioned results suggest that SBNP-stabilized Pickering W/O/W emulsions could be a potential alternative to co-encapsulate betanin and curcumin with enhancement of shelf stability and bioaccessibility.

Advanced High-Performance Potassium-Chalcogen (S, Se, Te) Batteries.

Current great progress on potassium-chalcogen (S, Se, Te) batteries within much potential to become promising energy storage systems opens a new avenue for the rapid development of potassium batteries as a complementary option to lithium ion batteries. The discussion mainly concentrates on recent research advances of potassium-chalcogen (S, Se, Te) batteries and their corresponding cathode materials in this review. Initially, the development of cathode materials for four types of batteries is introduced, including: potassium-sulfur (K-S), potassium-selenium (K-Se), potassium-selenium sulfide (K-Sex Sy ), and potassium-tellurium (K-Te) batteries. Next, critical challenges for chalcogen-based electrodes in devices operation are summarized. In addition, some pragmatic strategies are proposed as well to relieve the low electronic conductivity, large volumetric expansion, shuttle effect, and potassium dendrite growth. At last, the perspectives on designing advanced cathode materials for potassium-chalcogen batteries are provided with the goal of developing high-performance potassium storage devices.

Identification of Potential Therapeutic Targets Among CXC Chemokines in Breast Tumor Microenvironment Using Integrative Bioinformatics Analysis.

BACKGROUND/AIMS: Breast cancer is a common cause of cancer mortality throughout the world. The cross-talk between cancer cells and interstitial cells exerts significant effects on neoplasia and tumor development and is modulated in part by chemokines. CXC is one of four chemokine families involved in mediating survival, angiogenesis, and immunosensitization by chemoattracting leukocytes, and it incentivizes tumor cell growth, invasion and metastasis in the tumor microenvironment. However, the differential expression profiles and prognostic values of these chemokines remains to be elucidated. METHODS: In this study, we compared transcriptional CXC chemokines and survival data of patients with breast carcinoma (BC) using the ONCOMINE dataset, Kaplan-Meier Plotter, TCGA and cBioPortal. RESULTS: We discovered increased mRNA levels for CXCL8/10/11/16/17, whereas mRNA expression of CXCL1/2/3/4/5/6/7/12/14 was lower in BC patients compared to non-tumor tissues. Kaplan-Meier plots revealed that high mRNA levels of CXCL1/2/3/4/5/6/7/12/14 correlate with relapse-free survival (RFS) in all types of BC patients. Conversely, high CXCL8/10/11 predicted worse RFS in BC patients. Significantly, high transcription levels of CXCL9/12/13/14 conferred an overall survival (OS) advantage in BC patients, while high levels of CXCL8 demonstrated shorter OS in all BC sufferers. CONCLUSIONS: Integrative bioinformatics analysis suggests that CXCL8/12/14 are potential suitable targets for precision therapy in BC patients compared to other CXC chemokines.

Metabolomics reveals the effect of Xuefu Zhuyu Decoction on plasma metabolism in rats with acute traumatic brain injury.

Xuefu Zhuyu Decoction (XFZY), an important traditional Chinese herbal formula, has been reported effective on traumatic brain injury (TBI) in rats. However, its cerebral protection mechanism has not been clarified at the metabolic level. This work aims to explore the global metabolic characteristics of XFZY in rats during the acute phase of TBI on days 1 and 3. A plasma metabolomics method based on gas chromatography-mass spectrometry coupled with univariate analysis and multivariate statistical analysis was performed in three groups (Sham, Vehicle, XFZY). Then, a pathway analysis using MetaboAnalyst 3.0 was performed to illustrate the pathways of therapeutic action of XFZY in TBI. XFZY treatment attenuates neurological dysfunction and cortical lesion volume post-injury on day 3, and reverses the plasma metabolite abnormalities (glutamic acid, lactic acid, 3-hydroxybutyric acid, and ribitol, etc.). These differential metabolites are mainly involved in D-glutamine and D-glutamate metabolism, alanine, aspartate and glutamate metabolism, and inositol phosphate metabolism. Our study reveals potential biomarkers and metabolic networks of acute TBI and neuroprotection effects of XFZY, and shows this metabolomics approach with MetaboAnalyst would be a feasible way to systematically study therapeutic effects of XFZY on TBI.

Mucosal MicroRNAs Expression Profiles before and after Exclusive Enteral Nutrition Therapy in Adult Patients with Crohn's Disease.

