Polydopamine-Modified 2D Iron (II) Immobilized MnPS3 Nanosheets for Multimodal Imaging-Guided Cancer Synergistic Photothermal-Chemodynamic Therapy.

Manganese phosphosulphide (MnPS3 ), a newly emerged and promising member of the 2D metal phosphorus trichalcogenides (MPX3 ) family, has aroused abundant interest due to its unique physicochemical properties and applications in energy storage and conversion. However, its potential in the field of biomedicine, particularly as a nanotherapeutic platform for cancer therapy, has remained largely unexplored. Herein, a 2D "all-in-one" theranostic nanoplatform based on MnPS3 is designed and applied for imaging-guided synergistic photothermal-chemodynamic therapy. (Iron) Fe (II) ions are immobilized on the surface of MnPS3 nanosheets to facilitate effective chemodynamic therapy (CDT). Upon surface modification with polydopamine (PDA) and polyethylene glycol (PEG), the obtained Fe-MnPS3 /PDA-PEG nanosheets exhibit exceptional photothermal conversion efficiency (η = 40.7%) and proficient pH/NIR-responsive Fenton catalytic activity, enabling efficient photothermal therapy (PTT) and CDT. Importantly, such nanoplatform can also serve as an efficient theranostic agent for multimodal imaging, facilitating real-time monitoring and guidance of the therapeutic process. After fulfilling the therapeutic functions, the Fe-MnPS3 /PDA-PEG nanosheets can be efficiently excreted from the body, alleviating the concerns of long-term retention and potential toxicity. This work presents an effective, precise, and safe 2D "all-in-one" theranostic nanoplatform based on MnPS3 for high-efficiency tumor-specific theranostics.

A novel protein encoded by circINSIG1 reprograms cholesterol metabolism by promoting the ubiquitin-dependent degradation of INSIG1 in colorectal cancer.

BACKGROUND: Hypoxia is a hallmark of solid tumors and leads to the metabolic reprogramming of cancer cells. The role of epigenetic regulation between hypoxia and aberrant cholesterol metabolism in colorectal cancer (CRC) remains elusive. METHODS: Hypoxia-responsive circular RNAs (circRNAs) were identified by high throughput RNA sequencing between CRC cells cultured under normoxia or hypoxia. The protein-coding potential of circINSIG1 was identified by polysome profiling and LC-MS. The function of circINSIG1 was validated in vitro and in vivo by gain or loss of function assays. Mechanistic results were concluded by immunoprecipitation analyses. RESULTS: A novel hypoxia-responsive circRNA named circINSIG1 was identified, which was upregulated in CRC tissues and correlated with advanced clinical stages and poor survival. Mechanistically, circINSIG1 encoded a 121 amino acid protein circINSIG1-121 to promote K48-linked ubiquitination of the critical cholesterol metabolism regulator INSIG1 at lysine 156 and 158 by recruiting CUL5-ASB6 complex, a ubiquitin E3 ligase complex, thereby inducing cholesterol biosynthesis to promote CRC proliferation and metastasis. The orthotopic xenograft tumor models and patient-derived xenograft models further identified the role of circINSIG1 in CRC progression and potential therapeutic target of CRC. CONCLUSIONS: circINSIG1 presents an epigenetic mechanism which provides insights into the crosstalk between hypoxia and cholesterol metabolism, and provides a promising therapeutic target for the treatment of CRC.

Robotic Intracellular Electrochemical Sensing for Adherent Cells.

