Black rice diet alleviates colorectal cancer development through modulating tryptophan metabolism and activating AHR pathway.

Consumption of dietary fiber and anthocyanin has been linked to a lower incidence of colorectal cancer (CRC). This study scrutinizes the potential antitumorigenic attributes of a black rice diet (BRD), abundantly rich in dietary fiber and anthocyanin. Our results demonstrate notable antitumorigenic effects in mice on BRD, indicated by a reduction in both the size and number of intestinal tumors and a consequent extension in life span, compared to control diet-fed counterparts. Furthermore, fecal transplants from BRD-fed mice to germ-free mice led to a decrease in colonic cell proliferation, coupled with maintained integrity of the intestinal barrier. The BRD was associated with significant shifts in gut microbiota composition, specifically an augmentation in probiotic strains Bacteroides uniformis and Lactobacillus. Noteworthy changes in gut metabolites were also documented, including the upregulation of indole-3-lactic acid and indole. These metabolites have been identified to stimulate the intestinal aryl hydrocarbon receptor pathway, inhibiting CRC cell proliferation and colorectal tumorigenesis. In summary, these findings propose that a BRD may modulate the progression of intestinal tumors by fostering protective gut microbiota and metabolite profiles. The study accentuates the potential health advantages of whole-grain foods, emphasizing the potential utility of black rice in promoting health.

Suicide among lymphoma patients.

BACKGROUND: Higher suicide rates were observed in patients diagnosed with lymphoma. In this study, we accurately identified patients with high-risk lymphoma for suicide by constructing a nomogram with a view to effective interventions and reducing the risk of suicide. METHODS: 235,806 patients diagnosed with lymphoma between 2000 and 2020 were picked from the Surveillance, Epidemiology, and End Results (SEER) database and randomly divided into training (N = 165,064) and validation set (N = 70,742). A combination of the Least absolute shrinkage and selection operator (LASSO) and Cox proportional hazards regression identified the predictors that constructed the nomogram. To assess the discrimination, calibration, clinical applicability, and generalization of this nomogram, we implemented receiver operating characteristic curves (ROC), calibration curves, decision curve analysis (DCA), and internal validation. The robustness of the results was assessed by the competing risks regression model. RESULTS: Age at diagnosis, gender, ethnicity, marital status, stage, surgery, radiotherapy, and annual household income were key predictors of suicide in lymphoma patients. A nomogram was created to visualize the risk of suicide after a lymphoma diagnosis. The c-index for the training set was 0.773, and the validation set was 0.777. The calibration curve for the nomogram fitted well with the diagonal and the clinical decision curve indicated its clinical benefit. LIMITATION: The effects of unmeasured and unnoticed biases and confounders were difficult to eliminate due to retrospective studies. CONCLUSION: A convenient and reliable model has been constructed that will help to individualize and accurately quantify the risk of suicide in patients diagnosed with lymphoma.

Manganese Dioxide/Gold-based Active Tumor Targeting Nanoprobes for Enhancing Photodynamic and Low-Temperature-Photothermal Combination Therapy in Lung Cancer.

Tumor drug resistance caused by the tumor microenvironment is an extremely difficult problem for researchers to solve. Nanoplatforms that integrate diagnosis and treatment have great advantages in tumor treatment, but the design and synthesis of simple and efficient nanoplatforms still face tremendous challenges. In this study, a novel Mn/Au@ir820/GA-CD133 nanoprobe was developed. The manganese dioxide/gold particles were prepared by coprecipitation/assembly, chemically coupled with CD133 antibody, and finally loaded with the photosensitive drug IR820 and the heat shock protein inhibitor Ganetespib. The nanoprobe demonstrated good tumor-targeting ability, increased the level of singlet oxygen produced from laser irradiation by effectively alleviating tumor hypoxia, and decreased the threshold of heat tolerance by downregulating the expression of HSP90 in tumor tissues. This nanoprobe successfully inhibited the growth and progression of tumor tissues in a tumor-bearing mouse model by improving the effectiveness of photodynamic and low-temperature photothermal combination therapy.

Male-Biased Gut Microbiome and Metabolites Aggravate Colorectal Cancer Development.

