Structural characterization and hypoglycemic effect of polysaccharides of Polygonatum sibiricum.

Polygonatum sibiricum polysaccharide (PSP) was extracted and purified from raw material obtained from P. sibiricum. The structural features of PSP were investigated by Congo red, circular dichroism spectrum, high-performance gel permeation chromatography, scanning electron microscope, atomic force microscope, ultraviolet spectroscopy, and Fourier transform infrared spectroscopy analysis. In vitro simulations were conducted to investigate the kinetics of PSP enzyme inhibition. Moreover, a type II diabetes mouse model (T2DM) with streptozotocin-induced insulin resistance was established, and the indexes of lipid quadruple, insulin resistance index, oral glucose tolerance (OGTT), organ index, and pancreatic morphology of model mice were measured. The results showed that PSP mainly consists of monosaccharides, such as mannose, glucose, galactose, xylose, and arabinose. It also has a ß-glycosidic bond of a pyranose ring and an irregular reticulated aggregated structure with a triple helix. In vitro enzyme inhibition assays revealed that PSP acts as a reversible competitive inhibitor of α-glucosidase and α-amylase. Furthermore, PSP was found to reduce insulin resistance index, increase OGTT and serum insulin levels, decrease free fatty acid content to improve lipid metabolism, and lower glycated serum protein content to enhance glucose metabolism in T2DM mice, thereby leading to a reduction in blood glucose concentration. Additionally, PSP exhibited reparative effects on the damaged liver tissue cells and pancreatic tissue in T2DM mice. The experiment results provide a preliminary basis for the therapeutic mechanism of PSP about type II diabetes and a theoretical reference for application in food and pharmaceutical development.

Ultrasound-assisted hydrogen peroxide-ascorbic acid method to degrade sweet corncob polysaccharides can help treat type 2 diabetes via multiple pathways in vivo.

In this study, we aimed to investigate the impact of various ultrasound durations on the structure and bioactivity of sweet corncob polysaccharides treated with ultrasound-assisted degradation using hydrogen peroxide and ascorbic acid (H2O2-Vc). We subjected sweet corncob polysaccharides to ultrasound treatment for 0, 30, 60, and 90 min alongside the H2O2-Vc method. We then analyzed their chemical composition and structure. Additionally, we administered these polysaccharides to mice with type 2 diabetes (T2DM) through gavage at a dosage of 200 mg/kg/day. The results indicated a significant reduction in the molecular weight of the degraded sweet corncob polysaccharides, while their composition remained relatively stable. However, the basic structure of the polysaccharides was retained. In vivo experiments demonstrated that ultrasound-assisted degradation of these polysaccharides had a positive impact on T2DM, particularly the 60-minute ultrasound treatment (UH-DSCBP-60 min), which effectively controlled blood glucose levels by regulating glycolipid metabolism in the livers of mice with T2DM. This approach also reduced inflammation and oxidative stress levels and inhibited disaccharide activity in the small intestine. We demonstrated that ultrasound can positively affect the sweet corncob polysaccharides hypoglycemic activity. The findings of our study provide a theoretical foundation for the valuable utilization of sweet corncob polysaccharides.

Structural Characterization, In Vitro Digestion Property, and Biological Activity of Sweet Corn Cob Polysaccharide Iron (III) Complexes.

This study aimed to enhance the utilization value of sweet corn cob, an agricultural cereal byproduct. Sweet corn cob polysaccharide-ron (III) complexes were prepared at four different temperatures (40 °C, 50 °C, 60 °C, and 70 °C). It was demonstrated that the complexes prepared at different temperatures were successfully bound to iron (III), and there was no significant difference in chemical composition; and SCCP-Fe-C demonstrated the highest iron content. The structural characterization suggested that sweet corn cob polysaccharide (SCCP) formed stable ß-FeOOH iron nuclei with -OH and -OOH. All the four complexes' thermal stability was enhanced, especially in SCCP-Fe-C. In vitro iron (III) release experiments revealed that all four complexes were rapidly released and acted as iron (III) supplements. Moreover, in vitro antioxidant, α-glucosidase, and α-amylase inhibition studies revealed that the biological activities of all four complexes were enhanced compared with those of SCCP. SCCP-Fe-B and SCCP-Fe-C exhibited the highest in vitro antioxidant, α-glucosidase, and α-amylase inhibition abilities. This study will suggest using sweet corn cobs, a natural agricultural cereal byproduct, in functional foods. Furthermore, we proposed that the complexes prepared from agricultural byproducts can be used as a potential iron supplement.