Nanopipette-based observation of intracellular biochemical processes is an important approach to revealing the intrinsic characteristics and heterogeneity of cells for better investigation of disease progression or early disease diagnosis. However, the manual operation needs a skilled operator and faces problems such as low throughput and poor reproducibility. This paper proposes an automated nanopipette-based microoperation system for cell detection, three-dimensional nonovershoot positioning of the nanopipette tip in proximity to the cell of interest, cell approaching and proximity detection between nanopipette tip and cell surface, and cell penetration and detection of the intracellular reactive oxygen species (ROS). A robust focus algorithm based on the number of cell contours was proposed for adherent cells, which have sharp peaks while retaining unimodality. The automated detection of adherent cells was evaluated on human umbilical cord vein endothelial cells (HUVEC) and NIH/3T3 cells, which provided an average of 95.65% true-positive rate (TPR) and 7.59% false-positive rate (FPR) for in-plane cell detection. The three-dimensional nonovershoot tip positioning of the nanopipette was achieved by template matching and evaluated under the interference of cells. Ion current feedback was employed for the proximity detection between the nanopipette tip and cell surface. Finally, cell penetration and electrochemical detection of ROS were demonstrated on human breast cancer cells and zebrafish embryo cells. This work provides a systematic approach for automated intracellular sensing for adherent cells, laying a solid foundation for high-throughput detection, diagnosis, and classification of different forms of biochemical reactions within single cells.

Proteomics, Phosphoproteomics and Mirna Analysis of Circulating Extracellular Vesicles through Automated and High-Throughput Isolation.

Extracellular vesicles (EVs) play an important role in the diagnosis and treatment of diseases because of their rich molecular contents involved in intercellular communication, regulation, and other functions. With increasing efforts to move the field of EVs to clinical applications, the lack of a practical EV isolation method from circulating biofluids with high throughput and good reproducibility has become one of the biggest barriers. Here, we introduce a magnetic bead-based EV enrichment approach (EVrich) for automated and high-throughput processing of urine samples. Parallel enrichments can be performed in 96-well plates for downstream cargo analysis, including EV characterization, miRNA, proteomics, and phosphoproteomics analysis. We applied the instrument to a cohort of clinical urine samples to achieve reproducible identification of an average of 17,000 unique EV peptides and an average of 2800 EV proteins in each 1 mL urine sample. Quantitative phosphoproteomics revealed 186 unique phosphopeptides corresponding to 48 proteins that were significantly elevated in prostate cancer patients. Among them, multiple phosphoproteins were previously reported to associate with prostate cancer. Together, EVrich represents a universal, scalable, and simple platform for EV isolation, enabling downstream EV cargo analyses for a broad range of research and clinical applications.

Cytoprotective effects of spleen-invigorating pill against 5-fluorouracil injury to mouse bone marrow stromal cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Spleen-invigorating pills (SIP) are composed of Codonopsis, fried Atractylodes, tangerine peel, Fructus aurantii immaturus (fried), fried hawthorn, and colored malt. SIP strengthens the spleen and increases appetite and is often used as a chemotherapy adjuvant. AIM OF THE STUDY: We aimed to explore the protective effects and mechanism of action for SIP on mouse bone marrow stromal cells (OP9) injured by 5-fluorouracil (5-FU). MATERIALS AND METHODS: The effects of SIP on OP9 cells injured by 5-FU were evaluated, and high-performance liquid chromatography (HPLC) was used as a quality control method. The experiments were divided into a control group, a model group, an epidermal growth factor (EGF) treatment group, and an SIP treatment group. The cell survival rate, apoptotic cell morphology, cell apoptosis rate, and the contents of caspase 3 were evaluated to determine the protective effects of SIP in OP9 cells injured by 5-FU. Network pharmacology was used to predict the mechanism through which SIP mediates anti-chemotherapy damage. The nitric oxide (NO) and nitric oxide synthase (iNOS) levels and the expression of nuclear factor erythroid-2 related factor 2 (Nrf2) and p62 protein were detected to explore the mechanism through which SIP mediates anti-chemotherapy damage through the regulation of oxidative stress. RESULTS: Cell counting kit-8 (CCK8) detection showed that 5-FU reduced OP9 cell survival, and SIP blocked the inhibition of OP9 cell growth induced by 5-FU. When OP9 cells were treated with both SIP (10 g L-1) and 5-FU (2.5 × 10-2 g L-1) for 24 h, compared with the model group, the early apoptosis rates significantly decreased, and the activity of caspase 3 was significantly reduced. The results of network pharmacology and Western blot showed that compared with the model group, in the SIP group, the NO levels decreased, iNOS release decreased, and the expression of Nrf2 and p62 proteins increased. CONCLUSION: The protective effects of SIP on OP9 cells injured by 5-FU were significant. SIP may play a cytoprotective role by mediating changes in oxidative stress-related proteins. The specific mechanism of action through which SIP mediates these effects remains to be further studied.