Men demonstrate higher incidence and mortality rates of colorectal cancer (CRC) than women. This study aims to explain the potential causes of such sexual dimorphism in CRC from the perspective of sex-biased gut microbiota and metabolites. The results show that sexual dimorphism in colorectal tumorigenesis is observed in both ApcMin/ + mice and azoxymethane (AOM)/dextran sulfate sodium (DSS)-treated mice with male mice have significantly larger and more tumors, accompanied by more impaired gut barrier function. Moreover, pseudo-germ mice receiving fecal samples from male mice or patients show more severe intestinal barrier damage and higher level of inflammation. A significant change in gut microbiota composition is found with increased pathogenic bacteria Akkermansia muciniphila and deplets probiotic Parabacteroides goldsteinii in both male mice and pseudo-germ mice receiving fecal sample from male mice. Sex-biased gut metabolites in pseudo-germ mice receiving fecal sample from CRC patients or CRC mice contribute to sex dimorphism in CRC tumorigenesis through glycerophospholipids metabolism pathway. Sexual dimorphism in tumorigenesis of CRC mouse models. In conclusion, the sex-biased gut microbiome and metabolites contribute to sexual dimorphism in CRC. Modulating sex-biased gut microbiota and metabolites could be a potential sex-targeting therapeutic strategy of CRC.

Peripheral Polyfunctional PD1+ CD8+ T cells demonstrated strong immune protection in non-small cell lung cancer.

Higher frequencies of polyfunctional PD1+ CD8+ T cells exhibited a stronger capacity to kill tumor cells in vitro and in vivo experiments. These results suggested that peripheral polyfunctional PD1+ CD8+ T cells demonstrated strong immune protection. This study also provided a potential combined treatment strategy with anti-PD1 and CAR-T therapy.

circ_0004140 promotes LUAD tumor progression and immune resistance through circ_0004140/miR-1184/CCL22 axis.

Lung adenocarcinoma (LUAD) is a highly prevalent cancer with high mortality. Immune resistance and tumor metastasis are the pivotal factors for the promotion of LUAD. CircRNAs have been revealed a crucial pre-clinical diagnostic and therapeutic potentials in LUAD. Herein, we identify a novel circRNA (circ_0004140), derived from the oncogene YAP1, which is up-regulated in LUAD. The high expression of circ_0004140 is correlated with poor prognosis and CTL cells dysfunction in LUAD patients. Knockdown of circ_0004140 regulated LUAD cells proliferation, migration, and apoptosis. Mechanistically, circ_0004140 served as a sponge of miR-1184 targeting C-C motif chemokine ligand 22(CCL22). Overexpression of CCL22 reversed the inhibitory effect induced by si-circ_0004140 on cells proliferation and migration. Moreover, we also revealed that elevated circ_ooo4140 was related to cytotoxic lymphocyte exhaustion, and a combination therapy of C-021 (CCL22/CCR4 axis inhibitor) and anti-PD-1 attenuated LUAD promotion and immune resistance. In conclusion, circ_0004140 may drive resistance to anti-PD-1 immunotherapy, providing a novel potential therapeutic target for LUAD treatment.

The Prognostic Value of New Index (LANR) Composed of Pre-operative Lymphocytes, Albumin, and Neutrophils in Patients With Resectable Colorectal Cancer.

Background: Inflammatory factors and nutritional status are critical to the prognosis of colorectal cancer patients. This study aimed to investigate the prognostic value of the combination of preoperative lymphocytes, albumin, and neutrophils (LANR) in patients with resectable colorectal cancer. Methods: A total of 753 patients with pathologically diagnosed primary colorectal cancer were included in the study. The value of LANR was defined as follows: LANR, lymphocyte × albumin/neutrophil. The ROC curve, subgroup analysis and Cox proportional hazard regression analysis were used to assess the prognostic value of LANR in overall survival and progression-free survival. Results: The median age of the patients was 60 years (range 52-67 years). In overall survival, the area under the curve of LANR was 0.6276, and the HR (95% CI) was 0.551 (0.393-0.772). And in progression-free survival, the area under the curve of LANR was 0.5963, and the HR (95% CI) was 0.697 (0.550-0.884). The results indicate that preoperative LANR may be a reliable predictor of overall and progression-free survival in resectable colorectal cancer patients. Conclusions: LANR is an important prognostic indicator for patients with resectable colorectal cancer, and it can also provide a reference for clinicians and patients to choose a treatment plan.

