Comprehensive analysis of basement membrane-related gene based on single-cell and bulk RNA sequencing data to predict prognosis and evaluate immune characteristics in colorectal cancer.

AIMS: Basement membrane-related genes (BMs) participate in regulating cell polarity, invasion, metastasis, and survival across different tumor types. Nevertheless, the specific functions of BMs in colorectal cancer (CRC) remain uncertain. METHODS: To investigate the clinical relevance of BMs in CRC, we retrieved both gene expression and clinical data from The Cancer Genome Atlas (TCGA) datasets for subsequent analysis. The Kaplan-Meier (K-M) survival curve was employed to evaluate prognosis in high- and low-risk groups. Furthermore, additional analyses, including nomogram construction, functional enrichment, examination of the tumor immune microenvironment, prediction of small-molecule drugs, and more, were conducted to delve into the significance of BM-related signatures in CRC. Single-cell data from seven CRC patients were obtained from the TISCH2 database, and expression validation and cell source exploration of BM-related signatures were performed. Lastly, the expression and function of TIMP1, a key gene in BMs that may play a role in the progression of CRC, was validated in vitro through a series of basic experiments. RESULTS: We constructed a seven BMs-based model to categorize CRC patients into high-risk and low-risk groups. K-M survival analysis indicated a poorer prognosis for high-risk CRC patients. Cox regression analysis further identified the risk score as an independent prognostic factor for CRC patients. The nomogram model exhibited superior discrimination and calibration abilities of CRC patients. Based on the results from GO/KEGG and GSEA, genes in the high-risk subgroup were implicated in immune-related pathways and exhibited a positive correlation with immune checkpoints. In single-cell data, we found that TIMP1 is highly expressed in many cells, especially in malignant tumor cells. We also observed up-regulation of TIMP1 in CRC cell lines, promoting cancer invasion and migration in vitro. CONCLUSIONS: Our study has discovered a novel prognostic index derived from BM-related genes in CRC patients. Specifically, the new model enables patient stratification, improving the selection of individuals likely to benefit from immunotherapy.

Comprehensive characterization of adipogenesis-related genes in colorectal cancer for clinical significance and immunogenomic landscape analyses.

OBJECTIVE: Colorectal cancer (CRC) is a major global health concern, necessitating the identification of biomarkers and molecular subtypes for improved clinical management. This study aims to evaluate the clinical value of adipogenesis-related genes and molecular subtypes in CRC. METHODS: A comprehensive analysis of adipogenesis-related genes in CRC was performed using publicly available datasets (TCGA and GEO database) and bioinformatics tools. Unsupervised cluster analysis was employed to identify the molecular subtypes of CRC, while LASSO regression analysis was utilized to develop a risk prognostic model. The immunogenomic patterns and immunotherapy analysis were used to predict patient response to immunotherapy. Furthermore, qPCR analysis was conducted to confirm the expression of the identified key genes in vitro. RESULTS: Through the analysis of RNAseq data from normal and tumor tissues, we identified 50 differentially expressed genes. Unsupervised cluster analysis identified two subtypes (Cluster A and Cluster B) with significantly different survival outcomes. Cluster A and B displayed differential immune cell compositions and enrichment in specific biological pathways, providing insights into potential therapeutic targets. A risk-scoring model was developed using five ARGs, which successfully classified patients into high and low-risk groups, showing distinct survival outcomes. The model was validated and showed robust predictive performance. High-risk patients exhibited altered immune cell proportions and gene expression patterns compared to low-risk patients. In qPCR validation, four out of the five key genes were consistent with the results of bioinformatics analysis. CONCLUSION: Overall, the findings of our investigation offer valuable understanding regarding the clinical relevance of ARGs and molecular subtypes in CRC, laying the groundwork for improved precision medicine applications and personalized treatment modalities.

Chemotactic NO/H2S Nanomotors Realizing Cardiac Targeting of G-CSF against Myocardial Ischemia-Reperfusion Injury.