MicroRNAs (miRNAs) have been shown to be important for the pathogenesis of Crohn's disease (CD). Exclusive enteral nutrition (EEN) is an effective therapy for inducing remission in CD. We aimed to investigate the alteration of miRNAs expression profile in the terminal ileal mucosa of CD patients before and after EEN. Twenty-five patients and ten healthy individuals were included. MiRNAs expression profile was firstly assessed using microarray technology and then validation was performed by qRT-PCR. The correlations between miRNAs and CD activity index (CDAI) score and serum C-reactive protein (CRP) level were also evaluated. Microarray analysis showed that mucosal miRNAs expression profile after EEN therapy was significantly changed compared with inflamed mucosa before treatment, and was most similar to the healthy one among all CD groups. Altered expressions of hsa-miR-192-5p, hsa-miR-423-3p, hsa-miR-99a-5p, hsa-miR-124-3p, hsa-miR-301a-5p, hsa-miR-495-5p, and hsa-let-7b-5p were confirmed by qRT-PCR. hsa-let-7b-5p was significantly correlated with serum CRP levels before and after EEN treatment (r = -0.518, p = 0.008, and r = -0.569, p = 0.003). Our study showed EEN induction therapy was associated with a trend for normalizing of the mucosal miRNAs expression profile, and expression of mucosal hsa-let-7b-5p was correlated with serum CRP level in patients with CD.

[Chemical constituents of Kadsura oblongifolia and evaluation of their toxicity].

To study the chemical constituents of K. oblongifolia, silica gel column chromatography, MCI and Sephadex LH-20 were used to separate the 70% acetone extract of the stems of K. oblongifolia. The structures of the isolated compounds have been established on the basis of physicochemical and NMR spectroscopic evidence as well as ESI-MS in some cases. Twenty compounds were obtained and identified as heteroclitalignan A (1), kadsulignan F (2), kadoblongifolin C (3), schizanrin F (4), heteroclitalignan C (5), kadsurarin (6), kadsulignan O (7), eburicol (8), meso-dihydroguaiaretic acid (9), kadsufolin A (10), tiegusanin M (11), heteroclitin B (12), (7'S)-parabenzlactone (13), angeloylbinankadsurin B (14), propinquain H (15), quercetin (16), kadsulignan P (17), schizanrin G (18), micrandilactone C (19) and (-)-shikimic acid (20). Compouds 1, 5, 8, 11-15, 18 and 20 were isolated from this plant for the first time. Toxicity of compounds 1-10 were evaluated with zebrafish model to observe the effect on its embryonic development and heart function. The results showed that compounds 7, 9 and 10 caused edema of zebrafish embryo and decreased the heart rate of zebrafish, which exhibited interference effect on heart development of zebrafish.

Combination therapy with sorafenib and radiofrequency ablation for BCLC Stage 0-B1 hepatocellular carcinoma: a multicenter retrospective cohort study.

OBJECTIVES: The objective of this study was to evaluate the efficacy of combined therapy using Sorafenib and radiofrequency ablation (RFA) with curative intent for all detectable lesions in patients with Barcelona Clinic Liver Cancer (BCLC) Stage 0-B1 hepatocellular carcinoma (HCC). METHODS: One hundred and twenty-eight patients with HCC from 12 centers were enrolled in this retrospective study; 64 patients who received Sorafenib plus RFA (Sorafenib-RFA) were compared with a control group treated with RFA alone. The two patient groups were selected with a predefined criterion and matched in terms of their clinical and tumor characteristics at baseline. The primary end point of the study was the incidence of post-RFA HCC recurrence. Secondary end points were overall survival (OS) and treatment toxicity. RESULTS: During a median follow-up of 134.1 weeks, 49 patients died and 79 survived. The 1-, 2-, and 3-year cumulative incidences of post-RFA recurrence were 40.5%, 62.9%, and 74.5%, respectively, in the Sorafenib-RFA group, and 62.8%, 85.4%, and 92.7%, respectively, in the RFA group. The 1-, 2-, 3-, and 4-year OS rates were 85.6%, 64.0%, 58.7%, and 50.3%, respectively, in the Sorafenib-RFA group, and 80.7%, 47.2%, 30.9%, and 30.9%, respectively, in the RFA group. Thus, the Sorafenib-RFA group exhibited better survival than the RFA alone group. CONCLUSIONS: Combined therapy with Sorafenib-RFA was associated with a lower incidence of post-RFA recurrence and better OS than RFA alone in patients with BCLC Stage 0-B1 HCC. Although these findings suggest that Sorafenib and RFA is safe and effective for the treatment of early HCC, prospective and randomized controlled trials are needed to validate them.