Preparation of Au-RGO/TiO2 nanotubes and study on the photocatalytic degradation of ciprofloxacin.

Au-RGO/TiO2 nanotubes were prepared by anodic oxidation and electrochemical deposition, and their performance in the photocatalytic degradation of ciprofloxacin was investigated. The results showed that, compared with TiO2 nanotubes and RGO/TiO2 nanotubes, the Au-RGO/TiO2 nanotubes had the highest ciprofloxacin degradation rate, reaching 96.93% in 180 min of photocatalysis. In addition, the possible degradation products of ciprofloxacin were analyzed by liquid chromatography-mass spectrometry, and the mechanism of degradation of ciprofloxacin by Au-RGO/TiO2 nanotubes was analyzed.

Using Weighted Gene Co-Expression Network Analysis to Identify Increased MND1 Expression as a Predictor of Poor Breast Cancer Survival.

Objective: We used bioinformatics analysis to identify potential biomarker genes and their relationship with breast cancer (BC). Materials and Methods: We used a weighted gene co-expression network analysis (WGCNA) to create a co-expression network based on the top 25% genes in the GSE24124, GSE33926, and GSE86166 datasets obtained from the Gene Expression Omnibus. We used the DAVID online platform to perform GO and KEGG pathway enrichment analyses and the Cytoscape CytoHubba plug-in to screen the potential genes. Then, we related the genes to prognostic values in BC using the Oncomine, GEPIA, and Kaplan-Meier Plotter databases. Findings were validated by immunohistochemical (IHC) staining in the Human Protein Atlas and the TCGA-BRCA cohort. LinkedOmics identified the interactive expressions of hub genes. We used UALCAN to evaluate the methylation levels of these hub genes. MethSurv and SurvivalMeth were used to assess the multilevel prognostic value. Finally, we assessed hub gene association with immune cell infiltration using TIMER. Results: The mRNA levels of MKI67, UBE2C, GTSE1, CCNA2, and MND1 were significantly upregulated in BC, whereas ESR1, THSD4, TFF1, AGR2, and FOXA1 were significantly downregulated. The DNA methylation signature analysis showed a better prognosis in the low-risk group. Further subgroup analyses revealed that MND1 might serve as an independent risk factor for unfavorable BC prognosis. Additionally, MND1 expression levels positively correlate with the immune infiltration statuses of CD4+ T cells, CD8+ T cells, B cells, neutrophils, dendritic cells, and macrophages. Conclusion: Our results indicate that the ten hub genes may be involved in BC's carcinogenesis, development, or metastasis, and MND1 may be a potential biomarker and therapeutic target for BC.

Pyrotinib in the Treatment of Women With HER2-Positive Advanced Breast Cancer: A Multicenter, Prospective, Real-World Study.

BACKGROUND: HER2-positive breast cancer was aggressive, resulting in a poorer prognosis. This multicenter study analyzed the real-world data of women treated with pyrotinib-based therapy, aiming to describe their characteristics, treatment regimens, and to investigate the clinical outcomes. METHODS: A total of 141 patients with HER2-positive breast cancer were enrolled from February 2019 to April 2020. Last follow-up time was February 2021. All patients were treated with pyrotinib-based therapy in 21-day cycles. The primary endpoint was progression-free survival (PFS). RESULTS: The median PFS (mPFS) for pyrotinib-based therapy was 12.0 months (95%CI 8.1-17.8) in all patients. Among the patients with liver metastases, mPFS was 8.7 months (95%CI, 6.3-15.4) compared to 12.3 months (95%CI, 8.8-23.3) for patients without liver metastases (P=0.172). In addition, patients receiving pyrotinib-based therapy as their >2 lines treatment had a numerically lower mPFS than those receiving pyrotinib-based therapy as their ≤2 lines treatment [8.4 (95%CI, 5.9-15.4) vs. 15.1 (95%CI, 9.3-22.9) months, P=0.107]. The mPFS was 12.2 months (95%CI, 7.9-18.8) in patients with previous exposure to trastuzumab and 11.8 months (95%CI, 6.8-22.9) in patients without previous exposure to trastuzumab (P=0.732). Moreover, mPFS in patients receiving regimens with and without capecitabine were 15.1 months (95%CI, 10.0-18.8) and 8.4 months (95%CI, 6.7-22.9), respectively (P=0.070). Furthermore, in patients with brain metastases, estimated 6-month PFS rate was 70.0%, and rate at 12 months was 60.0%. Seventy patients with measurable lesions were evaluable for response. The objective response rate was 38.6% and disease control rate was 85.7%. The most common adverse event was diarrhea (85.0%). CONCLUSION: Pyrotinib-based therapy showed promising efficacy in patients with HER2-positive breast cancer and was well tolerated, especially in patients treated with pyrotinib as ≤2 lines treatment and receiving regimens with capecitabine. The results of this real-world study further confirmed the intriguing efficacy of pyrotinib.