Recombinant granulocyte colony-stimulating factor (G-CSF), with a direct repair effect on injured cardiomyocytes against myocardial infarction ischemia-reperfusion-injury (IRI), displays a poor effect owing to the limited cardiac targeting efficacy. There are almost no reports of nanomaterials that deliver G-CSF to the IRI site. Herein, we propose a way to protect G-CSF by constructing one layer of nitric oxide (NO)/hydrogen sulfide (H2S) nanomotors on its outside. NO/H2S nanomotors with specific chemotactic ability to high expression of reactive oxygen species (ROS)/induced nitric oxide synthase (iNOS) at the IRI site can deliver G-CSF to the IRI site efficiently. Meanwhile, superoxide dismutase is covalently bound to the outermost part, reducing ROS at the IRI site through a cascade effect with NO/H2S nanomotors. The synergistic effect between NO and H2S on the effective regulation of the IRI microenvironment can not only avoid toxicity caused by excessive concentration of a single gas but also reduce inflammation level and relieve calcium overload, so as to promote G-CSF to play a cardioprotective role.

Identification of a Novel Tumor Inflammation Signature for Risk Stratification, Prognosis Prediction, and Immune Status in Colorectal Cancer.

Background: Inflammation and immune cell dysfunction have been widely known as an essential role in the tumorigenesis of colorectal cancer (CRC). Yet, the role of tumor inflammation signature (TIS) associated with CRC prognosis, immune infiltration, and drug resistance remained unknown. Method: The transcriptome sequencing data, as well as clinical data of CRC from the public dataset, were acquired for further investigation. Inflammation-related gene expression patterns were obtained and analyzed. Bioinformatics methods were used to build a prognostic TIS, and its prediction accuracy was verified by using ROC curve analyses. The independent prognostic factors in CRC were identified through multivariable Cox regression analysis. In addition, the specific features of the immunological landscape between low- and high-risk CRC cohorts were analyzed. Results: We firstly screened the differentially expressed inflammation-related genes in CRC and constructed a prognostic TIS. We further classified CRC patients into high or low TIS score groups based on the optimal cutoff of prognostic TIS, and patients with high-risk scores had shorter overall survival (OS) than those in the low-risk cohort. The diagnostic accuracy of TIS was evaluated and confirmed with ROC analysis. The result of the univariate and multivariate analysis found that TIS was directly and independently linked to OS of CRC. Otherwise, an optimal nomogram model based on TIS exhibited a better prognostic accuracy in OS. Finally, the immunological status and immune cell infiltration were observed different in the two-risk cohorts. Conclusion: In summary, the risk model of the TIS in CRC was found to be useful for predicting patient prognosis and guiding individual treatment. This risk signature could also serve as potential biomarkers and immunotherapeutic targets and indicate immunotherapy response for patients with CRC.

The characteristics and antioxidation of Oudemansiella radicata selenium polysaccharides on lipopolysaccharide-induced endo-toxemic mice.

The selenium polysaccharides (SPS) by Oudemansiella radicata were isolated, and two hydrolysates (enzymatic-SPS (ESPS) and acidic-SPS (ASPS)) were obtained by enzymolysis and acidolysis. The endo-toxemic-induced lung and kidney damages were successfully established by the lipopolysaccharides (LPS) injection (5 mg/kg/d). The in vivo mice experiments indicated that the ESPS showed superior antioxidant and protective effects against the LPS-toxicities by increasing the antioxidant activities, reducing lipid peroxidation, improving the inflammatory response and elevating the kidney and lung functions than SPS and ASPS. Furthermore, the selenium contents and structure of SPS, ESPS and ASPS were investigated through FAAS, GC, UV, HPGPC, FT-IR, NMR and the results indicated that SPS, ESPS and ASPS were homogeneous heteropolysaccharide with an average molecular weight of 3.12 × 104, 1.77 × 104, 1.41 × 104 Da, respectively. The conclusions demonstrated that the polysaccharides by O. radicata might be suitable for functional foods and natural drugs in preventing the endo-toxemia and its complications, and providing references for exploitation and utilization of natural substances.

Hepatoprotective effects of Auricularia cornea var. Li. polysaccharides against the alcoholic liver diseases through different metabolic pathways.