Synergistically Bifunctional Paramagnetic Separation Enables Efficient Isolation of Urine Extracellular Vesicles and Downstream Phosphoproteomic Analysis.

Extracellular vesicles (EVs) have emerged as important carriers for intercellular communication and biological sources for diagnosis and therapeutics. Low efficiency in EV isolation from biofluids, however, severely restricts their downstream characterization and analysis. Here, we introduced a novel strategy for EV isolation from urine for prostate cancer diagnosis using bifunctionalized magnetic beads through high affinity Ti(IV) ions and the insertion of a phospholipid derivative, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, into the EV membrane synergistically. We demonstrated its efficient isolation of EVs from urine samples with low contamination, high recovery (>80%), and short separation time (within 1 h), resulting in the identification of 36,262 unique EV peptides corresponding to 3302 unique proteins and 3233 unique phosphopeptides representing 1098 unique phosphoproteins using only 100 µL and 5 mL urine samples, respectively. Coupled with trapped ion mobility spectrometry and parallel accumulation-serial fragmentation for phosphosite-specific resolution, quantitative phosphoproteomics of urine samples from prostate cancer patients and healthy individuals revealed 121 upregulated phosphoproteins in cancer patients in contrast to the healthy group. These particular advantages indicate that the novel bifunctional material enables sensitive EV phosphoproteomic analysis for noninvasive biomarker screening and early cancer diagnosis.

Tongue Coating Bacteria as a Potential Stable Biomarker for Gastric Cancer Independent of Lifestyle.

BACKGROUND: Gastric cancer (GC) is one of the most common cancers, and the noninvasive diagnostic methods for monitoring GC are still lacking. Growing evidence shows that human microbiota has potential value for identifying digestive diseases. AIMS: The present study aimed to explore the association of the tongue coating microbiota with the serum metabolic features and inflammatory cytokines in GC patients and seek a potential, noninvasive biomarker for diagnosing GC. METHODS: The tongue coating microbiota was profiled by 16S rRNA and 18S rRNA genes sequencing technology in the original population with 181 GC patients and 112 healthy controls (HCs). Propensity score matching method was used to eliminate potential confounders including age, gender, and six lifestyle factors and a matching population with 66 GC patients and 66 HCs generated. Serum metabolomics profiling was performed by ultra-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) in the matching population. Random forest model was constructed for the diagnosis of GC. RESULTS: Linear discriminant analysis effect size (LEfSe) revealed that the differential bacterial taxa between GC patients and HCs in the matching population were similar to that in the original population, while the differential fungal taxa between GC patients and HCs dramatically changed before and after PSM. By random forest analysis, the combination of six bacterial genera (Peptostreptococcus, Peptococcus, Porphyromonas, Megamonas, Rothia, and Fusobacterium) was the optimal predictive model to distinguish GC patients from HCs effectively, with an area under the curve (AUC) value of 0.85. The model was verified with a high predictive potential (AUC = 0.76 to 0.96). In the matching population, eighteen specific HCs-enriched bacterial genera (Porphyromonas, Parvimonas, etc.) had negative correlations with lysophospholipids metabolites, and three of them had also negative correlations with serum IL-17α. CONCLUSIONS: The alteration of tongue coating microbiota had a possible linkage with the inflammations and metabolome, and the tongue coating bacteria could be a potential noninvasive biomarker for diagnosing GC, which might be independent of lifestyle.

Cytotoxic benzopyranone and xanthone derivatives from a coral symbiotic fungus Cladosporium halotolerans GXIMD 02502.