Physiological and proteomic responses of diploid and tetraploid black locust (Robinia pseudoacacia L.) subjected to salt stress.

Tetraploid black locust (Robinia pseudoacacia L.) is adaptable to salt stress. Here, we compared morphological, physiological, ultrastructural, and proteomic traits of leaves in tetraploid black locust and its diploid relatives under salt stress. The results showed that diploid (2×) plants suffered from greater negative effects than those of tetraploid (4×) plants. After salt treatment, plant growth was inhibited, photosynthesis was reduced, reactive oxygen species, malondialdehyde content, and relative electrolyte leakage increased, and defense-related enzyme activities decreased in 2× compared to those in 4×. In addition, salt stress resulted in distorted chloroplasts, swollen thylakoid membranes, accumulation of plastoglobules, and increased starch grains in 2× compared to those in 4×. However, 4× developed diverse responses under salt stress. A comparative proteomic analysis revealed that 41 and 37 proteins were differentially expressed in 2× and 4×, respectively. These proteins were mainly involved in photosynthesis, stress and defense, energy, metabolism, transcription/translation, and transportation. Distinct patterns of protein changes between 2× and 4× were analyzed. Collectively, our results suggest that the plants showed significantly different responses to salt stress based on ploidy level of the plant. The 4× possessed a better salt protection mechanism than that of 2×, suggesting salt tolerance in the polyploid plant.

[Effects of leflunomide in treating patients with rheumatoid arthritis of different Chinese medical syndrome patterns].

OBJECTIVE: To study whether the effects of Leflunomide were different in treating patients with rheumatoid arthritis (RA) of different Chinese medical syndrome patterns. METHODS: Totally 150 RA patients were recruited and assigned to 5 Chinese medical syndrome types, i.e., the heat-dampness blocking collateral type, cold-dampness blocking collateral type, Shen-qi deficiency cold type, Gan-Shen yin deficiency type, and stagnant blood blocking collateral type according to Chinese medical syndrome typing standards. They were treated with Leflunomide, 3 months as one therapeutic course. The parameters including numbers of joint tenderness and swelling, morning stiffness time, scores estimated by Visual Analog Scale (VAS), as well as laboratory indices involving rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), American College of Rheumatology 20% improvement (ACR20), and American College of Rheumatology 50% improvement (ACR50) were observed before and after treatment, and statistically analyzed. RESULTS: After treatment the numbers of joint tenderness, numbers of joint swelling, VAS scores, ESR, CRP, and RF all decreased, showing statistical difference when compared with those before treatment (P < 0.05). The morning stiffness time was shortened in the heat-dampness blocking collateral type, cold-dampness blocking collateral type, and stagnant blood blocking collateral type, showing statistical difference (P < 0.05). Of them, the numbers of joint tenderness, the numbers of joint swelling, the morning stiffness time, RF, VAS scores, and the improvement of the total effective rate were obviously better in the heat-dampness blocking collateral type, cold-dampness blocking collateral type, and stagnant blood blocking collateral type than in the Shen-qi deficiency cold type and Gan-Shen yin deficiency type, showing statistical difference (P < 0.05). CONCLUSIONS: Leflunomide showed significant effects in treating RA. Of them, its effects were obviously better in the heat-dampness blocking collateral type, cold-dampness blocking collateral type, and stagnant blood blocking collateral type than in the Shen-qi deficiency cold type and Gan-Shen yin deficiency type.

Herbal compound "Songyou Yin" attenuates hepatoma cell invasiveness and metastasis through downregulation of cytokines secreted by activated hepatic stellate cells.