The present work was designed to evaluate the antioxidation and hepatoprotective effects of Auricularia cornea var. Li. polysaccharides (APS) and enzymatic-extractable APS (EAPS) on the acute alcohol-induced alcoholic liver diseases (ALD). The in vitro antioxidant activities demonstrated that both APS and EAPS had strong reducing power and potential effects on scavenging reactive oxygen species. The in vivo mice experiments showed that the pretreatment with APS or EAPS showed potential hepatoprotective effects on the ALD possibly by increasing the antioxidant activities, reducing the lipid peroxidation, improving the alcohol metabolism, inhibiting the expression levels of inflammatory mediators and preventing the alcohol-induced histopathological alterations. In addition, the fourier-transform infrared (FT-IR), 1H and 13C nuclear magnetic resonance spectroscopy (NMR) and gas chromatography (GC) had been analyzed to obtained the primarily characteristics. The results indicated that abundant xylose and glucose contents probably had potential effects on possessing the bioactivities. The findings suggested that the A. cornea var. Li. might be considered as promising natural resource on exploring clinical drugs for the prevention and treatment with ALD and its complications.

Antioxidant Activity and Protective Effects of Enzyme-Extracted Oudemansiella radiata Polysaccharides on Alcohol-Induced Liver Injury.

This work was to examine the antioxidation in vitro and hepatoprotective effects of enzyme-extracted Oudemansiella radiata polysaccharides (En-OPS) on alcohol-induced liver damage in mice. The antioxidant activities were determined according to the scavenging effects of En-OPS on hydroxyl, superoxide, and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals, and the level of reducing power. En-OPS showed hepatoprotective activities on decreasing the serum levels of aspertate aminotransferase (AST), alamine aminotransferase (ALT), and alkaline phosphatase (ALP), as well as hepatic lipid levels of total cholesterol (TC) and triacylglycerols (TG). En-OPS treatment reversed the acute impairment induced by alcohol consumption, including reactive oxygen species (ROS) generation, malondialdehyde (MAD), and lipid peroxide (LPO) elevation; and superoxide dismutase (SOD), GSH peroxide (GSH-Px), catalase (CAT), and total antioxidant capacity (T-AOC) impairment. The En-OPS effectively ameliorated alcohol metabolism by activating alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), and reducing cytochrome P450 2E1 (CYP2E1) levels. Furthermore, the histopathological observations also displayed that En-OPS could alleviate liver damage. These results indicated that En-OPS could be suitable to be an ingredient of preventing alcoholic liver diseases (ALD). In addition, the preliminary structure characteristics of En-OPS were also analyzed by Fourier transform infrared (FT-IR) spectroscopy and a gas chromatography-flame ionization detector (GC-FID).

Characterization, anti-oxidation and anti-inflammation of polysaccharides by Hypsizygus marmoreus against LPS-induced toxicity on lung.

In our present work, the polysaccharides (MPS) were successfully extracted from the mycelia of Hypsizygus marmoreus, and purpose of our work was to evaluate the analysis of the characterization, anti-inflammation and anti-oxidation against the lung failure induced by lipopolysaccharide (LPS) in mice. Pretreatment with MPS at 800mg/kg markedly ameliorated the lung wet-to-dry weight (W/D) ratio and pulmonary histopathological conditions, reduced the tumor necrosis factor-alpha (TNF)-α, interleukin (IL)-6, and IL-1ß levels in bronchoalveolar lavage fluid (BALF), myeloperoxidase (MPO) activities. In addition, the protective effects of MPS might be attributed to the down-regulations of the serum complement 3 (C3), glutamyl transpeptidase (GGT) and high-sensitivity C-reactive protein (hs-CPR) contents, as well as improving the antioxidant status by enhancing pulmonary enzyme activities (catalase (CAT), superoxide dismutase(SOD), glutathione peroxidase (GSH-Px) and total antioxidant capacity (T-AOC)) and eliminating the lipid peroxidation (LPO) and malondialdehyde (MDA), respectively. What's more, our work investigated the characterization of the MPS.

Polysaccharides with Antioxidative and Antiaging Activities from Enzymatic-Extractable Mycelium by Agrocybe aegerita (Brig.) Sing.