Interaction of Soy Protein Isolate Hydrolysates with Cyanidin-3-O-Glucoside and Its Effect on the In Vitro Antioxidant Capacity of the Complexes under Neutral Condition.

The interaction of soy protein isolate (SPI) and its hydrolysates (SPIHs) with cyanidin-3-O-glucoside (C3G) at pH 7.0 were investigated to clarify the changes in the antioxidant capacity of their complexes. The results of intrinsic fluorescence revealed that C3G binds to SPI/SPIHs mainly through hydrophobic interaction, and the binding affinity of SPI was stronger than that of SPIHs. Circular dichroism and Fourier-transform infrared spectroscopy analyses revealed that the interaction with C3G did not significantly change the secondary structures of SPI/SPIHs, while the surface hydrophobicity and average particle size of proteins decreased. Furthermore, the SPI/SPIHs-C3G interaction induced an antagonistic effect on the antioxidant capacity (ABTS and DPPH) of the complex system, with the masking effect on the ABTS scavenging capacity of the SPIHs-C3G complexes being lower than that of the SPI-C3G complexes. This study contributes to the design and development of functional beverages that are rich in hydrolysates and anthocyanins.

Effect of preheated milk proteins and bioactive compounds on the stability of cyanidin-3-O-glucoside.

Native and preheated whey protein isolates (WPI) and casein (at 55 °C-90 °C) were used as protective carriers. Three bioactive compounds, including (-)-Epigallocatechin-3-gallte (EGCG), gallic acid, and vitamin C, were added to enhance the stability of cyanidin-3-O-glucoside (C3G). Under acidic (pH 3.6) and neutral (pH 6.3) conditions, both native and preheated milk proteins showed significant protective effect on C3G. WPI preheated at 85 °C presented the best protective effect on C3G under neutral condition by reducing its thermal, oxidation, and photo degradation rates 25.0%, 38.0%, and 41.1%, respectively. The addition of vitamin C into the protein-anthocyanin solutions accelerated the color loss of C3G, whereas EGCG and gallic acid improved its thermal stability. Among the bioactive compounds, gallic acid provided the most significant protective effect on C3G by further decreasing the thermal degradation rate of C3G 44.6% as a result of the formation of 85 °C preheated WPI-gallic acid-C3G complexes.

Analysis of the interaction between cyanidin-3-O-glucoside and casein hydrolysates and its effect on the antioxidant ability of the complexes.

The interaction between cyanidin-3-O-glucoside with casein and casein hydrolysates and its effects on the antioxidant activity of complexes were investigated. Fluorescence spectroscopy results indicated that the interaction between cyanidin-3-O-glucoside and casein was primarily mediated by Van der Waals forces or hydrogen bonds and stronger than the interaction between cyanidin-3-O-glucoside and casein hydrolysates mainly via hydrophobic interaction. Circular dichroism and Fourier-transform infrared spectroscopy analysis showed the secondary structure of casein/casein hydrolysates had a slight change after binding with cyanidin-3-O-glucoside. And larger particles formed due to the protein aggregation induced by the complexation of casein/casein hydrolysates with cyanidin-3-O-glucoside. The antioxidant activity assessments revealed that the synergistic effect was observed in FRAP assay, whereas an antagonistic effect in ABTS assay between casein/casein hydrolysates and cyanidin-3-O-glucoside, which were produced due to the casein/casein hydrolysates-cyanidin-3-O-glucoside interaction. These results would be helpful in designing functional beverages containing anthocyanins and protein hydrolysates with enhanced antioxidant ability.

A Low Advanced Lung Cancer Inflammation Index Predicts a Poor Prognosis in Patients With Metastatic Non-Small Cell Lung Cancer.