Coral-derived microorganisms have been historically proven to be prolific sources of bioactive secondary metabolites. Twelve benzopyranone and/or xanthone derivatives, including a new benzopyranone with an uncommon carboxyl group at C-8, coniochaetone K (1), were obtained from the Beibu Gulf-derived coral symbiotic fungus Cladosporium halotolerans GXIMD 02502. Their structures were determined by extensive spectroscopic data interpretation and comparison with literature values. The absolute configuration of 1 was accomplished by comparison of specific optical rotation as well as quantum chemical ECD calculations. The in vitro cytotoxicity of compounds 1-12 against two human prostatic cancer cell lines, C4-2B and 22RV1, were evaluated. And compounds 1, 3, 6-8, and 10-11 demonstrated significant cytotoxicity with inhibitions ranging from 55.8% to 82.1% at the concentration of 10 µM.

Prevalence and Risk Factors for Malnutrition in Patients With Parkinson's Disease.

Objectives: This study aimed to investigate the relationship between nutritional status and Parkinson's disease (PD) features. Methods: The cohort was composed of 556 Parkinson's patients who were admitted to the hospital. Patients were categorized as normal nutrition or at risk of malnutrition/already malnourished. Questionnaires, physical examinations, and biochemical tests were conducted. The relationship between nutrition status and PD was analyzed using t-tests, χ2-tests, and logistic regression models. Results: The prevalence of malnutrition [defined as a Mini Nutritional Assessment (MNA) score <17] was 39.2%, and 30.3% of patients were at risk of malnutrition (17 ≤ MNA score ≤ 23.5). There was no difference in gender and age between the different nutrition groups (P < 0.05). Patients at risk of malnutrition and those who were malnourished had a longer course of disease, more severe motor symptoms, a higher stage of PD according to the Hoehn and Yahr (H-Y) classification, a lower body mass index (BMI) index, a lower cognitive score, higher levels of depression and anxiety, and more serious non-motor symptoms (P < 0.05) than patients with normal nutrition. There were differences in adenosine deaminase, albumin, phosphorus, chlorine, total protein, and uric acid between the two groups (P < 0.05). High Unified PD Rating Scale (UPDRS-III) scores, high H-Y stages, and dyskinesia were risk factors for malnutrition in PD patients, while high levels of total protein, uric acid, and chlorine were protective factors that led to good nutrition (P < 0.05). Conclusions: Our results showed that dyskinesia, disease severity, total protein levels, uric acid levels, and chlorine levels were associated with nutritional status among Chinese PD patients. The findings of this study indicate the significance of the early detection and prevention of malnutrition to improve the quality of life of PD patients.

Glass Fiber-Supported Hybrid Monolithic Spin Tip for Enrichment of Phosphopeptides from Urinary Extracellular Vesicles.

Extracellular vesicles (EVs) are attracting increasing interest with their intriguing role in intercellular communications. Protein phosphorylation in EVs is of great importance for understanding intercellular signaling processes. However, the study of EV phosphoproteomics is impeded by their relatively low amount in limited clinical sample volumes, and it is necessary to have a sensitive and efficient enrichment method for EV phosphopeptides. Herein, a novel Ti(IV)-functionalized and glass fiber-supported hybrid monolithic spin tip, termed PhosTip, was prepared for enriching phosphopeptides from urinary EVs. Glass fiber as the stationary phase positions the hybrid monolith in a standard pipet tip and prevents the monolith from distortion during experiments. The preparation procedure for the new PhosTip is simple and time-saving. The hybrid monolithic PhosTip provides excellent enrichment efficiency of low-abundance phosphopeptides from cell digests and urinary EVs with minimum contamination and sample loss. Using the PhosTip, we demonstrate that 5373 and 336 unique phosphopeptides were identified from 100 and 1 µg of cell lysates, while 3919 and 217 unique phosphopeptides were successfully identified from 10 and 1 mL of urinary samples, respectively. The PhosTip was finally applied to enrich phosphopeptides in urine EVs from prostate cancer patients and healthy controls and quantify 118 up-regulated proteins with phosphosites in prostate cancer samples. These results demonstrated that the PhosTip could be a simple and convenient tool for enriching phosphopeptides from clinical samples and for broader applications in biomarker discovery.

A novel bis-aryl urea compound inhibits tumor proliferation via cathepsin D-associated apoptosis.