This study aimed to investigate the antioxidant, antiaging, and organ protective effects of the water-extractable mycelium polysaccharides (MPS) and enzymic-extractable mycelium polysaccharides (En-MPS) by Agrocybe aegerita (Brig.) Sing in D-galactose-induced (D-gal-induced) aging mice. In in vitro assays, the En-MPS demonstrated stronger antioxidant activities in dose-dependent manners. The mice experiments revealed that both En-MPS and MPS had potential effects on antioxidation, antiaging, and organ protection mainly by improving the antioxidant enzyme activities, decreasing the lipid peroxidation, and remitting the lipid metabolism. Furthermore, chemical composition and monosaccharide composition of polysaccharides were also measured, and the results indicated that differences in biological activity of MPS and En-MPS samples showed a significant correlation to their purity. The findings demonstrated that the polysaccharides by A. aegerita (Brig.) Sing could be exploited as natural and functional foods for the prevention and alleviation of aging and its complications.

The regulation of inflammation and oxidative status against lung injury of residue polysaccharides by Lentinula edodes.

In present study, two hydrolyzed residue polysaccharides (RPS) of enzymatic-RPS (ERPS) and acidic-RPS (ARPS) were successfully obtained from the residue of Lentinula edodes, and the anti-inflammatory as well as antioxidative effects on lipopolysaccharide-induced (LPS-induced) lung injured mice were investigated. The results demonstrated that ERPS showed superior lung protective effects by ameliorating the lung wet-to-dry weight (W/D) ratio, reducing the TNF-α, IL-6, and IL-1ß levels in BALF, lowing the pulmonary MPO activity, decreasing the serum C3 and hs-CPR contents, as well as improving the antioxidant status by enhancing pulmonary enzyme activities (SOD, GSH-Px, CAT, and T-AOC) and eliminating the lipid peroxidation (MDA and LPO), respectively. These conclusions indicated that both RPS and its hydrolysates (ARPS and ERPS) might be suitable for functional foods and a potentially effective candidate medicine for the treatment of lung injury.

The antioxidative and anti-aging effects of acidic- and alkalic-extractable mycelium polysaccharides by Agrocybe aegerita (Brig.) Sing.

Two extractable polysaccharides of Ac-MPS and Al-MPS were extracted from the mycelium of Agrocybe aegerita (Brig.) Sing and the in vitro antioxidant activities and in vivo anti-aging activities in a d-gal-induced aging mice were investigated in the present study. The in vitro antioxidant analysis showed that Ac-MPS showed superior scavenging effects on hydroxyl of 68.62±2.59% and DPPH of 85.19±3.26% at the concentration of 4500µg/mL. Biochemical indices and antioxidant analysis in vivo showed that Ac-MPS had better effects in raising hepatic activities of SOD, CAT, GPx and T-AOC, inhibiting hepatic contents of LPO and MDA, as well as improving serum lipid levels of LDL-C, HDL-C, LDL-C/HDL-C, TG and TC. Furthermore, HYP measurements suggested that skin collagen in aging mice could be maintained. This study suggested that both Ac-MPS and Al-MPS could be used as potential natural agents or dietary supplements in attenuating aging and its complications.

Characterization, antioxidation, anti-inflammation and renoprotection effects of selenized mycelia polysaccharides from Oudemansiella radicata.

The present work investigated the characteristics, antioxidative, anti-inflammative and renoprotective effects of mycelia selenized polysaccharides (MSPS) from Oudemansiella radicata on lipopolysaccharide (LPS)-induced kidney damaged mice. The results demonstrated that both MSPS and mycelia polysaccharides (MPS) showed potential renoprotective effects reflecting by decreasing the serum levels of CRE, BUN and UA, increasing the nephritic enzyme activities of SOD, GSH-Px, CAT and T-AOC, reducing the activities of MPO, as well as down-regulating the contents of MDA and LPO, respectively. And the MSPS showed superior effects. Furthermore, the selenium contents and physical properties of polysaccharides were investigated by FAAS, GC, HPGPC, FT-IR, NMR and AFM analysis, and the results indicated that MSPS was a homogeneous heteropolysaccharide with an average molecular weight of 3.12×104Da. These results may provide theoretical basis in applying natural and functional foods for the prevention and alleviation of kidney damages and its complications.

Purification, in vitro antioxidant and in vivo anti-aging activities of soluble polysaccharides by enzyme-assisted extraction from Agaricus bisporus.