BACKGROUND: Activated hepatic stellate cells (aHSCs) play an important role in the progression of hepatocellular carcinoma (HCC). Here, we determined if cytokines secreted in response to the herbal compound "Songyou Yin" (SYY) treatment of aHSCs could influence invasiveness and metastatic capabilities of hepatoma cells. METHODS: Primary rat hepatic stellate cells (HSCs) were isolated, activated, divided into SYY treated and untreated (nSYY) groups, and conditioned media (CM-SYY and CM-nSYY, respectively) were collected. The hepatoma cell line, McA-RH7777 was cultured for 4 weeks with SYY, CM-SYY, and CM-nSYY, designated McA-SYY, McA-SYYCM and McA-nSYYCM. The invasiveness and metastatic capabilities were evaluated using Matrigel invasion assay in vitro and pulmonary metastasis in vivo. Matrix metalloproteinase-2 (MMP-2), MMP-9, E-cadherin, N-cadherin, and vimentin protein levels in McA-SYYCM and McA-nSYYCM were evaluated by Western blot. Cytokine levels in conditioned media were tested using enzyme-linked immunosorbent assay (ELISA). RESULTS: Matrigel invasion assay indicated that the number of McA-SYYCM cells passing through the basement membrane was less than in McA-nSYYCM cells (P < 0.01). Similar results were also observed in vivo for lung metastasis. McA-SYYCM cells showed less pulmonary metastasis capabilities than McA-nSYYCM cells (P < 0.001). The reduced expression of MMP-2 and reversed epithelial to mesenchymal transition with E-cadherin upregulation, and N-cadherin and vimentin downregulation were also found in McA-SYYCM compared to McA-nSYYCM. Metastasis-promoting cytokines hepatocyte growth factor, interleukin-6, transforming growth factor-ß1, and vascular endothelial growth factor were markedly decreased in CM-SYY compared to CM-nSYY. CONCLUSIONS: SYY attenuates hepatoma cell invasiveness and metastasis capabilities through downregulating cytokines secreted by activated hepatic stellate cells.

[Impact of AJCC staging system (2010 edition) on the choice of postoperative adjuvant chemotherapy after radical resection of gastric cancer].

OBJECTIVE: To investigate whether AJCC staging system(2010 edition) for gastric cancer has influence on the adoption of adjuvant chemotherapy. METHODS: This was a cohort study and the data were collected from patients who underwent radical surgery and received adjuvant chemotherapy from January 2004 to December 2009. There were 48 patients with stage II( disease and 95 patients with stage III( disease according to TNM staging(2010 edition). Doublets were defined as 5-fluorouracil or capecitabine plus cisplatin or oxaliplatin, while triplets had epirubicin added. Ninety-six patients received doublet chemotherapy and 47 received triplet. All the patients were followed-up in the outpatient clinic until death or the censor time of May 2011. RESULTS: The median follow-up time was 48 months in this cohort of 143 patients. The two groups had similar disease-free survival(DFS)(median, 23 months vs. 30 months, P>0.05). The median overall survival was 48 months in both groups. Subgroup analysis by TNM staging(2010 edition) showed that the median DFS of patients with stage III( gastric cancer was 15 months in the doublet group, significantly shorter than that of patients in the triplet group (18 months, P<0.05). However, the difference in overall survival was not statistically significant between the two groups. Patients with stage II( disease had comparable DFS and OS between the two groups(all P>0.05). CONCLUSIONS: Triplets regimens (epirubicin, platins and fluorouracil) show benefit on disease-free survival for the stage III( gastric cancer patients staged by TNM staging 2010 edition.

Herbal Compound "Songyou Yin" Renders Hepatocellular Carcinoma Sensitive to Oxaliplatin through Inhibition of Stemness.

We investigated the effect of Chinese herbal compound Song-you Yin on HCC stemness. MHCC97H and Hep3B cell lines were pretreated with SYY for 4 weeks, and their chemosensitivity to oxaliplatin was evaluated. The expression of CSC-related markers, cell invasion and migration, and colony formation were also examined. SYY-treated orthotopic nude mouse models of human HCC were developed to explore the effect of oxaliplatin on tumor growth, metastasis, and survival. The CSC-related molecular changes in vivo were also evaluated. The result showed that MHCC97H and Hep3B cells pretreated with SYY showed significantly increased chemosensitivity to oxaliplatin and the downregulation of CSC-related markers CD90, CD24, and EPCAM. SYY also attenuated cell motility, invasion, and colony formation in MHCC97H and Hep3B cell lines. The reduced tumorigenicity and pulmonary metastasis were observed in SYY-pretreated cell lines. Combination treatment with oxaliplatin and SYY significantly reduced tumor volume and pulmonary metastasis and prolonged survival compared with oxaliplatin treatment alone. Immunohistochemical analysis showed reduced expression of CD90, ABCG2, ALDH, CD44, EPCAM, vimentin, and MMP-9 and increased the expression of E-cadherin, in HCC cells following combination treatment. These data clearly demonstrate that SYY renders hepatocellular carcinoma sensitive to oxaliplatin through the inhibition of stemness.