Derivatives of bis-aryl urea have been widely investigated for their various biological activities, such as antiviral, anti-inflammatory and antiproliferative. We evaluated a new chemical entity consisting of bis-aryl urea moiety, N69B, for its anticancer activities and explored their underlying molecular mechanism. The compound inhibited proliferation of multiple types of murine and human cancer cells in vitro, and reduced tumor growth in mouse 4T1 breast tumor model in vivo. Protein microarray analysis revealed and western blot confirmed that the compound significantly increased protein levels of cathepsins, especially cathepsin D, a lysosomal aspartyl protease known to have various pathophysiological functions. Further studies showed that the compound induced tumor cell apoptosis through the Bid/Bax/Cytochrome C/caspase 9/caspase 3 pathway, in which cathepsin D appeared to be a main mediator. Unlike kinase inhibition commonly seen with many other anticancer bis-aryl urea derivatives, this unique mechanism of N69B may suggest potential of the compound as a novel anticancer drug.

Efficacy and complications of argon plasma coagulation for hemorrhagic chronic radiation proctitis.

BACKGROUND: Chronic radiation proctitis (CRP) is a complication which occurs in 1%-5% of patients who undergo radiotherapy for pelvic malignancies. Although a wide range of therapeutic modalities are available, there is no literature to date showing any particularly appropriate therapeutic modality for each disease stage. Argon plasma coagulation (APC) is currently recommended as the first-choice treatment for hemorrhagic CRP, however, its indication based on long-term follow-up is still unclear. On the hypothesis that the long-term efficacy and safety of APC are not fully understood, we reviewed APC treatment for patients with hemorrhagic CRP from a single center. AIM: To assess the long-term efficacy and safety of APC for hemorrhagic CRP. METHODS: This is a retrospective study of consecutive patients treated with APC for hemorrhagic CRP from January 2013 to October 2017. Demographics, clinical variables, and typical endoscopic features were recorded independently. Success was defined as either cessation of bleeding or only occasional traces of bloody stools with no further treatments for at least 12 mo after the last APC treatment. We performed univariate and multivariate analyses to identify factors associated with success and risk factors for fistulas. RESULTS: Forty-five patients with a median follow-up period of 24 mo (range: 12-67 mo) were enrolled. Fifteen (33.3%) patients required blood transfusion before APC. Successful treatment with APC was achieved in 31 (68.9%) patients. The mean number of APC sessions was 1.3 (1-3). Multivariate analysis showed that APC failure was independently associated with telangiectasias present on more than 50% of the surface area [odds ratio (OR) = 6.53, 95% confidence interval (CI): 1.09-39.19, P = 0.04] and ulcerated area greater than 1 cm2 (OR = 8.15, 95%CI: 1.63-40.88, P = 0.01). Six (13.3%) patients had severe complications involving rectal fistulation. The only factor significantly associated with severe complications was ulcerated area greater than 1 cm2 (P = 0.035). CONCLUSION: The long-term efficacy of APC for hemorrhagic CRP is uncertain in patients with telangiectasias present on > 50% of the surface area and ulceration > 1 cm2.

Relationship between serum inflammatory cytokines and lifestyle factors in gastric cancer.

Chronic inflammation is associated with increased risk of gastric cancer (GC), and GC risk is significantly associated with lifestyle. The aim of the present study was to explore the association between serum inflammatory cytokines and lifestyle factors in GC. A total of 20 serum inflammatory cytokines were measured in a hospital-based case-control population with 142 GC patients and 98 healthy controls. Controls without the selected healthy lifestyle factors were regarded as baseline, and correlation analysis was conducted to establish the association between serum inflammatory cytokines and lifestyle factors. The results demonstrated that several lifestyle factors (including eating fried and salty foods, eating quickly, smoking and drinking) could increase the risk of GC, while only eating fresh fruits could decrease the risk of GC. Correlation analysis revealed that increased serum interleukin (IL)-12/IL-23P40 levels was associated with GC risk as significant differences were observed in all lifestyle factors. Increased serum IL-8 was closely associated with smoking in GC patients, while increased IL-17α and IL-8 levels were associated with GC patients who ate salty foods. Increased IL-10 and decreased TGF-ß levels were also associated with GC patients who ate fresh fruits. In conclusion, GC risk was strongly affected by lifestyle factors, which may regulate the expression of inflammatory cytokines and promote gastric carcinogenesis.