In present study, the soluble polysaccharides by enzyme-assisted extraction from Agaricus bisporus (EnAPS) and its purified fractions of EnAPS-1, -2 and -3 were successfully obtained, and the antioxidant activities and anti-aging effects were investigated. The in vitro antioxidant assay demonstrated that EnAPS-2 had superior scavenging activities on DPPH and hydroxyl radicals, chelating activities of Fe2+ and reducing power. The in vivo animal experiments showed that both EnAPS and its purifies fractions had potential anti-aging effects against the d-galctose-induced aging diseases on liver, kidney, brain and skin, possibly by increasing the antioxidant enzymes, reducing the lipid peroxidation, improving the organ functions and remitting the lipid metabolism. The conclusions demonstrated that the polysaccharides by A. bisporus might be suitable for applying functional foods and natural drugs in preventing and delaying the aging and its complications.

Antioxidant and anti-aging effects of acidic-extractable polysaccharides by Agaricus bisporus.

This study was designed to investigate the antioxidant and anti-aging effects of D-galatose-induced (D-gal-induced) aging mice as well as monosaccharide compositions of acidic-extractable polysaccharides (AcAPS) and its major purified fractions (AcAPS-1, AcAPS-2 and AcAPS-3) from the fruiting body of Agaricus bisporus. In the in vitro assays, AcAPS-2 showed superior scavenging activities on hydroxyl (82.98±4.67%) and DPPH (64.47±4.05%) radicals at the concentration of 1.0mg/mL than AcAPS and other polysaccharides fractions. For in vivo anti-aging analysis, AcAPS-2 showed superior effects on hepatic and nephric protection by improving serum enzyme activities, biochemical levels, lipid contents and antioxidant status, respectively. The monosaccharide analysis showed that rhamnose (Rha) and glucose (Glu) may play vital roles in maintaining the antioxidant and anti-aging activities. The results suggested that both AcAPS and its purified fractions might be suitable for functional foods and natural drugs in preventing the acute aging-associated diseases.

The Antioxidative, Antiaging, and Hepatoprotective Effects of Alkali-Extractable Polysaccharides by Agaricus bisporus.

The aim of this work was designed to investigate the antioxidant, antiaging, and hepatoprotective effects of alkali-extractable polysaccharides (AlAPS) and their three purified fractions (AlAPS-1, AlAPS-2, and AlAPS-3) from Agaricus bisporus in D-galactose induced aging mice. For in vitro antioxidant analysis, both AlAPS and its fractions exhibited moderate reducing power, Fe2+-chelating activities, and potent scavenging activities on hydroxyl and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals. The in vivo results demonstrated that the polysaccharides, especially AlAPS-2, showed potential antiaging and hepatoprotective effects by enhancing the antioxidant status, decreasing serum hepatic enzyme activities, and improving the lipid metabolism. This study suggested that the polysaccharides extracted and purified from A. bisporus could be exploited as a potent dietary supplement to attenuate aging and prevent age-related diseases.

Anti-hyperlipidemic and antioxidant effects of alkali-extractable mycelia polysaccharides by Pleurotus eryngii var. tuolensis.

In this study, we noted that the Al-MPS from Pleurotus eryngii var. tuolensis provoked pharmacological effects on blood lipid profiles and oxidative stress. Animal studies demonstrated that Al-MPS showed potential effects on relieving hyperlipidemia and preventing oxidative stress, reflecting by decreasing the levels of serum enzyme activities (ALP, ALT and AST), restoring the activities of antioxidant enzymes (SOD, GSH-Px, CAT and T-AOC), down-regulating the MDA and LPO contents, as well as remitting the hepatic and cardiac tissues injury, respectively. The serum levels of TC, TG, LDL-C, VLDL-C, and HDL-C on mice treated with Al-MPS (500mg/kg bw) reached 2.48±0.08, 1.24±0.03, 0.84±0.02, 0.34±0.02, and 1.80±0.03mmol/L, which were lower/higher against the hyperlipidemia mice. The results clearly indicated that the Al-MPS could be used as a beneficial health food and potentially natural candidate medicine in preventing the high-fat emulsion-induced hyperlipidemia.

Antioxidative, anti-inflammation and lung-protective effects of mycelia selenium polysaccharides from Oudemansiella radicata.