Introduction: Inflammation plays a crucial role in cancers, and the advanced lung cancer inflammation index (ALI) is considered to be a potential factor reflecting systemic inflammation. Objectives: This work aimed to explore the prognostic value of the ALI in metastatic non-small cell lung cancer (NSCLC) and classify patients according to risk and prognosis. Methods: We screened 318 patients who were diagnosed with stage IV NSCLC in Hubei Cancer Hospital from July 2012 to December 2013. The formula for ALI is body mass index (BMI, kg/m2) × serum albumin (Alb, g/dl)/neutrophil-lymphocyte ratio (NLR). Categorical variables were analyzed by the chi-square test or Fisher's exact test. The overall survival (OS) rates were analyzed by the Kaplan-Meier method and plotted with the R language. A multivariate Cox proportional hazard model was used to analyze the relationship between ALI and OS. Results: According to the optimal cut-off value determined by X-tile software, patients were divided into two groups (the ALI <32.6 and ALI ≥32.6 groups), and the median OS times were 19.23 and 39.97 months, respectively (p < 0.01). A multivariable Cox regression model confirmed that ALI and chemotherapy were independent prognostic factors for OS in patients with NSCLC. OS in the high ALI group was better than that in the low ALI group (HR: 1.39; 95% CI: 1.03-1.89; p = 0.03). Conclusions: Patients with a low ALI tend to have lower OS among those with metastatic NSCLC, and the ALI can serve as an effective prognostic factor for NSCLC patients.

Prognostic Prediction Models Based on Clinicopathological Indices in Patients With Resectable Lung Cancer.

Serum enzymes, blood cytology indices, and pathological features are associated with the prognosis of patients with lung cancer, and we construct prognostic prediction models based on clinicopathological indices in patients with resectable lung cancer. The study includes 420 patients with primary lung cancer who underwent pneumonectomy. Cox proportional hazards regression was conducted to analyze the prognostic values of individual clinicopathological indices. The prediction accuracies of models for overall survival (OS) and progression-free survival (PFS) were estimated through Harrell's concordance indices (C-index) and Brier scores. Nomograms of the prognostic models were plotted for individualized evaluations of death and cancer progression. We find that the prognostic model based on alkaline phosphatase (ALP), lactate dehydrogenase (LDH), age, history of tuberculosis, and pathological stage present exceptional performance for OS prediction [C-index: 0.74 (95% CI, 0.69-0.79) and Brier score: 0.10], and the prognostic model based on ALP, LDH, and platelet distribution width (PDW), age, pathological stage, and histological type presented outstanding performance for PFS prediction [C-index: 0.71 (95% CI, 0.66-0.75) and Brier score: 0.18]. These findings show that the models based on clinicopathological indices might serve as economic and efficient prognostic tools for resectable lung cancer.

Lung Carcinoma Cells Secrete Exosomal MALAT1 to Inhibit Dendritic Cell Phagocytosis, Inflammatory Response, Costimulatory Molecule Expression and Promote Dendritic Cell Autophagy via AKT/mTOR Pathway.

OBJECTIVE: To investigate the potential mechanism underlying the effect of lung carcinoma cell-derived exosomes on dendritic cell function. MATERIALS AND METHODS: C57BL/6 (B6) mice were randomly divided into five groups: control, dendritic cell (DC), DC-NC, DC-siMALAT1, and siMALAT1. Tumor cell proliferation was measured by Ki-67 staining. LLC cells were divided into control, NC, and si-MALAT1 groups, and exosomes secreted by each group were labeled as PEX, PEXN, and PEX-si, respectively. Exosomes and autophagic vacuoles were observed by transmission electron microscopy. MALAT1 expression in LLC, A549, and Beas-2b cells was examined by RT-PCR. The expression of IFN-γ, IL-12, IL-10, and TGF-ß was observed by Elisa assay. Flow cytometry was used to observe the phagocytic function of DCs, costimulatory molecule expression, and T cell proliferation and differentiation. The protein expression of p-AKT, AKT, p-mTOR, mTOR, ALIX, TSG101, and CD63 was detected by Western blot. RESULTS: Compared with Beas-2b cells, MALAT1 expression was significantly increased in both LLC and A549 cells and in their secreted exosomes, and LLC cells showed the highest expression of MALAT1 (P < 0.05). Tumor cell proliferation and tumor volume were significantly decreased in the siMALAT1 and DC-siMALAT1 groups compared to those in the control group. DC phagocytosis, inflammatory response, costimulatory molecule expression, and T cell proliferation in the siMALAT1 and PEX-si groups were significantly enhanced (P < 0.05), while DC autophagy and T cell differentiation were reduced (P < 0.05). The levels of p-AKT, AKT, p-mTOR, and mTOR in the PEX and PEXN groups were increased compared with those in the control group, while those in the siMALAT1 and PEX-si groups were significantly decreased (P < 0.05). CONCLUSION: Inhibition of MALAT1 expression in LLC-derived exosomes promoted DC function and T cell proliferation and suppressed DC autophagy and T cell differentiation, suggesting that MALAT1 inhibition may be a potential strategy for the clinical treatment of lung cancer.