Microbial biomarkers of common tongue coatings in patients with gastric cancer.

PURPOSE: The study aims to explore the characteristic microorganisms of the common tongue coatings in patients with gastric cancer (GC). METHODS: A total of 115 GC patients were assigned to four groups: White-thin coating (W-thin) group, White-thick coating (W-thick) group, Yellow-thin coating (Y-thin) group and Yellow-thick coating (Y-thick) group. Thirty-five healthy volunteers with White-thin coating were recruit as controls. High-throughput sequencing was used to describe the microbial community of the tongue coatings based on 16S rRNA and 18S rRNA genes. Multi-factors statistical analysis was carried out to present the microbial biomarkers of the tongue coating in GC patients. RESULTS: At bacterial phylum level, Saccharibacteria had higher relative abundance in W-thick group than W-thin group, Proteobacteria was more abundant in W-thin group than Y-thick group and less abundant in Y-thick group than Y-thin group. At fungal genus level, Guehomyces and Aspergillus presented to be significantly different among the common tongue coatings. Forteen significantly increased taxa were sorted out as the microbial biomarkers of common tongue coatings by LEfSe and ROC analysis. At species level, bacterial Capnocytophaga leadbetteri and fungal Ampelomyces_sp_IRAN_1 may be the potential biomarkers of W-thin coating, four bacterial species (Megasphaera micronuciformis, Selenomonas sputigena ATCC 35185, Acinetobacter ursingii, Prevotella maculosa) may be the potential biomarkers of W-thick coating. In general, the white coatings held more complex commensal relationship than the yellow coatings. CONCLUSION: The common tongue coating owned characteristic microorganisms and special commensal relationship in the GC patients.

Tongue Coating Microbiota Community and Risk Effect on Gastric Cancer.

Background: Although oral hygiene and health have long been reported to be associated with increased risk of gastric cancer (GC), the direct relationship of oral microbes with the risk of GC have not been evaluated fully. We aimed to test whether tongue coating microbiome was associated with GC risk. Methods: Pyrosequencing of 16S rRNA gene of tongue coating microbiome was used in 57 newly diagnosed gastric adenocarcinomas and 80 healthy controls. Benjamini-Hochberg (BH) was applied for multiple comparison correction. Co-abundance group (CAGs) analysis was adopted. Results: We found that higher relative abundance of Firmicutes, and lower of Bacteroidetes were associated with increased risk of GC. In genus level, Streptococcus trended with a higher risk of GC, the four other genera (Neisseria, Prevotella, Prevotella7, and Porphyromonas) were found to have a decreased risk of GC. Different from overall GC and non-cardia cancer, Alloprevotella and Veillonella trended with the higher risk of cardia cancer. Finally, we analyzed the microbiota by determining CAGs and six clusters were identified. Except the Cluster 2 (mainly Streptococcus and Abiotrophia), the other clusters had an inverse association with GC. Of them, the Cluster 6 (mainly Prevotella and Prevotella7 etc) had a relatively good classification power with 0.76 of AUC. Conclusion: Microbiome in tongue coating may have potential guiding value for early detection and prevention of GC.

Enteral immunonutrition versus enteral nutrition for gastric cancer patients undergoing a total gastrectomy: a systematic review and meta-analysis.