Adjuvant Capecitabine With Docetaxel and Cyclophosphamide Plus Epirubicin for Triple-Negative Breast Cancer (CBCSG010): An Open-Label, Randomized, Multicenter, Phase III Trial.

PURPOSE: Standard adjuvant chemotherapy for triple-negative breast cancer (TNBC) includes a taxane and an anthracycline. Concomitant capecitabine may be beneficial, but robust data to support this are lacking. The efficacy and safety of the addition of capecitabine into the TNBC adjuvant treatment regimen was evaluated. PATIENTS AND METHODS: This randomized, open-label, phase III trial was conducted in China. Eligible female patients with early TNBC after definitive surgery were randomly assigned (1:1) to either capecitabine (3 cycles of capecitabine and docetaxel followed by 3 cycles of capecitabine, epirubicin, and cyclophosphamide) or control treatment (3 cycles of docetaxel followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide). Randomization was centralized without stratification. The primary end point was disease-free survival (DFS). RESULTS: Between June 2012 and December 2013, 636 patients with TNBC were screened, and 585 were randomly assigned to treatment (control, 288; capecitabine, 297). Median follow-up was 67 months. The 5-year DFS rate was higher for capecitabine than for control treatment (86.3% v 80.4%; hazard ratio, 0.66; 95% CI, 0.44 to 0.99; P = .044). Five-year overall survival rates were numerically higher but not significantly improved (capecitabine, 93.3%; control, 90.7%). Overall, 39.1% of patients had capecitabine dose reductions, and 8.4% reported grade ≥ 3 hand-foot syndrome. The most common grade ≥ 3 hematologic toxicities were neutropenia (capecitabine, 136 [45.8%]; control, 118 [41.0%]) and febrile neutropenia (capecitabine, 50 [16.8%]; control, 46 [16.0%]). Safety data were similar to the known capecitabine safety profile and generally comparable between arms. CONCLUSION: Capecitabine when added to 3 cycles of docetaxel followed by 3 cycles of a 3-drug anthracycline combination containing capecitabine instead of fluorouracil significantly improved DFS in TNBC without new safety concerns.

A four-gene signature for prognosis in breast cancer patients with hypermethylated IL15RA.

Previous studies have revealed that upregulation of interleukin 15 receptor α (IL15RA) contributes to improved prognosis of breast cancer. The present study aimed to elucidate the molecular mechanisms underlying the antitumor effect induced by IL15RA upregulation, and to identify a gene signature capable of predicting the survival of patients with breast cancer. Using paired gene expression and methylation data of breast cancer samples from The Cancer Genome Atlas data portal, differentially expressed genes (DEGs) were identified in hypermethylated and hypomethylated IL15RA breast cancer samples. Furthermore, a gene signature-based risk-scoring model was developed according to the Cox regression coefficients of survival-associated DEGS. The gene signature was applied to classify patients with breast cancer and hypermethylated IL15RA into two risk groups via Kaplan-Meier survival analysis of overall survival (OS) time. Functional enrichment analysis was conducted to decipher the biological roles of the DEGs between the two risk groups. A total of 326 DEGs were present in the hypomethylation and hypermethylation samples compared with in the normal samples. A four-gene signature [SH3 and cysteine rich domain 2 (STAC2), proline rich 11 (PRR11), homeobox C11 (HOXC11) and nucleolar and spindle associated protein 1 (NUSAP1)] was identified as able to successfully separate patients with breast cancer and hypermethylated IL15RA into two risk groups with significantly different OS time. The signature revealed similar predictive performance in an independent set. Significant enrichment of the 'receptor interaction' and 'cell adhesion molecules (CAM)' pathways, which involved the DEGs, occurred between the two risk groups. These findings suggested that IL15RA may participate in the regulation of STAC2, PRR11, HOXC11, NUSAP1, and 'ECM-receptor interaction' and 'cell adhesion molecules' pathways, and therefore in the suppression of breast cancer development and progression. The four-gene signature may have potential prognostic value for breast cancer.