The present work was designed to investigated the antioxidant, anti-inflammation, and pulmonary protective effects of SMPS and MPS from Oudemansiella radicata on LPS-induced lung injured mice. The results demonstrated that SMPS showed potential effects on relieving lung injury and preventing oxidative stress, reflecting by decreasing the serum levels of C3, CRP and GGT, increasing the pulmonary activities of SOD, GSH-Px, CAT and T-AOC, as well as down-regulating the MDA and LPO contents, respectively. Furthermore, the levels of TNF-α (224.211±3.12ng/mL), IL-1ß (254.557±2.18ng/L), and IL-6 (18.214±0.15ng/L) in BALF of mice treated with SMPS at the dosage of 400mg/kg/d significantly lower than that in the lung injured mice. These conclusions indicated that both SMPS and MPS possessed potent antioxidants and anti-inflammation activities, and could be used as functional foods and natural drugs in preventing lung injury.

Protective effects on liver, kidney and pancreas of enzymatic- and acidic-hydrolysis of polysaccharides by spent mushroom compost (Hypsizigus marmoreus).

The present work investigated the protective effects on liver, kidneys and pancreas of spent mushroom compost polysaccharide (SCP) and its hydrolysates (enzymatic- (ESCP) and acid-hydrolyzed SCP (ASCP)) from Hypsizigus marmoreus, in streptozotocin (STZ)-induced diabetic mice. The results showed that enzymatic (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT)) and non-enzymatic activities (total antioxidant capacity (T-AOC)) were significantly increased, the lipid peroxide contents (lipid peroxide (LPO) and malonaldehyde (MDA)) were remarkably reduced, and the clinical parameters were observably mitigated in diabetic mice treated with these three polysaccharides. Furthermore, histological observations also indicated recovery. These conclusions demonstrated that both SCP and its hydrolysates ESCP and ASCP possessed potent antioxidant activities and can be used as a potentially functional food for the prevention of diabetes and its complications induced by STZ.

Processing optimization and anti-oxidative activity of enzymatic extractable polysaccharides from Pleurotus djamor.

In present study, a quadratic regression model based on the response surface methodology (RSM) coupled with Box-Behnken design (BBD) was employed to optimize the enzyme-assisted extraction (EAE) process of enzymatic-extractable Pleurotus djamor polysaccharides (EnPPs). By solving the regression equations and analyzing the model graphs, the optimum conditions were at pH 7.36, water to material ratio 56.78, extraction time 44.77min and extraction temperature 35.36°C, respectively. Under these conditions, the experimental yields of EnPPs reached 3.61%, which were in good agreement with the validated values (3.57±0.51%). Basic physicochemical properties including molecular weights, structural identification by FT-IR and monosaccharide compositions were processed. In addition, the in vivo inhibiting activities against oxidative stress were investigated. The results provided an alternative bioresource for the exploitation of EnPPs under EAE from P. djamor, and the EnPPs had potential effects in prevention of oxidative stress.

Hepatoprotection of enzymatic-extractable mycelia zinc polysaccharides by Pleurotus eryngii var. tuoliensis.

The purpose of this work was designed to investigate the hepatoprotective and antioxidant effects of enzymatic-extractable mycelia zinc polysaccharides (En-MZPS) from Pleurotus eryngii var. tuoliensis on the hyperlipidemic mice induced by high-fat-high-cholesterol emulsion (HFHCM). The results showed that the supplementation of En-MZPS had potential anti-hyperlipidemia effects on reducing hepatic lipid levels by monitoring the serum enzyme activities (ALP, ALT and AST) and serum lipid levels (TC, TG, HDL-C, LDL-C and VLDL-C), enhancing the antioxidant enzymes (SOD, GSH-Px, CAT and T-AOC), and decreasing the lipid peroxidation (MDA and LPO). Furthermore, the in vitro scavenging results indicated that the inhibition effects of En-MZPS on hydroxyl radicals and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals reached 59.98±6.29% and 37.01±2.15%, respectively. These conclusions demonstrated that the En-MZPS might be suitable for functional foods and natural drugs in preventing the HFHCM-induced hyperlipidemia and non-alcoholic fatty liver.