BACKGROUND: Nutrition support is a common means for patients with gastric cancer, especially for those undergoing elective surgery. Recently, enteral immunonutrition (EIN) was increasingly found to be more effective than enteral nutrition (EN) in enhancing the host immunity and eventually improving the prognosis of gastric cancer patients undergoing gastrectomy. However, the results reported were not consistent. This meta-analysis aimed to assess the impact of EIN for patients with GC on biochemical, immune indices and clinical outcomes. METHODS: Four electronical databases (Medline, EMBASE, Scopus and Cochrane library) were used to search articles in peer-reviewed, English-language journals. Mean difference (MD), Relative risk (RR), or standard mean difference (SMD) with 95% confidence interval (CI) were calculated. Heterogeneity was assessed by Cochrane Q and I2 statistic combined with corresponding P-value. The analysis was carried out with RevMan 5.3. RESULTS: Seven studies involving 583 patients were eligible for the pooled analysis. EIN, when beyond a 7-day time-frame post-operatively (D ≥ 7), increased level of CD4+ (SMD = 0.99; 95% CI, 0.65-1.33; P < 0.00001), CD4+/ CD8+ (SMD = 0.34; 95% CI, 0.02-0.67; P = 0.04), the IgM (SMD = 1.15; 95% CI, 0.11-2.20; P = 0.03), the IgG (SMD = 0.98; 95% CI, 0.55-1.42; P < 0.0001), the lymphocyte (SMD = 0.69; 95% CI, 0.32-1.06; P = 0.0003), and the proalbumin (SMD = 0.73; 95% CI, 0.33-1.14; P = 0.0004). However, those increased effects were not obvious within a 7-day time-frame post-operatively (D < 7). The levels of CD8+ and other serum proteins except proalbumin were not improved both on D ≥ 7 and D < 7. Clinical outcomes such as systemic inflammatory response syndrone (SIRS) (MD, - 0.89 days; 95% CI, - 1.40 to - 0.39; P = 0.005), and postoperative complications (RR, 0.29; 95% CI, 0.14-0.60; P = 0.001) were significantly reduced in EIN group. Pulmonary infection and length of hospitalization (LHS) were not improved no matter what time after surgery. CONCLUSIONS: EIN was found to improve the cellular immunity, modulate inflammatory reaction and reduce postoperative complication for GC patients undergoing radical gastrointestinal surgery. Exclusion of grey literature and non-English language studies was the key limitation in this study.

Effect of immunonutrition on colorectal cancer patients undergoing surgery: a meta-analysis.

PURPOSE: Immunonutrition has been used to prevent the complications after colorectal elective surgery. This systematic review aimed to analyze and assess the effect of immunonutrition on colorectal cancer patients who received elective surgery. METHODS: Three electronic databases (Medline, Embase, Cochrane) were used to search the latent studies which investigated the effects of enteral immunonutrition (EIN) compared with standard enteral nutrition (EN) or parenteral immunonutrition (PIN) compared with standard parenteral nutrition (PN) on colorectal cancer patients who are undergoing surgery until 21st of April, 2017. Meta-analysis was conducted to calculate odd risk (OR), mean difference (MD), or standard mean difference (SMD) with 95% confidence interval (CI), and heterogeneity was tested by Q test. RESULTS: Nine publications were included. The meta-analysis results presented that EIN improved the length of hospital stay (pooled MD, 2.53; 95% CI, 1.29-3.41), infectious complications (pooled OR, 0.33; 95% CI, 0.21-0.53) which contains the Surgical Site Infections (pooled OR, 0.25; 95% CI, 0.22-0.58) and Superficial/Deep incisional infections (pooled OR, 0.27; 95% CI, 0.12-0.64); meanwhile, PIN improved the length of hospital stay (pooled MD, 2.66; 95% CI, 0.62-4.76), IL-6 (pooled MD, - 6.09; 95% CI, - 10.11 to - 2.07), CD3 (pooled MD, 7.50; 95% CI, 3.57-11.43), CD4 (pooled MD, 5.47; 95% CI, 2.54-8.40), and CD4/CD8 (pooled MD, 0.50; 95% CI, 0.22-0.78); the level of CD8 was lower (pooled MD, - 4.32; 95% CI, - 7.09 to - 1.55) in PIN. CONCLUSION: Immunonutrition could be an effective approach to enhance the immune function of colorectal cancer patients undergoing elective surgery and to improve the clinical and laboratory outcomes.

Proteomic analysis of serum deprivation in tongue squamous cell carcinoma.