Patterns of Use of Docetaxel-Containing Adjuvant Chemotherapy Among Chinese Patients with Operable Breast Cancer: A Multicenter Observational Study.

INTRODUCTION: Adjuvant docetaxel-based chemotherapy is frequently used in the treatment of operable early breast cancer (EBC). This study investigated patterns of docetaxel use in patients with EBC in real-world clinical practice in China. METHODS: This was a multicenter, prospective, observational study of Chinese women with operable breast cancer in tier 1 non-oncology-specific hospitals and other city hospitals in China. Adult Chinese female patients (≥ 18 years) with newly diagnosed breast cancer who underwent surgery and received docetaxel-containing adjuvant chemotherapy were eligible for inclusion. The primary end point of the study was to assess patterns of docetaxel use for adjuvant therapy in Chinese clinical practice. Secondary end points included factors associated with treatment selection, patterns of G-CSF use and safety. RESULTS: In total, 502 patients were enrolled, 475 of whom were included in the analysis. The results showed that 31.6% of patients received docetaxel and anthracyclines in combination, 47.2% received docetaxel and anthracyclines sequentially, 18.5% received docetaxel and other medication either in combination or sequentially and 2.7% received 'other' chemotherapy regimens. Factors influencing selection of docetaxel/anthracycline in combination versus sequentially included age, breast cancer subgroup, PR status, and preoperative neoadjuvant chemotherapy. A total of 258 (54.3%), 35 (7.4%), and 108 (22.7%) patients received G-CSF as primary prevention, secondary prevention and treatment, respectively. Treatment-emergent adverse events (TEAEs) occurred in 54.5% (259) of patients, and the most frequently reported TEAEs (≥ 5% of patients) included bone marrow failure (10.1%), granulocytopenia (9.9%), nausea (8.8%) and vomiting (6.9%). Neutropenia and febrile neutropenia were reported by 10 and 12 patients, respectively. CONCLUSION: Docetaxel for adjuvant chemotherapy of operable EBC in China was most commonly given in combination or sequentially with anthracyclines. The study also showed that in China G-CSF is most frequently used as primary prophylactic, and no unexpected safety events were observed during docetaxel treatment. FUNDING: Sanofi (China).

Self-assembled reduced graphene oxide/polyacrylamide conductive composite films.

Substrate supported conductive thin films are prepared by the self-assembly of graphene oxide (GO) on a cationic polyacrylamide (CPAM) layer followed by a subsequent chemical reduction. During self-assembly, the dispersed GO nanosheets with a negative zeta potential from solution are spontaneously assembled onto the positively charged CPAM adsorption layer. In addition, CPAM adsorption on the substrate is studied with an electrochemical quartz crystal microbalance (EQCM), showing adsorption stabilization could be established in less than 150 s. The electrostatic interactions between GO and CPAM are investigated by changing the polarization potential with EQCM for the first time, and optimal conditions for facilitating self-assembly are determined. The self-assembled GO/CPAM films are further characterized by Raman spectroscopy, infrared spectroscopy and atomic force microscopy. Importantly, reduced GO (R-GO)/CPAM composite films exhibiting a sheet resistance of 3.1 kΩ/sq can be obtained via in situ reduction in sodium borohydride for 20 min at room temperature. This provides a simple, highly effective, and green route to prepare conductive graphene-based composite thin films.