The Impact of Javanica Oil Emulsion Injection on Chemotherapy Efficacy and Cellular Immune Indicators in Patients with Advanced NSCLC: A Systematic Review and Meta-Analysis.

BACKGROUND: This meta-analysis aimed to evaluate the efficacy and safety of Javanica oil emulsion injection (JOI) combined with chemotherapy versus chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). METHODS: Electronic databases including EMBASE, PUBMED, the Cochrane library, and Chinese Biological Medical disc (CBM) were searched until May 2018. The clinical trials reporting efficacy and immune function of JOI combined with chemotherapy versus chemotherapy in advanced NSCLC were included according to the inclusion and exclusion criteria. Stata 11 and RevMan 5.3 were used for meta-analysis. RESULTS: Twenty-four studies involving 2089 cases were included. The results of the meta-analysis showed that there were significant differences in objective response rate (risk ratio (RR) = 1.17; 95% confidence interval (CI): 1.05-1.29; P < 0.05), improvement in Karnofsky Performance Status (standard mean difference (SMD) = 1.59; 95% CI: 1.41-1.77; P < 0.01), incidence of adverse events (RR = 0.78; 95% CI: 0.7-0.87; P < 0.05), percentage changes of CD3 + cells (SMD = 2.0; 95% CI: 1.49-2.50; P < 0.01), CD4 + cells (SMD = 1.55; 95% CI, 1.2-1.9; P < 0.01), natural killer cells (SMD = 1.98; 95% CI: 1.15-2.82; P < 0.01), but not CD8 + (SMD = -1.44; 95% CI: -4.53-1.65; P=0.36), and value of CD4 +/CD8 + (SMD = 0.32; 95% CI: 0.28-0.36; P < 0.01) between the JOI combination group and control group. Funnel plot and Begg's and Egger's analysis indicated that there was no significant publication bias (P > 0.05). CONCLUSIONS: JOI may be effective to improve the efficacy of chemotherapy in advanced NSCLC patients, accompanied with better levels of immune cells.

Therapeutic role of glutamine in management of radiation enteritis: a meta-analysis of 13 randomized controlled trials.

OBJECTIVE: To systematically evaluate the clinical efficacy of glutamine in treating radiation enteritis in cancer patients treated with radiotherapy. METHODS: Electronic databases including Pubmed, Embase, the Cochrane library, and CNKI were systematically searched, until April 2016. Randomized controlled trials (RCT) of glutamine in the treatment of radiation enteritis in cancer patients were searched, and RevMan 5.3 software was used for Meta-analysis. RESULTS: A total of 13 RCTs were included, involving 979 patients. The results of meta-analysis showed that the total efficacy of glutamine was higher for patients with radiation enteritis compared with that in control group, however, there was no statistically significant difference(OR = 3.07, 95%CI: 0.79-11.96; P > 0.05). The combined ORs for all 5 grades(from grade 0 to grade 4) of radiation enteritis in patients receiving glutamine were 2.06, 1.35, 0.55, 0.62 and 0.59, respectively(P > 0.05 for all). Glutamine also failed to significantly improve the symptoms of radiation enteritis in terms of tenesmus, abdominal cramping and blood in bowel movement(P > 0.05). CONCLUSIONS: Implementation of glutamine fails to improve the severity and symptoms in patients with radiation enteritis.