The occurrence of tongue squamous cell carcinoma (TSCC) is closely correlated with serum components; however, the detailed mechanism remains to be fully elucidated. Proteomic analysis contributed to the discovery of potential biomarkers and provided an insight into TSCC at a molecular level. The present study investigated the effect of serum deprivation on the Tca­8113 TSCC cell line through protein profiling using two­dimensional gel electrophoresis and mass spectrometry, with the aim of improving TSCC diagnosis. The results showed that the Tca­8113 cells maintained proliferative capacity and resisted apoptosis following serum deprivation. A total of 43 proteins were upregulated and 45 were downregulated following serum deprivation for 24 h, compared with untreated controls (0 h). The upregulated caspase-7, heat shock protein 27 and Annexin A1, and the downregulated peroxiredoxin­6 and heat shock protein 70, were selected for verification using reverse transcription­polymerase chain reaction analysis following serum deprivation for 16 h. The results indicated that reactive oxygen species may be important in serum deprivation­induced oxidative stress.

Expression of NUAK2 in gastric cancer tissue and its effects on the proliferation of gastric cancer cells.

The present study aimed to analyze the expression and effects of NUAK2 in gastric cancer and adjacent normal gastric tissues. The protein expression levels of NUAK2 were detected by western blot analysis. The effects of NUAK2 expression on the proliferation of gastric cancer cells was detected using an MTT and BrdU incorporation assay. Furthermore, the effects of NUAK2 on proliferation and cancer stem cell markers, both protein and microRNA (miRNA), were investigated by western blot analysis and miRNA microarrays, respectively. The results demonstrated that NUAK2 was able to significantly promote the proliferation of SGC-7901 gastric cancer cells. In addition, NUAK2 overexpression decreased the percentage of cells in the G1 phase and increased the percentage of cells in the S phase. Western blot analysis and miRNA microarrays revealed that overexpression of NUAK2 resulted in increased expression levels of proliferation markers, including c-myc, proliferating cell nuclear antigen, cyclin-dependent kinase 2, miRNA 21, and gastric cancer stem cell markers, including aldehyde dehydrogenase 1, CD44 and CD133. In conclusion, NUAK2 expression differed between the tumor and normal gastric tissues. NUAK2 was able to promote the proliferation of gastric cancer cells and regulate their cell cycle. Proliferation and cancer stem cell markers were upregulated by NUAK2 expression. Therefore, the results from the present study suggest that NUAK2 may be a promising target for gastric cancer therapy in the future.

Genetic variants in the 3' untranslated region of sFRP1 gene and risk of gastric cancer in a Chinese population.

BACKGROUND: Secreted frizzled-related protein 1 (sFRP1), a negative regulator of the Wnt signaling pathway, is frequently inactivated in human gastric cancer. Genetic variants in the 3' untranslated region (UTR) of the gene may influence the strength of miRNA binding and the regulation of mRNA transcription, affecting the individual's cancer risk. This study aims to investigate the impact of variants in the 3' UTR of sFRP1 on the gastric cancer susceptibility in a Chinese population. PATIENTS AND METHODS: The association between 2 sFRP1 gene variation loci (rs1127379 and rs10088390) with minor allele frequency more than 0.1 in the 3' UTR and gastric cancer risk was assessed in a case-control study including 419 gastric cancer cases and 571 healthy controls. PCR-restriction fragment length polymorphism analysis was used for genotyping; the odds ratio and 95% confidence interval were calculated to estimate the relative risk. RESULTS: Compared with the AA genotype, the GG genotype of rs1127379 was significantly associated with a reduced risk of gastric cancer overall. In the subgroup analysis, the protective effect of the GG genotype was also found for noncardia cancer and intestinal gastric cancer. Furthermore, haplotype analysis showed that the A rs1127379 G rs10088390 haplotype conferred a risk effect for gastric cancer. CONCLUSIONS: Genetic variants at the sFRP1 gene may be involved in gastric tumorigenesis, especially in noncardia and intestinal gastric cancer. Further prospective studies with different ethnicities and large sample sizes are needed to confirm our findings.